Search

Current risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity. Genomic classifiers (GC) enable improved risk stratification after surgery, but less data exist for patients treated with definitive radiation therapy (RT) or RT in oligo-/metastatic disease stages. To guide future perspectives of GCs for RT, we conducted (1) a systematic review on the evidence of GCs for patients treated with RT and (2) a survey of experts using the Delphi method, addressing the role of GCs in personalized treatments to identify relevant fields of future clinical and translational research. We performed a systematic review and screened ongoing clinical trials on ClinicalTrials.gov. Based on these results, a multidisciplinary international team of experts received an adapted Delphi method survey. Thirty-one and 30 experts answered round 1 and round 2, respectively. Questions with ≥75% agreement were considered relevant and included in the qualitative synthesis. Evidence for GCs as predictive biomarkers is mainly available to the postoperative RT setting. Validation of GCs as prognostic markers in the definitive RT setting is emerging. Experts used GCs in patients with PCa with extensive metastases (30%), in postoperative settings (27%), and in newly diagnosed PCa (23%). Forty-seven percent of experts do not currently use GCs in clinical practice. Expert consensus demonstrates that GCs are promising tools to improve risk-stratification in primary and oligo-/metastatic patients in addition to existing classifications. Experts were convinced that GCs might guide treatment decisions in terms of RT-field definition and intensification/deintensification in various disease stages. This work confirms the value of GCs and the promising evidence of GC utility in the setting of RT. Additional studies of GCs as prognostic biomarkers are anticipated and form the basis for future studies addressing predictive capabilities of GCs to optimize RT and systemic therapy. The expert consensus points out future directions for GC research in the management of PCa. ispartof: Int J Radiat Oncol Biol Phys vol:116 issue:3 pages:503-520 ispartof: location:United States status: published

Purpose Integrating moderate hypofractionation to the macroscopic tumor with elective nodal irradiation while sparing the organs at risk (OAR) in chemoradiotherapy of locally advanced non-small-cell lung cancer. Methods From 2010–2018, treatment, patient and tumor characteristics of 138 patients from two radiation therapy centers were assessed. Chemoradiotherapy by intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) to the primary tumor and macroscopic lymph node metastases was used. Results A total of 124 (90%) patients received concurrent chemotherapy. 106 (76%) patients had UICC (Union for International Cancer Control) stage ≥IIIB and 21 (15%) patients had an oligometastatic disease (UICC stage IV). Median SIB and elective total dose was 61.6 and 50.4 Gy in 28 fractions, respectively. Furthermore, 64 patients (46%) had an additional sequential boost to the primary tumor after the SIB-IMRT main series: median 6.6 Gy in median 3 fractions. The median cumulative mean lung dose was 15.6 Gy (range 6.2–29.5 Gy). Median follow-up and radiological follow-up for all patients was 18.0 months (range 0.6–86.9) and 16.0 months (range 0.2–86.9), respectively. Actuarial local control rates at 1, 2 and 3 years were 80.4, 68.4 and 57.8%. Median overall survival and progression-free survival was 30.0 months (95% confidence interval [CI] 23.5–36.4) and 12.1 months (95% CI 8.2–16.0), respectively. Treatment-related toxicity was moderate. Radiation-induced pneumonitis grade 2 and grade 3 occurred in 13 (9.8%) and 3 (2.3%) patients. Conclusions Chemoradiotherapy using SIB-IMRT showed promising local tumor control rates and acceptable toxicity in patients with locally advanced and in part oligometastatic lung cancer. The SIB concept, resulting in a relatively low mean lung dose, was associated with low numbers of clinically relevant pneumonitis. The overall survival appears promising in the presence of a majority of patients with UICC stage ≥IIIB disease.

Due to its low fractionation sensitivity, also known as “alpha/beta ratio,” in relation to its surrounding organs at risk, prostate cancer is predestined for hypofractionated radiation schedules assuming an increased therapeutic ratio compared to normofractionated regimens. While moderate hypofractionation (2.2–4 Gy) has been proven to be non-inferior to normal fractionation in several large randomized trials for localized prostate cancer, level I evidence for ultrahypofractionation (>4 Gy) was lacking until recently. An accumulating body of non-randomized evidence has recently been strengthened by the publication of two randomized studies comparing ultrahypofractionation with a normofractionated schedule, i.e., the Scandinavian HYPO-RT trial by Widmark et al. and the first toxicity results of the PACE‑B trial. In this review, we aim to give a brief overview of the current evidence of ultrahypofractionation, make an overall assessment of the level of evidence, and provide recommendations and requirements that should be followed before introducing ultrahypofractionation into routine clinical use.

