Immunotherapy and stereotactic body radiotherapy for older patients with non-metastatic renal cancer unfit for surgery or decline nephrectomy: practical proposal by the International Geriatric Radiotherapy Group.

The standard of care for non-metastatic renal cancer is surgical resection followed by adjuvant therapy for those at high risk for recurrences. However, for older patients, surgery may not be an option due to the high risk of complications which may result in death. In the past renal cancer was considered to be radio-resistant, and required a higher dose of radiation leading to excessive complications secondary to damage of the normal organs surrounding the cancer. Advances in radiotherapy technique such as stereotactic body radiotherapy (SBRT) has led to the delivery of a tumoricidal dose of radiation with minimal damage to the normal tissue. Excellent local control and survival have been reported for selective patients with small tumors following SBRT. However, for patients with poor prognostic factors such as large tumor size and aggressive histology, there was a higher rate of loco-regional recurrences and distant metastases. Those tumors frequently carry program death ligand 1 (PD-L1) which makes them an ideal target for immunotherapy with check point inhibitors (CPI). Given the synergy between radiotherapy and immunotherapy, we propose an algorithm combining CPI and SBRT for older patients with non-metastatic renal cancer who are not candidates for surgical resection or decline nephrectomy.

Immunotherapy and radiotherapy for older patients with locally advanced rectal cancer unfit for surgery or decline surgery: a practical proposal by the International Geriatric Radiotherapy Group.

The standard of care for locally advanced rectal cancer is total neoadjuvant therapy followed by surgical resection. Current evidence suggests that selected patients may be able to delay or avoid surgery without affecting survival rates if they achieve a complete clinical response (CCR). However, for older cancer patients who are too frail for surgery or decline the surgical procedure, local recurrence may lead to a deterioration of patient quality of life. Thus, for clinicians, a treatment algorithm which is well tolerated and may improve CCR in older and frail patients with rectal cancer may improve the potential for prolonged remission and potential cure. Recently, immunotherapy with check point inhibitors (CPI) is a promising treatment in selected patients with high expression of program death ligands receptor 1 (PD- L1). Radiotherapy may enhance PD-L1 expression in rectal cancer and may improve response rate to immunotherapy. We propose an algorithm combining immunotherapy and radiotherapy for older patients with locally advanced rectal cancer who are too frail for surgery or who decline surgery.

Longer time to testosterone recovery impacts favorably on outcomes for prostate cancer following androgen deprivation and radiotherapy.

PURPOSE: To evaluate the impact of sustained hypogonadism after androgen deprivation therapy (ADT) associated with radiotherapy in prostate cancer (PCa) patients with biochemical relapse-free survival (bRFS). METHODS: A retrospective cohort analysis of 213 consecutive PCa patients referred for radiotherapy plus ADT was carried out. Follow-up times including time to testosterone recovery (TTR) and bRFS were calculated from the end of ADT. Univariate and multivariate Cox regression analyses predicting bRFS were used. The optimal cutoffs for TTR and duration of ADT were determined using the maximally selected rank statistics (MSRS). RESULTS: After a median follow-up of 104 months, 18 patients relapsed among those who had recovered testosterone levels and 9 among those who did not. Median ADT duration was 36 months. The optimal cutoff for TTR was determined using MSRS. TTR >48 months was significantly associated with better bRFS (logrank, p < 0.0027). Five-year bRFS was 100% for >48 months vs. 85% for <48 months. TTR was the only significant variable for bRFS in multivariate Cox analysis. CONCLUSION: Our data show an association between longer TTR and bRFS values among PCa patients treated with ADT.

Metabolomics and triple-negative breast cancer: A systematic review.

Triple-negative breast cancer stands out as the most aggressive subtype of breast malignancy and is characterized by an unfavourable prognosis. Objective: This systematic review summarizes the insights gleaned from metabolomic analyses of individuals afflicted with this cancer variant. The overarching goal was to delineate the molecular alterations associated with triple-negative breast cancer, pinpointing potential therapeutic targets and novel biomarkers. Methods: We systematically searched for evidence using the PubMed database and followed the PRISMA and STARLITE guidelines. The search parameters were delimited to articles published within the last 13 years. Results: From an initial pool of 148 scrutinized articles, 17 studies involving 1686 participants were deemed eligible for inclusion. The current body of research shows a paucity of studies, and the available evidence presents conflicting outcomes. Notwithstanding, Pathway Enrichment Analysis identified the urea and glucose-alanine cycles as the most affected metabolic pathways, followed by arginine, proline, and aspartate metabolism. Conclusion: Future investigations need to focus on elucidating which of those metabolites and/or pathways might be reliable candidates for novel therapeutic interventions or reliable biomarkers for diagnosis and prognosis of this subtype of breast cancer.

