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• The dual therapy strategy was based on co-formulated protease inhibitors plus lamivudine in treatment-naïve people living with human immunodeficiency virus. • This randomized trial shows the non-inferiority of a fixed dose co-formulation of darunavir/ritonavir (DRV/r) combined with lamivudine (3TC) compared with a three-drug regimen based on these drugs plus tenofovir. • The combination was well tolerated. • Co-formulated DRV/r plus 3TC is an effective and safe option as initial antiretroviral therapy. Tenofovir-containing antiretroviral therapy regimens may have long-term toxicity-related side effects. This study aimed to compare the virological efficacy of co-formulated darunavir/ritonavir plus lamivudine with darunavir/ritonavir plus tenofovir and emtricitabine or lamivudine. The ANDES study was a 48-week, phase 4, randomized, open-label, non-inferiority trial in treatment-naïve adults living with human immunodeficiency virus (HIV). Patients were randomized on a 1:1 basis to receive a daily oral regimen of either dual therapy based on a generic co-formulation of darunavir/ritonavir (800/100 mg) plus a generic lamivudine 300 mg pill, or triple therapy with darunavir/ritonavir plus tenofovir/emtricitabine (300/200 mg) or tenofovir/lamivudine (300/300 mg). The primary endpoint was the proportion of patients with a viral load of <50 copies/mL at week 48 in the intention-to-treat population. The US Food and Drug Administration snapshot algorithm and a non-inferiority margin of -12% were used. The secondary objective was to analyse safety in the per-protocol population. This study has been registered at ClinicalTrials.gov (NCT02770508). Between November 2015 and 31 October 2020, 336 participants were assigned at random to the triple therapy arm (n =165) or the dual therapy arm (n =171). After 48 weeks, 153 patients in the triple therapy group (93%) and 155 patients in the dual therapy group (91%) achieved virological suppression (difference -2.1%, 95% confidence interval -7.0 to 2.9). Drug-related adverse events were more common in the triple therapy group (P =0.04). Two toxicity-related events led to discontinuation in each group. Co-formulated darunavir/ritonavir plus lamivudine showed non-inferiority and a safer toxicity profile compared with the standard-of-care triple therapy regimen including tenofovir in treatment-naïve patients. [Display omitted] [ABSTRACT FROM AUTHOR]

The incidence of breast cancer has increased from 900 000 to 2.3 million new annual cases over the last 25 years. The 5-year survival rate has markedly risen to over 90% worldwide due to significant therapeutic advancements. Longer survival in patients with breast cancer means more patients may experience long-term effects of their treatments, including cancer therapy-related cardiac dysfunction (CTRCD). To date, there is no established primary prevention to minimise CTRCD. The Cardiac Health in Breast Cancer study is a two-arm, single-centre, randomised controlled trial investigating the impact of an exercise programme on cardiac changes in patients with breast cancer undergoing cardiotoxic cancer therapy. 48 females with breast cancer will be randomised to either a 12-month intervention group (IG) or a control group (CG). The IG will receive a combination of supervised high-intensity interval training (HIIT) and high-intensity resistance training (HIRT) for 6 months, while the CG will follow WHO guidelines for physical activity independently. All participants will undergo transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging and cardiopulmonary exercise testing at baseline, after 6 months and after 12 months. The primary endpoint is the occurrence of symptomatic or asymptomatic CTRCD at the time points of examination, detected by cardiac imaging, which may be mitigated by structured physical exercise. Secondary endpoints include assessments of cardiac inflammation as detected by CMR, mitochondrial dysfunction, health-related quality of life, the occurrence of fatigue, depression and anxiety, as well as exercise capacity, average heart rate, heart rate variability and daily physical activity., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The current standard for the preoperative marking of non-palpable breast lesions is wire guided localization (WGL) which is associated with logistical efforts and patient discomfort. Non-radioactive seeds (NRS) recently challenged the use of WGL; but do they provide a better alternative from a logistical and environmental perspective?, Methods: WGL standard was compared with NRS available in Germany: Magseed®, Pintuition®, SAVI SCOUT ® and LOCalizer™ on a logistical and carbon-footprinting basis. In the logistical analysis the number of patient contacts with the healthcare system for lesion localization/removal and the number of breast punctures were evaluated in two different clinical scenarios (primary surgery and secondary surgery after neoadjuvant treatment). The carbon footprints of WGL and NRS (with exception of LOCalizer) were assessed based on their material compositions and operating energy in a streamlined approach., Results: Application of NRS reduces the number of contacts by 33.3 % (2 vs. 3) in