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Simple Summary: Breast cancer is the most common cancer in women worldwide, with a high prevalence and incidence, configuring an important issue in cancer epidemiology. Over the years, the combination of primary and secondary prevention programs and multidisciplinary treatment approaches has improved the overall survival (OS) and quality of life (QoL) of patients. However, although treatment pathways should be standardized in evidence-based medicine, clinical practice (real-world evidence) may differ from expected. To improve OS and QoL, having a clear picture of the Patterns of Care actually applied is essential. To this aim, Breast IRRADIATA (Italian Repository of RADIotherapy dATA), a collaborative nationwide project, was developed as a simple tool to probe the current pattern of radiotherapy care in Italy and tested in a feasibility study. This pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of pattern of care radiotherapy directed to other cancers. Aim. Breast IRRADIATA (Italian Repository of RADIotherapy dATA) is a collaborative nationwide project supported by the Italian Society of Radiotherapy and Clinical Oncology (AIRO) and the Italian League Against Cancer (LILT). It focuses on breast cancer (BC) patients treated with radiotherapy (RT) and was developed to create a national registry and define the patterns of care in Italy. A dedicated tool for data collection was created and pilot tested. The results of this feasibility study are reported here. Methods. To validate the applicability of a user-friendly data collection tool, a feasibility study involving 17 Italian Radiation Oncology Centers was conducted from July to October 2021, generating a data repository of 335 BC patients treated between January and March 2020, with a minimum follow-up time of 6 months. A snapshot of the clinical presentation, treatment modalities and radiotherapy toxicity in these patients was obtained. A Data Entry Survey and a Satisfaction Questionnaire were also sent to all participants. Results. All institutions completed the pilot study. Regarding the Data Entry survey, all questions achieved 100% of responses and no participant reported spending more than 10 min time for either the first data entry or for the updating of follow-up. Results from the Satisfaction Questionnaire revealed that the project was described as excellent by 14 centers (82.3%) and good by 3 (17.7%). Conclusion. Current knowledge for the treatment of high-prevalence diseases, such as BC, has evolved toward patient-centered medicine, evidence-based care and real-world evidence (RWE), which means evidence obtained from real-world data (RWD). To this aim, Breast IRRADIATA was developed as a simple tool to probe the current pattern of RT care in Italy. The pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of the pattern of care radiotherapy directed to other cancers. [ABSTRACT FROM AUTHOR]

This paper focuses on stereotactic radiotherapy (SRT) interactions with targeted therapies and immune system modulating agents because SRT inevitably interacts with them in the treatment of oligometastatic patients. Radiation oncologists need to be aware of the advantages and risks of these interactions which can, on one hand, enhance the effect of therapy or, on the other, potentiate reciprocal toxicities. To date, few prospective studies have evaluated the interactions of SRT with new-generation drugs and data are mainly based on retrospective experiences, which are often related to small sample sizes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Approximately 50% of melanomas, 30-40% of lung and breast cancers and 10-20% of renal and gastrointestinal tumors metastasize to the adrenal gland. Metastatic adrenal involvement is diagnosed by computed tomography (CT) with contrast medium, ultrasound (which does not explore the left adrenal gland well), magnetic resonance imaging (MRI) with contrast medium and 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18FDGPET -CT) which also evaluates lesion uptake. The simulation CT should be performed with contrast medium; an oral bolus of contrast medium is useful, given adrenal gland proximity to the duodenum. The simulation CT may be merged with PET -CT images with 18FDG in order to evaluate uptaking areas. In contouring, the radiologically visible and/or uptaking lesion provides the gross tumor volume (GTV). Appropriate techniques are needed to overcome target motion. Single fraction stereotactic radiotherapy (SRT) with median doses of 16-23 Gy is rarely used. More common are doses of 25-48 Gy in 3-10 fractions although 3 or 5 fractions are preferred. Local control at 1 and 2 years ranges from 44 to 100% and from 27 to 100%, respectively. The local control rate is as high as 90%, remaining stable during follow-up when BED10Gy is equal to or greater than 100 Gy. SRT -related toxicity is mild, consisting mainly of gastrointestinal disorders, local pain and fatigue. Adrenal insufficiency is rare. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

