Prostate Cancer (PCa) is the second leading cause of cancer death in the elderly (≥75 years). There is currently little data on hypofractionated radiotherapy in older patients affected by localized PCa. We present the long-term results of hypofractionated radiotherapy in elderly patients with localized PCa from the IPOPROMISE database. retrospective analysis of 719 PCa elderly (≥75 years) patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020. For survival endpoints, we used Kaplan-Meier survival curves and univariate and multivariable Cox’s proportional hazards regression models. Median age at PCa diagnosis was 78.4 years (interquartile [IQR], 76.8–80.3 years), 74

PURPOSE:The Breast Cancer Study Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey aiming to provide an overview of the policies on radiation therapy (RT) dose and fractionation for whole breast irradiation (WBI), partial breast irradiation (PBI), chest wall (CW) irradiation and regional nodal irradiation (RNI). MATERIALS AND METHODS:In February 2023, 183 Italian RT centres were invited to answer a survey: after a first section investigating general aspects, the questionnaire focused on radiation oncologists' (ROs) attitude regarding breast cancer post-operative RT dose and fractionation. Surveyed ROs were also asked to express their interest in being involved in prospective trials evaluating post-operative ultra-hypofractionated RT (ultra-HF). RESULTS:One hundred and twenty/183 (65.6%) centres answered the survey. Regarding WBI 99.1% of ROs prescribed moderate hypofractionated (HF) RT and 70.3% ultra-HF RT, sequential administration is the preferred choice for delivering tumour bed boost (60.4% of centres). Moderate HF was the preferred choice for CW irradiation and RNI in 60.3% and 63.6% of centres, respectively. PBI was adopted in clinical practice in only 57.5% of centres. Furthermore, 29.1% of centres are already involved and 34.6% would like to be involved in prospective studies evaluating ultra-HF RT. CONCLUSION:Hypofractionated RT is widely adopted for WBI, while its use in post-mastectomy RT (PMRT) appears uneven. Adoption of ultra-HF RT is high for WBI, but it is not a standard for CW irradiation and RNI. Regarding PBI, the survey highlighted the need for enhanced expertise to improve its adoption.

Importance:Integration of molecular biomarker information into systemic therapy has become standard practice in breast cancer care. However, its implementation in guiding radiotherapy (RT) is slower. Although postoperative RT is recommended for most patients after breast-conserving surgery and, depending on risk factors, following mastectomy, emerging evidence has indicated that patients with low scores on gene expression signatures or selected clinical-pathological features may have very low local recurrence rates. This narrative review explored the potential of biomarker-directed personalized RT approaches, which may optimize treatment strategies and be associated with improved patient outcomes and experiences. Observations:Distinctions between prognostic and predictive biomarkers were highlighted, emphasizing the importance of analytical and clinical validity in biomarker-based studies. Findings from studies investigating the prognostic and predictive value of various genomic signatures and immunohistochemical markers for guiding breast RT were presented. These included the Adjuvant Radiotherapy Intensification Classifier and the Profile for the Omission of Local Adjuvant Radiation, which have shown potential in predicting RT benefits. The genomic-adjusted radiation dose and role of tumor-infiltrating lymphocytes were also discussed. Ongoing clinical trials exploring the use of biomarkers in ductal carcinoma in situ and invasive breast cancer to refine RT decision-making were illustrated. Conclusions and Relevance:The results of this narrative review suggest that evidence-based shared decision-making is crucial to optimize treatment according to the individual's predicted benefits and risks along with their personal preferences. Incorporation of biomarker-directed approaches in RT for breast cancer may hold promise for personalized treatment, potentially facilitating omission of RT for patients at low risk of recurrence, while identifying those who may benefit from intensified therapy. This personalized RT approach may be associated with improved clinical outcomes and quality of life and facilitate decision-making for people with breast cancer. However, there remains a need for robust clinical and analytical validation of biomarkers to ensure reliability and clinical utility for RT optimization.

