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Male breast cancer (MaBC) is an uncommon disease. It is generally assimilated to post-menopausal female breast cancer and treated accordingly. However, the real impact of radiation therapy, after both mastectomy and breast conservation, has yet to be established. We performed a systematic review and meta-analysis to assess the clinical impact of radiation therapy in MBC patients to support the clinical decision-making process and to inform future research. We performed a systematic search of 'male', 'breast', 'cancer', 'radiotherapy' and corresponding synonyms on PubMed/MEDLINE and EMBASE databases. We included interventional studies reporting on radiation therapy effect on overall survival (OS) in MBC patients. Reviews, editorials, letters to the editor, conference abstracts and case reports, and studies with less than 20 MaBC patients or without data on OS were excluded. We extracted relevant characteristics and outcomes for each study, including the hazard ratio (HR) for OS, after adjustment for potential confounders. We calculated an overall adjusted hazard ratio (aHR) for OS for patients receiving radiation therapy compared to those who did not. A random effect model was used. The search strategy yielded 10,260 articles. After removal of duplicates (n = 8254), 2006 articles remained and underwent abstract screening. A total of 168 manuscripts was selected for full text screening. After full text screening, 22 articles were included in the qualitative systematic review. Among them, 14 were included in the quantitative synthesis, reporting on 80.219 MaBC patients. A statistically significant reduction in the risk of death was observed for patients receiving radiation therapy, with a pooled aHR = 0.73 (95 %CI: 0.66-0.81) for OS. Significant heterogeneity among reported aHR estimates was seen (I2=77 %). A significant clinical benefit on OS has been observed when including radiation therapy in the therapeutic algorithm of patients with MaBC. These findings, which are based on retrospective studies and tumour registry reports, deserve further investigation to identify MaBC patient subgroups who most benefit from radiation therapy., Competing Interests: Declaration of Competing Interest no conflict of interest to disclose related to the present manuscript, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The "Assisi Think Tank Meeting" (ATTM) on Breast Cancer, endorsed by the European Society for Radiotherapy & Oncology (ESTRO) and the Italian Association of Radiotherapy and Clinical Oncology (AIRO), and conducted under the auspices of the European Society of Breast Cancer Specialists (EUSOMA), is a bi-annual meeting aiming to identify major clinical challenges in breast cancer radiation therapy (RT) and proposing clinical trials to address them. The topics discussed at the meeting are pre-selected by the steering committee. At the meeting, these topics are discussed in different working groups (WG), after preparation of the meeting by performing a systematic review of existing data and of ongoing trials. Prior to the meeting, each WG designs a survey on the topic to be discussed to reflect current clinical practice and to identify areas requiring further research. Herein, we present the work done by the Assisi WG focusing on lobular carcinoma and the RT perspectives in its treatment, including providing recommendations for locoregional therapy, mainly RT for patients with non-metastatic lobular breast cancer., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: Reliable and accessible biomarkers for patients with Head and Neck Squamous Cell Carcinoma (HNSCC) are warranted for biologically driven radiotherapy (RT). This study aimed to investigate the prognostic value of putative cancer stem cell (CSC) markers, hypoxia, and tumor volume using loco-regional high-dose failure (HDF) as endpoint., Materials and Methods: Tumor tissue was retrieved from patients treated with primary chemo-(C-)RT and nimorazole for HNSCC in the Danish Head and Neck Cancer Study Group (DAHANCA) 19 study. Tumor volume, hypoxic classification, and expression of CSC markers CD44, SLC3A2, and MET were analyzed. For patients with eligible data on all parameters (n = 340), the risk of HDF following primary chemo-(C-)RT were analyzed by these biomarkers as a whole and stratified for p16-positive oropharynx (p16 + OPSCC) vs p16-negative (p16-) tumors (oral cavity, p16- oropharynx, hypopharynx and larynx)., Results: Higher risk of HDF was seen for patients with larger primary and nodal volume (>25 cm 3 , Hazard Ratio (HR): 3.00 [95 % CI: 1.73-5.18]), high SLC3A2 (HR: 2.99 [1.28-6.99]), CD44 (>30 % positive, HR: 2.29 [1.05-5.00]), and p16- tumors (HR: 2.53 [1.05-6.11]). p16- tumors had a higher CSC marker expression than p16 + OPSCC. The factors associated with the highest risk of HDF were larger volume (HR: 3.29 [1.79-6.04]) for p16- tumors (n = 178) and high SLC3A2 (HR: 6.19 [1.58-24.23]) for p16 + OPSCC (n = 162)., Conclusion: Tumor volume, p16, and CSC markers are potential biomarkers for HDF for patients with HNSCC treated with (C-)RT. Lower expression of CSC in p16 + OPSCC may contribute to better tumor control., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Between 1982 and 1990 the Danish Breast Cancer Cooperative Group (DBCG) conducted a randomized trial in high-risk pre- and postmenopausal (<70 years) breast cancer patients comparing mastectomy plus adjuvant systemic therapy alone versus the same treatment plus postoperative irradiation., Aim: To present a comprehensive analysis of the complete DBCG 82bc study with a 30-year long-term follow-up of the cancer therapeutic effect and