About 60-90% of cancer patients are estimated to develop bone metastases, particularly in the spine. Bone scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI) are currently used to assess metastatic bone disease; positron emission tomography/computed tomography (PET -CT) has become more widespread in clinical practice because of its high sensitivity and specificity with about 95% diagnostic accuracy. The most common and well-known radiotracer is 18F-fluorodeoxyglucose (18FDG); several other PET -radiotracers are currently under investigation for different solid tumors, such as 11C or 18FDG-choline and prostate specific membrane antigen (PSMA)-PET/CT for prostate cancer. In treatment planning, standard and investigational imaging modalities should be registered with the planning CT so as to best define the bone target volume. For target volume delineation of spine metastases, the International Spine Radiosurgery Consortium (ISRC) of North American experts provided consensus guidelines. Single fraction stereotactic radiotherapy (SRT) doses ranged from 12 to 24 Gy; fractionated SRT administered 21-27 Gy in 3 fractions or 20-35 Gy in 5 fractions. After spine SRT, less than 5% of patients experienced grade ≥ 3 acute toxicity. Late toxicity included the extremely rare radiation-induced myelopathy and a 14% risk of de novo vertebral compression fractures. [ABSTRACT FROM AUTHOR]

The liver is the first metastatic site in 15-25% of colorectal cancer patients and one of the first metastatic sites for lung and breast cancer patients. A computed tomography (CT) scan with contrast medium is a standard procedure for assessing liver lesions but magnetic resonance imaging (MRI) characterizes small lesions better thanks to its high soft-tissue contrast. Positron emission tomography with computed tomography (PET -CT) plays a complementary role in the diagnosis of liver metastases. Triphasic (arterial, venous and time-delayed) acquisition of contrast-medium CT images is the first step in treatment planning. Since the liver exhibits a relatively wide mobility due to respiratory movements and bowel filling, appropriate techniques are needed for target identification and motion management. Contouring requires precise recognition of target lesion edges. Information from contrast MRI and/or PET -CT is crucial as they best visualize metastatic disease in the parenchyma. Even though different fractionation schedules were reported, doses and fractionation schedules for liver stereotactic radiotherapy (SRT) have not yet been established. The best local control rates were obtained with BED10 values over 100 Gy. Local control rates from most retrospective studies, which were limited by short follow-ups and included different primary tumors with intrinsic heterogeneity, ranged from 60% to 90% at 1 and 2 years. The most common SRT -related toxicities are increases in liver enzymes, hyperbilirubinemia and hypoalbuminemia. Overall, late toxicity is mild even in long-term follow-ups. [ABSTRACT FROM AUTHOR]

30-60% of cancer patients develop lung metastases, mostly from primary tumors in the colon-rectum, lung, head and neck area, breast and kidney. Nowadays, stereotactic radiotherapy (SRT) is considered the ideal modality for treating pulmonary metastases. When lung metastases are suspected, complete disease staging includes a total body computed tomography (CT) and/or positron emission tomography-computed tomography (PET -CT) scan. PET -CT has higher specificity and sensitivity than a CT scan when investigating mediastinal lymph nodes, diagnosing a solitary lung lesion and detecting distant metastases. For treatment planning, a multi-detector planning CT scan of the entire chest is usually performed, with or without intravenous contrast media or esophageal lumen opacification, especially when central lesions have to be irradiated. Respiratory management is recommended in lung SRT, taking the breath cycle into account in planning and delivery. For contouring, co-registration and/or matching planning CT and diagnostic images (as provided by contrast enhanced CT or PET -CT) are useful, particularly for central tumors. Doses and fractionation schedules are heterogeneous, ranging from 33 to 60 Gy in 3-6 fractions. Independently of fractionation schedule, a BED10 > 100 Gy is recommended for high local control rates. Single fraction SRT (ranges 15-30 Gy) is occasionally administered, particularly for small lesions. SRT provides tumor control rates of up to 91% at 3 years, with limited toxicities. The present overview focuses on technical and clinical aspects related to treatment planning, dose constraints, outcome and toxicity of SRT for lung metastases. [ABSTRACT FROM AUTHOR]