ImportanceIntegration of molecular biomarker information into systemic therapy has become standard practice in breast cancer care. However, its implementation in guiding radiotherapy (RT) is slower. Although postoperative RT is recommended for most patients after breast-conserving surgery and, depending on risk factors, following mastectomy, emerging evidence has indicated that patients with low scores on gene expression signatures or selected clinical-pathological features may have very low local recurrence rates. This narrative review explored the potential of biomarker-directed personalized RT approaches, which may optimize treatment strategies and be associated with improved patient outcomes and experiences.ObservationsDistinctions between prognostic and predictive biomarkers were highlighted, emphasizing the importance of analytical and clinical validity in biomarker-based studies. Findings from studies investigating the prognostic and predictive value of various genomic signatures and immunohistochemical markers for guiding breast RT were presented. These included the Adjuvant Radiotherapy Intensification Classifier and the Profile for the Omission of Local Adjuvant Radiation, which have shown potential in predicting RT benefits. The genomic-adjusted radiation dose and role of tumor-infiltrating lymphocytes were also discussed. Ongoing clinical trials exploring the use of biomarkers in ductal carcinoma in situ and invasive breast cancer to refine RT decision-making were illustrated.Conclusions and RelevanceThe results of this narrative review suggest that evidence-based shared decision-making is crucial to optimize treatment according to the individual’s predicted benefits and risks along with their personal preferences. Incorporation of biomarker-directed approaches in RT for breast cancer may hold promise for personalized treatment, potentially facilitating omission of RT for patients at low risk of recurrence, while identifying those who may benefit from intensified therapy. This personalized RT approach may be associated with improved clinical outcomes and quality of life and facilitate decision-making for people with breast cancer. However, there remains a need for robust clinical and analytical validation of biomarkers to ensure reliability and clinical utility for RT optimization.

Prostate cancer (PCa) ranks among the most prevalent malignancies in men, with notable associations to Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Lynch Syndrome, both linked to germline likely pathogenetic variant/pathogenetic variant (LPV/PV) in genes involved in DNA repair. Among these genes, BRCA2 in PCa patients is the most frequently altered. Despite progresses, challenges in BRCA carriers detection persist, with a quarter of PCa cases lacking family history. To address these challenges, a multidisciplinary expert panel from six Italian Scientific Societies, formulated a care pathway to integrate BRCA testing into routine clinical practice in different Italian geographical areas. The development process, promoted by the Italian Society of Uro-Oncology (SIUrO), involved three key stages. A preliminary meeting convened teams from different Italian regions to establish minimal requirements for a mini-counseling program (defined as a pre-test consultation carried out by clinicians responsible of patients’ management) and propose care pathway models. At the same time, a comprehensive survey was launched to highlight regional variations in BRCA testing and identify eventual obstacles to testing activities. A subsequent meeting synthesized care pathway proposals and formulated a unified framework, acknowledging regional legislative variations as enriching factors. Lastly, implementation of the unified framework was promoted by the project faculty and identified regional team leaders. Survey results revealed significant regional disparities in BRCA testing, reimbursement policies, and access to genetic counseling. The proposed mini-counseling program outlined essential steps for patient identification, information provision, and multidisciplinary review, aiming to streamline BRCA testing processes. Expert recommendations emphasized offering tumor genetic testing to metastatic PCa patients eligible for PARP-i treatment and outlined criteria for genetic counseling and germline testing. Key considerations included family history and tumor characteristics. In conclusion, the proposed care pathway represents a critical step towards integrating BRCA testing into routine PCa care, aiming to optimize patient management and familial risk assessment within the constraints of the Italian healthcare system. • BRCA likely pathogenetic/pathogenetic variants significantly increase the risk of developing prostate cancer (PCa) and enhance sensitivity to PARP-inhibitor treatment, underscoring the clinical need to incorporate genetic testing into the routine management of PCa patients. • A comprehensive survey revealed significant regional disparities in BRCA testing availability, reimbursement policies, and access to genetic counseling across different geographical regions of Italy. • A multidisciplinary panel from six Italian Scientific Societies, led by the Italian Society of Uro-Oncology (SIUrO), developed a care pathway to integrate BRCA testing into routine clinical practice within the Italian healthcare system.