primary, by 50 % (2 vs. 4) in secondary surgery, and the number of breast punctures by 33.3 % (2 vs.3). Annual Germany-wide material- and energy-based carbon footprints of NRS (1.6-3.2 tons CO 2 eq) are significantly lower in comparison to WGL (10.3 tons CO 2 eq). The implementation of NRS would lead to a CO 2 eq reduction by around 79 % compared to WGL., Conclusions: The use of NRS for the localization of non palpable breast lesions is more favorable from the environmental and logistical perspective, when compared to WGL with possible benefits for patients, healthcare providers and the environment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thorsten Kuehn reports a relationship with Merit Medical Systems, Hologic, Sirius Medical Systems, and Endomag that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The third-generation antibody-drug conjugates (ADC), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), recently obtained approval for metastatic breast cancer treatment across various subtypes and therapeutic contexts., Materials and Methods: This retrospective, multicentric study evaluated real-world tolerability, feasibility and efficacy in a pre-treated, real-world cohort at three major German breast cancer centers., Results: 125 patients treated with T-DXd or SG from November 2020 to June 2023 were included (T-DXd: 77 patients; SG: 48 patients). The median treatment duration was 6.0 months for T-DXd and 3.5 months for SG therapy, with a median follow-up duration of 10.4 months for T-DXd (95% CI: 8.4-11.6) and 11.8 months for SG (95% CI: 8.0-14.4). Severe neutropenia (CTC ≥ III°) occurred in 33.3% during SG therapy, with a numerical reduction observed following primary, prophylactic use of G-CSF. T-DXd-associated pneumonitis occurred in 8 out of 77 patients (10.4 %). Median progression-free survival (mPFS) was 8.6 months (95% CI: 5.8-12.4) with T-DXd (HER2+: 10.8; HER2-low: 4.7) and 4.9 months (95% CI: 2.8-6.3) with SG (TNBC 4.9; HR+/HER2-: not reached). Median overall survival (OS) was 23.8 months (95% CI: 16.1-not estimable) with T-DXd (HER2+: 27.1; HER2-low: not reached), and 12.4 months (95% CI: 8.7-not estimable) with SG therapy (TNBC: 12.4, HR+/HER2-: not reached). 95.7% of the protocol-specified, therapeutic dose was administered for T-DXd and 89.6% for SG., Conclusion: Overall, this indicates good feasibility, tolerability, and effectiveness of ADC therapies in the real-world setting., Competing Interests: Conflict of Interest H. Schäffler: Travel Support by Daiichi Sankyo and Gilead, Honoraria by Novartis; D. Jakob: none; S. Huesmann: none; K. Pfister: Honoraria by Pfizer Novartis and Gilead; K. Veselinovic: Honoraria by Roche, Pfizer, AstraZeneca; F. Schochter: Travel Support, Honoraria and Consulting Fees by AstraZeneca, Roche, Karyopharm, Merck, GlaxoSmithKline, Eisai, Clovis; E. Leinert: none; V. Fink: none; B. Rack: Honoraria and research funding by AstraZeneca and Novartis; A. Englisch: none; L. Volmer: none; T. Engler: Travel Support, Honoraria and Consulting Fees by AstraZeneca, GSK, Gilead, Novartis, Lilly, Pfizer, MSD, Pierre Fabre, Stemline, Roche, Daiichi Sankyo; ML. Frevert: Honoraria by Novartis; I. Juhasz-Böss: none; S. Brucker: Travel Support and Consulting Fees by Hologic, Sanofi, AstraZeneca, Lilly, MSD, Medtronic, Pfizer; S. Heublein: research funding and honoraria from Clovis Oncology, Inc., GlaxoSmithKline, Novartis, Roche, AstraZeneca and Pfizer. Participation in advisory boards for Novartis, GlaxoSmithKline, and Merck Sharp & Dohme Corporation; W. Janni: Travel Support, Honoraria and Consulting Fees by Daiichi Sankyo, AstraZeneca, Gilead; FA. Taran: Travel Support by Gilead, Consulting Fees by AstraZeneca, Gilead, MSD, ImmunoGen, Onkowissen, Roche, GSK; A. Hartkopf: Travel Support by Daiichi Sankyo, Gilead, Roche, AstraZeneca, Pfizer, Honoraria by Daiichi Sankyo, Gilead, Seagen, Roche, AstraZeneca, Pfizer, Lilly, MSD, Novartis; D. Dannehl: Travel Support by Gilead and Daiichi Sankyo, Honoraria by 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 commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

We review the intersection of human immunodeficiency virus (HIV) and cancer globally, including the complex interplay of oncogenic infections, chronic inflammation, and behavioral and other factors in increasing cancer risk among people with HIV (PWH). We discuss current cancer screening, prevention, and treatment recommendations for PWH. Specific interventions include vaccination, behavioral risk reduction, timely HIV diagnosis and treatment, screening for specific cancer sites, and multifaceted treatment considerations unique to PWH including supportive care and drug interactions. Finally, the potential of novel therapies and the need for inclusive cancer clinical trials are highlighted. Collaborative multidisciplinary efforts are critical for continued progress against cancer among PWH., Competing Interests: Disclosure T.A. Odeny received grant funding from Gilead Sciences. V. Fink participated as speaker and expert discussant for MSD. The opinions expressed in this article are the authors own and do not reflect the view of the NIH, the Department of Health and Human Services, or the United States Government., (Published by Elsevier Inc.)