Brain metastases, the most common metastases in adults, will develop in up to 40% of cancer patients, accounting for more than one-half of all intracranial tumors. They are most associated with breast and lung cancer, melanoma and, less frequently, colorectal and kidney carcinoma. Magnetic resonance imaging (MRI) is the gold standard for diagnosis. For the treatment plan, computed tomography (CT) images are co-registered and fused with a gadolinium-enhanced T1-weighted MRI where tumor volume and organs at risk are contoured. Alternatively, plain and contrast-enhanced CT scans are co-registered. Single-fraction stereotactic radiotherapy (SRT) is used to treat patients with good performance status and up to 4 lesions with a diameter of 30 mm or less that are distant from crucial brain function areas. Fractionated SRT (2-5 fractions) is used for larger lesions, in eloquent areas or in proximity to crucial or surgically inaccessible areas and to reduce treatment-related neurotoxicity. The single-fraction SRT dose, which depends on tumor diameter, impacts local control. Fractionated SRT may encompass different schedules. No randomized trial data compared the safety and efficacy of single and multiple fractions. Both single-fraction and fractionated SRT provide satisfactory local control rates, tolerance, a low risk of transient acute adverse events and of radiation necrosis the incidence of which correlated with the irradiated brain volume. [ABSTRACT FROM AUTHOR]

This paper describes how to select the most appropriate stereotactic radiotherapy (SRT) dose and fractionation scheme according to lesion size and site, organs at risk (OARs) proximity and the biological effective dose. In single-dose SRT, 15-34 Gy are generally used while in fractionated SRT 30 and 75 Gy in 2-5 fractions are administered. The ICRU Report No. 91, which is specifically dedicated to SRT treatments, provided indications for dose prescription (with its definition and essential steps), dose delivery and optimal coverage which was defined as the best planning target volume coverage that can be obtained in the irradiated district. Calculation algorithms and OAR s dose constraints are provided as well as treatment planning system characteristics, suggested beam energy and multileaf collimator leaf size. Finally, parameters for irradiation geometry and plan quality are also reported. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Sentinel lymph node biopsy (SLNB) is the gold standard in invasive breast cancer. Axillary dissection (ALND) is controversial in some presentations. Areas covered: Key questions were formulated and explored focused on four different scenarios in adjuvant axillary radiation management in early and locally advanced breast cancer. Answers to these questions were searched in MEDLINE, PubMed from June 1946 to August 2020. Clinical trials, retrospective studies, international guidelines, meta-analysis, and reviews were explored. Expert opinion: Analysis according to biological disease characteristics is necessary to establish the impact of ALND avoidance in unexpectedly positive SLNB (pN1) in cN0 patients. A low-risk probability of axillary recurrence was observed if axillary radiotherapy (ART) or ALND were offered without impact on outcomes. Adjuvant RNI in pT1-3 pN1 treated with mastectomy or BCS should be proposed in unfavorable disease and risk factors. In ycN0 after NACT, SLNB can be offered in selected cases or ALND should be performed. After SLNB post-NACT (ypN1), ALND and adjuvant radiotherapy are mandatory. [ABSTRACT FROM AUTHOR]

Aim: To investigate the actual attitude of Radiation Oncologists in the prescription of hormonal therapy in prostate cancer (PC) with or without Radiation Therapy (RT). Materials and methods: In 2019, a survey named Prescription of Radiation Oncologists ACtual Attitude including 18 items was sent to all Italian Radiation Oncologists of the Italian Association of Radiotherapy and Clinical Oncology. The first 4 items were about the Radiation Oncology Centers characteristics and years of practice of the respondents. The remaining 14 items concerned the setting in which hormone therapy was prescribed in PC patients (radical, postprostatectomy/oligometastatic state), the kind of drug, the choice modality (Multidisciplinary Group/autonomy decision) and other factors. Results: A total of 127 questionnaires were returned, mainly by Northern Italy Radiation Oncology Centres (44.9%), and by experienced Radiation Oncologists (78%), who declared to prescribe independently hormone therapy in 85.8% of cases. The Androgen deprivation therapy (ADT) prescription in castration naive PC was made independently by 56.7% of respondents and associated with radical RT, postoperative or salvage RT according to various risk factors. In castration-sensitive oligorecurrent PC, the majority (51.2%) administered ADT only if local ablative treatment was not feasible, while in metastatic castration resistant disease novel hormone therapy use was established in almost half of cases within multidisciplinary board. Radiation Oncologists could prescribe these drugs independently in 64% of cases. Conclusion: Our survey established the prescription attitude of ADT and new hormonal agents (abiraterone, enzalutamide, apalutamide) by Italian Radiation Oncologists and highlighted the importance of expertise in global PC management. [ABSTRACT FROM AUTHOR]