Metabolic adaptations in severe obesity: Insights from circulating oxylipins before and after weight loss.

BACKGROUND: The relationship between lipid mediators and severe obesity remains unclear. Our study investigates the impact of severe obesity on plasma concentrations of oxylipins and fatty acids and explores the consequences of weight loss. METHODS: In the clinical trial identifier NCT05554224 study, 116 patients with severe obesity and 63 overweight/obese healthy controls matched for age and sex (≈2:1) provided plasma. To assess the effect of surgically induced weight loss, we requested paired plasma samples from 44 patients undergoing laparoscopic sleeve gastrectomy one year after the procedure. Oxylipins were measured using ultra-high-pressure liquid chromatography coupled to a triple quadrupole mass spectrometer via semi-targeted lipidomics. Cytokines and markers of interorgan crosstalk were measured using enzyme-linked immunosorbent assays. RESULTS: We observed significantly elevated levels of circulating fatty acids and oxylipins in patients with severe obesity compared to their metabolically healthier overweight/obese counterparts. Our findings indicated that sex and liver disease were not confounding factors, but we observed weak correlations in plasma with circulating adipokines, suggesting the influence of adipose tissue. Importantly, while weight loss restored the balance in circulating fatty acids, it did not fully normalize the oxylipin profile. Before surgery, oxylipins derived from lipoxygenase activity, such as 12-HETE, 11-HDoHE, 14-HDoHE, and 12-HEPE, were predominant. However, one year following laparoscopic sleeve gastrectomy, we observed a complex shift in the oxylipin profile, favoring species from the cyclooxygenase pathway, particularly proinflammatory prostanoids like TXB2, PGE2, PGD2, and 12-HHTrE. This transformation appears to be linked to a reduction in adiposity, underscoring the role of lipid turnover in the development of metabolic disorders associated with severe obesity. CONCLUSIONS: Despite the reduction in fatty acid levels associated with weight loss, the oxylipin profile shifts towards a predominance of more proinflammatory species. These observations underscore the significance of seeking mechanistic approaches to address severe obesity and emphasize the importance of closely monitoring the metabolic adaptations after weight loss.

Serum Arylesterase, Paraoxonase, and Lactonase Activities and Paraoxonase-1 Concentrations in Morbidly Obese Patients and Their Relationship with Non-Alcoholic Steatohepatitis.

Paraoxonase-1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). Reduced serum PON1 activity is found in diseases marked by oxidative stress and inflammation, but its role in obesity remains unclear. This study investigated PON1 activities and concentrations in morbidly obese individuals and explored the impacts of the genetic polymorphism PON1 rs662 and non-alcoholic fatty liver disease on enzymatic properties. We recruited 1349 morbidly obese patients undergoing bariatric surgery and 823 non-obese volunteers. PON1-related variables, including arylesterase, paraoxonase, and lactonase activities and PON1 concentrations, were examined. Our results showed that morbidly obese individuals exhibited higher PON1 concentrations but lower enzymatic activities than non-obese individuals. We observed inverse associations of arylesterase and paraoxonase activities with waist circumference (rho = -0.24, p < 0.001, and rho = -0.30, p < 0.001, respectively) and body mass index (rho = -0.15, p = 0.001, and rho = -0.23, p < 0.001), as well as direct associations of arylesterase, paraoxonase, and lactonase activities with HDL cholesterol (rho = 0.11, p = 0.005, rho = 0.20, p < 0.001, and rho = 0.20, p < 0.001). No significant differences were observed regarding metabolic syndrome, type 2 diabetes mellitus, hypertension, dyslipidemia, rs662 polymorphism allele frequencies, or the diagnosis of non-alcoholic steatohepatitis. Nevertheless, correlations were found between certain PON1-related variables, steatosis, and ballooning. In conclusion, changes in PON1-related variables in morbidly obese patients are dependent on the disease itself and HDL levels. The relationships between these variables and specific liver histological changes raise intriguing questions for consideration in future studies.

