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Our rationale was to investigate whether 18 F-FDG PET/MRI in addition to (guideline-recommended) conventional staging leads to changes in therapeutic management in patients with newly diagnosed breast cancer and compare the diagnostic accuracy of 18 F-FDG PET/MRI with that of conventional staging for determining the Union for International Cancer Control (UICC) stage. Methods: In this prospective, double-center study, 208 women with newly diagnosed, therapy-naïve invasive breast cancer were enrolled in accordance with the inclusion criteria. All patients underwent guideline-recommended conventional staging and whole-body 18 F-FDG PET/MRI with a dedicated breast examination. A multidisciplinary tumor board served to determine 2 different therapy recommendations for each patient, one based on conventional staging alone and another based on combined assessment of conventional staging and 18 F-FDG PET/MRI examinations. Major changes in therapy recommendations and differences between the conventional staging algorithm and 18 F-FDG PET/MRI for determining the correct UICC stage were reported and evaluated. Results: Major changes in therapeutic management based on combined assessment of conventional staging and 18 F-FDG PET/MRI were detected in 5 of 208 patients, amounting to changes in therapeutic management in 2.4% (95% CI, 0.78%-5.2%) of the study population. In determining the UICC stage, the guideline-based staging algorithm and 18 F-FDG PET/MRI were concordant in 135 of 208 (64.9%; 95% CI, 58%-71.4%) patients. The conventional guideline algorithm correctly determined the UICC stage in 130 of 208 (62.5%; 95% CI, 55.5%-69.1%) patients, and 18 F-FDG PET/MRI correctly determined the UICC stage in 170 of 208 (81.9%; 95% CI, 75.8%-86.7%) patients. Conclusion: Despite the diagnostic superiority of 18 F-FDG PET/MRI over conventional staging in determining the correct UICC stage, the current (guideline-recommended) conventional staging algorithm is sufficient for adequate therapeutic management of patients with newly diagnosed breast cancer, and 18 F-FDG PET/MRI does not have an impact on patient management., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Over 40% stage-III non-small-cell lung cancer (NSCLC) patients (pts) experience 5-year survival following multimodality treatment. Nevertheless, little is known about relevant late toxicities and quality-of-life (QoL) in the further long-term follow-up. Therefore, we invited pts from our randomized phase-III trial (Eberhardt et al., Journal of Clinical Oncology 2015) after 10 years from diagnosis to participate within a structured survivorship program (SSP) including follow-up imaging, laboratory parameters, cardio-pulmonary investigations, long-term toxicity evaluations and QoL questionnaires. Of 246 pts initially accrued, 161 were considered potentially resectable following the induction therapy and were randomized (80 to arm A: definitive chemoradiation; 81 to arm B: definitive surgery; 85 not randomized for different reasons; group C). 31 from 37 pts still alive after 10 years agreed to the SSP (13 in A; 12 in B; 6 in C). Clinically relevant long-term toxicities (grade 3 and 4) were rarely observed with no signal favoring any of the randomization arms. Furthermore, available data from the global QoL analysis did not show a signal favoring any definitive locoregional approach (Mean QoL in SSP A pts: 56.41/100, B pts: 64.39/100) and no late decline in comparison to baseline and early 1-year follow-up. This is the first comprehensive SSP of very late survival follow-up reported in stage-III NSCLC treated within a randomized multimodality trial and it may serve as important baseline information for physicians and pts deciding for a locoregional treatment option., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Pathological complete response (pCR) is a well-established prognostic factor in breast cancer treated with neoadjuvant systemic therapy (naST). The determining factors of pCR are known to be intrinsic subtype, proliferation index, grading, clinical tumor and nodal stage as well as type of systemic therapy. The addition of neoadjuvant radiotherapy (naRT) to this paradigm might improve response, freedom from disease, toxicity and cosmetic outcome compared to adjuvant radiotherapy. The factors for pCR and primary tumor regression when neoadjuvant radiation therapy is added to chemotherapy have not been thoroughly described., Methods: We performed a retrospective analysis of 341 patients (cT1-cT4/cN0-N+) treated with naRT and naST between 1990 and 2003. Patients underwent naRT to the breast and mostly to the supra-/infraclavicular lymph nodes combined with an electron or brachytherapy boost. NaST was given either sequentially or simultaneously to naRT using different regimens. We used the univariate and multivariate regression analysis to estimate the effect of different subgroups and treatment modalities on pCR (ypT0/Tis and ypN0) as well as complete primary tumor response (ypT0/Tis; bpCR) in our cohort. Receiver operating characteristic (ROC) analysis was performed to evaluate the interval between radiotherapy (RT) and resection (Rx) as well as radiotherapy dose., Results: Out of 341 patients, pCR and pbCR were achieved in 31% and 39%, respectively. pCR rate was influenced by resection type, breast cancer subtype, primary tumor stage and interval from radiation to surgery in the multivariate analysis. Univariate analysis of bpCR showed age, resection type, breast cancer subtype, clinical tumor stage and grading as significant factors. Resection type, subtype and clinical tumor stage remained significant in multivariate analysis. Radiation dose to the tumor and interval from radiation to surgery were not significant factors for pCR. However, when treatment factors were added to the model, a longer interval from radiotherapy to resection was a significant predictor for pCR., Conclusions: The factors associated with pCR following naST and naRT are similar to known factors after naST alone. Longer interval to surgery might to be associated with higher pCR rates. Dose escalation beyond 60 Gy did not result in higher response rates., (© 2024. The Author(s).)

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2024 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer., Competing Interests: Prof. Dr. med. Marc Thill was a member of advisory board Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Neodynamics, Novartis, Onkowissen, Organon, Pfizer, pfm medical, Pierre Fabre, Roche, RTI Surgical, Seagen, Sirius Medical, and Sysmex; received manuscript support from Amgen, ClearCut, Clovis, Organon, pfm medical, Roche, and Servier; received travel expenses from Amgen, Art Tempi, AstraZeneca, Clearcut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, MSD, Neodynamics, Novartis, Pfizer, pfm medical, Roche, RTI Surgical, and Seagen; received congress support from Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Gilead, Hexal, Lilly, Neodynamics, Novartis, Pfizer, Pierre Fabre, Roche, and Sirius Medical; has received lecture honoraria from Amgen, Art Tempi, AstraZeneca, Clovis, Connect Medica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al. Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, StreamedUp, Stemline, Sysmex, Vifor, Viatris, and ZP Therapeutics; has received trial funding from Endomag, Exact Sciences; and received trial honoraria (institutional) from AstraZeneca, Biom’Up, Cairn Surgical, Celgene, Clearcut, Neodynamics, Novartis, pfm medical, Roche, and RTI Surgical. Prof. Dr. med. Wolfgang Janni has received research grants and/or honoraria from AstraZeneca, Celgene, Chugai, Daiichi Sankyo, Eisai, ExactScience, GSK, Janssen, Lilly, Menarini, MSD, Novartis, Sanofi Aventis, Roche, Pfizer, Seagen, Gilead, Inivata, and Guardant Health. Prof. Dr. med. Ute-Susann Albert has received lectures from Pfizer, Novartis, AstraZeneca, was a member of advisory board Daiichi Sankyo, and Pfizer. Prof. Dr. Malgorzata Banys-Paluchowski has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Stemline, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Medical, Syantra, Pierre Fabre, and ExactSciences; received study support from EndoMag, Mammotome, MeritMedical, Gilead, Hologic, and ExactSciences; and received travel/congress support from Eli Lilly, ExactSciences, Pierre Fabre, Pfizer, AstraZeneca, Daiichi Sankyo, and Roche. Dr. med. Ingo Bauerfeind has received honoraria and travel reimbursement from Brustkrebs Deutschland e.V., Krankenhaus Kempten, Akademie für Psychoonkologie, IF-Kongress Management. Prof. Dr. med. Jens-Uwe Blohmer has received honoraria for advisory boards and lectures from Astra Zeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, and Seagen. Prof. Dr. med. Wilfried Budach has received honoraria for lectures and advisory boards from Merck, BMS, Jörg Eickeler Veranstaltungen, medpublico GmbH, and BVDST. Prof. Dr. med. Peter Dall has received honoraria for lectures and advisory boards from Novartis, Pierre Fabré, MSD, Lilly, and AstraZeneca. Prof. Dr. Nina Ditsch was a member of advisory boards and speakers bureaus AstraZeneca, Aurikamed, BGGF, Daiichi Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead Sciences, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molekular Health, MSD, Novartis, onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, and Seagen. Prof. Dr. med. Eva Maria Fallenberg has received research grant from DFG and speaker honorarium from GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO, and B-Rayz. Prof. Dr. med. Peter A. Fasching participate on a data safety monitoring board or advisory board: Novartis, Pfizer, Roche, Daiichi Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, and Mylan; has received honoraria for lecture, speakers bureaus, manuscript writing, or educational events from Novartis, Pfizer, Roche, Daiichi Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, and Mylan; and has received consulting from Novartis, Pfizer, Roche, Daiichi Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, and Mylan. Medical Writing: Merck, to institution: Biontech, Cepheid, Pfizer. Prof. Dr. med. Tanja N. Fehm has receiverd honoraria from Onkowissen. Prof. Dr. med. Michael Friedrich was a member of advisory board: Gilead Sciences has received other honoraria from Roche, MSD. Prof. Dr. med. Bernd Gerber has received travel support from Pfizer. PD Dr. med. Oleg Gluz has received honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi Sanyko, Eisai, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, Agendia, MedConcept, and GynUpdate, Minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Nadia Harbeck, MD has received honoraria for lectures and/or consulting from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Viatris, and Zuelligpharma; received other from Co-Director West German Study Group (WSG). Prof. Dr. med. Andreas Daniel Hartkopf has received honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, Daichi Sankyo, Eisai, ExactScience, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen, Stemline, and Verazyte. Prof. Dr. med. Jens Huober has received honoraria for lectures from Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Seagen, Gilead, and Daiichi; has received honoraria for consulting/advisory board from Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Daiichi, and Gilead; and has received travel grants from Roche, Pfizer, Daiichi, and Gilead. Prof. Dr. med. Christian Jackisch was a member of advisory board Astra Zeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre Fabre, Roche, and Seagen and received lecture from Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre Fabre, Exact Sciences, MSD, GynUpdate, and StreamedUp. Prof. Dr. med. Cornelia Kolberg-Liedtke was a member of advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, and Onkowissen; has received lecture from NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, and Daiichi Sankyo; received other honoraria from Gilead Science and POMME; and stockholding Theraclion SA. Prof. Dr. med. Hans-Heinrich Kreipe was a member of advisory board: Lilly; has received lecture from AstraZeneca, Roche, Daiichi Sankyo, and Pfizer. PD Dr. David Krug has received lecture from Merck Sharp and Dohme, Pfizer, Astra Zeneca, onkowissen, med update; was a member of advisory board: Gilead; and has received research funding from Merch KGaA and Deutsche Krebshilfe. Prof. Dr.med. Thorsten Kühn was a member of advisory board/lecture Sysmex, Neodynamics, Pfizer, MSD, Merit Medical, Sirius Medical, Hologic, Endomag, Lilly; and has received trial funding from Merit Medical, Endomag, Mammotome. Prof. Dr. med. Sherko Kümmel has received lecture from Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, MSD, Pfizer, Seagen, Gilead, Agendia; Hologic, PINK!, and Stemline; has received other honoraria from Roche, Daiichi Sankyo, and Sonoscape; was a member of advisory board Lilly, MSD, Roche, Astra Zeneca, Stemline, Novartis, Daiichi Sankyo, MSD, Seagen, Gilead, and Exact Science. Prof. Dr. med. Sibylle Loibl was a member of advisory board, institutional: Abbvie, Amgen, AstraZeneca, BMS, Celgene, DSI, Eirgenix, GSK, Gilead Science, Lilly, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeuticas, Puma, Roche, Seagen, and Stemline-Menarini; invited speaker, personal: Medscape; and has received trial funding/others from Astra Zeneca, Abbvie, Celgene, Daiichi Sankyo, Greenwich Life Sciences, GSK, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Stemline-Menarini, and VM Scope GmbH. Prof. Dr. med. Diana Lüftner D.L. has received honoraria for advisory board activities and/or oral presentations from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, GSK, high5md, Loreal, MSD, Mundipharma, Novartis, onkowissen.de, Pfizer, Pierre Fabre, Roche, and TEVA. Prof. Dr. med. Michael Patrick Lux M.P.L. has received honoraria from Lilly, Pfizer, Roche, MSD, Hexal, Novartis, AstraZeneca, Eisai, Exact Sciences, Agendia, Daiichi Sankyo, Grünenthal, Gilead, Pierre Fabre, PharmaMar, Samantree, Endomag, and medac for advisory boards, lectures, and travel support. Prof. Dr. med. Nicolai Maass was a member of advisory board Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, and Seagen has received lecture from Astra Zeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, and Roche. Prof. Dr. med. Christoph Mundhenke was a member of advisory board AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, and Novartis and has received lecture from Pfizer and Novartis. Prof. Dr. med. Toralf Reimer has received trial funding from German Cancer Aid and Else Kroener-Fresenius-Stiftungwas a member of advisory board MSD, Novartis, and Myriad; and has received lecture from Pfizer, Novartis, Roche, and AstraZeneca. Prof. Dr. med. Kerstin Rhiem has received honoraria from AstraZeneca, Roche, Novartis, streamed up. Prof. Dr. med. Achim Rody was a member of advisory board AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, MSD, Gilead; has received lecture from Pfizer, Celgene, Eisai; and has received trial funding from Eisai. Prof. Dr. med. Marcus Schmidt M.S. reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, GILEAD, Lilly, Menarini-Stemline, Molecular Health, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen, His institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. med. Andreas Schneeweiss has received research grants from Celgene, Roche; has received honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, ClinSol, Clovis Oncology, coma UroGyn, Connectmedica, Daiichi Sankyo, Gilead, GSK, if-kongress, I-MED, iOMEDICO, Lilly, MCI Deutschland, med publico, Metaplan, MSD, Mylan, NanoString Technologies, Novartis, onkowissen.de, Pfizer, Pierre Fabre, promedicis, Roche, Seagen, streamedup, and Tesaro; and has received travel support from AstraZeneca, Celgene, Daiichi Sankyo, Gilead, Pfizer, and Roche. Prof. Dr. med. Florian Schütz has received lecture from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, ExactSciences, Gilead, Lilly, MSD, Novartis, ClinSol, Pfizer, and Roche Pharma; was a member of advisory board Lilly, MSD, Gilead, Atheneum Partners, and ClinSol; and received travel expenses from Lilly, Gilead. Prof. Dr. med. Hans-Peter Sinn was a member of advisory board Astra Zeneca, Exact Sciences, and Daiichi Sankyo; has received lecture from AstraZeneca and Diacentus; and has received trial funding from AstraZeneca. Prof. Dr. med. Christine Solbach has received lecture from DiaLog Service GmbH, Jörg Eickeler, Pfizer, Roche, AstraZeneca, MedConcept, I-Med, GBG, BVF Akademie, and LÄK Hessen Akademie was a member of advisory board: MSD, Roche. Prof. Dr. med. Erich Solomeyer has received honoraria from Roche, Amgen, Celgen, Tesaro, Astra Zeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson Johnson, Daiichi Sankyo, Gilead, Exact Sciences, GSK, and Pierre Fabre. Prof. Dr. med. Elmar Stickeler was a member of advisory boards Amgen, Astra Zeneca, Gilead, Iomedico, Lilly, MSD, Novartis, Seagen, and Roche and received lecture from Astra Zeneca, BSH Düsseldorf, Gilead, Iomedico, MSD, Novartis, Onkowissen, Pfizer, PharmaMar, and Roche. Prof. Dr. med. Christoph Thomssen has received compensation for advisory boards, lectures or publications from Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, Nanostring, Novartis, Onkowissen, Pfizer, Roche, Seagen, Vifor. Prof. Dr. med. Michael Untch M. U. has received honoraria to travel support, lectures, and consulting or advisory role from AstraZeneca, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, and Eisai, all honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel has received lecture from Astra Zeneca, Lilly, Seagen, Daiichi Sankyo, Gilead, Pfizer and Novartis, and Onkowissen and has received Travel support from Roche and Lilly. Prof. Dr. med. Achim Wöckel has received compensation for advisory boards, lectures, trial funding advisory board from Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Exact Sciences, Pierre Fabre, Clovis, Organon, Daiji Sankyo, Seagen, Stemline, and Gilead. PD. Dr. Rachel Würstlein served as advisor, consultant, speaker, and travel grant Agendia, Amgen, Apogepha, Aristo, Astra Zeneca, Celgene, Clovis Oncology, Daiichi Sankyo, Eisai, Esteve, Exact Sciences, Gilead, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Sidekick, Stemline, Tesaro Bio, Teva, Veracyte, Viatris, Wiley, FOMF, Aurikamed, Clinsol, Pomme Med, medconcept, MCI, and MediSeminar. Prof. Dr. med. Volkmar Müller has received speaker honoraria Astra Zeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, and i-MED Institute; has received consultancy honoraria from Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Seagen, Gilead, and Stemline; has received institutional research support from Novartis, Roche, Seagen, Genentech, and Astra Zeneca; and has received travel grants from Astra Zeneca, Roche, Pfizer, Daiichi Sankyo, and Gilead. Prof. Dr. Tjoung-Won Park-Simon has received honoraria for lectures and/or consulting from Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, Exact Sciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, and Seagen and has received travel compensation from Roche, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Gilead, and Pierre Fabre. Prof. Dr. med. Jörg Heil has none to declare., (© 2024 S. Karger AG, Basel.)

Purpose: To summarize the radiotherapy-relevant statements of the 18th St. Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations., Methods: Statements and voting results from the 18th St. Gallen International Breast Cancer Consensus Conference were collected and analyzed according to their relevance for the radiation oncology community. The voting results were discussed in two hybrid meetings among the authors of this manuscript on March 18 and 19, 2023, in light of the German S3 guideline and the 2023 version of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) guidelines., Results and Conclusion: There was a high level of agreement between the radiotherapy-related statements of the 18th St. Gallen International Breast Cancer Consensus Conference and the German S3 and AGO guidelines. Discrepancies include the impact of number of lymph node metastases for the indication for postmastectomy radiotherapy., (© 2024. The Author(s).)