Background: Focal therapy (FT) is an option to treat localized prostate cancer (PCa) and preserve healthy prostate tissue in order to reduce known side effects from primary whole-gland treatment. The available FT modalities are manifold. Until now, national and international PCa guidelines have been cautious to propose recommendations regarding FT treatment since data from prospective controlled trials are lacking for most FT modalities. Moreover, none of the international guidelines provides a separate section on FT. In this purpose, we provide a synopsis of the consensus-based German S3 guidelines for a possible international use. Summary: The recently published update of the German S3 guidelines, an evidence- and consensus-based guideline, provides a section on FT with recommendations for diagnostic work-up, indications, modalities, and follow-up. This section consists of 12 statements and recommendations for FT in the treatment of localized PCa. Key Message: The German S3 guidelines on PCa are the first to incorporate recommendations for FT based on evidence and expert consensus including indication criteria for FT, pretreatment, and follow-up diagnostic pathways as well as an extended overview of FT techniques and the current supportive evidence.

Die primare perkutane Strahlentherapie mit oder ohne begleitende Hormontherapie bildet eine der Behandlungsoptionen beim Prostatakarzinom der intermediaren Risikogruppe. Es soll eine kurze Ubersicht der derzeit noch unterschiedlichen Behandlungsansatze im Rahmen der definitiven perkutanen Strahlentherapie gegeben werden. Es erfolgte eine Sichtung der aktuellen Leitlinien und eine Literaturrecherche via PubMed-Datenbank. Es existieren verschiedene Empfehlungen zur Einteilung in Risikogruppen beim lokalisierten Prostatakarzinom. Um der Heterogenitat der intermediaren Risikogruppe Rechnung zu tragen, scheint die Untergruppierung in ein gunstiges und ungunstiges Stadium, einen sinnvollen Ansatz zur Individualisierung der Therapie darzustellen. Randomisierte Studien konnten auch bei Patienten der intermediaren Risikogruppe eine Verbesserung der Therapieergebnisse bei Kombination von Strahlentherapie und Hormontherapie nachweisen. Zeitgleich erhoht der Einsatz der Hormontherapie die Rate an Nebenwirkungen und sollte daher individuell gepruft werden. Die Anwendung der alleinigen dosiseskalierten Strahlentherapie scheint insbesondere bei gunstigerem intermediaren Risikoprofil eine gleichwertige therapeutische Option darzustellen. Bei gunstigerem Risikoprofil scheint eine alleinige dosiseskalierte Strahlentherapie und bei ungunstigem intermediaren Risikoprofil die Kombination mit kurzzeitiger (4–6 Monate) Hormontherapie eine sinnvolle Therapiestrategie zu sein. Weitere Evidenz zu dieser Fragestellung werden die noch ausstehenden Ergebnisse der RTOG-0815-Studie bieten.