Making Radiation Oncology specialty more attractive to young medical graduates: pulling back the invisibility curtain

Purpose Radiation Oncology is one of the least-known medical specialties for young graduates at the end of their studies. An in-depth analysis of the strengths and weaknesses of the Radiation Oncology visibility, the training plan, and why it is less attractive for new medical residents during the last years appears as the initial need to turn out this lack of knowledge. Materials and Methods An anonymous pilot survey of 24 questions addressed to specialists in-training in Radiation Oncology in Spain during August and September of 2022. Results A total of 50 in-training radiation oncologists answered the questionnaire and 90% of them believe that a lack of knowledge, mainly at the School of Medicine, was a major reason why choosing Radiation Oncology was unattractive. All responders were satisfied by choosing Radiation Oncology, and 76% were in favor of extending the residency to 5 years to improve their training. Research activity was considered essential (78%) to complete their training. Conclusion Increasing the presence of Radiation Oncology at the School of Medicine may be one solution to achieve greater attractiveness among future residents. Likewise, extending the training period to five years could help to enhance the learning of all radiotherapy techniques while promoting clinical research (AU)

Interventional Radiotherapy in Gynecological Cancer.

This special issue of "Cancers" explores unusual and very particular aspects of interventional radiotherapy (brachytherapy) in gynecological cancer [...].

Immunotherapy and Hypofractionated Radiotherapy in Older Patients with Locally Advanced Cutaneous Squamous-Cell Carcinoma of the Head and Neck: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

Cutaneous skin carcinoma is a disease of older patients. The prevalence of cutaneous squamous-cell carcinoma (cSCC) increases with age. The head and neck region is a frequent place of occurrence due to exposure to ultraviolet light. Surgical resection with adjuvant radiotherapy is frequently advocated for locally advanced disease to decrease the risk of loco-regional recurrence. However, older cancer patients may not be candidates for surgery due to frailty and/or increased risk of complications. Radiotherapy is usually advocated for unresectable patients. Compared to basal-cell carcinoma, locally advanced cSCC tends to recur locally and/or can metastasize, especially in patients with high-risk features such as poorly differentiated histology and perineural invasion. Thus, a new algorithm needs to be developed for older patients with locally advanced head and neck cutaneous squamous-cell carcinoma to improve their survival and conserve their quality of life. Recently, immunotherapy with checkpoint inhibitors (CPIs) has attracted much attention due to the high prevalence of program death ligand 1 (PD-L1) in cSCC. A high response rate was observed following CPI administration with acceptable toxicity. Those with residual disease may be treated with hypofractionated radiotherapy to minimize the risk of recurrence, as radiotherapy may enhance the effect of immunotherapy. We propose a protocol combining CPIs and hypofractionated radiotherapy for older patients with locally advanced cutaneous head and neck cancer who are not candidates for surgery. Prospective studies should be performed to verify this hypothesis.

Matrix Metalloproteinase-9 Expression Is Associated with the Absence of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients.

Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets.

Making Radiation Oncology specialty more attractive to young medical graduates: pulling back the invisibility curtain.

PURPOSE: Radiation Oncology is one of the least-known medical specialties for young graduates at the end of their studies. An in-depth analysis of the strengths and weaknesses of the Radiation Oncology visibility, the training plan, and why it is less attractive for new medical residents during the last years appears as the initial need to turn out this lack of knowledge. MATERIALS AND METHODS: An anonymous pilot survey of 24 questions addressed to specialists in-training in Radiation Oncology in Spain during August and September of 2022. RESULTS: A total of 50 in-training radiation oncologists answered the questionnaire and 90% of them believe that a lack of knowledge, mainly at the School of Medicine, was a major reason why choosing Radiation Oncology was unattractive. All responders were satisfied by choosing Radiation Oncology, and 76% were in favor of extending the residency to 5 years to improve their training. Research activity was considered essential (78%) to complete their training. CONCLUSION: Increasing the presence of Radiation Oncology at the School of Medicine may be one solution to achieve greater attractiveness among future residents. Likewise, extending the training period to five years could help to enhance the learning of all radiotherapy techniques while promoting clinical research.

