Purpose: Bone metastases frequently occur during malignant disease. Palliative radiation therapy (PRT) is a crucial part of palliative care because it can relieve pain and improve patients’ quality of life. Often, a clinician's survival estimation is too optimistic. Prognostic scores (PSs) can help clinicians tailor PRT indications to avoid over- or undertreatment. Although the PS is supposed to aid radiation oncologists (ROs) in palliative-care scenarios, it is unclear what type of support, and to what extent, could impact daily clinical practice. Methods and Materials: A national-based investigation of the prescriptive decisions on simulated clinical cases was performed in Italy. Nine clinical cases from real-world clinical practice were selected for this study. Each case description contained complete information regarding the parameters defining the prognosis class according to the PS (in particular, the Mizumoto Prognostic Score, a validated PS available in literature and already applied in some clinical trials). Each case description contained complete information regarding the parameters defining the prognosis class according to the PS. ROs were interviewed through questionnaires, each comprising the same 3 questions per clinical case, asking (1) the prescription after detailing the clinical case features but not the PS prognostic class definition; (2) whether the RO wanted to change the prescription once the PS prognostic class definition was revealed; and (3) in case of a change of the prescription, a new prescriptive option. Three RO categories were defined: dedicated to PRT (RO-d), nondedicated to PRT (RO-nd), and resident in training (IT). Interviewed ROs were distributed among different regions of the country. Results: Conversion rates, agreements, and prescription trends were investigated. The PS determined a statistically significant 11.12% of prescription conversion among ROs. The conversion was higher for the residents and significantly higher for worse prognostic scenario subgroups, respectively. The PS improved prescriptive agreement among ROs (particularly for worse-prognostic-scenario subgroups). Moreover, PS significantly increased standard prescriptive approaches (particularly for worse-clinical-case presentations). Conclusions: To the best of our knowledge, the PROPHET study is the first to directly evaluate the potential clinical consequences of the regular application of any PS. According to the Prophet study, a prognostic score should be integrated into the clinical practice of palliative radiation therapy for bone metastasis and training programs in radiation oncology.

Objective: To describe the rationale and the technique summarizing the most recent and relevant results reported in the scientific literature on stereotactic radiotherapy for pulmonary metastases.Background: Stereotactic body radiation therapy (SBRT) is a radiation therapy technique that delivers a high dose of radiation very precisely to an extracranial target, using either a single dose or a small number of fractions.The lung is the main site of metastatic spread for most solid tumors and local treatments have an emerging role, especially in oligometastatic patients.SBRT requires a coordinated team effort between radiation oncologists, medical physicists, radiation therapists and nurses.With this review, we present and analyze the most recent data in terms of clinical results and toxicity that also in the absence of phase III randomized trial allow to reach clinically relevant findings on the cost-benefit balance of stereotactic radiotherapy of lung metastasis (LM). Methods:In this review, we analyzed the literature data of the last ten years on patients treated with SBRT for lung oligometastasis.We found a number of non-randomized retrospective studies heterogeneous in terms of primary tumour, number of lesions and techniques.Conclusions: All authors conclude that SBRT represents an effective, safe option, with a low toxicity profile, which improves local control of the disease and the overall survival (OS) of patients with lung metastases.These characteristics together with the convenience of the few treatment sessions make it an excellent alternative to other more invasive therapy.Future randomized studies will enable people to better define the most appropriate dose and fractionation, the most suitable patients in terms of histology of the primary tumors and the best integration with systemic therapies.