Background: Recent studies have reported improvement of outcomes (progression‐free survival, overall survival, and prolongation of androgen deprivation treatment‐free survival) with stereotactic body radiotherapy (SBRT) in non‐small cell lung cancer and prostate cancer. The aim of this retrospective, multicenter study (MITO RT‐01) was to define activity and safety of SBRT in a very large, real‐world data set of patients with metastatic, persistent, and recurrent ovarian cancer (MPR‐OC). Materials and Methods: The endpoints of the study were the rate of complete response (CR) to SBRT and the 24‐month actuarial local control (LC) rate on "per‐lesion" basis. The secondary endpoints were acute and late toxicities and the 24‐month actuarial late toxicity‐free survival. Objective response rate (ORR) included CR and partial response (PR). Clinical benefit (CB) included ORR and stable disease (SD). Toxicity was evaluated by the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) and Common Terminology Criteria for Adverse Events (CTCAE) scales, according to center policy. Logistic and Cox regression were used for the uni‐ and multivariate analysis of factors predicting clinical CR and actuarial outcomes. Results: CR, PR, and SD were observed in 291 (65.2%), 106 (23.8%), and 33 (7.4%) lesions, giving a rate of CB of 96.4%. Patient aged ≤60 years, planning target volume (PTV) ≤18 cm3, lymph node disease, and biologically effective dose α/β10 > 70 Gy were associated with higher chance of CR in the multivariate analysis. With a median follow‐up of 22 months (range, 3–120), the 24‐month actuarial LC rate was 81.9%. Achievement of CR and total dose >25 Gy were associated with better LC rate in the multivariate analysis. Mild toxicity was experienced in 54 (20.7%) patients; of 63 side effects, 48 were grade 1, and 15 were grade 2. The 24‐month late toxicity‐free survival rate was 95.1%. Conclusions: This study confirms the activity and safety of SBRT in patients with MPR‐OC and identifies clinical and treatment parameters able to predict CR and LC rate. Implications for Practice: This study aimed to define activity and safety of stereotactic body radiotherapy (SBRT) in a very large, real life data set of patients with metastatic, persistent, recurrent ovarian cancer (MPR‐OC). Patient age <60 years, PTV <18 cm3, lymph node disease, and biologically effective dose α/β10 >70 Gy were associated with higher chance of complete response (CR). Achievement of CR and total dose >25 Gy were associated with better local control (LC) rate. Mild toxicity was experienced in 20.7% of patients. In conclusion, this study confirms the activity and safety of SBRT in MPR‐OC patients and identifies clinical and treatment parameters able to predict CR and LC rate. Traditional management of recurrent ovarian cancer is system chemotherapy. This article considers an alternative, focusing on the activity and safety of stereotactic body radiotherapy for patients with ovarian cancer. [ABSTRACT FROM AUTHOR]

Writing a scientific article and being able to get it published in an important journal is the last step before considering your study project completed. Scientific publications have a well-defined structure, aimed at greater communication efficiency. Whoever is preparing a paper to be published must therefore know these rules in order to get accepted his article. The aim of this review is therefore to provide authors with practical advice on how to prepare the manuscript. Ethical aspects which are a precise responsibility of the authors, reviewers and publisher, and which concern the entire publication process are also considered. At the same time, we give to readers the keys to assess the quality of a publication. The review is structured into three parts: preparation of an article, how to write the various types of articles and finally the path from sending to the magazine to the publication. [ABSTRACT FROM AUTHOR]