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure syndrome whose development can be triggered by environmental, autoimmune, and/or genetic factors. The latter comprises germ line pathogenic variants in genes that bring about habitually predisposing syndromes as well as immune deficiencies that do so only occasionally. One of these disorders is the autosomal dominant form of chronic mucocutaneous candidiasis (CMC), which is defined by germ line STAT1 gain-of-function (GOF) pathogenic variants. The resultant overexpression and constitutive activation of STAT1 dysregulate the Janus kinase/signal transducer and activator of transcription 1 (STAT) signaling pathway, which normally organizes the development and proper interaction of different components of the immunologic and hematopoietic system. Although SAA is an extremely rare complication in this disorder, it gained a more widespread interest when it became clear that the underlying causative pathomechanism may, in a similar fashion, also be instrumental in at least some of the idiopathic SAA cases. Based on these premises, we present herein what is the historically most likely first cord blood-transplanted SAA case in a CMC family with a documented STAT1 GOF pathogenic variant. In addition, we recapitulate the characteristics of the six CMC SAA cases that have been reported so far and discuss the significance of STAT1 GOF pathogenic variants and other STAT1 signaling derangements in the context of these specific types of bone marrow failure syndromes. Because a constitutively activated STAT1 signaling, be it driven by STAT1 GOF germ line pathogenic variants or any other pathogenic variant-independent events, is apparently important for initiating and maintaining the SAA disease process, we propose to acknowledge that SAA is one of the definite disease manifestations in STAT1 -mutated CMC cases. For the same reason, we deem it necessary to also incorporate molecular and functional analyses of STAT1 into the diagnostic work-up of SAA cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Fink, Höpfl, Witsch-Baumgartner, Kropshofer, Martin, Fink, Heeg, Peters, Zschocke and Haas.)

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy linked to high-risk human papillomavirus (HPV) infection, which develops from precursor lesions like low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions (HGSILs). ASCC incidence varies across populations and poses increased risk for people living with HIV. Our investigation focused on transcriptomic and metatranscriptomic changes from squamous intraepithelial lesions to ASCC. Metatranscriptomic analysis highlighted specific bacterial species (e.g., Fusobacterium nucleatum, Bacteroides fragilis) more prevalent in ASCC than precancerous lesions. These species correlated with gene-encoding enzymes (Acca, glyQ, eno, pgk, por) and oncoproteins (FadA, dnaK), presenting potential diagnostic or treatment markers. Unsupervised transcriptomic analysis identified distinct sample clusters reflecting histological diagnosis, immune infiltrate, HIV/HPV status, and pathway activities, recapitulating anal cancer progression's natural history. Our study unveiled molecular mechanisms in anal cancer progression, aiding in stratifying HGSIL cases based on low or high risk of progression to malignancy.