Brain metastases (BMs) are prevalent among patients diagnosed with human epidermal growth factor receptor 2 (HER2)positive metastatic breast cancer (BC), with the incidence rate exceeding 30

•PBI is valid alternative to WBI in patients at low-risk of local relapse•PBI is delivered by means of various techniques, one of which is IOeRT•After IOeRT, an unexpectedly high LR rate was observed in the only phase III RCT•Patient selection impacts on LR rates after IOeRT•With appropriate patient selection IOeRT outcomes overlap with other RT techniques

Background Moderate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series. Materials and methods We retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan–Meier survival curves and fitted univariate and multivariable Cox’s proportional hazards regression models to study the association between the clinical variables and each survival type. Results At the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3–99.6%) and 85.5% (95%CI 81.9–89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4–6%) and 6% (95%CI 4–8%), respectively. Conclusion Real-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.

PURPOSE:Data from recently trials have provided practice-changing recommendations in management of the axilla in early breast cancer (eBC). However, further controversies have been raised, resulting in heterogeneous diffusion of these recommendations. Our purpose was to obtain a better homogeneity.MATERIAL AND METHODS:In 2021, the Tuscan Breast Network (TBN) established a consensus with the aim to update recommendations in this area. We performed a literature review on axillary management in eBC patients which led to an expert Delphi consensus aiming to explore the gray areas, build consensus and propose evidence-based suggestions for an appropriate management. Thereafter, we investigate their implementation in clinical practice.RESULTS:(1) DCIS patients should have SLN biopsy only in case of mastectomy or in conservative surgery if tumor is in a location that would preclude future nodal sampling or in case of a mass; (2) ALND may be omitted for 1-2 positive SLN patients undergoing BCS in T1-2 tumors with 1-2 SLN positive, eligible for whole-breast irradiation and adjuvant systemic therapies; (3) consider the option of RNI in patients with 1-3 positive lymph nodes and one or more high-risk characteristics; (4) the population identified in 2) should NOT undergo lymph node irradiation as an alternative to axillary surgery and (5) patients with clinically (pre-operatively) positive axilla, or undergoing primary systemic therapy, or outside the criteria reported in 2) must receive additional ALND and/or RT as per local policy.CONCLUSION:This consensus provided a practical tool to stimulate local and national breast surgical and radiotherapy protocols.

Purpose. We present a large real -world multicentric dataset of ovarian, uterine and cervical oligometastatic lesions treated with SBRT exploring efficacy and clinical outcomes. In addition, an exploratory machine learning analysis was performed. Methods. A pooled analysis of gynecological oligometastases in terms of efficacy and clinical outcomes as well an exploratory machine learning model to predict the CR to SBRT were carried out. The CR rate following radiotherapy (RT) was the study main endpoint. The secondary endpoints included the 2 -year actuarial LC, DMFS, PFS, and OS. Results. 501 patients from 21 radiation oncology institutions with 846 gynecological metastases were analyzed, mainly ovarian (53.1%) and uterine metastases(32.1%).Multiple fraction radiotherapy was used in 762 metastases(90.1%).The most frequent schedule was 24 Gy in 3 fractions(13.4%). CR was observed in 538(63.7%) lesions. The Machine learning analysis showed a poor ability to find covariates strong enough to predict CR in the whole series. Analyzing them separately, in uterine cancer, if RT dose >= 78.3Gy, the CR probability was 75.4%; if volume was <13.7 cc, the CR probability became 85.1%. In ovarian cancer, if the lesion was a lymph node, the CR probability was 71.4%; if volume was <17 cc, the CR probability rose to 78.4%. No covariate predicted the CR for cervical lesions. The overall 2 -year actuarial LC was 79.2%, however it was 91.5% for CR and 52.5% for not CR lesions(p < 0.001). The overall 2 -year DMFS, PFS and OS rate were 27.3%, 24.8% and 71.0%, with significant differences between CR and not CR. Conclusions. CR was substantially associated to patient outcomes in our series of gynecological cancer oligometastatic lesions. The ability to predict a CR through artificial intelligence could also drive treatment choices in the context of personalized oncology. (c) 2024 Elsevier Inc. All rights reserved.