Aim: To translate the Xerostomia Quality-of-Life Scale (XeQoLS) into Italian language (XeQoLS-IT). Xerostomia is the most relevant acute and late toxicity in patients with head and neck cancer treated with radiotherapy (RT). Patient-reported outcome (PRO) instruments are subjective report on patient perception of health status. The XeQoLS consists of 15 items and measures the impact of salivary gland dysfunction and xerostomia on the four major domains of oral health-related QoL. Methods: The XeQoLS-IT was created through a linguistic validation multi-step process: forward translation (TF), backward translation (TB) and administration of the questionnaire to 35 Italian patients with head and neck cancer. Translation was independently carried out by two radiation oncologists who were Italian native speakers. The two versions were compared and adapted to obtain a reconciled version, version 1 (V1). V1 was translated back into English by an Italian pro skilled in teaching English. After review of discrepancies and choice of the most appropriate wording for clarity and similarity to the original, version 2 (V2) was reached by consensus. To evaluate version 2, patients completed the XeQoLS-IT questionnaire and also underwent a cognitive debriefing. Results: The questionnaire was considered simple by the patients. The clarity of the instructions and the easiness to answer questions had a mean value of 4.5 (± 0.71) on a scale from 1 to 5. Conclusion: A valid multi-step process led to the creation of the final version of the XeQoLS-IT, a suitable instrument for the perception of xerostomia in patients treated with RT. [ABSTRACT FROM AUTHOR]

The efficacy of postoperative radiotherapy (RT) in the treatment of early-stage endometrial carcinoma (EC) is still under debate. This study was aimed to review the outcome and adverse effects in patients treated for EC with postoperative RT at a single center.A total of 883 patients with pathological stages I to II EC were retrospectively analyzed. Surgery consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy, or vaginal hysteroannessiectomy in 532 patients (60.2%) with pelvic lymphadenectomy in 351 patients (39.8%). Seven hundred forty-seven patients (84.6%) underwent whole pelvic RT (WPRT) and 136 (15.4%) combined WPRT and vaginal brachytherapy (BT) boost.At a median follow-up of 9 years (range, 1.2-27.6 years), we observed 10.6% disease relapse. Forty-seven patients experienced local recurrence (LR), and 38 patients experienced distant metastases (DMs). At univariate analysis, age at diagnosis (P < 0.0001), stage (P < 0.04), and histological subtype (P < 0.0001) resulted in significant prognostic factors. At multivariate analysis, histotype emerged as an independent relapse predictor (P = 0.0001). Acute WPRT-related toxicity was mild; diarrhea was the most common adverse effect (19.8%). We recorded long-term adverse effects in 7.8% of the patients.Our study showed that patients with early-stage EC have a good outcome in overall survival and disease-free survival. In our experience, standard surgery (including hysterectomy and bilateral salpingo-oophorectomy followed by WPRT with or without BT) showed an acceptable toxicity profile. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the relationship between a delay in radiotherapy (RT) after breast-conserving surgery and ipsilateral breast recurrence (BR). Methods and Materials: We included in our analysis 4,820 breast cancer patients who had undergone postoperative RT at the University of Florence. The patients were categorized into four groups according to the interval between surgery and RT (T1, <60 days; T2, 61–120 days; T3, 121–180 days; and T4, >180 days). Results: On multivariate analysis, the timing of RT did not reach statistical significance in patients who received only postoperative RT (n = 1,935) or RT and hormonal therapy (HT) (n = 1,684) or RT, chemotherapy (CHT), and HT (n = 529). In the postoperative RT-only group, age at presentation, surgical margin status, and a boost to the tumor bed were independent prognostic factors for BR. In the RT plus HT group, age at presentation and boost emerged as independent prognostic factors for BR (p = 0.006 and p = 0.049, respectively). Finally, in the RT, CHT, and HT group, only multifocality was an independent BR predictor (p = 0.01). Only in the group of patients treated with RT and CHT (n = 672) did multivariate analysis with stepwise selection show RT timing as an independent prognostic factor (hazard ratio, 1.59; 95% confidence interval, 1.01–2.52; p = 0.045). Analyzing this group of patients, we found that most patients included had worse prognostic factors and had received CHT consisting of cyclophosphamide, methotrexate, and 5-fluorouracil before undergoing RT. Conclusion: The results of our study have shown that the timing of RT itself does not affect local recurrence, which is mainly related to prognostic factors. Thus, the “waiting list” should be thought of as a “programming list,” with patients scheduled for RT according to their prognostic factors. [Copyright &y& Elsevier]