The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high-risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV. For other people with HIV and MSM and TW not with HIV, screening initiation at age 45 years was recommended. For solid organ transplant recipients, screening initiation beginning from 10 years post-transplant was recommended. For persons with a history of vulvar precancer or cancer, screening initiation was recommended starting within 1 year of diagnosis of vulvar precancer or cancer. Persons aged ≥45 years with a history of cervical/vaginal HSIL or cancer, perianal warts, persistent (>1 year) cervical HPV16, or autoimmune conditions could be considered for screening with shared decision-making, provided there is adequate capacity to perform diagnostic procedures (high-resolution anoscopy [HRA]). Anal cytology, high-risk (hr) human papillomavirus (HPV) testing (including genotyping for HPV16), and hrHPV-cytology co-testing are different strategies currently used for anal cancer screening that show acceptable performance. Thresholds for referral for HRA or follow-up screening tests are delineated. These recommendations from IANS provide the basis to inform management of abnormal screening results, considering currently available screening tools. These guidelines provide a pivotal foundation to help generate consensus among providers and inform the introduction and implementation of risk-targeted screening for anal cancer prevention., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Ex vivo confocal microscope (EVCM) rapidly images freshly excised tissue at a histopathological resolution. EVCM features of keratinocyte skin cancers are well-established, but those of benign clinical mimickers remain scarce. We describe EVCM features of common benign lesions and compare them with their malignant differentials. EVCM was used to image 14 benign and 3 cancer tissues. We compared EVCM features of benign lesions with corresponding histopathology and with those of keratinocyte cancers. Key features of benign lesions were identified and differentiated from malignant lesions. Elastin and fat appeared prominent in EVCM; while koilocytes and melanin were difficult to identify. Visualization of entire epidermis was challenging due to difficulty of tissue flattening during imaging. Benign lesions can be differentiated from keratinocyte cancers with EVCM. Using EVCM, a rapid, bedside diagnosis and management of skin neoplasms is possible, especially in a remote location without a histopathology lab., (© 2024 Wiley‐VCH GmbH.)

Introduction: Axillary Ultrasound (AUS) is standard for pre-therapeutic axillary staging in early breast cancer patients. 35-75 % of the breast cancer (BC) patients with positive axillary lymph nodes receiving neoadjuvant chemotherapy (NACT) convert to pathological node negative. For those patients, axillary surgery after NACT could be de-escalated, if an accurate prediction of the pathologic nodal status following NACT was possible. This study aims to answer the question, whether AUS can be used as a reliable diagnostic tool for restaging of axillary nodal status after NACT., Patients and Methods: We collected data of 96 patients with nodal positive primary breast cancer who received NACT between 2009 and 2015 at the Breast Cancer Center of the University Hospital Ulm. Patients were classified as node negative or positive by AUS after NACT (ycN + or ycN0) and the results were compared to the pathological result obtained after axillary lymph node dissection (ypN + vs ypN0) in all patients., Results: 58.3 % of the patients had pathological complete remission of axillary lymph nodes after NACT (ypN0). The sensitivity and specificity of AUS were 57.5 % and 78.6 %, respectively. The FNR was 42.5 %. The Positive and Negative Predictive Values (PPV and NPV) were 65.7 % and 72.1 %, respectively. The accuracy of AUS was 69.8 % and not associated with any of the investigated clinico-pathological parameters., Conclusion: AUS alone is not accurate enough to replace surgical restaging of the axilla after NACT in initially node positive breast cancer patients., Competing Interests: Declaration of competing interest Thomas W. P. Friedl has received honoraria from Novartis and Lilly, unrelated to this work. The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Breast cancer is a common and increasingly treatable disease. However, survivors have a significantly elevated risk of cardiac events afterwards. This study aimed to characterise cardiac changes during cardiotoxic cancer therapy using cardiovascular magnetic resonance (CMR) imaging., Methods: This study involved 34 patients with histologically proven breast cancer and planned cardiotoxic therapy. All patients underwent CMR before starting therapy, and 6 and 12 months thereafter. The CMR protocol included volumetric and functional analyses, parametric mapping, and deformation analysis using feature tracking. As the control group, 10 healthy female volunteers were scanned using the same protocol., Results: With therapy, there was a significant reduction of left ventricular and right ventricular ejection fractions (both p < 0.05) without reaching pathologic values. Left ventricular radial (p = 0.008), circumferential (p = 0.010), and longitudinal strain (p = 0.036) were also reduced at follow-up. In the parametric mapping, there was a significant increase in native T1 time (start: 1037 ± 41 ms vs. 6 months: 1068 ± 51 ms vs. 12 months: 1017 ± 57 ms, p < 0.001) and T2 time (start: 55 ± 4 ms vs. 6 months: 59 ± 3 ms vs. 12 months: 57 ± 3 ms, p = 0.001), with unchanged extracellular volume and relative late gadolinium enhancement. Twelve months after cancer diagnosis, the breast cancer patients exhibited significant impairments in left ventricular global radial (p = 0.001), circumferential (p = 0.001), and longitudinal strain (p = 0.002) and T2 time (p = 0.008) compared to the healthy controls., Discussion: Breast cancer patients receiving cardiotoxic chemotherapy show persistent deterioration in left ventricular strain values. This is accompanied by inflammatory changes in non-invasive tissue characterisation. Larger studies with longer follow-up periods are needed to identify patients at risk and establish preventive and therapeutic approaches., (© 2023. The Author(s).)