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, German Gynecological Oncology Group) Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer., Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024., Results and Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter., Competing Interests: Prof. Dr. Tjoung-Won Park-Simon has received honoraria for lectures and/or consulting from Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, ExactSciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, Seagen. Travel compensation: Roche, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Gilead, and Pierre Fabre. Prof. Dr. med. Ute-Susann Albert has received honoraria for lectures from Pfizer, Novartis, AstraZeneca and is a member of advisory board Daiichi Sankyo, Pfizer. Prof. Dr. Malgorzata Banys-Paluchowski has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Stemline, Samsung,Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Medical, Syantra, Pierre Fabre, ExactSciences, study support from EndoMag, Mammotome, Merit Medical, Gilead, Hologic, ExactSciences, and travel/congress support from Eli Lilly, ExactSciences, Pierre Fabre, Pfizer, AstraZeneca, Daiichi Sankyo, and Roche. Prof. Dr. med. Jens-Uwe Blohmer has received honoraria for advisory boards and lectures: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Seagen. Prof. Dr. med. Wilfried Budach has received honoraria for lectures and advisory boards: Merck, BMS, Jörg Eickeler Veranstaltungen, med publico GmbH, BVDST. Prof. Dr. med. Peter Dall has received honoraria for lectures and advisory boards from Novartis, Pierre Fabré, MSD, Lilly, AstraZeneca. Prof. Dr. Nina Ditsch was a member of advisory boards and speakers bureaus: AstraZeneca, Aurikamed, BGGF, Daiichi-Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead Sciences, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molekular Health, MSD, Novartis, Onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, Seagen. Prof. Dr. med. Eva Maria Fallenberg has received research grant from DFG and received speaker honorarium from GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO, B-Rayz. Prof. Dr. med. Peter A. Fasching: participation on a data safety monitoring board or advisory board: Novartis, Pfizer, Roche, Daiichi-Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, Mylan, has received honoraria for lecture, speakers bureaus, manuscript writing, or educational events from Novartis, Pfizer, Roche, Daiichi-Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, Mylan, consulting from Novartis, Pfizer, Roche, Daiichi-Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, Mylan. Medical Writing: Merck. To institution: Biontech, Cepheid, Pfizer. Prof. Dr. med. Michael Friedrich is a member of the advisory board Gilead Sciences and has received other honoraria from Roche, MSD. Prof. Dr. med. Bernd Gerber has received travel support from Pfizer. PD Dr. med. Oleg Gluz has received honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi Sanyko, Eisai, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, Agendia, MedConcept, GynUpdate, and minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Nadia Harbeck, MD has received honoraria for lectures and/or consulting from AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Viatris, Zuelligpharma, other are Co-Director West German Study Group (WSG). Prof. Dr. med. Andreas Daniel Hartkopf has received honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, DaichiiSankyo, Eisai, Exact Science, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen, Stemline, and Verazyte. Prof. Dr. med. Jens Huober has received honoraria for lectures: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Seagen, Gilead, Daiichi and honoraria for consulting/advisory board: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Daiichi, Gilead and received travel grants: Roche, Pfizer, Daiichi, Gilead. Prof. Dr. med. Christian Jackisch is a member of advisory board: AstraZeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre Fabre, Roche, Seagen; Lecture: Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre Fabre, Exact Sciences, MSD, GynUpdate, StreamedUp. Prof. Dr. med. Cornelia Kolberg-Liedtke is a member of advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, Onkowissen, has received honoraria for lectures from NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, Daiichi Sankyo. Other: Gilead Science, POMME. Stockholding: Theraclion SA. Prof. Dr. med. Hans-Heinrich Kreipe is a member of advisory board: Lilly, has received honoraria for lecture: AstraZeneca, Roche, Daiichi Sankyo, Pfizer. PD Dr. David Krug has received honoraria for lecture from Merck Sharp and Dohme, Pfizer, AstraZeneca, Onkowissen, med update is a member of advisory board: Gilead, has received research funding from Merch KGaA, Deutsche Krebshilfe. Prof. Dr. med. Thorsten Kühn is a member of advisory board/lecture: Sysmex, Neodynamics, Pfizer, MSD, Merit Medical, Sirius Medical, Hologic, Endomag, Lilly has received trial funding from Merit Medical, Endomag, Mammotome. Prof. Dr. med. Sherko Kümmel has received honoraria for lecture: Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, MSD, Pfizer, Seagen, Gilead, Agendia; Hologic, PINK!; Stemline, other honoraria from Roche, Daiichi Sankyo, Sonoscape, is a member of advisory board: Lilly, MSD, Roche, AstraZeneca, Stemline, Novartis, Daiichi Sankyo, MSD, Seagen, Gilead, Exact Science. Prof. Dr. med. Sibylle Loibl is a member of advisory board, institutional: Abbvie, Amgen, AstraZeneca, BMS, Celgene, DSI, Eirgenix, GSK, Gilead Science, Lilly, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeuticas, Puma, Roche, Seagen, Stemline-Menarini, invited speaker, personal: Medscape received trial funding/others from: AstraZeneca, Abbvie, Celgene, Daiichi-Sankyo, Greenwich Life Sciences, GSK, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Stemline-Menarini, VM Scope GmbH. Prof. Dr. med. Diana Lüftner has received honoraria for advisory board activities and/or oral presentations from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, GSK, high5md, Loreal, MSD, Mundipharma, Novartis, onkowissen.de, Pfizer, Pierre Fabre, Roche and TEVA. Prof. Dr. med. Michael Patrick Lux has received honoraria from Lilly, Pfizer, Roche, MSD, Hexal, Novartis, AstraZeneca, Eisai, Exact Sciences, Agendia, Daiichi-Sankyo, Grünenthal, Gilead, Pierre Fabre, PharmaMar, Samantree, Endomag, and medac for advisory boards, lectures, and travel support. Prof. Dr. med. Nicolai Maass was a member of advisory board: Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen and has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, Roche. Prof. Dr. med. Christoph Mundhenke was a member of advisory board: AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, Novartis, has received honoraria for lecture: Pfizer, Novartis. Prof. Dr. med. Toralf Reimer has received trial funding from German Cancer Aid and Else Kroener-Fresenius-Stiftung, is a member of advisory board: MSD, Novartis, Myriad lecture from: Pfizer, Novartis, Roche, AstraZeneca. Prof. Dr. med. Achim Rody was a member of advisory board: AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, MSD, Gilead, lecture Pfizer, Celgene, Eisai, has received trial funding from Eisai. Prof. Dr. med. Marcus Schmidt reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, GILEAD, Lilly, Menarini-Stemline, Molecular Health, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen, his institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. med. Andreas Schneeweiss has received research grants from Celgene, Roche, honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, ClinSol, Clovis Oncology, coma UroGyn, Connect Medica, Daiichi Sankyo, Gilead, GSK, if-kongress, I-MED, iOMEDICO, Lilly, MCI Deutschland, med publico, Metaplan, MSD, Mylan, NanoString Technologies, Novartis, onkowissen.de, Pfizer, Pierre Fabre, promedicis, Roche, Seagen, StreamedUp, and Tesaro, received travel support from AstraZeneca, Celgene, Daiichi Sankyo, Gilead, Pfizer, Roche. Prof. Dr. med. Florian Schütz has received honoraria for lecture Amgen, AstraZeneca, Daiichi Sankyo, Eisai, ExactSciences, Gilead, Lilly, MSD, Novartis, ClinSol, Pfizer, Roche Pharma, was a member of advisory board: Lilly, MSD, Gilead, Atheneum Partners, ClinSol, has received travel expenses from Lilly, Gilead. Prof. Dr. med. Hans-Peter Sinn was a member of advisory board: AstraZeneca, Exact Sciences, Daiichi Sankyo, has received honoraria for lecture from AstraZeneca, Diacentus, has received trial funding from AstraZeneca. Prof. Dr. med. Christine Solbach has received honoraria for lecture: DiaLog Service GmbH, Jörg Eickeler, Pfizer, Roche, AstraZeneca, MedConcept, I-Med, GBG, BVF Akademie, LÄK Hessen Akademie, was a member of advisory board: MSD, Roche. Prof. Dr. med. Elmar Stickeler was a member of advisory boards Amgen, AstraZeneca, Gilead, Iomedico, Lilly, MSD, Novartis, Seagen, Roche; has received honoraria for lecture: AstraZeneca, BSH Düsseldorf, Gilead, Iomedico, MSD, Novartis, Onkowissen, Pfizer, PharmaMar, Roche. Prof. Dr. med. Christoph Thomssen: compensation for advisory boards, lectures or publications. Amgen, AstraZeneca, Aurikamed, Daiichi-Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, med update, MSD, Nanostring, Novartis, Onkowissen, Pfizer, Roche, Seagen, Vifor. Prof. Dr. med. Michael Untch has received honoraria to travel support, lectures, and consulting or advisory role from AstraZeneca, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi-Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, Eisai, all honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel has received honoraria for lecture: AstraZeneca, Lilly, Seagen, Daiichi Sankyo, Gilead, Pfizer and Novartis, Onkowissen. travel support from Roche and Lilly. Prof. Dr. med. Achim Wöckel compensation for advisory boards, lectures, trial funding Advisory board: Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Exact Sciences, Pierre Fabre, Clovis, Organon, Daiji Sankyo, Seagen, Stemline, Gilead. PD. Dr. Rachel Würstlein served as advisor, consultant, speaker, and travel grant from Agendia, Amgen, Apogepha, Aristo, AstraZeneca, Celgene, Clovis Oncology, Daiichi-Sankyo, Eisai, Esteve, Exact Sciences, Gilead, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics /Seagen, Sidekick, Stemline, Tesaro Bio, Teva, Veracyte, Viatris, Wiley, FOMF, Aurikamed, Clinsol, Pomme Med, medconcept, MCI, MediSeminar. Prof. Dr. med. Volkmar Müller has received speaker honoraria from: AstraZeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, iMED Institute, consultancy honoraria from Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Seagen, Gilead, Stemline, institutional research support from Novartis, Roche, Seagen, Genentech, AstraZeneca, travel grants form AstraZeneca, Roche, Pfizer, Daiichi Sankyo, Gilead. Prof. Dr. med. Wolfgang Janni has received research grants and/or honoraria from AstraZeneca, Celgene, Chugai, Daiichi Sankyo, Eisai, Exact Science, GSK, Janssen, Lilly, Menarini, MSD, Novartis, Sanofi-Aventis, Roche, Pfizer, Seagen, Gilead, Inivata, Guardant Health. Prof. Dr. med. Marc Thill is a member of advisory board: Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Neodynamics, Novartis, Onkowissen, Organon, Pfizer, pfm Medical, Pierre Fabre, Roche, RTI Surgical, Seagen, Sirius Medical, Sysmex, has received manuscript support from Amgen, ClearCut, Clovis, Organon, pfm medical, Roche, Servier, has received travel expenses from Amgen, Art Tempi, AstraZeneca, Clearcut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, MSD, Neodynamics, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, Seagen; Congress support: Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Gilead, Hexal, Lilly, Neodynamics, Novartis, Pfizer, Pierre Fabre, Roche, Sirius Medical; Lecture honoraria: Amgen, Art Tempi, AstraZeneca, Clovis, Connect Medica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al., Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, StreamedUp, Stemline, Sysmex, Vifor, Viatris, ZP Therapeutics has received trial funding from Endomag, Exact Sciences, and trial honoraria from AstraZeneca, Biom’Up, Celgene, Clearcut, Neodynamics, Novartis, pfm medical, Roche, RTI Surgical. Prof. Dr. med. Jörg Heil: none to disclose. Dr. I. Bauerfeind received speaker honoraria from Brustkrebs Deutschland e.V., Krankenhaus Kempten, Akademie für Psychoonkologie, IF Kongressmanagement. Prof. Dr. med. Kerstin Rhiem received honoraria for lectures from AstraZeneca, Roche, Novartis, streamed up. Prof. Dr. med. Tanja N. Fehm received honoraria for lectures from Onkowissen. Prof. Dr. med. Erich-Franz Solomayer received honoraria for lectures and/or consulting from Roche, Amgen, Celgen, Tesaro, Astra Zeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson Johnson, Daiichi-Sankyo, Gilead, Exact Sciences, GSK, Pierre Fabre., (© 2024 S. Karger AG, Basel.)

The targeted elimination of radio- or chemotherapy-induced senescent cells by so-called senolytic substances represents a promising approach to reduce tumor relapse as well as therapeutic side effects such as fibrosis. We screened an in-house library of 178 substances derived from marine sponges, endophytic fungi, and higher plants, and determined their senolytic activities towards DNA damage-induced senescent HCT116 colon carcinoma cells. The Pan-PI3K-inhibitor wortmannin and its clinical derivative, PX-866, were identified to act as senolytics. PX-866 potently induced apoptotic cell death in senescent HCT116, MCF-7 mammary carcinoma, and A549 lung carcinoma cells, independently of whether senescence was induced by ionizing radiation or by chemotherapeutics, but not in proliferating cells. Other Pan-PI3K inhibitors, such as the FDA-approved drug BAY80-6946 (Copanlisib, Aliqopa®), also efficiently and specifically eliminated senescent cells. Interestingly, only the simultaneous inhibition of both PI3K class I alpha (with BYL-719 (Alpelisib, Piqray®)) and delta (with CAL-101 (Idelalisib, Zydelig®)) isoforms was sufficient to induce senolysis, whereas single application of these inhibitors had no effect. On the molecular level, inhibition of PI3Ks resulted in an increased proteasomal degradation of the CDK inhibitor p21 WAF1/CIP1 in all tumor cell lines analyzed. This led to a timely induction of apoptosis in senescent tumor cells. Taken together, the senolytic properties of PI3K-inhibitors reveal a novel dimension of these promising compounds, which holds particular potential when employed alongside DNA damaging agents in combination tumor therapies., (© 2024. The Author(s).)

Background: The PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06; NCT05871021) is designed to determine whether a dose escalation with 75.0 Gy in 30 fractions can enhance the median overall survival (OS) in patients with methylguanine methyltransferase (MGMT) promotor unmethylated glioblastoma compared to historical median OS rates, while being isotoxic to historical cohorts through the addition of concurrent bevacizumab (BEV). To ensure protocol-compliant irradiation planning with all study centers, a dummy run was planned and the plan quality was evaluated., Methods: A suitable patient case was selected and the computed tomography (CT), magnetic resonance imaging (MRI) and O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) contours were made available. Participants at the various intended study sites performed radiation planning according to the PRIDE clinical trial protocol. The treatment plans and dose grids were uploaded as Digital Imaging and Communications in Medicine (DICOM) files to a cloud-based platform. Plan quality and protocol adherence were analyzed using a standardized checklist, scorecards and indices such as Dice Score (DSC) and Hausdorff Distance (HD)., Results: Median DSC was 0.89, 0.90, 0.88 for PTV60, PTV60ex (planning target volume receiving 60.0 Gy for the standard and the experimental plan, respectively) and PTV75 (PTV receiving 75.0 Gy in the experimental plan), respectively. Median HD values were 17.0 mm, 13.9 mm and 12.1 mm, respectively. These differences were also evident in the volumes: The PTV60 had a volume range of 219.1-391.3 cc (median: 261.9 cc) for the standard plans, while the PTV75 volumes for the experimental plans ranged from 71.5-142.7 cc (median: 92.3 cc). The structures with the largest deviations in Dice score were the pituitary gland (median 0.37, range 0.00-0.69) and the right lacrimal gland (median 0.59, range 0.42-0.78)., Conclusions: The deviations revealed the necessity of systematic trainings with appropriate feedback before the start of clinical trials in radiation oncology and the constant monitoring of protocol compliance throw-out the study., Trial Registration: NCT05871021., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Due to the association with the causal HPV-16 infection, the oropharyngeal carcinoma spreads into two separate entities depending on HPV-16 positivity. More recent data show a diversified picture of the importance and prevalence of the surrogate parameter p16 (discordance) for a definitive HPV-16 association, which varies worldwide. In the context of prevention options, vaccination is of major and HPV screening of healthy people only of little importance., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis., Materials and Methods: For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation)., Conclusion and Recommendations: Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1-4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5-10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8-12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting., (© 2024. The Author(s).)

There are different initial situations in the treatment of local or locoregional recurrences, secondary carcinomas or residual squamous cell carcinomas of the head and neck region after primary therapy. The majority of patients with locoregional recurrences have had prior treatment consisting of surgery and/or postoperative radiotherapy or radiochemotherapy or primary radiotherapy or radiochemotherapy. In any case, it is a matter of new tumor growth in a previously treated area, which must be taken into account for the therapy decision. The biological backgrounds are diverse and are described in more detail and clinically classified in the present work., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose/objective: Adjuvant whole breast radiotherapy and systemic therapy are part of the current evidence-based treatment protocols for early breast cancer, after breast-conserving surgery. Numerous randomized trials have investigated the therapeutic effects of partial breast irradiation (PBI) compared to whole breast irradiation (WBI), limiting the treated breast tissue. These trials were designed to achieve equal control of the disease with possible reduction in adverse events, improvements in cosmesis and quality of life (QoL). In this meta-analysis, we aimed to investigate the differences between PBI and WBI in side effects and QoL., Material/methods: We performed a systematic literature review searching for randomized trials comparing WBI and PBI in early-stage breast cancer with publication dates after 2009. The meta-analysis was performed using the published event rates and the effect-sizes for available acute and late adverse events. Additionally, we evaluated cosmetic outcomes as well as general and breast-specific QoL using the EORTC QLQ-C30 and QLQ-BR23 questionnaires., Results: Sixteen studies were identified (n = 19,085 patients). PBI was associated with a lower prevalence in any grade 1 + acute toxicity and grade 2 + skin toxicity (OR = 0.12; 95% CI 0.09-0.18; p < 0.001); (OR = 0.16; 95% CI 0.07-0.41; p < 0.001). There was neither a significant difference in late adverse events between the two treatments, nor in any unfavorable cosmetic outcomes, rated by either medical professionals or patients. PBI-technique using EBRT with twice-daily fractionation schedules resulted in worse cosmesis rated by patients (n = 3215; OR = 2.08; 95% CI 1.22-3.54; p = 0.007) compared to WBI. Maximum once-daily EBRT schedules (n = 2071; OR = 0.60; 95% CI 0.45-0.79; p < 0.001) and IORT (p = 0.042) resulted in better cosmetic results grade by medical professionals. Functional- and symptom-based QoL in the C30-scale was not different between PBI and WBI. Breast-specific QoL was superior after PBI in the subdomains of "systemic therapy side effects" as well as "breast-" and "arm symptoms"., Conclusion: The analysis of multiple randomized trials demonstrate a superiority of PBI in acute toxicity as well breast-specific quality of life, when compared with WBI. Overall, late toxicities and cosmetic results were similar. PBI-technique with a fractionation of twice-daily schedules resulted in worse cosmesis rated by patients., (© 2023. The Author(s).)