Simple Summary: This is a safety and efficacy analysis from a very large dataset of patients affected by localized prostate cancer having received radiotherapy with or without concomitant androgen deprivation therapy in twelve academic and non-academic Italian Institutions. The aim of this retrospective "real life" study was to provide additional data on clinical presentation, diagnostic workup, radiation therapy management and toxicity as collected within the framework of POP III. Though the usual limitations for a retrospective analysis apply, it nevertheless may expand the current knowledge in this area showing the progress of radiation therapy techniques and clinical outcomes in the period between 2004 and 2011 after a significant period of follow up. Background and purpose: Two previous "Patterns Of Practice" surveys (POP I and POP II), including more than 4000 patients affected by prostate cancer treated with radical external beam radiotherapy (EBRT) between 1980 and 2003, established a "benchmark" Italian data source for prostate cancer radiotherapy. This report (POP III) updates the previous studies. Methods: Data on clinical management and outcome of 2525 prostate cancer patients treated by EBRT from 2004 to 2011 were collected and compared with POP II and, when feasible, also with POP I. This report provides data on clinical presentation, diagnostic workup, radiation therapy management, and toxicity as collected within the framework of POP III. Results: More than 50% of POP III patients were classified as low or intermediate risk using D'Amico risk categories as in POP II; 46% were classified as ISUP grade group 1. CT scan, bone scan, and endorectal ultrasound were less frequently prescribed. Dose-escalated radiotherapy (RT), intensity modulated radiotherapy (IMRT), image guided radiotherapy (IGRT), and hypofractionated RT were more frequently offered during the study period. Treatment was commonly well tolerated. Acute toxicity improved compared to the previous series; late toxicity was influenced by prescribed dose and treatment technique. Five-year overall survival, biochemical relapse free survival (BRFS), and disease specific survival were similar to those of the previous series (POP II). BRFS was better in intermediate- and high-risk patients treated with ≥ 76 Gy. Conclusions: This report highlights the improvements in radiotherapy planning and dose delivery among Italian Centers in the 2004–2011 period. Dose-escalated treatments resulted in better biochemical control with a reduction in acute toxicity and higher but acceptable late toxicity, as not yet comprehensively associated with IMRT/IGRT. CTV-PTV margins >8 mm were associated with increased toxicity, again suggesting that IGRT—allowing for tighter margins—would reduce toxicity for dose escalated RT. These conclusions confirm the data obtained from randomized controlled studies. [ABSTRACT FROM AUTHOR]

Radionecrosis (RN) is the most important side effect after stereotactic radiotherapy (SRT) for brain metastases, with a reported incidence ranging from 3% to 24%. To date, there are no unanimously accepted criteria for iconographic diagnosis of RN, as well as no definitive dose-constraints correlated with the onset of this late effect. We reviewed the current literature and gave an overview report on imaging options for the diagnosis of RN and on dosimetric parameters correlated with the onset of RN. We performed a PubMed literature search according to the preferred reporting items and meta-analysis (PRISMA) guidelines, and identified articles published within the last ten years, up to 31 December 2019. When analyzing data on diagnostic tools, perfusion magnetic resonance imaging (MRI) seems to be very useful allowing evaluation of the blood flow in the lesion using the relative cerebral blood volume (rCBV) and blood vessel integrity using relative peak weight (rPH). It is necessary to combine morphological with functional imaging in order to match information about lesion morphology, metabolism and blood-flow. Eventually, serial imaging follow-up is needed. Regarding dosimetric parameters, in radiosurgery (SRS) V12 < 8 cm3 and V10 < 10.5 cm3 of normal brain are the most reliable prognostic factors, whereas in hypo-fractionated stereotactic radiotherapy (HSRT) V18 and V21 are considered the main predictive independent risk factors of RN. [ABSTRACT FROM AUTHOR]

Purpose: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. Patients and Methods: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and 5-fluorouracil 600 mg/m2) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46–52 Gy) with standard fractionation. The boost dose was 6–16 Gy according to resection margins and at the discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. Results: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). Conclusions: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity. [Copyright &y& Elsevier]

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.