Paraoxonase-1: How a xenobiotic detoxifying enzyme has become an actor in the pathophysiology of infectious diseases and cancer.

Both infectious and non-infectious diseases can share common molecular mechanisms, including oxidative stress and inflammation. External factors, such as bacterial or viral infections, excessive calorie intake, inadequate nutrients, or environmental factors, can cause metabolic disorders, resulting in an imbalance between free radical production and natural antioxidant systems. These factors may lead to the production of free radicals that can oxidize lipids, proteins, and nucleic acids, causing metabolic alterations that influence the pathogenesis of the disease. The relationship between oxidation and inflammation is crucial, as they both contribute to the development of cellular pathology. Paraoxonase 1 (PON1) is a vital enzyme in regulating these processes. PON1 is an enzyme that is bound to high-density lipoproteins and protects the organism against oxidative stress and toxic substances. It breaks down lipid peroxides in lipoproteins and cells, enhances the protection of high-density lipoproteins against different infectious agents, and is a critical component of the innate immune system. Impaired PON1 function can affect cellular homeostasis pathways and cause metabolically driven chronic inflammatory states. Therefore, understanding these relationships can help to improve treatments and identify new therapeutic targets. This review also examines the advantages and disadvantages of measuring serum PON1 levels in clinical settings, providing insight into the potential clinical use of this enzyme.

LDR brachytherapy offers superior tumor control to single-fraction HDR prostate brachytherapy: A prospective study.

PURPOSE: To compare the clinical outcomes of single-fraction high-dose-rate (HDR) brachytherapy and single-fraction low-dose-rate (LDR) brachytherapy as the sole treatment for primary prostate cancer. MATERIAL AND METHODS: A quasi-randomized study that allocated, from March 2008 to February 2012, 129 low and intermediate risk prostate cancer patients to one single-fraction HDR of 19 Gy (61 patients) or to a 145 Gy 125 I LDR permanent implant (68 patients. Biochemical relapse-free survival (bRFS) and overall survival (OS) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: After a median follow-up of 72 months in the HDR group, 26 patients relapsed, and after a median follow-up of 84 months in the LDR group, 7 patients relapsed (p < 0.0001). The 5-year bRFS was significantly better for the LDR group than for the HDR group (93.7% and 61.1%, respectively) (p < 0.0001). The 5-year OS also was significantly better in the LDR group (95.5% vs. 89.9%) (p = 0.0436). CONCLUSIONS: Permanent LDR prostate implant brachytherapy offers better clinical outcomes than single-fraction HDR for prostate cancer.

SARS-CoV-2 Serum Viral Load and Prognostic Markers Proposal for COVID-19 Pneumonia in Low-Dose Radiation Therapy Treated Patients.

Several studies have shown that the plasma RNA of SARS-CoV-2 seems to be associated with a worse prognosis of COVID-19. In the present study, we investigated plasma RNA in COVID-19 patients treated with low-dose radiotherapy to determine its prognostic value. Data were collected from the IPACOVID prospective clinical trial (NCT04380818). The study included 46 patients with COVID-19 pneumonia treated with a whole-lung dose of 0.5 Gy. Clinical follow-up, as well as laboratory variables, and SARS-CoV-2 serum viral load, were analyzed before LDRT, at 24 h, and one week after treatment. The mean age of the patients was 85 years, and none received any of the SARS-CoV-2 vaccine doses. The mortality ratio during the course of treatment was 33%. RT-qPCR showed amplification in 23 patients. Higher mortality rate was associated with detectable viremia. Additionally, C-reactive protein, lactate dehydrogenase, and aspartate aminotransferase were significant risk factors associated with COVID-19 mortality. Our present findings show that detectable SARS-CoV-2 plasma viremia 24 h before LDRT is significantly associated with increased mortality rates post-treatment, thus downsizing the treatment success.

Prognostic Implications of the Residual Tumor Microenvironment after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients without Pathological Complete Response.

With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan-Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling.

A nationwide survey of the current status of radiation oncology teaching in Spanish medical schools.