This year's 18th St. Gallen (SG) consensus conference on the treatment of early breast cancer (SGBCC: St. Gallen International Breast Cancer Conference) focused on practice-oriented questions. The individual situation and risk-benefit assessment were discussed in great detail. As in previous years, a German working group of leading breast cancer experts presented the results of the international SGBCC 2023 against the background of German treatment recommendations - especially the updated treatment recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie e. V. (AGO) - for everyday clinical practice in Germany. The German treatment recommendations of AGO are based on the current evidence. The comparison with the clinical approach in Germany has proven useful, as the SGBCC panel consists of experts from different countries and disciplines. That is why country-specific characteristics can be incorporated into the SGBCC recommendations., Competing Interests: Conflict of Interest/Interessenkonflikt Prof. Michael Untch, MD: All remuneration to the AG/institution (referent and consultant activity): Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Lilly, MSD Merck, Myriad Genetics, Pfizer, Roche, Pierre Fabre, Novartis, Molecular Health, Agendia, GSK, Seagen, Gilead, Medac, Stemline Genzyme. Maggie Banys-Paluchowski, MD, Associate Professor, received remuneration from: Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, ExactSciences, Syantra, Stemline, and study support from: EndoMag, Mammotome, MeritMedical, Gilead, Hologic, ExactSciences, Sirius Medical. Prof. Sara Y. Brucker, MD, received remuneration from AstraZeneca, Roche, Novartis, Medtronic, Sanofi, Lilly, MSD, and Hologic. Prof. Wilfried Budach, MD, received remuneration from Merck, BMS, Jörg Eickeler Veranstaltungen, medpublico. Prof. Carsten Denkert, MD, received remuneration from Novartis, Roche, MSD Oncology, Daiichi Sankyo, AstraZeneca, Merck, Molecular Health and study support from the European Commission, German Cancer Aid, BMBF, GBG, Myriad, and Roche. He is involved in patents for digital pathology (VMscope digital pathology software) and biomarker signatures (patents WO2015114146A1 and WO2010076322A1). Prof. Nina Ditsch, MD, received remuneration from AstraZeneca, Daiichi Sankyo, Gilead Sciences, Lilly, Merit Medical, Molecular Health, MSD, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, Teva. Prof. Peter A. Fasching, MD, received grants from Biontech, Pfizer, Cepheid, and remuneration from Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Esai, Merck Sharp & Dohme, Lilly, Pierre Fabre, SeaGen, Roche, Agendia, Sanofi Aventis, Gilead, Mylan, and Menarini. Renate Haidinger has no conflicts of interest. Prof. Dr. med. Jörg Heil has no conflicts of interest. Prof. Dr. med. Christian Jackisch received remuneration from AstraZeneca, Lilly, Celgene, MSD; Eisai, Novartis, Pfizer, Gilead, Daiichi Sankyo, Medupdate, Streamed Up, Roche, and research support from Exact Sciences. Prof. Dr. med. Wolfgang Janni received remuneration from AstraZeneca, Celgene, Chugai, Daiichi Sankyo, Eisai, ExactScience, GSK, Janssen, Lilly, Menarini, MSD, Novartis, Sanofi-Aventis, Roche, Pfizer, Seagen, Gilead, Inivata. Hans-Christian Kolberg, MD, Associate Professor, received remuneration from Pfizer, Novartis, Seagen, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, SurgVision, Onkowissen, Gilead, Daiichi Sankyo, and MSD, as well as travel support from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro, and owns shares in Theraclion SA and Phaon Scientific GmbH. David Krug, MD, Associate Professor, received remuneration from Merck Sharp & Dohme, med update, onkowissen, and Pfizer, as well as research support from Merck KGaA. Prof. Dr. med. Sibylle Loibl did not receive any remuneration. The following companies granted support and remuneration to the GBG: Abbvie, Amgen; AZ; Celgene/BMS, Daiichi Sankyo, Gilead, GSK, Incyte, Lilly, MSD, Merck KG, Medupdate, Streamedup, Novartis, Olema, Pfizer; Relay, Sanofi, Seagen, Roche. Prof. Diana Lüftner, MD, received remuneration from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eli Lilly, Gilead, GSK, high5md, Loreal, Novartis, onkowissen, Pfizer, Roche, Teva. Marion van Mackelenbergh, MD, Associate Professor, received remuneration from Amgen, AstraZeneca, Daiichi Sankyo, GenomicHealth, Gilead, GSK, Lilly, Molecular Health, MSD, Mylan, Novartis, Pfizer, PierreFabre, Roche, Seagen, and travel fees from Daiichi Sankyo, Gilead, Lilly. Prof. Julia Radosa, MD, received remuneration from Pfizer, Eisai, MSD, Medac GmbH, Roche, Novartis, Gedeon Richter, Lilly, Pierre Fabre, Daiichi Sankyo, Seagen, Theramex. Prof. Toralf Reimer received remuneration from AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, Myriad, Novartis, Pfizer, and Roche. Manfred Welslau, MD, received remuneration from Amgen, Astellas, AstraZeneca, Celgene, Gilead, Hexal, Janssen, Lilly, Novartis, Roche, Sanofi and has consulted and reviewed for Amgen, Bristol-Myers Squibb, Celgene, Gilead, Hexal, Janssen, Lilly, Medac, Novartis, Roche, Sanofi, AstraZeneca. Rachel Würstlein, MD, Associate Professor, received remuneration from Agendia, Amgen, Aristo, Astra Zeneca, Celgene, Clovis Oncology, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, GlaxoSmithKline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, PumaBiotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Stemline, Tesaro Bio, Teva, Veracyte, Viatris, FOMF, Aurikamed, Clinsol, Pomme Med, medconcept, MCI. Prof. Nadia Harbeck, MD, received remuneration from Amgen, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Sanofi, Seagen, Viatris, Zuelligpharma. Prof. Jens Huober, MD, received research support from Celgene, Novartis, Hexal, and Lilly. Remuneration for lectures from Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene, Eisai, Abbvie, Seagen, Gilead, and Daiichi Sankyo. Consultancy fees from Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, Abbvie, Daiichi, Gilead. Travel fees from Roche, Pfizer, Novartis, Celgene, Daiichi Sankyo, and Gilead. / Prof. Dr. med. Michael Untch: Alle Honorare an den AG/Institution (Referenten- und Beratertätigkeit): Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Lilly, MSD Merck, Myriad Genetics, Pfizer, Roche, Pierre Fabre, Novartis, Molecular Health, Agendia, GSK, Seagen, Gilead, Medac, Stemline Genzyme. PD Dr. med. Maggie Banys-Paluchowski erhielt Honorar von: Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, ExactSciences, Syantra, Stemline, und Studienunterstützung von: EndoMag, Mammotome, MeritMedical, Gilead, Hologic, ExactSciences, Sirius Medical. Prof. Dr. med. Sara Y. Brucker erhielt Honorar von AstraZeneca, Roche, Novartis, Medtronic, Sanofi, Lilly, MSD und Hologic. Prof. Dr. med. Wilfried Budach erhielt Honorar von Merck, BMS, Jörg Eickeler Veranstaltungen, medpublico. Prof. Dr. med. Carsten Denkert erhielt Honorar von Novartis, Roche, MSD Oncology, Daiichi Sankyo, AstraZeneca, Merck, Molecular Health und Studienunterstützung von der Europäischen Kommission, der Deutschen Krebshilfe, dem BMBF, der GBG, Myriad und Roche. Er ist an Patenten zur digitalen Pathologie (VMscope digital pathology software) und zu Biomarkersignaturen beteiligt (Patent WO2015114146A1 und WO2010076322A1). Prof. Dr. med. Nina Ditsch erhielt Honorar AstraZeneca, Daiichi Sankyo, Gilead Sciences, Lilly, Merit Medical, Molecular Health, MSD, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, Teva. Prof. Dr. med. Peter A. Fasching erhielt Zuschüsse von Biontech, Pfizer, Cepheid sowie Honorar von Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Esai, Merck Sharp & Dohme, Lilly, Pierre Fabre, SeaGen, Roche, Agendia, Sanofi Aventis, Gilead, Mylan und Menarini. Renate Haidinger hat keine Interessenkonflikte. Prof. Dr. med. Jörg Heil hat keine Interessenkonflikte. Prof. Dr. med. Christian Jackisch erhielt Honorar von AstraZeneca, Lilly, Celgene, MSD; Eisai, Novartis, Pfizer, Gilead, Daiichi Sankyo, Medupdate, Streamed Up, Roche und Forschungsunterstützung von Exact Sciences. Prof. Dr. med. Wolfgang Janni erhielt Honorar von AstraZeneca, Celgene, Chugai, Daiichi Sankyo, Eisai, ExactScience, GSK, Janssen, Lilly, Menarini, MSD, Novartis, Sanofi-Aventis, Roche, Pfizer, Seagen, Gilead, Inivata. PD Dr. med. Hans-Christian Kolberg erhielt Honorar von Pfizer, Novartis, Seagen, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, SurgVision, Onkowissen, Gilead, Daiichi Sankyo und MSD sowie Reisekostenunterstützung von Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro und besitzt Anteile von Theraclion SA and Phaon Scientific GmbH. PD Dr. med. David Krug erhielt Honorar von Merck Sharp & Dohme, med update, onkowissen und Pfizer sowie Forschungsunterstützung von Merck KGaA. Prof. Dr. med. Sibylle Loibl erhielt keine persönlichen Honorare. Unterstützung und Honorare an die GBG wurde von folgenden Firmen gewährt: Abbvie, Amgen; AZ; Celgene/BMS, Daiichi Sankyo, Gilead, GSK, Incyte, Lilly, MSD, Merck KG, Medupdate, Streamedup, Novartis, Olema, Pfizer; Relay, Sanofi, Seagen, Roche. Prof. Dr. med. Diana Lüftner erhielt Honoraria von Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eli Lilly, Gilead, GSK, high5md, Loreal, Novartis, onkowissen, Pfizer, Roche und Teva. PD Dr. med. Marion van Mackelenbergh erhielt Honorar von Amgen, AstraZeneca, Daiichi Sankyo, GenomicHealth, Gilead, GSK, Lilly, Molecular Health, MSD, Mylan, Novartis, Pfizer, PierreFabre, Roche, Seagen sowie Reisekostenunterstützung von Daiichi Sankyo, Gilead, Lilly. Prof. Dr. med. Julia Radosa erhielt Honorar von Pfizer, Eisai, MSD, Medac GmbH, Roche, Novartis, Gedeon Richter, Lilly, Pierre Fabre, Daiichi Sankyo, Seagen, Theramex. Prof. Toralf Reimer erhielt Honorar von AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, Myriad, Novartis, Pfizer und Roche. Dr. med. Manfred Welslau erhielt Honorar von Amgen, Astellas, AstraZeneca, Celgene, Gilead, Hexal, Janssen, Lilly, Novartis, Roche, Sanofi und hat Beratungs- bzw. Gutachtertätigkeit bei Amgen, Bristol-Myers Squibb, Celgene, Gilead, Hexal, Janssen, Lilly, Medac, Novartis, Roche, Sanofi, AstraZeneca. PD Dr. med. Rachel Würstlein erhielt Honorar von Agendia, Amgen, Aristo, AstraZeneca, Celgene, Clovis Oncology, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, GlaxoSmithKline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, PumaBiotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Stemline, Tesaro Bio, Teva, Veracyte, Viatris, FOMF, Aurikamed, Clinsol, Pomme Med, medconcept, MCI. Prof. D. med. Nadia Harbeck erhielt Honorar von Amgen, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Sanofi, Seagen, Viatris, Zuelligpharma. Prof. Dr. med. Jens Huober erhielt Forschungsunterstützung von Celgene, Novartis, Hexal, Lilly. Honorar für Vortragstätigkeiten von Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene, Eisai, Abbvie, Seagen, Gilead, Daiichi Sankyo. Honorar für Beratertätigkeit von Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, Abbvie, Daiichi, Gilead. Reisekostenunterstützung von Roche, Pfizer, Novartis, Celgene, Daiichi Sankyo, Gilead., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Multiple randomized trials have established adjuvant endocrine therapy (ET) and whole breast irradiation (WBI) as the standard approach after breast-conserving surgery (BCS) in early-stage breast cancer. The omission of WBI has been studied in multiple trials and resulted in reduced local control with maintained survival rates and has therefore been adapted as a treatment option in selected patients in several guidelines. Omitting ET instead of WBI might also be a valuable option as both treatments have distinctly different side effect profiles. However, the clinical outcomes of BCS + ET vs. BCS + WBI have not been formally analyzed., Methods: We performed a systematic literature review searching for randomized trials comparing BCS + ET vs. BCS + WBI in low-risk breast cancer patients with publication dates after 2000. We excluded trials using any form of chemotherapy, regional nodal radiation and mastectomy. The meta-analysis was performed using a two-step process. First, we extracted all available published event rates and the effect sizes for overall and breast-cancer-specific survival (OS, BCSS), local (LR) and regional recurrence, disease-free survival, distant metastases-free interval, contralateral breast cancer, second cancer other than breast cancer and mastectomy-free interval as investigated endpoints and compared them in a network meta-analysis. Second, the published individual patient data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) publications were used to allow a comparison of OS and BCSS., Results: We identified three studies, including a direct comparison of BCS + ET vs. BCS + WBI ( n = 1059) and nine studies randomizing overall 7207 patients additionally to BCS only and BCS + WBI + ET resulting in a four-arm comparison. In the network analysis, LR was significantly lower in the BCS + WBI group in comparison with the BCS + ET group (HR = 0.62; CI-95%: 0.42-0.92; p = 0.019). We did not find any differences in OS (HR = 0.93; CI-95%: 0.53-1.62; p = 0.785) and BCSS (OR = 1.04; CI-95%: 0.45-2.41; p = 0.928). Further, we found a lower distant metastasis-free interval, a higher rate of contralateral breast cancer and a reduced mastectomy-free interval in the BCS + WBI-arm. Using the EBCTCG data, OS and BCSS were not significantly different between BCS + ET and BCS + WBI after 10 years (OS: OR = 0.85; CI-95%: 0.59-1.22; p = 0.369) (BCSS: OR = 0.72; CI-95%: 0.38-1.36; p = 0.305)., Conclusion: Evidence from direct and indirect comparison suggests that BCS + WBI might be an equivalent de-escalation strategy to BCS + ET in low-risk breast cancer. Adverse events and quality of life measures have to be further compared between these approaches.