Objectives: The prognosis of brain metastatic colorectal cancer patients (BMCRC) is poor. Several local treatments have been used, but the optimal treatment choice remains an unresolved issue. We evaluated the clinical outcomes of a large series of BMCRC patients treated in several Italian centers using stereotactic radiosurgery (SRS)., Methods: 185 BMCRC patients for a total of 262 lesions treated were evaluated. Treatments included surgery followed by post-operative SRS to the resection cavity, and SRS, either single-fraction, then hypofractionated SRS (HSRS). Outcomes was measured in terms of local control (LC), toxicities, brain distant failure (BDF), and overall survival (OS). Prognostic factors influencing survival were assed too., Results: The median follow-up time was 33 months (range 3-183 months). Surgery plus SRS have been performed in 28 (10.7%) cases, SRS in 141 (53.8%), and HSRS in 93 (35.5%). 77 (41.6%) patients received systemic therapy. The main total dose and fractionation used were 24 Gy in single fraction or 24 Gy in three daily fractions. Local recurrence occurred in 32 (17.3%) patients. Median, 6 months,1-year-LC were 86 months (95%CI 36-86), 87.2% ± 2.8, 77.8% ± 4.1. Median,6 months,1-year-BDF were 23 months (95%CI 9-44), 66.4% ± 3.9, 55.3% ± 4.5. Median,6 months,1-year-OS were 7 months (95% CI 6-9), 52.7% ± 3.6, 33% ± 3.5. No severe neurological toxicity occurred. Stage at diagnosis, Karnofsky Performance Status (KPS), presence and number of extracranial metastases, and disease-specific-graded-prognostic-assessment (DS-GPA) score were observed as conditioning survival., Conclusion: SRS/HSRS have proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors as well as a multidisciplinary evaluation is a valid aid to manage the optimal therapeutic strategy for CTC patients with BMs., Advances in Knowledge: The prognosis of BMCRC is poor. Several local treatments was used, but optimal treatment choice remains undefined. Radiosurgery has proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors and a multidisciplinary evaluation needed.

Background/aim: This multicenter, retrospective, 'field-practice' study investigated treatment outcomes of ongoing abiraterone therapy with the addition of radiotherapy (RT) - initiated for oligoprogression or with a palliative intent., Patients and Methods: Consecutive patients affected by metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate were considered if they had received RT after the initiation of abiraterone treatment., Results: A total of 32 patients were enrolled in the study. Median duration of abiraterone treatment was 13.0 months (range=3.8-40.9 months). Median duration of abiraterone treatment before RT was 5.9 months (range=0.4-40.0 months), and 7.2 months after RT (range=0.1-29.7 months). Median progression-free survival (PFS) was 12.6 months (95%CI=10.5-14.7) from the initiation of abiraterone treatment. From RT administration, PFS was 9.6 months (95%CI=6.4-12.9). Median overall survival (OS) since abiraterone initiation was 18.9 months (95%CI=4.7-33.0)., Conclusion: RT prolongs abiraterone treatment in mCRPC patients leading to better clinical outcomes with this molecule., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aims and Background: In 2002, a survey including 1759 patients treated from 1980 to 1998 established a "benchmark" Italian data source for prostate cancer radiotherapy. This report updates the previous one., Methods: Data on clinical management and outcomes of 3001 patients treated in 15 centers from 1999 through 2003 were analyzed and compared with those of the previous survey., Results: Significant differences in clinical management (-10% had abdominal magnetic resonance imaging; +26% received ≥70 Gy, +48% conformal radiotherapy, -20% pelvic radiotherapy) and in G3-4 toxicity rates (-3.8%) were recorded. Actuarial 5-year overall, disease-specific, clinical relapse-free, and biochemical relapse-free survival rates were 88%, 96%, 96% and 88%, respectively. At multivariate analysis, D'Amico risk categories significantly impacted on all the outcomes; higher radiotherapy doses were significantly related with better overall survival rates, and a similar trend was evident for disease-specific and biochemical relapse-free survival; cumulative probability of 5-year late G1-4 toxicity was 24.8% and was significantly related to higher radiotherapy doses (P <0.001)., Conclusions: The changing patterns of practice described seem related to an improvement in efficacy and safety of radiotherapy for prostate cancer. However, the impact of the new radiotherapy techniques should be prospectively evaluated.