Methods and materials: Patients with ongoing or planned anticancer treatment at 19 Italian Radiation Oncology centers were included in the study retrospectively from 3 February 2020 to 31 December 2020 and prospectively from 1 January 2021 to 31 May 2021. Anonymized data were processed through a specific website and database. Antineoplastic treatment characteristics and timing and outcomes of COVID-19 and its impact on radiotherapy or systemic therapy were described. Results: The retrieved cohort included 41,039 patients that received treatment or were planned for therapy in the study period. Overall, 123 patients had a confirmed COVID-19 diagnosis during antineoplastic treatment (group A) and 99 patients before treatment start (group B). The incidence of COVID-19 across the whole cohort in the index period was 0.54% (groups A + B) and 0.30% considering only group A. A total of 60 patients developed severe COVID-19, and a total of 45 patients died as a consequence of the infection (incidence of 0.15% and 0.11%, respectively). Nonetheless, mortality among COVID-19 patients was high, with an attributable death rate after confirmed infection of 20.27%. Among the 123 patients in group A, 37.4% required temporary treatment suspension, 32.5% definitive suspension and 37 patients continued treatment while positive. As for the 99 patients in group B, 53.5% experienced temporary delay, 20.2% experienced definitive treatment suspension and 26.3% had no delay. Conclusions: Most of the patients with a COVID-19 diagnosis in our cohort recovered and completed their treatment; nonetheless, the attributable death rate after confirmed infection was 20.27%, and mortality was high among cancer patients with severe COVID-19 presentation. The global incidence of death due to COVID-19 or severe COVID-19 was low and decreased over time. Radiation oncology activity could be safely continued during the COVID-19 pandemic with the adoption of adequate preventive measures.

The present white paper, referring to the 4th Assisi Think Tank Meeting on breast cancer, reviews state-of-the-art data, on-going studies and research proposals. <70% agreement in an online questionnaire identified the following clinical challenges: 1: Nodal RT in patients who have a) 1-2 positive sentinel nodes without ALND (axillary lymph node dissection); b) cN1 disease transformed into ypN0 by primary systemic therapy and c) 1-3 positive nodes after mastectomy and ALND. 2. The optimal combination of RT and immunotherapy (IT), patient selection, IT-RT timing, and RT optimal dose, fractionation and target volume. Most experts agreed that RT-IT combination does not enhance toxicity. 3: Re-irradiation for local relapse converged on the use of partial breast irradiation after second breast conserving surgery. Hyperthermia aroused support but is not widely available. Further studies are required to finetune best practice, especially given the increasing use of re-irradiation.