Background: Each year the interdisciplinary Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), German Gynecological Oncology Group Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer., Summary: The updated evidence-based treatment recommendation for early and metastatic breast cancer has been released in March 2023., Key Messages: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter., Competing Interests: Prof. Dr. Tjoung-Won Park-Simon. Honoraria for lectures and/or consulting: Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, Exact Sciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, Seagen. Travel compensation: Roche, AstraZeneca, Pfizer. Prof. Dr. med. Ute-Susann Albert. Lectures: Pfizer, Novartis, AstraZeneca. Advisory board: Daiichi Sankyo. PD. Dr. Malgorzata Banys-Paluchowski. M.B. has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre and ExactSciences, study support from EndoMag, Mammotome, MeritMedical, Gilead, Hologic, ExactSciences, and travel/congress support from Eli Lilly, ExactSciences, Pierre Fabre, Pfizer, Daiichi Sankyo and Roche. Dr. med. Ingo Bauerfeind. Honoraria for lectures: Pfizer, Roche, Seagen. Prof. Dr. med. Jens-Uwe Blohmer. Honoraria for advisory boards and lectures: Astrazeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Seagen Prof. Dr. med. Wilfried Budach. Lecture: Merck, BMS, Jörg Eickeler Veranstaltungen, medpublico GmbH, BVDST. Prof. Dr. med. Peter Dall, Honoraria for lectures and advisory boards: Novartis, Pierre Fabre, Gilead, MSD, Daiichi Sankyo, Lilly, AstraZeneca, Pfizer, Roche. Prof. Dr. Nina Ditsch. Advisory Boards and speakers bureaus. AstraZeneca, Aurikamed, BGGF, Daiichi-Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molekular Health, MSD, Novartis, onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, Seagen Prof. Dr. med. Eva Maria Fallenberg. Research grant: DFG. Speaker honorarium: GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO. Prof. Dr. med. Peter A. Fasching. Advisory board: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, Agendia, Pierre Fabre, Sanofi Aventis, Gilead Science. Lecture: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, Gilead Sciences. Other: Onkowissen, art tempi. Prof. Dr. med. Tanja N. Fehm. Onkowissen Prof. Dr. med. Michael Friedrich. Advisory Board: Gilead Sciences. Other honoraria: Roche, MSD. Prof. Dr. med. Bernd Gerber. Lecture honoraria: Roche, AstraZeneca, Seagen, Novartis, Pfizer, MedConcept. Others: Pfizer. PD Dr. med. Oleg Gluz. Honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sanyko, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, Agendia. Minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Dr. med. Nadia Harbeck. Honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sanyko, Gilead, Lilly, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sandoz, Sanofi, Seagen, Viatris, Zuelligpharma Minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Dr. med. Andreas Hartkopf. Honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, DaichiiSankyo, Eisai, ExactScience, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre-Fabre, Seagen, Stemline and Verazyte. Prof. Dr. med. Jörg Heil. None. Prof. Dr. med. Jens Huober. Trial funding: Novartis, Lilly. Honoraria for lectures: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; Abbvie, Seagen, Gilead, Daiichi. Honoraria for consulting/advisory board: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Abbvie, Daiichi, Gilead. Travel grants: Roche, Pfizer, Daiichi, Gilead. Prof. Dr. med. Christian Jackisch. Advisory board: Astra Zeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre-Fabre, Roche, Seagen; Lecture: Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre-Fabre, Exact Sciences, MSD, GynUpdate, StreamedUp. Prof. Dr. med. Cornelia Kolberg-Liedtke. Advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, Onkowissen; Lecture: Novartis Ireland, NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, Daiichi Sankyo. Other: Gilead Science, POMME. Stockholding: Phaon Scientific, Theraclion SA. Trial Funding: Gilead Science. Prof. Dr. med. Hans-Heinrich Kreipe. Advisory board: Lilly. Lecture: AstraZeneca, Roche, Daiichi Sankyo, Pfizer. PD Dr. David Krug. Lecture: Merck Sharp & Dohme, onkowissen, Pfizer. Research funding: Merck KGaA. Advisory Board: Gilead. Prof. Dr.med. Thorsten Kühn. Advisory Board: Sysmex, Neodynamics. Trial funding: Merit Medical, Endomag, Mammotome. Lecture: Pfizer. Prof. Dr. med. Sherko Kümmel. Lecture: Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, Somatex, MSD, Pfizer, pfm medical, Seagen, Gilead Science, Agendia. Other honoraria: Roche, Daiichi Sankyo, Sonoscape Advisory board: Lilly, MSD, Roche. Prof. Dr. med. Sibylle Loibl. Advisory Board, institutional: Abbvie, Amgen, AstraZeneca, BMS, Celgene, DSI, Eirgenix, GSK, Gilead Science, Lilly, Merck, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeuticas, Puma, Roche, Samsung, Sanofi, Seagen Invited speaker, institutional: Astra Zeneca, DSI, Gilead, Novartis, Pfizer, Pierre Fabre, Roche, Seagen Invited speaker, personal: Medscape, Stemline-Menarini. Trial funding/others: Astra Zeneca, Abbvie, Celgene, Daiichi-Sankyo, Greenwich Life Sciences, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Seagen, VM Scope GmbH. Prof. Dr. med. Diana Lüftner. Lecture: Lilly, Roche, MSD, Onkowissen, Novartis, Pfizer, Daiichi Sankyo, Gilead, AstraZeneca, Loreal, high4md. Advisory board: Lilly, Roche, MSD, Novartis, Pfizer, Daiichi Sankyo, Gilead, AstraZeneca, Other: Novartis. Prof. Dr. med. Michael Patrick Lux. M.P.L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi-Sankyo, PharmaMar, Roche, SamanTree, Sysmex and Hexal and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi-Sankyo, Grünenthal, pfm, Gilead, AstraZeneca, and Eisai. Prof. Dr. med. Nicolai Maass. Advisory board: Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen Lecture: AstraZeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, Roche. Prof. Dr. med. Christoph Mundhenke. Advisory board: AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, Novartis. Lecture: Pfizer, Novartis. Prof. Dr. med. Toralf Reimer. Trial funding: German Cancer Aid and Else Kroener-Fresenius-Stiftung. Advisory board: MSD, Novartis, Myriad. Lecture: Pfizer, Novartis, Roche, AstraZeneca. Prof. Dr. med. Kerstin Rhiem. Lecture: AstraZeneca, Amgen, Roche. Prof. Dr. med. Achim Rody. Advisory board: AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, MSD. Lecture: Pfizer, Celgene, Eisai. Trial funding: Eisai. Prof. Dr. med. Marcus Schmidt. MS reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen, His institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. med. Andreas Schneeweiss. Lecture: Amgen, AstraZeneca, Aurikamed, Clinsol, ConnectMedica, Gilead Science, GSK, I-Med, Lilly, MSD, Nanostring, Novartis, Onkowissen, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, StreamedUp. Other: Thieme. Prof. Dr. med. Florian Schütz. Lecture: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, ExactSciences, Gilead, Pfizer, MSD, Novartis, Onkowissen, Roche Pharma. Advisory board: Lilly, MSD, Atheneum Partners. Travel expanses: Lilly, Daiichi-Sankyo, Amgen, Prof. Dr. med. Hans-Peter Sinn. Advisory board: Exact Sciences, Daiichi Sankyo. Lecture: AstraZeneca. Trial Funding: AstraZeneca. Prof. Dr. med. Christine Solbach. Lecture: DiaLog Service GmbH, Jörg Eickeler, Pfizer, MedConcept, Medicultus, GBG, Dt. Röntgengesellschaft, BVF Akademie, LÄK Hessen Akademie, Meet the Expert Academy. Advisory board: MSD, Roche. Prof. Dr. med. Erich-Franz Solomayer. Roche, Amgen, Celgen, Tesaro, Astra Zeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson Johnson, Daiichi-Sankyo, Gilead, Exact Sciences, GSK, Pierre Fabre. Prof. Dr. med. Elmar Stickeler. Advisory boards: Gilead, Iomedico, Lilly, MSD, Seagen Lecture: Pfizer, Bsh Düsseldorf, Gilead, Iomedico, PharmaMar, Onkowissen, Roche. Prof. Dr. med. Christoph Thomssen. Compensation for advisory boards, lectures or publications. Amgen, AstraZeneca, Aurikamed, Daiichi-Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, Nanostring, Novartis, Onkowissen, Pfizer, Roche, Seagen, Vifor Prof. Dr. med. Michael Untch. M.U. has received honoraria for lectures and consulting or advisory role from AstraZeneca, Art tempi, Amgen, Daiji Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi-Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, Eisai, All honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel. Lecture: Daiichi Sankyo, Pfizer, Roche, MSD, Lilly, Seagen, AstraZeneca, Gilead. Other: Onkowissen Prof. Dr. med. Achim Wöckel. Advisory board: Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Genomic Health, Pierre Fabre, Clovis, Organon. PD. Dr. Rachel Würstlein. Agendia, Amgen, Aristo, Astra Zeneca, Aurikamed, Celgene, Clinsol, Clovis Oncology, Daiichi-Sankyo, Eisai, Exact Sciences, FOMF, Gilead, Glaxo Smith Kline, Hexal, Lilly, MCI, medconcept, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, Pomme Med, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Stemline, Tesaro Bio, Teva, Veracyte, Viatris Prof. Dr. med. Volkmar Müller. V.M. received speaker honoraria from Amgen, Astra Zeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics, Genomic Health, Hexal, Roche, Pierre Fabre, ClinSol, Daiichi-Sankyo, Eisai, Lilly, Tesaro, Seattle Genetics and Nektar. Institutional research support from Novartis, Roche, Seattle Genetics, Genentech. Travel grants: Roche, Pfizer, Daiichi Sankyo. Prof. Dr. med. Wolfgang Janni. Lecture: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Gilead Science. Trial Funding: Amgen, AstraZeneca, Lilly, Novartis, Roche. Prof. Dr. med. Marc Thill. M.T. received personal fees for consulting from Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Norgine, Neodynamics, Novartis, Onkowissen, Organon, Pfizer, pfm Medical, Pierre-Fabre, Roche, RTI Surgical, Seagen, Sirius Pintuition, Sysmex, for manuscript support from Amgen, ClearCut, Clovis, pfm medical, Roche, Servier, for travel expenses from Amgen, Art Tempi, AstraZeneca, Clearcut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, Medtronic, MSD, Neodynamics, Norgine, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, Seagen, for congress support Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Hexal, Neodynamics, Novartis, Pfizer, Roche, Sirius Medical, for lectures from Amgen, Art Tempi, AstraZeneca, Clovis, Connect Medica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al. Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, StreamedUp, Sysmex, Vifor, Viatris, for trial funding from Endomag, Exact Sciences and institutional fees from AstraZeneca, Biom’Up, Celgene, Clearcut, Neodynamics, Novartis, pfm medical, Roche, RTI Surgical., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2023 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer (mBC)., Competing Interests: The authors have the following conflicts of interest: Prof. Dr. Med. Marc Thill: MT received personal fees for consulting from Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Norgine, NeoDynamics, Novartis, Onkowissen, Organon, Pfizer, pfm Medical, Pierre Fabre, Roche, RTI Surgical, Seagen, Sirius Pintuition, and Sysmex; for manuscript support from Amgen, ClearCut, Clovis, pfm medical, Roche, and Servier; for travel expenses from Amgen, Art Tempi, AstraZeneca, ClearCut, Clovis, ConnectMedica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, Medtronic, MSD, NeoDynamics, Norgine, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, and Seagen; for congress support Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Hexal, NeoDynamics, Novartis, Pfizer, Roche, and Sirius Medical; for lectures from Amgen, Art Tempi, AstraZeneca, Clovis, ConnectMedica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther, Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, STREAMED UP, Sysmex, Vifor, and Viatris; for trial funding from Endomag, Exact Sciences; and institutional fees from AstraZeneca, Biom’Up, Celgene, ClearCut, NeoDynamics, Novartis, pfm medical, Roche, and RTI Surgical. Prof. Dr. Med. Ute-Susann Albert, lectures: Pfizer, Novartis, and AstraZeneca; advisory board: Daiichi Sankyo. PD Dr. Malgorzata Banys-Paluchowski: M.B. has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, and Exact Sciences; study support from Endomag, Mammotome, Merit Medical, Gilead, Hologic, and Exact Sciences; and travel/congress support from Eli Lilly, Exact Sciences, Pierre Fabre, Pfizer, Daiichi Sankyo, and Roche. Dr. Med. Ingo Bauerfeind, honoraria for lectures: Pfizer, Roche, and Seagen. Prof. Dr. Med. Jens-Uwe Blohmer, honoraria for advisory boards and lectures: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, and Seagen. Prof. Dr. Med. Wilfried Budach, lecture: Merck, BMS, Jörg Eickeler Veranstaltungen, medpublico GmbH, and BVDST. Prof. Dr. Med. Peter Dall, honoraria for lectures and advisory boards: Novartis, Pierre Fabre, Gilead, MSD, Daiichi Sankyo, Lilly, AstraZeneca, Pfizer, and Roche. Prof. Dr. Nina Ditsch, advisory boards and speakers bureaus advisory boards and speakers bureaus: AstraZeneca, Aurikamed, BGGF, Daiichi Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molecular Health, MSD, Novartis, Onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, and Seagen. Prof. Dr. Med. Eva Maria Fallenberg, research grant: DFG; speaker honorarium: GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO. Prof. Dr. Med. Peter A. Fasching, advisory board: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, Agendia, Pierre Fabre, Sanofi-Aventis, and Gilead Science; lecture: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, and Gilead Sciences; and other: Onkowissen, art tempi. Prof. Dr. Med. Tanja N. Fehm, Onkowissen. Prof. Dr. Med. Michael Friedrich, advisory board: Gilead Sciences; other honoraria: Roche and MSD. Prof. Dr. Med. Bernd Gerber, lecture honoraria: Roche, AstraZeneca, Seagen, Novartis, Pfizer, and MedConcept; and others: Pfizer. PD Dr. Med. Oleg Gluz, honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sankyo, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, and Agendia; and minority share holder: Westdeutsche Studiengruppe (WSG)mmc1. Prof. Dr. Med. Nadia Harbeck, honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Sanofi, Seagen, Viatris, and Zuellig Pharma; minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Dr. Med. Andreas Hartkopf, honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, Daiichi Sankyo, Eisai, Exact Science, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen, Stemline, and Verazyte. Prof. Dr. Med. Jörg Heil, none. Prof. Dr. Med. Jens Huober, trial funding: Novartis and Lilly; honoraria for lectures: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; AbbVie, Seagen, Gilead, and Daiichi; honoraria for consulting/advisory board: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, AbbVie, Daiichi, and Gilead; and travel grants: Roche, Pfizer, Daiichi, and Gilead. Prof. Dr. Med. Christian Jackisch, advisory board: AstraZeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre Fabre, Roche, and Seagen; lecture: Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre Fabre, Exact Sciences, MSD, Gyn Update, and STREAMED UP. Prof. Dr. Med. Cornelia Kolberg-Liedtke, advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, and Onkowissen; and lecture: Novartis Ireland, NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, and Daiichi Sankyo; other: Gilead Science and POMME; stockholding: Phaon Scientific and Theraclion SA; and trial Funding: Gilead Science. Prof. Dr. Med. Hans-Heinrich Kreipe, advisory board: Lilly; lecture: AstraZeneca, Roche, Daiichi Sankyo, and Pfizer. PD Dr. David Krug, lecture: Merck Sharp and Dohme, Onkowissen, and Pfizer; research funding: Merck KGaA; and advisory board: Gilead. Prof. Dr. med. Thorsten Kühn, advisory board: Sysmex and NeoDynamics; trial funding: Merit Medical, Endomag, and Mammotome; and lecture: Pfizer. Prof. Dr. Med. Sherko Kümmel, lecture: Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, Somatex, MSD, Pfizer, pfm medical, Seagen, Gilead Science, and Agendia; other honoraria: Roche, Daiichi Sankyo, and Sonoscape; and advisory board: Lilly, MSD, and Roche. Prof. Dr. Med. Sibylle Loibl, board, advisory board, institutional: AbbVie, Amgen, AstraZeneca, BMS, Celgene, DSI, EirGenix, GSK, Gilead Science, Lilly, Merck, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeutics, Puma, Roche, Samsung, Sanofi, and Seagen; invited speaker, institutional: AstraZeneca, DSI, Gilead, Novartis, Pfizer, Pierre Fabre, Roche, and Seagen; invited speaker, personal: Medscape and Stemline-Menarini; trial funding/others: AstraZeneca, AbbVie, Celgene, Daiichi Sankyo, Greenwich Life Sciences, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Seagen, VM Scope Gmbp. Prof. Dr. Med. Diana Lüftner, lecture: Lilly, Roche, MSD, Onkowissen, Novartis, Pfizer, Daiichi Sankyo, Gilead, AstraZeneca, Loreal, and high4md; advisory board: Lilly, Advisory board: Lilly, Roche, MSD, Novartis, Pfizer, Daiichi Sankyo, Gilead, and AstraZeneca; and other: Novartis. Prof. Dr. Med. Michael Patrick Lux: M.P.L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi Sankyo, PharmaMar, Roche, SamanTree, Sysmex, and Hexal; and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Grünenthal, pfm, Gilead, AstraZeneca, and Eisai. Prof. Dr. Med. Nicolai Maass, advisory board: Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, and Seagen; and lecture: AstraZeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, and Roche. Prof. Dr. Med. Christoph Mundhenke, advisory board: AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, and Novartis; and lecture: Pfizer and Novartis. Prof. Dr. Med. Toralf Reimer; trial funding: German Cancer Aid and Else Kroener-Fresenius-Stiftung; advisory board: MSD, Novartis, and Myriad; and lecture: Pfizer, Novartis, Roche, and AstraZeneca. Prof. Dr. Med. Kerstin Rhiem, lecture: AstraZeneca, Amgen, and Roche. Prof. Dr. Med. Achim Rody, advisory board: AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, and MSD; lecture: Pfizer, Celgene, and Eisai; and trial funding: Eisai. Prof. Dr. Med. Marcus Schmidt: MS reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen; his institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. Med. Andreas Schneeweiss, lecture: Amgen, AstraZeneca, Aurikamed, Clinsol, ConnectMedica, Gilead Science, GSK, I-Med, Lilly, MSD, NanoString, Novartis, Onkowissen, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, and STREAMED UP; and other: Thieme. Prof. Dr. Med. Florian Schütz, lecture: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Pfizer, MSD, Novartis, Onkowissen, and Roche Pharma; and advisory board: Lilly, MSD, and Atheneum Partners; and travel expenses: Lilly, Daiichi Sankyo, and Amgen. Prof. Dr. Med. Hans-Peter Sinn, advisory board: Exact Sciences and Daiichi Sankyo; lecture: AstraZeneca; and trial Funding: AstraZeneca. Prof. Dr. Med. Christine Solbach, lecture: DiaLog Service GmbH, Jörg Eickeler, Pfizer, MedConcept, Medicultus, GBG, Dt. Röntgengesellschaft, BVF Akademie, LÄK Hessen Akademie, Meet the Expert Academy; advisory board: MSD and Roche. Prof. Dr. Med. Erich-Franz Solomayer, Roche, Amgen, Celgen, Tesaro, AstraZeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson & Johnson, Daiichi Sankyo, Gilead, Exact Sciences, GSK, and Pierre Fabre. Prof. Dr. Med. Elmar Stickeler, advisory boards: Gilead, Iomedico, Lilly, MSD, and Seagen; and lecture: Pfizer, Bsh Düsseldorf, Gilead, Iomedico, PharmaMar, Onkowissen, and Roche. Prof. Dr. Med. Christoph Thomssen, compensation for advisory boards, lectures or publications: Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, NanoString, Novartis, Onkowissen, Pfizer, Roche, Seagen, and Vifor. Prof. Dr. Med. Michael Untch: M. U. has received honoraria for lectures and consulting or advisory role from AstraZeneca, Art tempi, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi-Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, Eisai; all honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel, lecture: Daiichi Sankyo, Pfizer, Roche, MSD, Lilly, Seagen, AstraZeneca, and Gilead; other: Onkowissen. Prof. Dr. Med. Achim Wöckel; advisory board: Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Genomic Health, Pierre Fabre, Clovis, and Organon. PD. Dr. Rachel Würstlein, Agendia, Amgen, Aristo, AstraZeneca, Aurikamed, Celgene, Clinsol, Clovis Oncology, Daiichi Sankyo, Eisai, Exact Sciences, FOMF, Gilead, Glaxo Smith Kline, Hexal, Lilly, MCI, medconcept, Medstrom Medical, MSD, Mundipharma, Mylan, NanoString, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, Pomme-med, Puma Biotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Stemline, Tesaro Bio, Teva, Veracyte, and Viatris. Prof. Dr. Med. Volkmar Müller: VM received speaker honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics, Genomic Health, Hexal, Roche, Pierre Fabre, Clinsol, Daiichi Sankyo, Eisai, Lilly, Tesaro, Seattle Genetics, and Nektar; institutional research support from Novartis, Roche, Seattle Genetics, and Genentech; and travel grants: Roche, Pfizer, and Daiichi Sankyo. Prof. Dr. Med. Wolfgang Janni, lecture: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, and Gilead Science; trial Funding: Amgen, AstraZeneca, Lilly, Novartis, and Roche. Prof. Dr. Tjoung-Won Park-Simon, honoraria for lectures and/or consulting: Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, Exact Sciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, and Seagen; and travel compensation: Roche, AstraZeneca, and Pfizer., (© 2023 S. Karger AG, Basel.)

We present a case of mild radiation recall dermatitis triggered by cisplatin chemotherapy given simultaneously to re-irradiation. The dermatitis area correlated to skin exposure of the previous radiation therapy, characterizing the reaction clearly as a recall. Cisplatin has not yet been recognized as a potential trigger for recall reactions. Although it was part of several reported multidrug trigger combinations, all review works referred to cisplatin as not suspicious, suggesting the combination partner as the effector. We performed a focused systematic literature review aiming to re-evaluate the real role of cisplatin as a (co-)triggering factor. In total, 30 reported cases were found, 90% triggered by multidrug combinations. The latter tended to cause more severe symptoms. Besides findings supporting the 20 Gy-threshold theory, no correlation between radiation dose and severity or prevalence was found. Recognition of cisplatin as a trigger of the recall phenomenon and its supportive management may prevent unnecessary cessation of systemic chemotherapy. Systematic reporting of recall events as a secondary endpoint of prospective clinical trials applying radiation therapy could support understanding the recall phenomenon., (© 2023. The Author(s).)