survival, together with an additional focus on the potential long-term life-threatening morbidity related to cardiac irradiation and/or the risk of secondary cancer induction., Methods: A total of 3083 patients with pathological stage II and stage III breast cancer were after mastectomy randomly assigned to receive adjuvant systemic therapy and postoperative irradiation to the chestwall and regional lymph nodes (1538 pts), or adjuvant systemic therapy alone (1545 pts). Pre- and menopausal patients (DBCG 82b) received 8-9 cycles of CMF with an interval of 4 weeks, whereas postmenopausal patients (DBCG 82c) received tamoxifen 30 mg daily for one year. The median follow-up time was 34 years. The primary endpoints were loco-regional recurrence (LRR) and overall mortality, and the secondary endpoints were distant metastasis, breast cancer mortality, and irradiation related late morbidity., Results: Overall the 30-year cumulative incidence of loco-regional recurrence was 9% in irradiated patients versus 37% in non-irradiated patients who received adjuvant systemic therapy alone (HR: 0.21 [95% cfl 0.18-0.26]). Distant metastasis probability at 30 years was 49% in irradiated patients compared to 60% in non-irradiated (HR: 0.77 [0.70-0.84]). Consequently, these figures resulted in a reduced breast cancer mortality: 56% vs 67% (HR: 0.75 [0.69-0.82], and overall mortality (81% vs 86% at 30 years (p < 0.0001), HR: 0.83 [0.77-0.90] in favor of irradiation. Radiotherapy did not result in any significant excess death of other courses, such as ischemic heart disease, HR: 0.82 [0.58-1.18]; nor secondary lung cancer HR: 1.44 [0.92-2.24], or other non-cancer related death HR: 1.15 [0.92-1.45]., Conclusion: The study definitely demonstrate that optimal long-term treatment benefit of high-risk breast cancer can only be achieved if both loco-regional and systemic tumor control are aimed for. Therefore, radiotherapy has an important role in the multidisciplinary treatment of breast cancer. The PMRT treatment did not result in excess ischemic heart damage, nor in other non-breast cancer related death., Competing Interests: Conflict of interest The authors declare that none of them have any conflicts on interest in relation to the present publication., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Skin-sparing and nipple-sparing mastectomies with immediate reconstruction for breast cancer are increasing. The superficial fascia is considered a natural border and the superficial margin may not be evaluated. We emphasize the need for reporting of the superficial margin status in these procedures to obtain valid information on its association with local recurrence risks., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Breast reconstruction and oncoplastic surgery have become an important part of breast cancer care. The use of autologous breast reconstruction (ABR) has evolved significantly with advances in microsurgery, aiming to reduce donor site complications and improve cosmesis. For years, immediate-ABR was considered a contraindication if postmastectomy irradiation (PMRT) was planned. As a result of de-escalation of axillary surgery the indication of PMRT are increasing along-side with observations that PMRT in the setting of ABR is not contraindicated. Surgical techniques may result in different amount and areas of breast residual glandular tissue and patient selection is important to reduce potential residual disease. Meticulus radiation planning is important to potentially reduce complications without compromising oncologic outcomes. Surgical techniques change constantly in aim to improve aesthetic results but should most importantly maintain priority to the oncological indications. By multidisciplinary team work with a comprehensive understanding of each discipline, we can preserve the accomplishments of breast surgery in the setting of PMRT, without compromising disease control., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: HPV/p16-positive head and neck cancers (HNSCC) show superior response to radiotherapy, compared with virus-negative tumours. Tumour hypoxia induces radioresistance and the randomised DAHANCA 5 trial found that the hypoxic cell radiosensitiser nimorazole significantly improved the outcome in HNSCC. Using p16-status as a retrospective stratification parameter, we aimed to assess the influence of p16-expression on the response to nimorazole in HNSCC., Materials and Methods: Pre-treatment tumour blocks were available from 331 of the 414 patients in the DAHANCA 5 trial and evaluated by immunohistochemistry for p16-expression. The influence of p16-expression on outcome was analysed as a function of treatment group (nimorazole/placebo) 5 years after radiotherapy., Results: Overall, patients treated with nimorazole had significantly better loco-regional control than did those given placebo: hazard ratio (HR) 0.70 [95% CI 0.52-0.93]. Positive expression of p16 also significantly improved outcome after radiotherapy (0.41 [0.28-0.61]). In the subgroup of patients with p16-negative tumours, loco-regional failure was more frequent in the placebo group than in the nimorazole group (0.69 [0.50-0.95]). However, in the p16-positive group, patients treated with nimorazole had a loco-regional control rate similar to patients given placebo (0.93 [0.45-1.91])., Conclusions: HPV/p16-expression significantly improved outcome after radiotherapy in HNSCC. Hypoxic modification improved outcome in HPV/p16-negative tumours but was of no significant benefit in HPV/p16-positive tumours, suggesting that hypoxic radioresistance may not be clinically relevant in these tumours., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)