Ein Paradigmenwechsel beim Prostatakarzinom mit nur wenigen Metastasen hat eingesetzt und eine Metastasierung bedeutet nicht mehr zwingend eine klassische palliative Situation. Darstellung der aktuellen diagnostischen Moglichkeiten des Prostatakarzinoms im Rahmen der metastasengerichteten interdisziplinaren Therapie und des therapeutischen Vorgehens. Es erfolgte eine Sichtung der aktuellen Literatur inklusive Metaanalysen sowie der Leitlinien und Expertenempfehlungen. Essenziell zur genauen Lokalisation und Detektion und konsekutiv der Therapie von (Oligo‑)Metastasen ist eine moglichst sensitive und prazise diagnostische Bildgebung. Hierzu zahlen neben der etablierten bildgebenden Basisdiagnostik zunehmend auch schnittbildbasierte, funktionale Verfahren wie die multiparametrische Magnetresonanztomographie (mMRT) sowie das PSMA-PET-CT (PSMA: prostataspezifisches Membranantigen). Hinsichtlich der Therapie kann die Bestrahlung von bis zu 3 Metastasen bei Oligometastasierung die androgendeprivationsfreie Zeit und das progressionsfreie Uberleben verlangern sowie die Lebensqualitat erhohen. Ossare und lymphogene Metastasen konnen mit einer hohen Einzeldosis, aber wenigen Fraktionen als hypofraktionierte stereotaktische Bestrahlung therapiert und eine lokale Kontrolle von mehr als 90 %, ein klinisch progressionsfreies Uberleben bis zu 71 % bei sehr niedrigen Toxizitatsraten erreicht werden. Die metastasengerichtete, interdisziplinare Therapie bei oligometastasiertem Prostatakarzinom fuhrt zu einer weiteren Personalisierung sowie zunehmenden Risikoadaption der Behandlungskonzepte und weicht die bisherigen harten Grenzen mit Unterteilung in „palliativ“ und „kurativ“ auf. Hierzu werden vermehrt auch hypofraktionierte Bestrahlungsschemata sowie die stereotaktische Bestrahlung eingesetzt.

Die Salvage-Strahlentherapie (SRT) ist Standard bei Patienten mit biochemischem Progress nach Prostatektomie im primaren Stadium pN0. Randomisierte Studien haben nun den Nutzen einer zusatzlichen Androgendeprivationstherapie (ADT) untersucht. Eine evidenzbasierte, systematische Ubersicht uber die Kombination einer ADT mit einer SRT bei rezidiviertem Prostatakarzinom soll erstellt werden. Die verfugbare Literatur wurde ausgewertet und daraus Behandlungsempfehlungen unter Berucksichtigung von Risikoprofilen abgeleitet. Es liegen die Ergebnisse von zwei randomisierten und mehreren retrospektiven Analysen vor. Die RTOG-9601-Studie zeigte eine Verbesserung des Gesamtuberlebens und des tumorspezifischen Uberlebens durch die Kombination von 24 Monaten Bicalutamid 150 mg/Tag und SRT im Vergleich zur alleinigen SRT. Dieser Vorteil war jedoch nur bei Patienten mit PSA-Werten ≥0,7 ng/ml vor SRT, einem Gleason-Score 7 oder positivem Schnittrand nachweisbar. Die GETUG-AFU-16-Studie zeigte lediglich eine Verbesserung des progressionsfreien Uberlebens (PFS) durch die zusatzliche Gabe von 6 Monaten Goserelin zur SRT. In beiden Studien wurde keine Zunahme schwerer Spatfolgen durch die ADT beobachtet. Retrospektive Studien deuten darauf hin, dass eine zusatzliche ADT das PFS bei Hochrisikopatienten verbessert. Bei Patienten mit PSA-Werten ≥0,7 ng/ml vor SRT verbessert eine ADT zur SRT das Gesamtuberleben. Beim PSA-Wert

Objective The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. Materials and methods A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. Results Metastasis-directed radiotherapy results in high local control (often > 90% within a follow-up of 1–2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. Conclusion ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations.

Korrespondenz zu 10.1200/JCO.21.01980

Purpose Various randomized phase III clinical trials have compared moderately hypofractionated to normofractionated radiotherapy (RT). These modalities showed similar effectiveness without major differences in toxicity. This project was conducted by the Prostate Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO) and the Working Party on Radiation Oncology of the German Cancer Society. We aimed to investigate expert opinions on the use of moderately hypofractionated RT as a definitive treatment for localized prostate cancer in German-speaking countries. Methods A 25-item, web-based questionnaire on moderate-hypofractionation RT was prepared by an internal committee. The experts of the DEGRO were asked to complete the questionnaire. Results Fourteen active members of DEGRO completed the questionnaire. The questions described indications for selecting patients eligible to receive moderate hypofractionation based on clinical and pathological factors such as age, urinary symptoms, and risk-group. The questions also collected information on the technical aspects of selection criteria, including the definition of a clinical target volume, the use of imaging, protocols for bladder and rectal filling, the choice of a fractionation schedule, and the use of image guidance. Moreover, the questionnaire collected information on post-treatment surveillance after applying moderately hypofractionated RT. Conclusion Although opinions varied on the use of moderate-hypofractionation RT, the current survey reflected broad agreement on the notion that moderately hypofractionated RT could be considered a standard treatment for localized prostate cancer in German-speaking countries.