Background: Vascular surgery of the inguinal area can be complicated by persistent lymphatic fistulas. Rapid and effective treatment is essential to prevent infection, sepsis, bleeding, and possible leg amputation. Current data on irradiation of lymphatic fistulas lack recommendation on the appropriate individual and total dose, the time of irradiation, and the target volume. Presumably, a dose of 0.3-0.5 to 1-12 Gy should be sufficient for the purpose. Currently, radiotherapy is a "can" recommendation, with a level 4 low evidence and a grade C recommendation, according to the DEGRO S2 guidelines. As part of a pilot study, we analyzed the impact and limitations of low-dose radiation therapy in the treatment of inguinal lymphatic fistulas., Patients and Methods: As a part of an internal quality control project, patients with lymphatic fistulas irradiated in the groin area after vascular surgery for arterial occlusive disease (AOD) III-IV, repair of pseudo aneurysm or lymph node dissection due to melanoma were selected, and an exploratory analysis on retrospectively collected data performed., Results: Twelve patients (10 males and 2 females) aged 62.83 ± 12.14 years underwent open vascular reconstruction for stage II (n = 2), III (n = 1), and IV (n = 7) arterial occlusive disease (AOD), lymph node dissection for melanoma (n = 1) or repair of a pseudoaneurysm (n = 1). Surgical vascular access was obtained through the groin and was associated with a persistent lymphatic fistula, secreting more than 50 ml/day. Patients were irradiated five times a week up to a maximum of 10 fractions for the duration of the radiation period. Fraction of 0.4 Gy was applied in the first 7 cases, while 5 patients were treated with a de-escalating dose of 0.3 Gy. There was a resolution of the lymphatic fistula in every patient without higher grade complications., Conclusion: Low-dose irradiation of the groin is a treatment option for persistent lymphatic fistula after inguinal vascular surgery., (© 2023. The Author(s).)

Midfacial reconstruction after tumor resection surgery is commonly conducted by using autologous bone grafts or alloplastic implants. Titanium is the most frequently used osteosynthesis material in these cases but causes disturbing metallic artifacts in CT imaging. The purpose of this experimental study was to evaluate whether the use of midfacial polymer implants reduces metallic artifacts in CT imaging to improve image quality. Zygomatic titanium (n = 1) and polymer (n = 12) implants were successively implanted in a human skull specimen. Implants were analyzed for their effect on Hounsfield Unit values (streak artifacts) and virtual growth in CT images (blooming artifacts) as well as image quality. Multi-factorial ANOVA and Bonferroni's post hoc test were used. Titanium (173.7 HU; SD ± 5.1) and hydroxyapatite containing polymers (155.3 HU; SD ± 5.9) were associated with significantly more streak artifacts compared to all other polymer materials. There was no significant difference in blooming artifacts between materials. The metallic artifact reduction algorithm showed no significant difference. Image quality was slightly better for polymer implants compared to titanium. Personalized polymer implants for midfacial reconstruction significantly reduce metallic artifacts in CT imaging which improves image quality. Hence, postoperative radiation therapy planning and radiological tumor aftercare around the implants are facilitated.

Background: The presentation of peptides and the subsequent immune response depend on the MHC characteristics and influence the specificity of the immune response. Several studies have found an association between HLA variants and differential COVID-19 outcomes and have shown that HLA genotypes are associated with differential immune responses against SARS-CoV-2, particularly in severely ill patients. Information, whether HLA haplotypes are associated with the severity or length of the disease in moderately diseased individuals is absent., Methods: Next-generation sequencing-based HLA typing was performed in 303 female and 231 male non-hospitalized North Rhine Westphalian patients infected with SARS-CoV2 during the first and second wave. For HLA-Class I, we obtained results from 528 patients, and for HLA-Class II from 531. In those patients, who became ill between March 2020 and January 2021, the 22 most common HLA-Class I (HLA-A, -B, -C) or HLA-Class II (HLA -DRB1/3/4, -DQA1, -DQB1) haplotypes were determined. The identified HLA haplotypes as well as the presence of a CCR5Δ32 mutation and number of O and A blood group alleles were associated to disease severity and duration of the disease., Results: The influence of the HLA haplotypes on disease severity and duration was more pronounced than the influence of age, sex, or ABO blood group. These associations were sex dependent. The presence of mutated CCR5 resulted in a longer recovery period in males., Conclusion: The existence of certain HLA haplotypes is associated with more severe disease., (© 2022. The Author(s).)

The recommendations of the AGO Breast Committee on the surgical therapy of breast cancer were last updated in March 2022 (www.ago-online.de). Since surgical therapy is one of several partial steps in the treatment of breast cancer, extensive diagnostic and oncological expertise of a breast surgeon and good interdisciplinary cooperation with diagnostic radiologists is of great importance. The most important changes concern localization techniques, resection margins, axillary management in the neoadjuvant setting and the evaluation of the meshes in reconstructive surgery. Based on meta-analyses of randomized studies, the level of recommendation of an intraoperative breast ultrasound for the localization of non-palpable lesions was elevated to "++". Thus, the technique is considered to be equivalent to wire localization, provided that it is a lesion which can be well represented by sonography, the surgeon has extensive experience in breast ultrasound and has access to a suitable ultrasound device during the operation. In invasive breast cancer, the aim is to reach negative resection margins ("no tumor on ink"), regardless of whether an extensive intraductal component is present or not. Oncoplastic operations can also replace a mastectomy in selected cases due to the large number of existing techniques, and are equivalent to segmental resection in terms of oncological safety at comparable rates of complications. Sentinel node excision is recommended for patients with cN0 status receiving neoadjuvant chemotherapy after completion of chemotherapy. Minimally invasive biopsy is recommended for initially suspect lymph nodes. After neoadjuvant chemotherapy, patients with initially 1 - 3 suspicious lymph nodes and a good response (ycN0) can receive the targeted axillary dissection and the axillary dissection as equivalent options., Competing Interests: Conflict of Interest/Interessenkonflikt Maggie Banys-Paluchowski received fees for lectures and consultancy activities from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, AstraZeneca, Amgen, Samsung, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre and study support from EndoMag, Mammotome, MeritMedical. Marcus Schmidt reports that he received personal fees for lectures and consulting activities from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche and SeaGen, which are not related to this publication. Jens Huober: Research support: Celgene, Novartis, Hexal, Lilly. Lecture activity: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; Eisai, Abbvie, Seagen, Gilead. Consultancy: Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, Abbvie. Travel expenses: Roche, Pfizer, Novartis, Celgene, Daiichi Sankyo. Peter Dall: Lecture fees: Novartis, Pfizer, AstraZeneca, Roche, Lilly. Ad Boards: Novartis, Seagen, Daiichi Sankyo, AstraZeneca, Roche, Gilead. David Krug: honoraria from Merck Sharp & Dohme and Pfizer as well as research funding from Merck KGaA. Other authors do not indicate any conflicts of interest./ Maggie Banys-Paluchowski erhielt Honorare für Vorträge und beratende Tätigkeiten von Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, AstraZeneca, Amgen, Samsung, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre und Studienunterstützung von EndoMag, Mammotome, MeritMedical. Marcus Schmidt berichtet, persönliche Honorare für Vorträge und Beratungstätigkeiten von AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche und SeaGen erhalten zu haben, die nicht im Zusammenhang mit der vorliegenden Publikation stehen. Jens Huober: Forschungsunterstützung: Celgene, Novartis, Hexal, Lilly. Vortragstätigkeit: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; Eisai, Abbvie, Seagen, Gilead. Beratertätigkeit: Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, Abbvie. Reisekosten: Roche, Pfizer, Novartis, Celgene, Daiichi Sankyo. Peter Dall: Vortragshonorare: Novartis, Pfizer, AstraZeneca, Roche, Lilly. Ad-Boards: Novartis, Seagen, Daiichi Sankyo, AstraZeneca, Roche, Gilead. David Krug: honoraria from Merck Sharp & Dohme and Pfizer as well as research funding from Merck KGaA. Weitere AutorInnen geben keine Interessenkonflikte an., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Neoadjuvant radiotherapy (naRT) in addition to neoadjuvant chemotherapy (naCT) has been used for locally advanced, inoperable breast cancer or to allow breast conserving surgery (BCS). Retrospective analyses suggest that naRT + naCT might result in an improvement in pathological complete response (pCR rate and disease-free survival). pCR is a surrogate parameter for improved event-free and overall survival (OS) and allows for the adaption of the post-neoadjuvant therapy regimens. However, it is not clear whether pCR achieved with the addition of naRT has the same prognostic value., Patients and Methods: We performed a retrospective re-analysis of 356 patients (cT1-cT4/cN0-N+) treated with naRT and naCT with a long-term follow-up. Patients underwent naRT on the breast and regional lymph nodes combined with a boost to the primary tumor. Chemotherapy with different agents was given either sequentially or concomitantly to naRT. We used the Cox proportional hazard regression model to estimate the effect of pCR in our cohort in different subgroups as well as chemotherapy protocols. Clinical response markers correlating with OS were also analyzed., Results: For patients with median follow-ups of 20 years, 10 years, 15 years, 20 years, and 25 years, OS rates were 69.7%, 60.6%, 53.1%, and 45.1%, respectively. pCR was achieved in 31.1% of patients and associated with a significant improvement in OS (HR = 0.58; CI-95%: 0.41-0.80; p = 0.001). The prognostic impact of pCR was evident across breast cancer subtypes and chemotherapy regimens. Multivariate analysis showed that age, clinical tumor and nodal stage, chemotherapy, and pCR were prognostic for OS., Conclusion: NaCT and naRT prior to surgical resection achieve good long-term survival in high-risk breast cancer. pCR after naRT maintains its prognostic value in breast cancer subtypes and across different subgroups. pCR driven by naRT and naCT independently influences long-term survival.

Background/Aims: Due to its favorable dose distribution and targeting of the region at highest risk of recurrence due to direct visualization of tumor bed, intraoperative electron radiation therapy (IOERT) is used as part of a breast-conserving treatment approach. The aim of this study was to analyze tumor control and survival, as well as the toxicity profile, and cosmetic outcomes in patients irradiated with an IOERT boost for breast cancer. Materials and Methods: 139 Patients treated at our institution between January 2010 and January 2015 with a single boost dose of 10 Gy to the tumor bed during breast-conserving surgery followed by whole-breast irradiation were retrospectively analyzed. Results: 139 patients were included in this analysis. The median age was 54 years (range 28−83 years). The preferred surgical strategy was segmental resection with sentinel lymphonodectomy (66.5%) or axillary dissection (23.1%). Regarding adjuvant radiotherapy, the vast majority received 5 × 1.8 Gy to 50.4 Gy. At a median follow-up of 33.6 months, recurrence-free and overall survival were 95.5% and 94.9%, respectively. No patient developed an in-field recurrence. Seven patients (5.0%) died during the follow-up period, including two patients due to disease recurrence (non-in-field). High-grade (CTCAE > 2) perioperative adverse events attributable to IOERT included wound healing disorder (N = 1) and hematoma (N = 1). High-grade late adverse events (LENT-SOMA grade III) were reported only in one patient with fat necrosis. Low-grade late adverse events (LENT-SOMA grade I-II) included pain (18.0%), edema (10.5%), fibrosis (21%), telangiectasia (4.5%) and pigmentation change (23.0%). The mean breast retraction assessment score was 1.66 (0−6). Both patients and specialists rated the cosmetic result “excellent/good” in 84.8% and 87.9%, respectively. Conclusion: Our study reports favorable data on the cosmetic outcome as well as the acute and early long-term tolerability for patients treated with an IOERT boost. Our oncologic control rates are comparable to the previous literature. However, prospective investigations on the role of IOERT in comparison to other boost procedures would be desirable.

Purpose: Surgical reconstruction after segmental mandibulectomy in patients with oral cancer commonly requires implantation of titanium plates, which cause metallic artifacts in CT examinations detrimental for image quality. Therefore, the aim of the present study was to evaluate CT artifacts and image quality of the polymer plate materials polyetheretherketone (PEEK), polyetherketoneketone (PEKK), polyphenylsulfone (PPSU), and polyethylene (PE) in mandible reconstruction., Methods: Five plates (titanium, PEEK, PEKK, PPSU, and PE) were successively surgically inserted in a human cadaveric specimen using eight (1) titanium and (2) zirconium oxide screws. Streak and blooming artifacts were assessed in 1 mm CT scans with and without metallic artifact reduction algorithms (MAR) in this cross-sectional study. The different plate materials were analyzed for their effect on Hounsfield unit (HU) values resulting in streak artifacts. Blooming artifacts were measured as virtual growth of plates compared to actual size. Subjective image quality was assessed by 3 independent observers. Statistics were conducted by multifactorial ANOVA and Bonferroni's post hoc test., Results: Titanium (182.42 HU; SD ± 3.09) was associated with significantly more streak and blooming artifacts compared to the polymers PEEK (86.41 HU; SD ± 1.72; P < .001), PEKK (85.50 HU; SD ± 2.75; P < .001), PPSU (85.51 HU; SD ± 1.97; P < .001), and PE (85.52 HU; SD ± 3.33; P < .001) implants. No significant differences could be seen between the screw types (titanium vs zirconium oxide) (P = .75) or the activation or inactivation of MAR (P = .85). Image quality was best for PE and worst for titanium implants in combination with zirconium oxide screws., Conclusions: Polymers plate materials PEEK, PEKK, PPSU, and PE significantly reduce CT artifacts and improve image quality facilitating the radiological interpretation of implant surrounding tissues. This effect is beneficial for radiological tumor follow-up and CT-based planning of adjuvant radiotherapy., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Evidence from a few small randomized trials and retrospective cohorts mostly including various tumor entities indicates a prolongation of disease free survival (DFS) and overall survival (OS) from local ablative therapies in oligometastatic disease (OMD). However, it is still unclear which patients benefit most from this approach. We give an overview of the several aspects of stereotactic body radiotherapy (SBRT) in extracranial OMD in breast cancer from a radiation oncology perspective. A PubMed search referring to this was conducted. An attempt was made to relate the therapeutic efficacy of SBRT to various prognostic factors. Data from approximately 500 breast cancer patients treated with SBRT for OMD in mostly in small cohort studies have been published, consistently indicating high local tumor control rates and favorable progression-free (PFS) and overall survival (OS). Predictors for a good prognosis after SBRT are favorable biological subtype (hormone receptor positive, HER2 negative), solitary metastasis, bone-only metastasis, and long metastasis-free interval. However, definitive proof that SBRT in OMD breast cancer prolongs DFS or OS is lacking, since, with the exception of one small randomized trial (n = 22 in the SBRT arm), none of the cohort studies had an adequate control group. Further studies are needed to prove the benefit of SBRT in OMD breast cancer and to define adequate selection criteria. Currently, the use of local ablative SBRT should always be discussed in a multidisciplinary tumor board., (© 2022. The Author(s).)

Background: Vaccination against SARS-CoV-2 has been the main tool to contain the pandemic. The rush development of the 3 vaccines and their expedited approval have led to inoculation of millions of patients around the world, leading to a containment of the disease. Despite continuous viral mutations and the identification of weaker variants, the severity of the infections has been mild, with many patients being either asymptomatic or recovering at home. Currently the focus has shifted from the host of organ damage related to the infection to potential side effects of the vaccine. Myocarditis has been reported as one of the potential side effects from the mRNA vaccine, affecting young healthy individuals. Up to September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© were registered in young adults by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©)., Patients and Methods: Eight patients between 13 and 56 years of age, vaccinated with either BNT162b2 or mRNA-1273 mRNA vaccine between January and August 2021 developed cardiac side effects shortly after either their first or second dose of the vaccine. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after the onset of symptoms, with further investigations in severe cases. Symptoms were defined as dyspnea, chest pain and cardiac arrhythmia as determined by electrocardiography., Results: Eight patients (5 males and 3 females) developed cardiac symptoms compatible with myocarditis, according to the CDC criteria, shortly after SARS-CoV-2 mRNA vaccination. Three patients (2 males, 1 female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within 7 days from the symptom onset., Conclusions: Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients., (© 2022. The Author(s).)

The general topic of this year's 17th St. Gallen (SG) International Consensus Conference on the treatment of patients with early breast cancer (SG-BCC) was "Customizing local and systemic therapies for women with early breast cancer." This topic considers that each treatment decision must also consider the cancer-specific situation of the individual patient. This year, the votes of the SG-BCC were again discussed taking into account the multidisciplinary German S3 Guidelines and the recommendations of the Breast Cancer Working Group of the AGO (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO Mamma). As the international panel of the SG-BCC consists of experts from different countries, the votes do represent an international cross-section of opinions. Therefore, it is useful to discuss the voting results with respect to the German evidence-based treatment guidelines. This publication focuses mainly on systemic treatment., Competing Interests: Prof. Cornelia Kolberg-Liedtke received honoraria from Roche, AstraZeneca, Celgene, Novartis, Pfizer, Lilly, Hexal, Amgen, Eisai, and SonoScape as well as honoraria for consultancy work from Phaon Scientific, Novartis, Pfizer, and Celgene as well as research assistance from Roche, Novartis, and Pfizer. Travel grant from Novartis and Roche, employment at Palleos Healthcare, and Managing Director and partner at Phaon Scientific. Prof. Diana Lüftner received honoraria from Amgen, AstraZeneca, Celgene, Pfizer, Novartis, Roche, L'Oréal, Teva, GSK, and Eli Lilly. Prof. Dr. med. Sara Y. Brucker received honoraria from Roche, Novartis, Pfizer, AstraZeneca, and Teva. Prof. Dr. med. Wilfried Budach has no conflict of interest. Prof. Dr. med. Carsten Denkert received honoraria from Novartis, Roche, MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca, and Merck as well as research funding (for the Pathology Institute) from Myriad Genetics and Roche. He was co-founder and (until 2016) shareholder of Sividon Diagnostics. He is a co-inventor of the VMscope software for identifying Ki-67. Prof. Peter A. Fasching received grants from BioNtech and Cepheid as well as honoraria from Novartis, Pfizer, Daiichi-Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, SeaGen, Roche, Hexal, and Agendia. Renate Haidinger has no conflict of interest. Prof. Nadia Harbeck received honoraria from AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, and Seattle Genetics. Prof. Jens Huober received honoraria from Celgene, Roche, Novartis, Hexal, Pfizer, AstraZeneca, Lilly, Amgen, Eisai, and MSD as well as research assistance from Celgene, Hexal, and Novartis and travel grants from Roche, Novartis, Daiichi Sankyo, and Celgene. Prof. Christian Jackisch received honoraria from AstraZeneca, Lilly, Celgene, Novartis, Pfizer, AstraZeneca, Pierre Fabre, and Roche as well as research assistance from Exact Sciences. Prof. Wolfgang Janni received honoraria from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Genomic Health, Hexal, Lilly, MSD, Novartis, Pfizer, Roche, Tesaro, and Teva. Dr. med. David Krug received honoraria from Merck Sharp & Dohme. Prof. Thorsten Kühn received honoraria from Celgene, Roche, and Pfizer as well as research assistance from Mammotome, Merit Medical, and Pfizer. Prof. Dr. med. Sibylle Loibl received honoraria from AbbVie, Amgen, AstraZeneca, Bayer, BMS, Celgene, Chugai, Daiichi Sankyo, EirGenix, GSK, Immunomedics, Ipsen, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Prime/Medscape, Puma, Roche, Samsung, Seagen, Teva, and Vifor and has a patent application (EP14153692.0) under review. Prof. Volkmar Müller received honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, and Seattle Genetics as well as honoraria for consultancy work from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro, Seattle Genetics, and Neltar as well as funding for travel expenses from Roche, Pfizer, and Daiichi Sankyo and research assistance for the employer from Novartis, Roche, Seattle Genetics, and Genentech. Prof. Andreas Schneeweiss received honoraria from Celgene, Roche, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, and Lilly as well as research assistance from Celgene, Roche, AbbVie, and Molecular Partner [sic: Molecular Partners] as well as travel grants from Celgene, Roche, and Pfizer. Prof. Christoph Thomssen received honoraria from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, and Vifor and research assistance from American Diagnostica, Affymetrix, and Nanostring. Prof. Michael Untch: honoraria to the employer (for AdBoard participation, presentations) as well as travel assistance from Amgen, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Eisai, Janssen Cilag, Johnson & Johnson, Lilly Deutschland, Lilly International, MSD Merck, Mundipharma, Myriad Genetics, Odonate, Pfizer, PUMA Biotechnology, Riemser, Roche, Pierre Fabre, Novartis, Abbie [sic: AbbVie], Molecular Health, Agendia, and GSK. Prof. Dr. Marc Thill received honoraria and travel assistance from Amgen, AstraZeneca, Aurikamed, Becton and Dickinson, Biom'Up, Celgene, Clearcut, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Grünenthal, Hexal, I-Med Institute, Lilly, MCI, Medtronic, MSD, Neodynamics, Norgine, Novartis, OnkoLive, OmniaMed, Organon, pfm medical, Pfizer, Roche, Seagen, Sysmex, Tesaro, Teva, RTI Surgical, and Vifor and research assistance from Endomagnetics and Exact Sciences., (Copyright © 2022 by S. Karger AG, Basel.)