Background: The present study was designed to collect information on the current status of radiation oncology (RO) teaching in undergraduate medical schools in Spain. Materials and methods: A cross-sectional survey was conducted with the support of the Spanish Society of Radiation Oncology (SEOR). An anonymous questionnaire was sent in two waves, one month apart, between January and June 2022, to all Medical Schools and affiliated Institutions having radiotherapy departments throughout the country. Data on load, curricular location of OR, the academic course (or courses) in which the subject of OR was taught, and teachers position were recorded. Results: Responses were obtained from 26 of the 46 available Medical Schools (response rate 56.5%). The average number of theoretical classes was 13 (0-30), seminars: 4.5 (0-12) and hours of practical training 17 (0-60). The scientific content of RO was covered very evenly. Medical physics and radiobiology were taught with different extension in 24 medical schools (92.3%). Information on technological equipment, brachytherapy, indications, and clinical results was provided in all but one medical school. In 13 medical schools (50.0%) the contents of RO were taught in more than one course, but the distribution of RO teaching during the six years of undergraduate training was quite dispersed. The teaching staff included 4 full professors, 8 tenured professors, and 68 clinical associate professors. The average number of associate professors per medical school was 2.2. Also, the average number of full professors and tenured lecturers was 0.42 per medical school, although there were none in 16 centers. Conclusions: The overall teaching content of RO in Spanish medical schools seems appropriate but actions to improve the heterogeneity in the curricular location of RO and the shortage of teachers should be implemented.

Gradient Boosting Machine Identified Predictive Variables for Breast Cancer Patients Pre- and Post-Radiotherapy: Preliminary Results of an 8-Year Follow-Up Study.

Radiotherapy (RT) is part of the standard treatment of breast cancer (BC) because of its effects on relapse reduction and survival. However, response to treatment is highly variable, and some patients may develop disease progression (DP), a second primary cancer, or may succumb to the disease. Antioxidant systems and inflammatory processes are associated with the onset and development of BC and play a role in resistance to treatment. Here, we report our investigation into the clinical evolution of BC patients, and the impact of RT on the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1), cytokines, and other standard biochemical and hematological variables. Gradient Boosting Machine (GBM) algorithm was used to identify predictive variables. This was a retrospective study in 237 patients with BC. Blood samples were obtained pre- and post-RT, with samples of healthy women used as control subjects. Results showed that 24 patients had DP eight years post-RT, and eight patients developed a second primary tumor. The algorithm identified interleukin-4 and total lymphocyte counts as the most relevant indices discriminating between BC patients and control subjects, while neutrophils, total leukocytes, eosinophils, very low-density lipoprotein cholesterol, and PON1 activity were potential predictors of fatal outcome.

Tasa de afectación de los márgenes quirúrgicos tras la cirugía conservadora de mama y estimación de los costes directos / Rate of effect of surgical margins after breast conserving surgery and estimation of direct costs

Objetivo: Valoración de la tasa de reintervención en pacientes con márgenes de resección positivos tras cirugía conservadora inicial por cáncer de mama y estimación del coste para el hospital. Métodos: Estudio observacional de la tasa de afectación de los márgenes quirúrgicos de la pieza de resección tras la cirugía conservadora inicial en mujeres con carcinoma de mama invasor durante los años 2018-2019 en el H. U. de Tarragona Joan XXIII (HUTJ23), estableciendo en qué casos fue precisa la realización de una segunda intervención sobre la mama. Se estiman los costes directos añadidos que supone el segundo procedimiento quirúrgico y se compara con el gasto según los pesos establecidos por el Servicio Catalán de Salud según el nivel del hospital y los Grupos Relacionados por el Diagnóstico (GRD) fijados por el Sistema Nacional de Salud.Resultados: Se incluyó a 146 pacientes con diagnóstico de cáncer de mama invasor. Encontramos márgenes positivos tras la cirugía conservadora inicial en el 20,55% de los casos. Se reintervino al 19,17% del total de pacientes, generando las reintervenciones un coste de 129.696,089€, siendo 82.654,34€ para cirugía conservadora (3.757,01€ de media por paciente) y de 47.042,55€ en las mastectomías (6.720,36€ de media por paciente). Conclusiones: La afectación de los márgenes tras cirugía conservadora de la mama es sinónimo de reintervención, lo que supone una serie de costes directos que dependen del tipo de cirurgia y el régimen escogido (ambulatoria u hospitalizada). Es recomendable controlar los factores que inciden en los márgenes afectos para minimizar su impacto. (AU)