INTRODUCTION:The COVID-19 pandemic has challenged healthcare systems worldwide over the last few months, and it continues to do so. Although some restrictions are being removed, it is not certain when the pandemic is going to be definitively over. Pandemics can be seen as a highly complex logistic scenario. From this perspective, some of the indications provided for palliative radiotherapy (PRT) during the COVID-19 pandemic could be maintained in the future in settings that limit the possibility of patients achieving symptom relief by radiotherapy. This paper has two aims: (1) to provide a summary of the indications for PRT during the COVID-19 pandemic; since some indications can differ slightly, and to avoid any possible contradictions, an expert panel composed of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) and the Palliative Care and Supportive Therapies Working Group (AIRO-palliative) voted by consensus on the summary; (2) to introduce a clinical care model for PRT [endorsed by AIRO and by a spontaneous Italian collaborative network for PRT named "La Rete del Sollievo" ("The Net of Relief")]. The proposed model, denoted "No cOmpRoMise on quality of life by pALliative radiotherapy" (NORMALITY), is based on an AIRO-palliative consensus-based list of clinical indications for PRT and on practical suggestions regarding the management of patients potentially suitable for PRT but dealing with highly complex logistics scenarios (similar to the ongoing logistics limits due to COVID-19).MATERIAL AND METHODS:First, a summary of the available literature guidelines for PRT published during the COVID-19 pandemic was prepared. A systematic literature search based on the PRISMA approach was performed to retrieve the available literature reporting guideline indications fully or partially focused on PRT. Tables reporting each addressed clinical presentation and respective literature indications were prepared and distributed into two main groups: palliative emergencies and palliative non-emergencies. These summaries were voted in by consensus by selected members of the AIRO and AIRO-palliative panels. Second, based on the summary for palliative indications during the COVID-19 pandemic, a clinical care model to facilitate recruitment and delivery of PRT to patients in complex logistic scenarios was proposed. The summary tables were critically integrated and shuffled according to clinical presentations and then voted on in a second consensus round. Along with the adapted guideline indications, some methods of performing the first triage of patients and facilitating a teleconsultation preliminary to the first in-person visit were developed.RESULTS:After the revision of 161 documents, 13 papers were selected for analysis. From the papers, 19 clinical presentation items were collected; in total, 61 question items were extracted and voted on (i.e., for each presentation, more than one indication was provided from the literature). Two tables summarizing the PRT indications during the COVID-19 pandemic available from the literature (PRT COVID-19 summary tables) were developed: palliative emergencies and palliative non-emergencies. The consensus of the vote by the AIRO panel for the PRT COVID-19 summary was reached. The PRT COVID-19 summary tables for palliative emergencies and palliative non-emergencies were adapted for clinical presentations possibly associated with patients in complex clinical scenarios other than the COVID-19 pandemic. The two new indication tables (i.e., "Normality model of PRT indications") for both palliative emergencies and palliative non-emergencies were voted on in a second consensus round. The consensus rate was reached and strong. Written forms facilitating two levels of teleconsultation (triage and remote visits) were also developed, both in English and in Italian, to evaluate the patients for possible indications for PRT before scheduling clinical visits.CONCLUSION:We provide a comprehensive summary of the literature guideline indications for PRT during COVID-19 pandemic. We also propose a clinical care model including clinical indications and written forms facilitating two levels of teleconsultation (triage and remote visits) to evaluate the patients for indications of PRT before scheduling clinical visits. The normality model could facilitate the provision of PRT to patients in future complex logistic scenarios.

PURPOSE: To evaluate feasibility and efficacy of Stereotactic Body Radiation Therapy (SBRT) for unresectable liver metastasis in oligometastatic patients. METHODS: Oligometastatic patients with up to three liver metastases of a maximum diameter of 6 cm were treated with SBRT. Total dose was 75 Gy in three consecutive fractions. Study endpoints were efficacy of this fractionation in terms of local control (LC), overall survival (OS), toxicity, and prognostic factors affecting OS and LC. RESULTS: Between February 2010 and December 2016, we enrolled 202 patients, with a total of 268 unresectable liver metastases. Median follow-up time from SBRT was 33 months (5-87 months). One-, 3‑, and 5‑year LC rates were 92%, 84%, and 84%, respectively. In univariate analysis, the primary histology and previous local ablative therapies were significant. Median OS was 21 months and the survival rates were 79%, 27%, and 15% at 1, 3, and 5 years after SBRT, respectively. At univariate analysis, sex, primary disease histology, intra-, and extra-hepatic progression were significant prognostic factors. This analysis confirmed the absence of late toxicity >G3. CONCLUSION: This study confirms the efficacy and safety of SBRT for unresectable liver metastases. Selection of cases may improve survival and LC.