Background and purpose: To investigate intraoperative electron radiation therapy (IOERT) as a tumor bed boost during breast conserving surgery (BCS) followed by hypofractionated whole breast irradiation (HWBI) on age-correlated in-breast recurrence (IBR) rates in patients with low- to high-risk invasive breast cancer. Material and methods: BCS and IOERT (11.1 Gy) preceded a HWBI (40.5 Gy) in 15 fractions. Five-year IBR-rates were compared by a sequential ratio test (SQRT) with best evidences in three age groups (35−40 y and 41−50 y: 3.6%, >50 y: 2%) in a prospective single arm design. Null hypothesis (H0) was defined to undershoot these benchmarks for proof of superiority. Results: Of 1445 enrolled patients, 326 met exclusion criteria, leaving 1119 as eligible for analysis. After a median follow-up of 50 months (range 0.7−104), we detected two local recurrences, both in the age group >50 y. With no observed IBR, superiority was demonstrated for the patient groups 41−50 and >50 y, respectively. For the youngest group (35−40 y), no appropriate statistical evaluation was yet possible due to insufficient recruitment. Conclusions: In terms of five-year IBR-rates, Boost-IOERT followed by HWBI has been demonstrated to be superior in patients older than 50 and in the age group 41−50 when compared to best published evidence until 2010.

Neoadjuvant chemotherapy enables close monitoring of tumor response in patients with breast cancer. Being able to assess tumor response during treatment provides an opportunity to evaluate new therapeutic strategies. Thus, for triple-negative breast tumors, it was demonstrated that additional immunotherapy could improve prognosis compared with chemotherapy alone. Furthermore, adjuvant therapy can be escalated or de-escalated correspondingly. The CREATE-X trial randomly assigned HER2-negative patients with residual tumor after neoadjuvant therapy to either observation or capecitabine. In HER2-negative patients with positive BRCA testing, the OlympiA study randomly assigned patients to either observation or olaparib. HER2-positive patients without pathologic remission were randomly assigned to trastuzumab or trastuzumab-emtansine within the KATHERINE study. These studies were all able to show an improvement in oncologic outcome associated with the escalation of therapy in patients presenting with residual tumor after neoadjuvant treatment. On the other hand, this individualization of therapy may also offer the possibility to de-escalate treatment, and thereby reduce morbidity. Among WSG-ADAPT HER2+/HR-, HER2-positive patients achieved comparable results without chemotherapy after complete remission following neoadjuvant treatment. In summary, the concept of post-neoadjuvant therapy constitutes a great opportunity for individualized cancer treatment, potentially improving outcome. In this review, the most important trials of post-neoadjuvant therapy are compiled and discussed.

Aim: Plantar enthesophyte is a common degenerative disorder. Surgical and medical treatment options are associated with either poor outcome or high percentage of relapse. Observations have indicated a beneficial effect of radiation therapy. We therefore wanted to evaluate pain reduction using orthovolt or cobalt-based radiation treatment for painful plantar enthesophyte and determine long-term response as well as prognostic parameters in this condition., Methods: We identified a total of 102 consecutive patients treated for a total of 117 symptomatic heel spurs. 59 patients were treated with cobalt radiation, 31 patients with orthovolt therapy and 12 patients with both radiation systems. Primary outcome measure was pain reduction being scored using the modified Rowe Score prior therapy, at the end of each treatment series as well as after 6 weeks. Secondary outcome measure was long-term outcome, evaluated in patients with a follow-up period of longer than 3 years., Results: Before radiation therapy, 61 patients (60.4%) had a score of 0, significant strong pain. At the time of completion of radiation treatment, 3 patients (2.7%) were pain-free (score of 30), whereas 8 patients (7.9%) had still severe pain (score 0). 6 weeks after radiation therapy, 33 patients (32.7%) were pain-free and 8 patients (7.9%) had severe pain (score 0), while at the time data of collection, 74 patients (73%) were free of pain and 1 patient (1%) had strong pain (score 0). Duration of pain before the start of radiation treatment was a significant prognostic factor (p = 0.012) for response to treatment., Conclusion: Radiotherapy of painful plantar enthesophyte is a highly effective therapy with little side effects providing long-term therapeutic response. The only significant prognostic parameter for response to treatment is the duration of pre-radiation therapy pain. Early integration of radiation therapy in the treatment seems to result in superior pain reduction., (© 2022. The Author(s).)

Background: During the last decade, partial breast irradiation (PBI) has gained traction as a relevant treatment option for patients with early-stage low-risk breast cancer after breast-conserving surgery. The TARGIT-A prospective randomized trial compared a "risk-adapted" intraoperative radiotherapy (IORT) approach with 50-kv X-rays (INTRABEAM®) as the PBI followed by optional whole-breast irradiation (WBI) and conventional adjuvant WBI in terms of observed 5-year in-breast recurrence rates. Recently, long-term data were published. Since the first publication of the TARGIT-A trial, a broad debate has been emerged regarding several uncertainties and limitations associated with data analysis and interpretation. Our main objective was to summarize the data, with an emphasis on the updated report and the resulting implications., Summary: From our point of view, the previously unresolved questions still remain and more have been added, especially with regard to the study design, a change in the primary outcome measure, the significant number of patients lost to follow-up, and the lack of a subgroup analysis according to risk factors and treatment specifications., Key Message: Taking into account the abovementioned limitations of the recently published long-term results of the TARGIT-A trial, the German Society of Radiation Oncology (DEGRO) Breast Cancer Expert Panel adheres to its recently published recommendations on PBI: "the 50-kV system (INTRABEAM) cannot be recommended for routine adjuvant PBI treatment after breast-conserving surgery.", Competing Interests: V.S. declares consultation fees from Nucletron Operations BV, an Elekta Company, outside the submitted work. D.K. has received honoraria from Merck Sharp & Dome, outside of the submitted work. F.S. has received a study grant from Intraop Medical. G.F. has received a honorarium from Roche, outside of the submitted work. M.P., R.B., S.C., M.-N.D., J.D., P.F., R.F., Wu.H., Wo.H., T.H., R.S., and W.B. have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included., (© 2021. The Author(s).)

Purpose: The first aim of the trial is to study feasibility of combined programmed death protein ligand 1/cytotoxic T-lymphocyte-associated protein 4 inhibition concomitant to radiotherapy. In addition, efficacy of the entire treatment scheme consisting of induction chemoimmunotherapy followed by chemotherapy-free radioimmunotherapy (RIT) after intratumoral CD8 +immune cell-based patient selection will be analyzed., Methods: Patients with stage III-IVB head and neck squamous cell carcinoma were eligible for this multicenter phase II trial. Treatment consisted of a single cycle of cisplatin 30 mg/m² days 1-3, docetaxel 75 mg/m² day 1, durvalumab 1500 mg fix dose day 5 and tremelimumab 75 mg fix dose day 5. Patients with increased intratumoral CD8 +immune cell density or pathological complete response (pCR) in the rebiopsy entered RIT up to a total dose of 70 Gy. Patients received further three cycles of durvalumab/tremelimumab followed by eight cycles of durvalumab mono (every 4 weeks). The intended treatment for patients not meeting these criteria was standard radiochemotherapy outside the trial. Primary endpoint was a feasibility rate of patients entering RIT to receive treatment until at least cycle 6 of immunotherapy of ≥80%., Results: Between September 2018 and May 2020, 80 patients were enrolled (one excluded). Out of these, 23 patients had human papilloma virus (HPV)-positive oropharyngeal cancer. Median follow-up was 17.2 months. After induction chemoimmunotherapy 41 patients had pCR and 31 had increased intratumoral CD8 +immune cells. Of 60 patients entering RIT (primary endpoint cohort), 10 experienced imiting toxic (mainly hepatitis) and four discontinued for other reasons, resulting in a feasibility rate of 82%. The RIT cohort (n=60) had a progression-free survival (PFS) rate at one and 2 years of 78% and 72%, respectively, and an overall survival rate at one and 2 years of 90% and 84%, respectively. Patients with HPV-positive oropharyngeal cancers had greater benefit from RIT with a 2-year PFS rate of 94% compared with 64% for HPV-negative oropharyngeal cancers and other locations. In the entire study cohort (n=79) the 2-year PFS rate was 68% (91% for HPV-positive oropharynx vs 59% for others). Toxicity grade 3-4 mainly consisted of dysphagia (53%), leukopenia (52%) and infections (32%)., Conclusions: The trial met the primary endpoint feasibility of RIT. Induction chemo-immunotherapy followed by chemotherapy-free RIT after intratumoral CD8 +immune cell-based patient selection has promising PFS., Trial Registration Number: The trial was registered with ClinicalTrials.gov (identifier: NCT03426657). The trial was conducted as investigator-sponsored trial (IST)., Competing Interests: Competing interests: MH conflict of interest with Merck Serono (advisory role, speakers’ bureau, honoraria, travel expenses, research funding); MSD (advisory role, speakers’ bureau, honoraria, travel expenses, research funding); AstraZeneca (research funding); Novartis (research funding); BMS (advisory role, honoraria, speakers’ bureau); Teva (travel expenses). ME conflict of interest with Diaceutics (employment, honoraria, advisory role, speakers’ bureau, travel expenses); Cepheid (research funding, advisory role); AstraZeneca (honoraria, advisory role, speakers’ bureau, travel expenses); Roche (honoraria, travel expenses); MSD (honoraria, speakers’ bureau); GenomicHealth (honoraria, advisory role, speakers bureau, travel expenses); Astellas (honoraria, speakers’ bureau); Janssen-Cilag (honoraria, advisory role, research funding, travel expenses); Stratifyer (research funding, patents). SR conflict of interest with AstraZeneca (research funding); MSD (research funding). GK conflict of interest with BMS (advisory role); Lilly (advisory role); Roche (advisory role). SL conflict of interest with AstraZeneca (honoraria, advisory role); BMS (honoraria, advisory role, speakers’ bureau); MSD (honoraria, advisory role); Merck Serono (honoraria, speakers’ bureau); ISA-Pharmaceuticals (research funding). MGH conflict of interest with Roche (stock); Varian (stock); Sanofi (stock); AstraZeneca (honoraria); BMS (honoraria, advisory role); MSD (honoraria, advisory role); Merck Serono (honoraria); Celgene (honoraria). AHi conflict of interest with Roche (honoraria). SS conflict of interest with Strycker (stock); Varian (stock); Abbot (stock); Crispr Techn. (stock); Pfitzer (stock); Merck Serono (stock); Symrise (stock); Ortho (honoraria, advisory role, speakers’ bureau, research funding, travel expenses); PharmaMar (speakers’ bureau, travel expenses); Haema (speakers’ bureau). AHa. conflict of interest with BMS (honoraria, advisory role); MSD (honoraria, advisory role); Roche (honoraria, advisory role, research funding); AstraZeneca (honoraria, advisory role, research funding); Boehringer Ingelheim (honoraria); Abbvie (honoraria); Cepheid (advisory role, research funding); Quiagen (advisory role); Janssen-Cilag (honoraria, advisory role, research funding); Ipsen (honoraria, advisory role); NanoString Technologies (advisory role, research funding, expert testimony); Illumina (advisory role); 3DHistech (advisory role); Diaceutics (advisory role); BioNTech (research funding). WB conflict of interest with BMS (advisory role); MSD (advisory role); Merck Serono (advisory role); Pfitzer (advisory role); AstraZeneca (advisory role). UG conflict of interest with AstraZeneca (advisory role, research funding); BMS (advisory role); MSD (research funding); Sennewald Medizintechnik (advisory role, travel expenses). RF conflict of interest with MSD (honoraria, advisory role, research funding, travel expenses); Fresenius (honoraria); BrainLab (honoraria); AstraZeneca (honoraria, advisory role, research funding, travel expenses); Merck Serono (advisory role, research funding, travel expenses); Novocure (advisory role, speakers’ bureau, research funding); Sennewald (speakers’ bureau, travel expenses). The other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Peter Dall: honoraria for lectures and advisory boards: Roche, Novartis, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo, Seagen. Jörg Heil: no conflict of interest to declare. Maggie Banys-Paluchowski: honoraria for lectures and advisory boards: Roche, Novartis, Pfizer, Lilly, Eisai, AstraZeneca, Amgen, GSK, pfm, Daiichi Sankyo. Study support: EndoMag, Mammotome, MeritMedical. David Krug: received honoraria from Merck Sharp & Dohme, the European School of Oncology and the European Society for Medical Oncology. Wilfried Budach: no conflict of interest to declare. Cornelia Kolberg-Liedtke: no conflict of interest to declare. Toralf Reimer: no conflict of interest to declare.

Background: The standard treatment of high-risk soft-tissue sarcoma consists of surgical resection followed by risk-adapted radiation therapy. Further treatment options that may improve local and systemic tumor control, including chemotherapy, are not well established. Due to the heterogeneity of the disease, different systemic approaches as well as their application at different time points have been attempted., Methods: We conducted a systematic literature search for randomized clinical trials in the treatment of localized, resectable high-risk adult soft-tissue sarcoma comparing different treatment modalities according to the PRISMA guidelines. We extracted published hazard ratios and number of events for the endpoints overall and disease-free survival (OS; DFS) as well as local and distant recurrence-free interval (LRFI; DRFI). The different modalities were compared in a network meta-analysis against the defined standard treatment surgery ± radiotherapy using the inverse-variance heterogeneity model., Results: The literature search identified 25 trials including 3453 patients. Five different treatment modalities were compared in the network meta-analysis. The addition of adjuvant chemotherapy significantly improved OS compared to surgery ± radiotherapy alone (HR = 0.86; CI-95%: 0.75-0.97; p = 0.017). Likewise, neoadjuvant chemotherapy combined with regional hyperthermia (naCTx + HTx) also led to superior OS (HR = 0.45; CI-95%: 0.20-1.00; p = 0.049). Both neoadjuvant chemotherapy alone (naCTx) and perioperative chemotherapy (periCTx) did not improve OS (HR = 0.61; CI-95%: 0.29-1.29; p = 0.195 and HR = 0.66; CI-95%: 0.30-1.48; p = 0.317, respectively). Histology-tailored chemotherapy (htCTx) also did not improve survival compared to surgery ± radiotherapy (HR = 1.08; CI-95%: 0.45-2.61; p = 0.868). The network analysis of DFS, LRFI, and DRFI revealed a similar pattern between the different treatment regimens. Adjuvant chemotherapy significantly improved DFS, LRFI, and DRFI compared to surgery ± radiotherapy. In direct comparison, this advantage of adjuvant chemotherapy was restricted to male patients (HR = 0.78; CI-95%: 0.65-0.92; p = 0.004) with no effect for female patients (HR = 1.08; CI-95%: 0.90-1.29; p = 0.410)., Conclusions: Standardized chemotherapy in high-risk soft-tissue sarcoma appears to be of added value irrespective of timing. The benefit of adjuvant chemotherapy seems to be restricted to male patients. The addition of regional hyperthermia to neodjuvant chemotherapy achieved the best effect sizes and might warrant further investigation.