Introduction: Senonetwork, an Italian no profit association, is committed in breast cancer care, to guarantee that all women have access to diagnostic and treatment pathways in compliance with the referring guidelines. The national discipline - related societies dedicated to breast cancer care and the advocacy are represented in Senonetwork scientific committee. Senonetwork has created a datawarehouse (Senonet) to collect Breast Centre data on a voluntary base and in return to issue for each participating Breast Centre a yearly data report towards Senonetwork quality indicators. Objectives: this paper aims at defining evidence-based quality indicators shared among the national discipline related societies dedicated to breast cancer care, to bring them to the attention of the regional and national authorities. Some of the Quality Indicators can be directly taken from the hospital discharge form, but this is not sufficient for a comprehensive evaluation of the different phases of breast cancer patients' diagnosis and treatment within a Breast Centre. Also in this regard, the collaboration among scientific societies and authorities is essential. Methods: to update and increase the set of quality indicators previously published, end 2020 Senonetwork set up a working group of experts and a revision committee including the scientific discipline-related societies represented in Senonetwork (AIOM, AIRO, ANISC, GISMa, SIAPEC-IAP, SICPRE, SIRM). For each quality indicator, based on literature and expert opinion, a minimum standard and a target have been defined. Conclusions: a set of quality indicators, defined by experts and aligned with the indications of the referring scientific societies, going through the different steps of breast cancer diagnosis and treatment, allows Breast Centres to have a complete and integrated vision of the performance reached by the multidisciplinary team. It also represents a help in improving quality of care through benchmarking, educational and research activities within a national network.

Even though systemic therapy is standard treatment for lymph node metastases, metastasis-directed stereotactic radiotherapy (SRT ) seems to be a valid option in oligometastatic patients with a low disease burden. Positron emission tomography-computed tomography (PET-CT ) is the gold standard for assessing metastases to the lymph nodes; co-registration of PET-CT images and planning CT images are the basis for gross tumor volume (GTV ) delineation. Appropriate techniques are needed to overcome target motion. SRT schedules depend on the irradiation site, target volume and dose constraints to the organs at risk (OARs) of toxicity. Although several fractionation schemes were reported, total doses of 48-60 Gy in 4-8 fractions were proposed for mediastinal lymph node SRT, with the spinal cord, esophagus, heart and proximal bronchial tree being the dose limiting OAR s. Total doses ranged from 30 to 45 Gy, with daily fractions of 7-12 Gy for abdominal lymph nodes, with dose limiting OARs being the liver, kidneys, bowel and bladder. SRT on lymph node metastases is safe; late side effects, particularly severe, are rare.

This paper focuses on the radiobiological mechanisms underlying the effects of stereotactic radiotherapy (SRT) which, despite SRT expansion, have not yet been fully elucidated. Some authors postulated that radiobiology principles, as applied to conventional fractionations (5R: reoxygenation, repair, repopulation, redistribution, radioresistence), suffice in themselves to account for the excellent clinical results of SRT; others argued that the role of the 5R was limited. Recent preclinical data showed that hypofractionated ablative treatments altered the microenvironment, thus determining cell death either directly or indirectly. Furthermore, dead tumor cells released quantities of antigens, which stimulated antitumor immunity, thus reducing the risk of relapse and metastasis. Better understanding of the radiobiological mechanisms underlying response to high-dose radiation treatment is essential for predicting its short- and long-term effects on the tumor and surrounding healthy tissues and, consequently, for improving its related therapeutic index.

Stereotactic radiotherapy (SRT) is a multi-step procedure with each step requiring extreme accuracy. Physician-dependent accuracy includes appropriate disease staging, multi-disciplinary discussion with shared decision-making, choice of morphological and functional imaging methods to identify and delineate the tumor target and organs at risk, an image-guided patient set-up, active or passive management of intra-fraction movement, clinical and instrumental follow-up. Medical physicist-dependent accuracy includes use of advanced software for treatment planning and more advanced Quality Assurance procedures than required for conventional radiotherapy. Consequently, all the professionals require appropriate training in skills for high-quality SRT. Thanks to the technological advances, SRT has moved from a "frame-based" technique, i.e. the use of stereotactic coordinates which are identified by means of rigid localization frames, to the modern "frame-less" SRT which localizes the target volume directly, or by means of anatomical surrogates or fiducial markers that have previously been placed within or near the target. This review describes all the SRT steps in depth, from target simulation and delineation procedures to treatment delivery and image-guided radiation therapy. Target movement assessment and management are also described.

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group. We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered. Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation). Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.