Purpose The aim of the present study was to provide predictive factors for survival outcomes of oligometastatic prostate cancer (PC) patients treated with stereotactic body radiation therapy (SBRT) as a metastases-directed therapy (MDT). Methods In this cohort study, endpoints included overall survival (OS), progression-free survival (PFS), distant progression-free survival (DFS) and local control of treated metastases (LC). The binary classification tree approach with recursive partitioning analysis (RPA) was applied to stratify the patients into risk groups based on OS, PFS and DPFS; for each endpoint, disease-free interval (DFI) was calculated. We included patients with synchronous or metachronous metastases from prostate adenocarcinoma treated with SBRT. Results 119 Metastases were treated with SBRT in 92 patients. Median follow-up was 22.2 months. Rates of OS at 1 and 3 years were 96.9% and 88.0%, while DPFS was 51.9% and 20.9%. Recursive partitioning analysis identified three prognostic classes for OS: Class 1: castration-sensitive patients (3 years OS 95%); Class 2: castration-resistant patients with low-intermediate risk NCCN disease (3 years OS 88.8%); Class 3: castration-resistant patients with high-risk NCCN disease (3 years OS 76.9%). Regarding DPFS, RPA divided patients into two classes, according to a cutoff value of DFI of 34 months (3 years PFS of 28.7% vs 5.8%). Three classes were identified for DPFS: Class 1: DFI < 34 months (3 years DPFS 9.1%); Class 2: DFI > 34 months and high-risk NCCN PC (3 years DPFS 21%); Class 3: DFI > 34 months and low-intermediate risk NCCN disease (3 years DPFS 60.2%). Conclusion Oligometastatic PC represents nowadays a setting of particular interest in which local ablative therapies play a decisive role. In the present study, we recognized the importance of DFI, together with NCCN class risk, to predict the risk of new metastases after SBRT in oligometastatic PC.

Purpose or ObjectiveThe re-irradiation of locally recurrent rectal cancer presents challenges due to the proximity of critical organs such as bowel.Ion beam therapy, specifically carbon ions radiotherapy (CIRT) have some advantages for the favorable relative biological effectiveness and physical dose distribution providing a highly conformal dose distribution while minimizing normal tissue damage.The aim of this study is to report our experience on feasibility and toxicity of carbon-ion radiotherapy (CIRT) in previously irradiated patients with locally recurrent rectal cancer. Material and MethodsBetween August 2014 and February 2017, a total of 10 patients (M:F= 8:2) were treated with CIRT as reirradiation for locally recurrent rectal cancer at National Centre of Oncological Hadrontherapy (CNAO).Patient ages ranged between 46 to 78 years (median 58.5 years).All patients had a history of surgery and pelvic radiotherapy.Specifically, the dose of previous radiotherapy ranged from 45 to 50.4 Gy in 9 patients one of which received a brachytherapy boost up to a total dose of 20Gy.One patient was irradiated with a total dose of 76 Gy for a prostatic cancer.One patient, at time of the first recurrence, underwent to re-irradiation with stereotactic radiotherapy (30 Gy in 6 fractions).They had 7 presacral, 1 perineal, 1 perianal and 1 pre-coccygeal relapses.Three patients received spacer implantation prior to CIRT to secure adequate distance between bowel and tumor.Toxicity was scored according CTCAE 4.0 scale. ResultsThe median interval between the two courses of radiotherapy was 89.3 months (range: 13.8 -138.2).Median total dose of CIRT was 60 GyRBE (range: 35-76.8)and was administered in a median number of 16 fractions (range: 15-20) over 4 weeks (from 3 to 4.8 Gy RBE/fraction).The GTV ranged from 7.21 to 300.8 cm 3 with a median of 28.42 cm 3 .The PTV ranged from 53.55 to 742.64 cm 3 .All patients completed the scheduled treatment course.Median follow-up was 13 months.Acute toxicity was mild and mainly neuropathic: grade 2 (G2) neuropathic pain in 1 (10%) and G1 in 2 (20%) patients.The major late toxicities were peripheral neuropathy (20%, G2).No G≥3 acute/late reaction nor pelvic infections were observed.Four patients were diagnosed with local progression after carbon ion radiotherapy with a median disease free survival of 11.4 months (range: 2.4-39.7).Three patients experienced systemic progression.The estimated 1-year-local control rate was 80%. ConclusionIn our experience, CIRT for locally recurrent rectal cancer appears to be safe and effective with an acceptable rate of morbidity of normal tissue.More data and longer follow-up are required to investigate the long-term disease control and to determine late effects.