For many decades, the standard procedure to treat breast cancer included complete dissection of the axillary lymph nodes. The aim was to determine histological node status, which was then used as the basis for adjuvant therapy, and to ensure locoregional tumour control. In addition to the debate on how to optimise the therapeutic strategies of systemic treatment and radiotherapy, the current discussion focuses on improving surgical procedures to treat breast cancer. As neoadjuvant chemotherapy is becoming increasingly important, the surgical procedures used to treat breast cancer, whether they are breast surgery or axillary dissection, are changing. Based on the currently available data, carrying out SLNE prior to neoadjuvant chemotherapy is not recommended. In contrast, surgical axillary management after neoadjuvant chemotherapy is considered the procedure of choice for axillary staging and can range from SLNE to TAD and ALND. To reduce the rate of false negatives during surgical staging of the axilla in pN+ CNB stage before NACT and ycN0 after NACT, targeted axillary dissection (TAD), the removal of > 2 SLNs (SLNE, no untargeted axillary sampling), immunohistochemistry to detect isolated tumour cells and micro-metastases, and marking positive lymph nodes before NACT should be the standard approach. This most recent update on surgical axillary management describes the significance of isolated tumour cells and micro-metastasis after neoadjuvant chemotherapy and the clinical consequences of low volume residual disease diagnosed using SLNE and TAD and provides an overview of this year's AGO recommendations for surgical management of the axilla during primary surgery and in relation to neoadjuvant chemotherapy., Competing Interests: Conflict of Interest/Interessenkonflikt PD DR Banys-Paluchowski: Honoraria for lectures and advisory role from Lilly, Pfizer, Roche, Amgen, Eisai, Astra Zeneca, Daiichi Sankyo, Novartis, GSK and study support from Endomag, Merit Medical and Mammotome. Prof. Dr. V. Müller: VM received speaker honoraria from Amgen, Astra Zeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Novartis, Roche, Teva, Seagen and consultancy honoraria from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Seagen. Institutional research support from Novartis, Roche, Seagen, Genentech. Travel grants: Roche, Pfizer, Daiichi Sankyo./ Vortragshonorare: Amgen, Astra Zeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics, GSK, Seagen. Beratertätigkeit: Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, GSK, Tesaro, Seagen und Nektar. Forschungsuntersützung an den Arbeitgeber: Novartis, Roche, Seattle Genetics, Genentech. Reisekosten: Roche, Pfizer, Daiichi Sankyo., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: COVID-19, the pandemic disease caused by infection with SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients' adaptive immune responses without progression to severe disease with patients' Human Leukocyte Antigen (HLA) genetics, AB0 blood group antigens, and the presence or absence of near-loss-of-function delta 32 deletion mutant of the C-C chemokine receptor type 5 (CCR5)., Patient and Methods: An exploratory observational study including 157 adult COVID-19 convalescent patients was performed with a median follow-up of 250 days. The impact of different HLA genotypes, AB0 blood group antigens, and the CCR5 mutant CD195 were investigated for their role in the clinical course of COVID-19. In addition, this study addressed levels of severity and morbidity of COVID-19. The association of the immunogenetic background parameters were further related to patients' humoral antiviral immune response patterns by longitudinal observation., Results: Univariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01). They were associated with reduced durations of disease instead decreased (rather than increased) total anti-S IgG levels. They had a higher virus neutralizing capacity compared to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:02 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A suggestive association of a heterozygous CCR5 delta 32 mutation status with prolonged disease duration was implied by univariate analyses but could not be confirmed by hierarchical multivariate testing., Conclusion: The current study shows that the presence of HLA class II DRB1*01:01 and HLA class I B*35:01 is of even stronger association with reduced disease duration in mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations also including novel SARS-CoV-2 variants will be required to assess the impact of HLA genetics on the capacity of mounting protective vaccination responses in the future., (© 2021. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) is associated with a wide clinical spectrum of skin manifestations, including urticarial, vesicular, vasculitic and chilblain-like lesions. Recently, delayed skin reactions have been reported in 1% individuals following mRNA vaccination against SARS-CoV-2. The exact pathophysiology and the risk factors still remain unclear., Patients and Methods: 6821 employees and patients were vaccinated at our institutions between February and June 2021. Every patient received two doses of the mRNA-1273 vaccine in our hospitals, and reported back in case of any side effects which were collected in our hospital managed database., Results: Eleven of 6821 vaccinated patients (0.16%) developed delayed skin reactions after either the first or second dose of the mRNA-1273 vaccine against SARS-CoV-2. Eight of 11 patients (73%) developed a rash after the first dose, while in 3/11 (27%), the rash occurred after the second dose. More females (9/11) were affected. Four of 11 patients required antihistamines, with two needing additional topical steroids. All the cutaneous manifestations resolved within 14 days. None of the skin reactions after the first dose of the vaccine prevented the administration of the second dose. There were no long-term cutaneous sequelae in any of the affected individuals., Conclusion: Our data suggests that skin reactions after the use of mRNA-1273 vaccine against SARS-CoV-2 are possible, but rare. Further studies need to be done to understand the pathophysiology of these lesions., (© 2021. The Author(s).)

Purpose/objective: The standard treatment for localized low-risk breast cancer is breast-conserving surgery, followed by adjuvant radiotherapy and appropriate systemic therapy. As the majority of local recurrences occur at the site of the primary tumor, numerous trials have investigated partial-breast irradiation (PBI) instead of whole-breast treatment (WBI) using a multitude of irradiation techniques and fractionation regimens. This meta-analysis addresses the impact on disease-specific endpoints, such as local and regional control, as well as disease-free survival of PBI compared to that of WBI in published randomized trials., Material and Methods: We conducted a systematic literature review and searched for randomized trials comparing WBI and PBI in early-stage breast cancer with publication dates after 2009. The meta-analysis was based on the published event rates and the effect sizes for available oncological endpoints of at least two trials reporting on them. We evaluated in-breast tumor recurrences (IBTR), local recurrences at the primary site and elsewhere in the ipsilateral breast, regional recurrences (RR), distant metastasis-free interval (DMFI), disease-free survival (DFS), contralateral breast cancer (CBC), and second primary cancer (SPC). Furthermore, we aimed to assess the impact of different PBI techniques and subgroups on IBTR. We performed all statistical analyses using the inverse variance heterogeneity model to pool effect sizes., Results: For the intended meta-analysis, we identified 13 trials (overall 15,561 patients) randomizing between PBI and WBI. IBTR was significantly higher after PBI (OR = 1.66; CI-95%: 1.07-2.58; p = 0.024) with an absolute difference of 1.35%. We detected significant heterogeneity in the analysis of the PBI technique with intraoperative radiotherapy resulting in higher local relapse rates (OR = 3.67; CI-95%: 2.28-5.90; p < 0.001). Other PBI techniques did not show differences to WBI in IBTR. Both strategies were equally effective at the primary tumor site, but PBI resulted in statistically more IBTRs elsewhere in the ipsilateral breast. IBTRs after WBI were more likely to be located at the primary tumor bed, whereas they appeared equally distributed within the breast after PBI. RR was also more frequent after PBI (OR = 1.75; CI-95%: 1.07-2.88; p < 0.001), yet we did not detect any differences in DMFI (OR = 1.08; CI-95%: 0.89-1.30; p = 0.475). DFS was significantly longer in patients treated with WBI (OR = 1.14; CI-95%: 1.02-1.27; p = 0.003). CBC and SPC were not different in the test groups (OR = 0.81; CI-95%: 0.65-1.01; p = 0.067 and OR = 1.09; CI-95%: 0.85-1.40; p = 0.481, respectively)., Conclusion: Limiting the target volume to partial-breast radiotherapy appears to be appropriate when selecting patients with a low risk for local and regional recurrences and using a suitable technique.

Competing Interests: N. Ditsch: MSD, Novartis, Pfizer, Roche, AstraZeneca, Teva, Mentor, MCI. M. Untch: Presentations and travel grants, all paid to his institution by Abbvie, Amgen GmbH München, AstraZeneca, BMS, Celgene GmbH München, Daiichi Sankyo, Eisai GmbH München, Janssen Cilag, Johnson & Johnson, Lilly Deutschland, Lilly Int., MSD, Mundipharma, Myriad Genetics GmbH Zürich, Odonate, Pfizer GmbH Berlin, PUMA Biotechnology, Riemser, Roche Pharma AG Grenzach-Wyhlen, Sanofi Aventis Deutschland GmbH, Sividon Diagnostics Köln, Teva Pharmaceuticals Ind. Ltd. Berlin. C. Kolberg-Liedtke: Advisory boards: Phaon Scientific, Novartis, Pfizer, SurgVision, Carl Zeiss Meditec, Amgen, Onkowissen. Lectures: Roche, Novartis, Pfizer, Lilly, Genomic Health, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion Janssen-Cilag, GSK, LIV Pharma, Theramex. Travel expenses: Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo. D. Krug: MSD. M. Friedrich: Roche, Pfizer, AstraZeneca, Novartis. W. Janni: Research grants and/or honoraria: Sanofi-Aventis, Novartis, Roche, Pfizer, AstraZeneca, Chugai, GSK, Eisai, Celgene, Lilly, Janssen, Menarini. V. Müller: Speaker honoraria: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics. Consultancy honoraria: Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro, Nektar. Institutional research support: Novartis, Roche, Seattle Genetics, Genentech. U.-S. Albert: Lectures and/or consulting: Medexo GmbH, Institut für Versiche­rungsmedizin, Pfizer. M. Banys-Paluchowski: Advisory board: Eisai. Lectures: AstraZeneca. Study support: Mammotome, EndoMag, MeritMedical. I. Bauerfeind: No conflicts of interest. J.-U. Blohmer: Honoraria: Amgen, AstraZeneca, Genomic Health, MSD Oncology, Myriad Genetics, Novartis, Pfizer, Roche, Sonoscape. Travel and accommodation expenses: Pfizer, Roche. W. Budach: No conflicts of interest. P. Dall: Advisory boards: Olympus, Roche, Novartis, Tesaro. Congress support: Roche. Lectures: Amgen, Roche. E.M. Fallenberg: GE Healthcare, Siemens, ECR, EUSOBI, ESOR, KCR, DFG. P.A. Fasching: Grants: Novartis, BioNTech, Cepheid. Personal fees: Novartis, Roche, Pfizer, Celgene, Daiichi Sankyo, AstraZeneca, MSD, Myelo Therapeutics, Macrogenics, Eisai, Puma, Lilly. T. Fehm: AstraZeneca, Celgene, Pfizer, Novartis, Roche, Teva, Daiichi Sankyo. B. Gerber: No conflicts of interest. O. Gluz: Lecture and consulting fees: Celgene, Roche, Genomic Health, Amgen, Pfizer, Novartis, Lilly, Nanostring, Eisai, MSD. Travel expenses: Celgene, Roche, Daiichi Sankyo. N. Harbeck: Lecture and/or consulting fees: Agendia, Amgen, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Genomic Health, Lilly, MSD, Novartis, Odonate, Pierre Fabre, Pfizer, Roche, Sandoz/Hexal, Seattle Genetics. Minority share holder: Westdeutsche Studiengruppe. J. Heil: No conflicts of interest. J. Huober: Research support: Celgene, Novartis, Hexal. Lectures: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene, Eisai, Abbvie. Consulting: Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, Abbvie. Travel expenses: Roche, Pfizer, Novartis, Celgene, Daiichi Sankyo. C. Jackisch: Advisory boards: Amgen, AstraZeneca, Novartis, Pierre Fabre, Exact Sciences, Roche, Lilly, Pfizer. Travel grants: Roche, Novartis, Pfizer, Exact Sciences, Amgen. Lectures: Amgen, AstraZeneca, Daiichi Sankyo, Novartis, Pierre Fabre, Exact Sciences, Roche, Lilly, Pfizer. H.-H. Kreipe: Reimbursement for attending symposia: Ventana. Other expenses (advisory boards, lectures): Amgen, AstraZeneca, Genomic Health, Lilly, Roche Pharma. T. Kühn: Celgene, Roche, Pfizer. S. Kümmel: Roche, Genentech, Novartis, AstraZeneca, Amgen, Celgene, SOMATEX, Daiichi Sankyo, Puma Biotechnology, pfm medical, Pfizer, MSD Oncology. S. Loibl: Advisory boards/lectures: Abbvie, Amgen, AstraZeneca, Celgene, Novartis, Pfizer, Roche, Seattle Genetics, PriME/Medscape, Daiichi Sankyo, Lilly, Samsung, Eirgenix, BMS, Puma, MSD, Merck, Pierre Fabre. D. Lüftner: Advisory boards/oral presentations: Amgen, AstraZeneca, GSK, Eli Lilly, L'Oréal, MSD, Mundipharma, Mylan, Novartis, Pfizer, Roche, Teva. M.P. Lux: Advisory boards, lectures, travel support: Lilly, Pfizer, Roche, MSD, Hexal, Novartis, AstraZeneca, Eisai, medac, Genomic Health. N. Maass: No conflicts of interest. C. Mundhenke: Not specified. U. Nitz: Not specified. T.-W. Park-Simon: Advisory role or expert testimony and lecture honoraria: Roche, AstraZeneca, Tesaro, Pfizer, Daiichi Sankyo, Lilly, MSD. Participation in clinical trials: Roche, AstraZeneca, Tesaro, Pfizer, Daiichi Sankyo, Lilly, MSD, Novartis, Seattle Genetics. Other financial relationships such as travel: Roche, AstraZeneca, Tesaro, Pfizer, Lilly, MSD, Novartis. T. Reimer: Grants: German Cancer Aid, Else Kröner-Fresenius-Stiftung. Personal fees. Pfizer, Roche, Novartis, AstraZeneca outside the submitted work. K. Rhiem: AstraZeneca, Tesaro, Pfizer, Roche. A. Rody: Roche, Pfizer, Novartis, Celgene, Novartis, Genomic Health/Exact Sciences, AstraZeneca, Eisai, MSD, Hexal, Amgen. M. Schmidt: Personal fees: AstraZeneca, Roche, Lilly, SeaGen, MSD, Eisai. Grants: Pierre Fabre, Pantarhei Bioscience, BioNTech, Genentech outside the submitted work. Patent issued for EP 2390370 B1 and EP 2951317 B1. A. Schneeweiss: Grants: Celgene, Roche, Abbvie, Molecular Partner. Personal fees: Roche, AstraZe­neca, Celgene, Pfizer, Novartis, MSD, Tesaro, Lilly. F. Schütz: Amgen, AstraZeneca, Lilly, Hexal, MSD, Novartis, Pfizer, Roche, Onkozert, Eickeler Kongressorganisation. H.-P. Sinn: No conflicts of interest related to the submitted manuscript. C. Solbach: Travel, accommodations: Roche, Novartis, AstraZeneca, Amgen, Celgene, Hexal, Daiichi Sankyo, Dialog Service GmbH, Lilly, Pfizer, MSD Oncology, ESAI, Gedon Richter, Mylan, Tesaro. E.-F. Solomayer: Roche, AstraZeneca, Pfizer, Amgen, Celgene, Tesaro, AstraZeneca, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon. E. Stickeler: Counseling: Novartis, Pfizer, AstraZeneca, Roche, Tesoro. Fees: Novartis, Pfizer, AstraZeneca, Roche. C. Thomssen: Advisory boards and lectures: Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Vifor. Research support (by discount prizes): American Diagnostica, Affymetrix, Nanostring. I. Witzel: Not specified. A. Wöckel: Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Genomic Health, Pierre Fabre, Clovis. M. Thill: Advisory boards: Amgen, AstraZeneca, Celgene, ClearCut, Clovis, Daiichi Sankyo, Exact Sciences, Lilly, MSD, Neodynamics, Novartis, Pfizer, pfm medical, Pierre Fabre, Roche, Tesaro. Manuscript support: Amgen, Celgene, Roche. Travel expenses: Amgen, Art Tempi, AstraZeneca, Celgene, Clovis, Connect Medica, Daiichi Sankyo, Exact Sciences, Hexal, I-Med Institute, Lilly, MCI, MSD, Novartis, Pfizer, pfm medical, Roche, Tesaro. Congress fees: Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Hexal, Novartis, Pfizer, Roche. Lectures: Amgen, Art Tempi, AstraZeneca, Celgene, Clovis, Connect Medica, Exact Sciences, Hexal, I-Med Institute, Lilly, MCI, MSD, Novartis, OnkoLive, Pfizer, pfm medical, Roche. Trial funding: Exact Sciences.