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose Using evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal extent of surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy if required. An evidence-based optimal use of different therapeutic modalities should improve the survival rates and quality of life of these patients. This S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources included reviews of evidence, which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one part of the guideline. Identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then subsequently modified during structured consensus conferences and/or additionally amended online using the DELPHI method, with consent between members achieved online. The guideline report is freely available online. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of endometrial cancer including precancers and early endometrial cancer as well as recommendations on palliative medicine, psycho-oncology, rehabilitation, patient information and healthcare facilities to treat endometrial cancer. The management of precancers of early endometrial precancerous conditions including fertility-preserving strategies is presented. The concept used for surgical primary therapy of endometrial cancer is described. Radiotherapy and adjuvant medical therapy to treat endometrial cancer and uterine carcinosarcomas are described. Recommendations are given for the follow-up care of endometrial cancer, recurrence and metastasis. Palliative medicine, psycho-oncology including psychosocial care, and patient information and rehabilitation are presented. Finally, the care algorithm and quality assurance steps for the diagnosis, therapy and follow-up of patients with endometrial cancer are outlined.

Im April 2018 erschien die erste deutsche interdisziplinare S3-Leitlinie fur die Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom. Dieser Beitrag ist die Zusammenfassung der Kap. 7, „Strahlentherapie des Endometriumkarzinoms“, und 8, „Adjuvante medikamentose Therapie des Endometriumkarzinoms“, mit dem Ziel, dem Leser eine klinisch orientierte Kurzfassung an die Hand zu geben. Dargestellt sind die Empfehlungen zur postoperativen Brachy- und externen Strahlentherapie sowie zur Gestagen- und Chemotherapie bei Endometriumkarzinom Typ I und II einschlieslich der Karzinosarkome.

OBJECTIVE This article aims to provide an overview of the role of combined radiation and androgen deprivation (ADT) therapy in patients with intermediate-risk prostate cancer. MATERIALS AND METHODS The current German, European, and NCCN (National Comprehensive Cancer Network) guidelines as well as relevant literature in the PubMed database which provide information on sub-classification within the intermediate-risk group and the use of ADT in terms of oncological outcome were reviewed. RESULTS Different recommendations for risk-group assessment of patients with localized prostate cancer are available. Subdivision of intermediate risk into a favorable and an unfavorable group seems to be justified to allow for a more individualized therapy in a quite heterogenous group of patients. So far, multiple randomized trials have shown a benefit when radiation therapy (RT) is combined with ADT. The use of dose-escalated RT without ADT also appears to be an adequate therapy associated with a very low rate of cancer-specific deaths. Therefore, taking into account the increased rate of toxicity associated with ADT, dose-escalated RT alone might be justified, especially in favorable intermediate-risk patients. CONCLUSION Dose-escalated RT alone appears to be an appropriate treatment in favorable intermediate-risk patients. Addition of short course ADT (4-6 months) might improve outcomes in unfavorable intermediate-risk patients.

AIM This article gives an overview on the current status of hypofractionated radiotherapy in the treatment of prostate cancer with a special focus on the applicability in routine use. METHODS Based on a recently published systematic review the German Society of Radiation Oncology (DEGRO) expert panel added additional information that has become available since then and assessed the validity of the information on outcome parameters especially with respect to long-term toxicity and long-term disease control. RESULTS Several large-scale trials on moderate hypofractionation with single doses from 2.4-3.4 Gy have recently finished recruiting or have published first results suggestive of equivalent outcomes although there might be a trend for increased short-term and possibly even long-term toxicity. Large phase 3 trials on extreme hypofractionation with single doses above 4.0 Gy are lacking and only very few prospective trials have follow-up periods covering more than just 2-3 years. CONCLUSION Until the results on long-term follow-up of several well-designed phase 3 trials become available, moderate hypofractionation should not be used in routine practice without special precautions and without adherence to the highest quality standards and evidence-based dose fractionation regimens. Extreme hypofractionation should be restricted to prospective clinical trials.