Background and purpose: Colorectal cancer (CRC) represents one of the major leading causes of death from cancer. Aim of the present study was to analyze outcome of oligometastatic CRC patients treated with stereotactic body radiation therapy (SBRT), and to evaluate predictive factors of survival. Materials and methods: We included patients with maximum 5 metastases. Previous/concomitant systemic treatments were allowed. End points of the present study were the outcome in terms of Local control of treated metastases (LC), progression free survival (PFS), and overall survival (OS). Results: 437 metastases were treated in 270 patients. Lung was site of metastases in 48.5% of cases, followed by liver (36.4%). Systemic treatment was administered before SBRT in 199 patients (73.7%). Median follow-up time was 23 months (3-98.7). Rates of LC at 1, 3 and 5 years were 95%, 73% and 73%, respectively. Time from diagnosis of metastases to SBRT was the only factor predictive of LC (HR 1.62, p = 0.023). Median PFS was 8.6 months. Rates of OS at 1, 3 and 5 years were 88.5%, 56.6%, and 37.2%, respectively. Lesion greater than 30 mm (HR 1.82, p = 0.030), presence of non-lung metastases (HR 1.67, p = 0.020), the use of systemic treatment before SBRT (HR 1.82, p = 0.023), and progression of treated metastases (HR 1.80, p = 0.007), were all predictive of worse OS. Conclusions: Stereotactic body radiation therapy represents an effective approach in the management of oligometastatic CRC. Control of treated oligometastases seems to be a strong positive predictive factor for both PFS and OS. (C) 2018 Elsevier B.V. All rights reserved.

PURPOSE: This study explores the efficacy and safety of reirradiation with modern radiation therapy techniques in patients previously irradiated for prostate cancer and affected by local relapse of disease. METHODS AND MATERIALS: Patients affected by previously irradiated prostate cancer were enrolled in this reirradiation study if they had a biochemical relapse and a 11C-choline positron emission tomography scan revealing the presence of a local recurrence of disease. Reirradiation consisted of a stereotactic treatment delivered by image guided radiation therapy-volumetric modulated arc therapy with flattening filter-free technology in 5 daily fractions. RESULTS: Twenty-three patients underwent reirradiation to the prostate, prostatic bed, or prostate and local recurrence. Re-treatment consisted of a median total dose of 25 Gy in 5 fractions. A biochemical response was observed in all cases. Acute toxicity was mainly genitourinary (GU) grade 1 to 2 (n = 13; 56.5%). One patient (4.3%) had grade 3 hematuria. A grade 1 GU late toxicity was registered in 4 patients (17.4%) and grade 3 in 1 patient (4.3%, urethral obstruction). Gastrointestinal toxicity was negligible. Regression analysis showed that only a short elapsed time in months from primary radiation therapy was significantly correlated with acute GU toxicity. After a median follow-up of 33 months (range, 5-58 months), the median biochemical recurrence-free survival was 19 months, and the 2-year biochemical recurrence-free survival (BRFS) was 41.7%. Median local control was 30 months; the 2-year local control rate was 58.1%. CONCLUSIONS: Reirradiation of patients with prostate cancer who underwent previous radiation therapy is a valuable option that can be safely considered to delay the beginning of hormonal treatment.

PURPOSE: To appraise the ability of a radiomics signature to predict clinical outcome after stereotactic body radiation therapy (SBRT) for pancreas carcinoma. METHODS: A cohort of 100 patients was included in this retrospective, single institution analysis. Radiomics texture features were extracted from computed tomography (CT) images obtained for the clinical target volume. The cohort of patients was randomly divided into two separate groups for the training (60 patients) and validation (40 patients). Cox regression models were built to predict overall survival and local control. The significant predictors at univariate analysis were included in a multivariate model. The quality of the models was appraised by means of area under the curve and concordance index. RESULTS: A clinical-radiomic signature associated with Overall Survival (OS) was found significant in both training and validation sets (p = 0.01 and 0.05 and concordance index 0.73 and 0.75 respectively). Similarly, a signature was found for Local Control (LC) with p = 0.007 and 0.004 and concordance index 0.69 and 0.75. In the low risk group, the median OS and LC in the validation group were 14.4 and 28.6 months while in the high-risk group were 9.0 and 17.5 months respectively. CONCLUSION: A CT based radiomic signature was identified which correlate with OS and LC after SBRT and allowed to identify low and high-risk groups of patients.