Objective: Assessment of the reoperation rate in patients with positive resection margins after initial breast-conserving surgery for breast cancer and estimation of the cost to the hospital. Method: 146 patients with diagnosis of invasive breast cancer were included, who were initially intervened with conservative surgery by the Gynecology and Obstetrics Service of Hospital Universitario de Tarragona Juan XXIII (HUTJ23) during the years 2018 and 2019. We calculated the rate of involvement of the surgical margins of the resection piece after initial conservative surgery, establishing in which cases it was necessary to carry out a second resection, estimating the added direct costs of the second surgical procedure, and comparing them with the costs established by the Catalan Health Service according to the level of the hospital and the Diagnosis-Related Groups (DRG) established by the National Health System. Results: The rate of positive margins after initial conservative surgery was 20.55% and 19.17% patients underwent reoperation, generating a total expense of € 129.696,89, € 82.654,34 in conservative surgeries (€ 3.757,01 on average per patient) and € 47.042,55 in mastectomies (€ 6.720,36 on average per patient).Conclusions: Margin involvement after breast-conserving surgery is synonymous for reoperation, this involves a series of direct costs. It is advisable to control the factors related to affected margins to minimize their impact. (AU)

Ways to improve breast cancer patients' management and clinical outcome: The 2020 Assisi Think Tank Meeting.

We report on the third Assisi Think Tank Meeting (ATTM) on breast cancer, a brainstorming project which involved European radiation and clinical oncologists who were dedicated to breast cancer research and treatment. Held on February 2020, the ATTM aimed at identifying key clinical questions in current clinical practice and "grey" areas requiring research to improve management and outcomes. Before the meeting, three key topics were selected: 1) managing patients with frailty due to either age and/or multi-morbidity; 2) stereotactic radiation therapy and systemic therapy in the management of oligometastatic disease; 3) contralateral breast tumour prevention in BCRA-mutated patients. Clinical practice in these areas was investigated by means of an online questionnaire. In the lapse period between the survey and the meeting, the working groups reviewed data, on-going studies and the clinical challenges which were then discussed in-depth and subjected to intense brainstorming during the meeting; research protocols were also proposed. Methodology, outcome of discussions, conclusions and study proposals are summarized in the present paper. In conclusion, this report presents an in-depth analysis of the state of the art, grey areas and controversies in breast cancer radiation therapy and discusses how to confront them in the absence of evidence-based data to guide clinical decision-making.

Evidence-based guidelines for hypofractionated radiation in breast cancer: conclusions of the Catalan expert working group

IntroductionDaily, moderate hypofractionation has become standard treatment for breast cancer following breast-conserving surgery, although substantial variation exists in its use. This paper describes the generation of consensus-based recommendations for the utilisation of this therapy at the healthcare system level and compares these to American Society for Radiation Oncology (ASTRO) guidelines.Materials and methodsConsensus-based guidelines were developed in three steps, including a systematic literature review and involvement of radiation oncologists specialising in breast cancer in Catalonia: (a) creation of a working group and evidence review; (b) consideration of the levels of evidence and agreement on the formulation of survey questions; and (c) performance of survey and development of consensus-based recommendations. Results were compared to the ASTRO recommendations.ResultsConsensus was above 80% for 10 of the 14 survey items. Experts supported hypofractionated radiotherapy for all breast cancer patients aged 40 years or more; with invasive carcinoma and breast-conserving surgery; without radiation of lymph nodes; and regardless of the tumour size, histological grade, molecular subtype, breast size, laterality, other treatment characteristics, or need for a boost. Over half favoured its use in all situations, even where available scientific evidence is insufficient. The resulting recommendations and the quality of the evidence are comparable to those from ASTRO, despite some differences in the degree of consensus.ConclusionSpecialists agree that hypofractionation is the standard treatment for breast cancer following breast-conserving surgery, but some specific areas require a higher level of evidence before unequivocally extending indications. (AU)