Aims and Background: Uterine serous cancer is associated with a poor outcome and poses a therapeutic challenge. We retrospectively evaluated the experience of the Radiotherapy Department of the University of Florence., Methods: Forty-three patients with stage I-III uterine serous cancer underwent surgery with (18 patients, group 1) or without complete surgical staging (25 patients, group 2) followed by adjuvant whole pelvic radiotherapy alone or combined with vaginal brachytherapy (in 35 and 8 cases, respectively). The median dose delivered with whole pelvic radiotherapy was 50 Gy (range, 45-56) and for brachytherapy was 20 Gy (range, 20-30)., Results: Actuarial overall survival and disease-free survival rates at 5 years were 62.5% and 61%, respectively. Local failure was observed in 17 patients (39.5%) and distant metastasis in 10 (23.2%). Nine patients had both local failure and distant metastasis, which had developed concurrently in 7 cases. Isolated abdominal failure occurred in 4 cases (9.3%). Local relapse was noted in 22.2% of patients in group 1 compared to 52% in group 2. A trend towards a better 5-year overall survival (67.2% vs 58%), disease-free survival (63% vs 59%) and local control (70% vs 59%) was observed in group 1 than group 2, although the difference between the two groups failed to reach statistical significance., Conclusions: Given the patterns of failure of patients with uterine serous cancer, adjuvant whole pelvic radiotherapy may be a reasonable approach, although novel integrated strategies are needed because the results achieved remain disappointing. Adjuvant whole pelvic radiotherapy might improve overall survival, disease-free survival and local control in complete surgically staged patients, but further investigations are required.

To evaluate efficacy and safety of fotemustine chemotherapy in temozolomide (TMZ) pretreated adults with recurrent glioblastoma multiforme (GBM). Primary endpoint was progression-free survival at 6 months. Twenty-seven patients (median age: 56 years; median Karnofsky performance status at progression: 80) with relapsed glioblastoma multiforme underwent fotemustine as second-line chemotherapy after failure of homogeneous postoperative treatment consisting of conformal radiotherapy (60 Gy in 30 fractions) with concomitant TMZ (75 mg/m2 per day), followed by six courses of TMZ (150-200 mg/m2 for 5 days every 28 days). Patients were assigned to Radiation Therapy Oncology Group recursive partitioning analysis classes for gliomas. After MRI-proven tumor relapse or progression, all patients underwent chemotherapy with fotemustine, given intravenously 100 mg/m2 every week for 3 consecutive weeks (induction phase) and then every 3 weeks (maintenance phase). Adequate liver, renal, and bone marrow functions were required. Toxicity grading was based on the National Cancer Institute's Common Toxicity Criteria (version 2.0). Response to treatment was assessed on MacDonald criteria. According to an intention-to-treat-analysis, data on all enrolled patients were included in statistical analysis. Eight partial responses (29.6%) and five cases of stable disease (18.5%) were observed. Median time to progression was 5.7 months. Progression-free survival at 6 months was 48.15%. Median survival from the beginning of fotemustine chemotherapy was 9.1 months. Median survival from diagnosis of glioblastoma was 21.2 months. Toxicity was manageable and mainly hematological (grade 3 thrombocytopenia: three cases; grade 4 leukopenia: one case). Fotemustine has shown therapeutic efficacy as single-drug second-line chemotherapy in treatment of TMZ pretreated patients.

In order to downstage locally advanced breast cancer, neoadjuvant chemotherapy consisting of intravenous vinorelbine 25 mg/m plus epirubicin 75 mg/m given on day 1 and oral vinorelbine 60 mg/m on day 8 was administered every 3 weeks for four courses. On day 2, all patients received a single subcutaneous injection of pegfilgrastim (6 mg). From March 2004 to June 2005, 22 patients were enrolled. Patients characteristics were: median age, 53 years (range: 39-70 years); postmenopausal, 7/22; clinical TNM stage, T2 (n=14), T3 (n=8), N0 (n=17) and N1 (n=5). The median number of courses was four (range: two to six courses) with full dose intensity. National Cancer Institute grade 3 haematological toxicities observed were neutropenia in 9% of patients, anaemia in 13% of patients and thrombocytopenia in 9% of patients; no toxicity grade 4 occurred. Two patients (9%) registered grade 2 polyneuropathy; no cardiac failure was observed. Conservative surgery was performed in 14 patients (63%). All patients were evaluable for response: complete pathological response was documented in three patients (13.6%); three patients (13.6%) obtained more than 75% of tumour size reduction; 11 other patients (50%) had 50% of tumour size reduction; stable disease was observed in five patients (22.7%). The present findings indicate that vinorelbine in combination with epirubicin is an effective and safe treatment in locally advanced breast cancer: this regimen obtained more than 50% of tumour size reduction in 77% of patients; the use of pegfilgrastim allowed full dose intensity. Oral vinorelbine on day 8 offers greater convenience to the patient by reducing the need for intravenous injection and the time spent in hospital.