S775ESTRO 37Fat Free Mass and Sub-Cutaneous Fat Mass optimal cut-off to predict the overall survival.Results 54 patients (55.6%) were sarcopenic.There were 50 deaths in sarcopenic patients (92.6%) versus 26 deaths in non sarcopenic patients (60.5%).The median overall survival was 21.5 months in sarcopenic patients versus 61.3 months in no sarcopenic patients (p<0.001).Sarcopenia (SMI), BMI<21, NRI<97.5, and WHO status>0 were the only significant features in univariate analysis.In multivariate analysis sarcopenia was the only significant independent prognostic factor (HR=2.32[1.24-4.34],p=0.008).We couldn't define an optimal cut-off for Fat Free Mass and Sub-Cutaneous Fat Mass. ConclusionSarcopenia is a powerful independent prognostic factor, associated with a rise of the overall mortality in patients treated by exclusive radiochemotherapy for a locally advanced oesophageal cancer.PET-CT images are easily gathering data and can allow one to identify population at risk who needed an adapted therapy.

treated by SBRT point out the usefulness of the functional evaluation of the response that seems to be predictive of encouraging local control at 2 years PV-0471

The introduction of IMRT, IGRT, and VMAT techniques, has substantially contributed to the delivery of more safe and effective radiation treatments to patients affected by prostate cancer, even if previously irradiated. In this study we report our experience on re-irradiation in a sample of 22 patients previously irradiated for prostate cancer and affected by local relapse of disease. Patients affected by recurrent prostate cancer previously irradiated were included in this study, provided that they had an increased PSA, diagnostic for biochemical relapse, a PET-Choline revealing the presence of a local recurrence of disease, and were unwilling to start an androgen deprivation therapy. Re-irradiation consisted of a stereotactic treatment delivered by FFF IGRT-VMAT technology in 5 daily fractions. Clinical response was evaluated with PSA and physical examination. Toxicity assessment according to CTCAE (v. 4.01) criteria. During follow-up, PET-Choline was performed in the cases of PSA rising. Between November, 2012, and November, 2017, 22 patients (median age 77 years, range 59-85) were submitted to re-irradiation on prostate (n=12, 54.5%), prostatic bed (n=8, 36.4%) or prostate and local recurrence (n=2 seminal vesicle, ischium 9.1%). Previous treatment consisted on a median total dose of 74 Gy on prostate or prostatic bed (range 66-76). Median time from previous radiotherapy was 87 months (range 26-137). Median PSA at the moment of recurrence was 2.9 ng/ml (mean 3.8, range 1.0-13.5). Re-irradiation delivered a median total dose of 25 Gy (range 25-30) in a median number of 5 fractions (range 5-6). An immediate biochemical response was observed in all cases. Median PSA nadir after treatment was 0.66 ng/ml (mean 1.41, range 0.11-6.0, p=0.0004). Median difference between initial and nadir PSA was 2.1 ng/ml (range 0.2-11.0). Median time to nadir was 5.4 months (range 2.2-20). Acute toxicity was mainly genito-urinary, represented by pollakiuria and dysuria grade 1 (n=10, 45.5%) or grade 2 (n=3, 13.6%). One patient (4.5%) had a grade 3 hematuria. A grade 1 GU late toxicity was observed in 3 patients (17.7%), G3 in 1 patient (4.5%, urethral obstruction). GI toxicity was negligeable. At a median follow-up of 28 months (range 5-57) all patients are still alive, a biochemical recurrence was experienced by 13 patients (59.1%), confirmed by a positive PET-choline in 12 cases (7 local recurrences, 1 distant metastasis, 4 local and distant progression). Median BFS was 19 months, 1- and 2-year BFS was 84.7% and 39.4%, respectively. Median LC was 30 months, 1- and 2-year LC was 94.4% and 58.1%, respectively. Re-irradiation of patients affected by prostate cancer, and previously treated with radiation therapy, is a valuable option, which can be safely considered in order to delay the beginning of an hormonal treatment.