Competing Interests: M. Thill: Advisory boards: Amgen, AstraZeneca, Celgene, ClearCut, Clovis, Daiichi Sankyo, Exact Sciences, GSK, Lilly, MSD, Neodynamics, Novartis, Pfizer, pfm medical, Pierre Fabre, Roche, Sysmex, Tesaro. Manuscript support: Amgen, Celgene, Clearcut, Roche. Travel reimbursement: Amgen, art tempi, AstraZeneca, Celgene, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Hexal, I-Med Institute, Lilly, MCI, Medtronic, MSD, Novartis, Pfizer, pfm medical, Roche, Sysmex, Tesaro. Congress support: Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Hexal, Novartis, Pfizer, Roche. Lectures: Amgen, art tempi, AstraZeneca, Celgene, Clovis, Connect Medica, Daiichi Sankyo, Exact Sciences, Hexal, I-Med Institute, Lilly, MCI, Medtronic, MSD, Novartis, Pfizer, pfm medical, Roche, Seagen, Sysmex, Tesaro, Vifor. Trial funding: Endomagnetics, Exact Sciences. M. Friedrich: Roche, Pfizer, AstraZeneca, Novartis. C. Kolberg-Liedtke: Advisory boards: Phaon Scientific, Novartis, Pfizer, SurgVision, Carl Zeiss Meditec, Amgen, Onkowissen. Lectures: Roche, Novartis, Pfizer, Lilly, Genomic Health, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, TEVA, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Theramex. Travel grants: Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo. U.-S. Albert: Lectures and/or consulting: Medexo GmbH, Institut für Versicherungsmedizin, Pfizer. M. Banys-Paluchowski: Pfizer, Roche, Novartis, Eli Lilly. I. Bauerfeind: Aurikamed, J. Eickeler. J.-U. Blohmer: Honoraria: Amgen, AstraZeneca, Genomic Health Recipient, MSD Oncology, Myriad Genetics, Novartis, Pfizer, Roche, Sonoscape. Travel, accommodations, expenses: Pfizer, Roche. W. Budach: No conflicts of interest. P. Dall: Advisory boards: Olympus, Roche, Novartis, Tesaro. Congress support: Roche. Lectures: Amgen, Roche. E.M. Fallenberg: GE Healthcare, Siemens, ECR, EUSOBI, ESOR, KCR, Esor, DFG. P.A. Fasching: Grants: Novartis, BioNTech, Cepheid. Personal fees: Novartis, Roche, Pfizer, Celgene, Daiichi Sankyo, AstraZeneca, MSD, Myelo Therapeutics, Macrogenics, Eisai, Puma, Lilly. T. Fehm: AstraZeneca, Celgene, Pfizer, Novartis, Roche, Teva, Daiichi Sankyo. B. Gerber: No conflicts of interest. O. Gluz: Advisory boards/lectures: Celgene, Roche, Genomic Health, Amgen, Pfizer, Novartis, Lilly, Nanostring, Eisai, MSD Travel. Grants: Celgene, Roche, Daiichi Sankyo. N. Harbeck: Honoraria for lectures and/or consulting: Agendia, Amgen, Astra Zeneca, BMS, Celgene, Daiichi Sankyo, Genomic Health, Lilly, MSD, Novartis, Odonate, Pierre Fabre, Pfizer, Roche, Sandoz/Hexal, Seattle Genetics. Minority share holder: Westdeutsche Studiengruppe. J. Heil: No conflicts of interest. J. Huober: Trial funding: Celgene, Novartis, Hexal. Lectures: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene, Eisai, Abbvie. Advisory boards: Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, Abbvie. Travel expenses: Roche, Pfizer, Novartis, Celgene, Daiichi Sankyo. C. Jackisch: Roche, AstraZeneca, Novartis. H.-H. Kreipe: Reimbursement for attending symposia: Ventana. Other expenses (advisory boards, lectures): Amgen, AstraZeneca, Genomic Health, Lilly, Roche. D. Krug: MSD. T. Kühn: Celgene, Roche, Pfizer. S. Kümmel: Roche, Genentech, Novartis, AstraZeneca, Amgen, Celgene, SOMATEX, Daiichi Sankyo, Puma Biotechnology, pfm medical, Pfizer, MSD Oncology. S. Loibl: Abbvie, Amgen, AstraZeneca, Celgene, Novartis, Pfizer, Roche, Seattle Genetics, PriME/Medscape, Chugai, Teva, Vifor, Daiichi Sankyo, Lilly, Samsung, Eirgenix, BMS, Puma, MSD, Immunomedics. D. Lüftner: Advisory boards/lectures: Amgen, AstraZeneca, Celgene, GSK, Lilly, L'Oréal, MSD, Mundi­pharma, Mylan, Novartis, Pfizer, Roche, Teva, Tesaro. M.P. Lux: Advisory boards, lectures, travel support: Lilly, Pfizer, Roche, MSD, Hexal, Novartis, AstraZeneca, Eisai, medac, Genomic Health. N. Maass: No conflicts of interest. C. Mundhenke: Not specified. U. Nitz: Not specified. T.-W. Park-Simon: Advisory role or expert testimony and lecture honoraria: Roche, AstraZeneca, Tesaro, Pfizer, Daiichi Sankyo, Lilly, MSD. Participation in clinical trials: Roche, AstraZeneca, Tesaro, Pfizer, Daiichi Sankyo, Lilly, MSD, Novartis, Seattle Genetics. Other financial relationships such as travel: Roche, AstraZeneca, Tesaro, Pfizer, Lilly, MSD, Novartis. T. Reimer: Grants: German Cancer Aid, Else Kröner-Fresenius-Stiftung. Personal fees: Pfizer, Roche, Novartis, AstraZeneca, outside the submitted work. K. Rhiem: AstraZeneca, Tesaro, Pfizer, Roche. A. Rody: Roche, Pfizer, Novartis, Celgen, Genomic Health/Exact Sciences, AstraZeneca, Eisai, MSD, Hexal, Amgen. M. Schmidt: Personal fees: AstraZeneca, Roche, Lilly, SeaGen, MSD, Eisai. Grants: Pierre Fabre, Pantarhei Bioscience, BioNTech, Genentech outside the submitted work. Patent issued for EP 2390370 B1 and EP 2951317 B1. A. Schneeweiss: Grants: Celgene, Roche, Abbvie, Molecular Partner. Personal fees: Roche, AstraZeneca, Celgene, Pfizer, Novartis, MSD, Tesaro, Lilly. F. Schütz: Amgen, AstraZeneca, Lilly, Hexal, MSD, Novartis, Pfizer, Roche, Onkozert, Eickeler Kongressorganisation. H.-P. Sinn: No conflicts of interest related to the submitted manuscript. C. Solbach: Travel, accommodation: Roche, Novartis, AstraZeneca, Amgen, Celgene, Hexal, Daiichi Sankyo, Dialog Service GmbH, Lilly, Pfizer, MSD Oncology, ESAI, Gedon Richter, Mylan, Tesaro. E.-F. Solomayer: Roche, AstraZeneca, Pfizer, Amgen, Celgen, Tesaro, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon. E. Stickeler: Advisory boards: Novartis, Pfizer, AstraZeneca, Roche, Tesoro. Fees: Novartis, Pfizer, AstraZeneca, Roche. C. Thomssen: Advisory boards, lectures: Amgen, AstraZeneca, Celgen, Daiichi Sankyo, Eisai, Lilly, MSD, Mundipharma, Medapharm, Novartis, Pfizer, Pierre Fabre, Roche, Tesaro, Vifor. M. Untch: presentations, travel grants, all paid to his institution by Abbvie, Amgen, AstraZe­neca, BMS, Celgene, Daiichi Sankyo, Eisai, Janssen Cilag, Johnson & Johnson, Lilly Deutschland, Lilly Int., MSD, Mundipharma, Myriad Genetics GmbH Zürich, Odonate, Pfizer GmbH Berlin, Puma Biotechnology, Riemser, Roche, Sanofi Aventis Deutschland GmbH, Sividon Diagnostics Köln, TEVA Pharmaceuticals Ind. Ltd. Berlin. I. Witzel: Not specified. A. Wöckel: Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro. V. Müller: Speaker honoraria: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics Consultancy honoraria: Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro, Nektar. Institutional research support: Novartis, Roche, Seattle Genetics, Genentech. W. Janni: Research grants and/or honoraria: Sanofi-Aventis, Novartis, Roche, Pfizer, AstraZeneca, Chugai, GSK, Eisai, Celgene, Lilly, Janssen, Menarini. N. Ditsch: MSD, Novartis, Pfizer, Roche, AstraZeneca, TEVA, Mentor, MCI Healthcare.

This year's 17th St. Gallen (SG) Consensus Conference on the Treatment of Patients with Early Breast Cancer (SG-BCC) with the title "Customizing local and systemic therapies for women with early breast cancer" focused on the challenge of targeting the treatment of early breast cancer more specifically to the individual disease situation of each patient. As in previous years, a German working group of leading breast cancer experts discussed the results of the international SG-BCC 2021 in the context of the German guideline. It is helpful to compare the SG recommendations with the recently updated treatment recommendations of the Breast Commission of the German Working Group on Gynaecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie e. V., AGO) and the S3 guideline because the SG-BCC panel comprised experts from different countries, which is why country-specific aspects can be incorporated into the SG recommendations. The German treatment recommendations of the AGO and the S3 guideline are based on current evidence. Nevertheless, any therapeutic decision must always undergo a risk-benefit analysis for the specific situation and to be discussed with the patient., Competing Interests: Conflict of Interest/Interessenkonflikt Prof. Michael Untch: Honoraria to employer (for AdBoard participation, lectures) and travel support from Amgen; AstraZeneca; BMS; Celgene; Daiichi Sankyo; Eisai; Janssen Cilag; Johnson & Johnson; Lilly Germany; Lilly International; MSD Merck; Mundipharma; Myriad Genetics; Odonate; Pfizer; PUMA Biotechnology; Riemser; Roche; Pierre Fabre; Novartis; Abbvie; Molecular Health; Agendia; GSK. Prof. Peter A. Fasching received grants from Biontech, Cepheid and honoraria from Novartis; Pfizer; Daiichi Sankyo; AstraZeneca; Esai; Merck Sharp & Dohme; Lilly; Pierre Fabre; SeaGen; Roche; Hexal; Agendia. Prof. Sara Y. Brucker; M. D., Ph. D., received honoraria from Roche, Novartis; Pfizer; AstraZeneca; Teva. Prof. Wilfried Budach, M. D., Ph. D. reports no conflict of interest. Prof. Carsten Denkert, M. D., Ph. D. received honoraria from Novartis; Roche; MSD Oncology; Daiichi Sankyo; Molecular Health; AstraZeneca; Merck; and research funding (to the institution) from Myriad Genetics and Roche. He was co-founder and (until 2016) shareholder of Sividon Diagnostics. He is co-inventor of the VMscope software for Ki-67 analysis. Renate Haidinger reports no conflict of interest. Prof. Jens Huober received honoraria from Celgene; Roche; Novartis; Hexal; Pfizer; AstraZeneca; Lilly; Amgen; Eisai; MSD; and research support from Celgene, Hexal, Novartis, and travel grants from Roche, Novartis, Daiichi and Celgene. Prof. Christian Jackisch has received honoraria from AstraZeneca; Lilly; Celgene; Novartis; Pfizer; Roche; and research funding from Exact Sciences. Prof. Wolfgang Janni received honoraria from Amgen; AstraZeneca; Celgene; Daiichi Sankyo; Eisai; Genomic Health; Hexal; Lilly; MSD; Novartis; Pfizer; Roche; Tesaro; Teva. Prof. Cornelia Kolberg-Liedtke received honoraria from Roche; AstraZeneca; Celgene; Novartis; Pfizer; Lilly; Hexal; Amgen; Eisai; SonoScape; and consulting fees from Phaon Scientific; Novartis; Pfizer; Celgene; and research funding from Roche, Novartis, Pfizer. Travel Grant from Novartis and Roche and employment at Palleos Healthcare, and Managing Director and shareholder of Phaon Scientific. David Krug, MD, received honoraria from Merck Sharp & Dohme. Prof. Thorsten Kühn received honoraria from Celgene; Roche; Pfizer; and research funding from Mammotome, Merit Medical, Pfizer. Prof. Sibylle Loibl, M. D., Ph.D., received honoraria from AbbVie, Amgen, AstraZeneca, Bayer, BMS, Celgene, Chugai, Daiichi Sankyo, Eirgenix, GSK, Immunomedics, Ipsen, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Prime/Medscape, Puma, Roche, Samsung, Seagen, Teva, Vifor, and has a patent application EP14153692.0 pending. Prof. Diana Lüftner received honoraria from Amgen; AstraZeneca; Celgene; Pfizer; Novartis; Amgen; Roche; Loreal; Teva; GSK; and Eli Lilly. Prof. Volkmar Müller received honoraria from Amgen; AstraZeneca; Daiichi Sankyo; Eisai; Pfizer; MSD; Novartis; Roche; Teva; Seattle Genetics; and for consulting services from Genomic Health; Hexal; Roche; Pierre Fabre; Amgen; ClinSol; Novartis; MSD; Daiichi Sankyo; Eisai; Lilly; Tesaro; Seattle Genetics; Neltar; and travel expenses from Roche; Pfizer; Daiichi Sankyo; and research funding to the employer from Novartis; Roche; Seattle Genetics; Genentech. Prof. Andreas Schneeweiss received honoraria from Celgene; Roche; Pfizer; AstraZeneca; Novartis; MSD; Tesaro; Lilly; and research funding from Celgene; Roche; AbbVie; Molecular Partner; and travel grants from Celgene, Roche and Pfizer. Prof. Dr. Marc Thill received honoraria and travel support from Amgen; AstraZeneca; Aurikamed; Becton and Dickinson, BiomʼUp; Celgene; Clearcut; Connect Medica; Daiichi Sankyo; Eisai; Exact Sciences; Grünenthal; Hexal; I-Med Institute; Lilly; MCI; Medtronic; MSD; Neodynamics; Norgine; Novartis; OnkoLive; OmniaMed, Organon, pfm Medical; Pfizer; Roche; Seagen; Sysmex; Tesaro; Teva; RTI Surgical; Vifor; and research funding from Endomagnetics and Exact Sciences. Prof. Nadia Harbeck received honoraria from AstraZeneca; Daiichi Sankyo; Lilly; MSD; Novartis; Pierre Fabre; Pfizer; Roche; Seattle Genetics. Prof. Christoph Thomssen received honoraria from Amgen; AstraZeneca; Celgene; Daiichi Sankyo; Eisai; Lilly; MSD; Mylan; Nanostring; Novartis; Pfizer; Pierre Fabre; Puma; Roche; Vifor; and research funding from American Diagnostica, Affymetrix, Nanostring. Prof. Michael Untch: Honoraria an den Arbeitgeber (für AdBoard-Teilnahme, Vorträge) sowie Reiseunterstützung von Amgen, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Eisai, Janssen Cilag, Johnson & Johnson, Lilly Deutschland, Lilly International, MSD Merck, Mundipharma, Myriad Genetics, Odonate, Pfizer, PUMA Biotechnology, Riemser, Roche, Pierre Fabre, Novartis, Abbvie, Molecular Health, Agendia, GSK. Prof. Peter A. Fasching erhielt Zuschüsse von Biontech, Cepheid sowie Honoraria von Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Esai, Merck Sharp & Dohme, Lilly, Pierre Fabre, SeaGen, Roche, Hexal, Agendia. Prof. Dr. med. Sara Y. Brucker erhielt Honoraria von Roche, Novartis, Pfizer, AstraZeneca, Teva. Prof. Dr. med. Wilfried Budach hat keinen Interessenkonflikt. Prof. Dr. med. Carsten Denkert erhielt Honoraria von Novartis, Roche, MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca, Merck sowie Forschungsförderung (an die Institution) von Myriad Genetics und Roche. Er war Mitgründer und (bis 2016) Shareholder von Sividon Diagnostics. Er ist Miterfinder der VMscope-Software zur Bestimmung von Ki-67. Renate Haidinger hat keinen Interessenkonflikt. Prof. Jens Huober erhielt Honoraria von Celgene, Roche, Novartis, Hexal, Pfizer, AstraZeneca, Lilly, Amgen, Eisai, MSD sowie Forschungsunterstützung von Celgene, Hexal, Novartis und Travel Grants von Roche, Novartis, Daiichi und Celgene. Prof. Christian Jackisch erhielt Honoraria von AstraZeneca, Lilly, Celgene, Novartis, Pfizer, Roche und Forschungsunterstützung von Exact Sciences. Prof. Wolfgang Janni erhielt Honoraria von Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Genomic Health, Hexal, Lilly, MSD, Novartis, Pfizer, Roche, Tesaro, Teva. Prof. Cornelia Kolberg-Liedtke erhielt Honoraria von Roche, AstraZeneca, Celgene, Novartis, Pfizer, Lilly, Hexal, Amgen, Eisai, SonoScape sowie Honorare für Beratertätigkeit von Phaon Scientific, Novartis, Pfizer, Celgene sowie Forschungsunterstützung von Roche, Novartis, Pfizer. Travel Grant von Novartis und Roche sowie Anstellung bei Palleos Healthcare sowie Managing Director und Gesellschafterin bei Phaon Scientific. Dr. med. David Krug erhielt Honoraria von Merck Sharp & Dohme. Prof. Thorsten Kühn erhielt Honoraria von Celgene, Roche, Pfizer sowie Forschungsunterstützung von Mammotome, Merit Medical, Pfizer. Prof. Dr. med. Sibylle Loibl erhielt Honoraria von Abbvie, Amgen, AstraZeneca, Bayer, BMS, Celgene, Chugai, Daiichi Sankyo, Eirgenix, GSK, Immunomedics, Ipsen, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Prime/Medscape, Puma, Roche, Samsung, Seagen, Teva, Vifor und hat einen Patentantrag EP14153692.0 laufen. Prof. Diana Lüftner erhielt Honoraria von Amgen, AstraZeneca, Celgene, Pfizer, Novartis, Amgen, Roche, Loreal, Teva, GSK und Eli Lilly. Prof. Volkmar Müller erhielt Honoraria von Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics sowie für Beratertätigkeit von Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro, Seattle Genetics, Neltar sowie Reisekosten von Roche, Pfizer, Daiichi Sankyo und Forschungsunterstützung an den Arbeitgeber von Novarts, Roche, Seattle Genetics, Genentech. Prof. Andreas Schneeweiss erhielt Honoraria von Celgene, Roche, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly sowie Forschungsunterstützung von Celgene, Roche, AbbVie, Molecular Partner sowie Travel Grant von Celgene, Roche und Pfizer. Prof. Dr. Marc Thill erhielt Honorare und Reiseunterstützung von Amgen, AstraZeneca, Aurikamed, Becton and Dickinson, BiomʼUp, Celgene, Clearcut, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Grünenthal, Hexal, I-Med Institute, Lilly, MCI, Medtronic, MSD, Neodynamics, Norgine, Novartis, OnkoLive, OmniaMed, Organon, pfmMedical, Pfizer, Roche, Seagen, Sysmex, Tesaro, Teva, RTI Surgical, Vifor und Forschungsunterstützung von Endomagnetics und Exact Sciences. Prof. Nadia Harbeck erhielt Honoraria von AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seattle Genetics. Prof. Christoph Thomssen erhielt Honoraria von Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Vifor und Forschungsunterstützung von American Diagnostica, Affymetrix, Nanostring., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

To determine whether a single dose of double immune checkpoint blockade (induction chemoimmunotherapy (ICIT)) adds benefit to induction single-cycle platinum doublet (induction chemotherapy (IC)) in locally advanced head and neck squamous cell carcinoma (HNSCC), patients treated with cisplatin 30 mg/m 2 d1-3 and docetaxel 75 mg/m 2 d1 combined with durvalumab 1500 mg fixed dose d5 and tremelimumab 75 mg fixed dose d5 (ICIT) within the CheckRad-CD8 trial were compared with a retrospective cohort receiving the same chemotherapy (IC) without immunotherapy. The endpoint of this analysis was the complete response rate (CR). A total of 53 patients were treated with ICIT and 104 patients with IC only. CR rates were 60.3% for ICIT and 40.3% for IC ( p = 0.018). In the total population ( n = 157), the most important predictor to achieve a CR was treatment type (OR: 2.21 for ICIT vs. IC; p = 0.038, multivariate analysis). The most diverse effects in CR rates between ICIT and IC were observed in younger (age ≤ 60) patients with HPV-positive OPSCCs (82% vs. 33%, p = 0.176), while there was no difference in older patients without HPV-positive OPSCCs (53% vs. 48%). The analysis provides initial evidence that ICIT could result in higher CR rates than IC. Young patients with HPV-positive OPSCCs may have the greatest benefit from additional immune checkpoint inhibitors.

Moderate hypofractionation is the standard of care for adjuvant whole-breast radiotherapy after breast-conserving surgery for breast cancer. Recently, 10-year results from the FAST and 5‑year results from the FAST-Forward trial evaluating adjuvant whole-breast radiotherapy in 5 fractions over 5 weeks or 1 week have been published. This article summarizes recent data for moderate hypofractionation and results from the FAST and FAST-Forward trial on ultra-hypofractionation. While the FAST trial was not powered for comparison of local recurrence rates, FAST-Forward demonstrated non-inferiority for two ultra-hypofractionated regimens in terms of local control. In both trials, the higher-dose experimental arms resulted in elevated rates of late toxicity. For the lower dose experimental arms of 28.5 Gy over 5 weeks and 26 Gy over 1 week, moderate or marked late effects were similar in the majority of documented items compared to the respective standard arms, but significantly worse in some subdomains. The difference between the standard arm and the 26 Gy of the FAST-Forward trial concerning moderate or marked late effects increased with longer follow-up in disadvantage of the experimental arm for most items. For now, moderate hypofractionation with 40-42.5 Gy over 15-16 fractions remains the standard of care for the majority of patients with breast cancer who undergo whole-breast radiotherapy without regional nodal irradiation after breast-conserving surgery.