AIM Overview on the use of androgen deprivation therapy (ADT) added to salvage radiation therapy (SRT) for prostate cancer patients with biochemical recurrence after prostatectomy. METHODS The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published between January 2009 and May 2017, and assessed the validity of the information on outcome parameters including overall survival (OS) and treatment-related toxicity. RESULTS Two randomized controlled trials and nine relevant retrospective analyses were identified. The RTOG 9601 trial showed an OS improvement for the combination of 2 years of bicalutamide and SRT compared to SRT alone after a median follow-up of 13 years. This improvement appeared to be restricted to those patients with a prostate specific antigen (PSA) level before SRT of ≥0.7 ng/mL. The GETUG AFU-16 trial showed that after a median follow-up of 5 years, the addition of 6 months of goserelin to SRT improved progression-free survival (PFS; based on biochemical recurrence) as compared to SRT alone. ADT in both trials was not associated with increased major late toxicities. Results of retrospective series were inconsistent with a suggestion that the addition of ADT improved biochemical PFS especially in patients with high-risk factors such as Gleason Score ≥8 and in the group with initially negative surgical margins. CONCLUSIONS ADT combined with SRT appears to improve OS in patients with a PSA level before SRT of ≥0.7 ng/mL. In patients without persistent PSA after prostatectomy and PSA levels of

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose The use of evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy where required. The evidence-based optimal use of different therapeutic modalities should improve survival rates and the quality of life of these patients. The S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources include reviews of evidence which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one area of the guideline. The identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then modified during structured consensus conferences and/or additionally amended online using the DELPHI method with consent being reached online. The guideline report is freely available online. Recommendations Part 1 of this short version of the guideline presents recommendations on epidemiology, screening, diagnosis and hereditary factors, The epidemiology of endometrial cancer and the risk factors for developing endomentrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer including the pathology of the cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer.

Aim This article gives an overview on the current status of hypofractionated radiotherapy in the treatment of prostate cancer with a special focus on the applicability in routine use. Methods Based on a recently published systematic review the German Society of Radiation Oncology (DEGRO) expert panel added additional information that has become available since then and assessed the validity of the information on outcome parameters especially with respect to long-term toxicity and long-term disease control. Results Several large-scale trials on moderate hypofractionation with single doses from 2.4–3.4 Gy have recently finished recruiting or have published first results suggestive of equivalent outcomes although there might be a trend for increased short-term and possibly even long-term toxicity. Large phase 3 trials on extreme hypofractionation with single doses above 4.0 Gy are lacking and only very few prospective trials have follow-up periods covering more than just 2–3 years. Conclusion Until the results on long-term follow-up of several well-designed phase 3 trials become available, moderate hypofractionation should not be used in routine practice without special precautions and without adherence to the highest quality standards and evidence-based dose fractionation regimens. Extreme hypofractionation should be restricted to prospective clinical trials.

Die Prognose des Urothelkarzinoms der Harnblase wird im Wesentlichen gepragt von den Kriterien Infiltrationstiefe und Differenzierungsgrad im Tumor. Um das Rezidiv- und Progressionsrisiko so gering wie moglich zu halten, werden nach transurethraler Blasentumorresektion (TUR-B) adjuvante Konzepte der Blaseninstillationstherapie angewandt (Mitomycin C und Bacillus-Calmette-Guerin). Moglicherweise kann das Rezidivrisiko durch den Einsatz der Hyperthermie in Verbindung mit Mitomycin weiter gesenkt werden. Fur Patienten, die aus Altersgrunden, aufgrund von Komorbiditaten oder einfach auch wegen des Wunsches nach Organerhalt eine Zystektomie beim muskelinvasiven Harnblasentumor ablehnen, besteht die Moglichkeit einer kombinierten Radiochemotherapie. Grundvoraussetzung ist eine geringe Resttumorlast nach TUR-B. Blasenteilresektionen bleiben nur streng selektionierten Patientengruppen mit guter Blasenkapazitat, unifokalen Tumoren und einer hohen Compliance vorbehalten.