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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. [ABSTRACT FROM AUTHOR]

Earlier treatment intensification with systemic potent androgen receptor inhibition has been shown to improve clinical outcomes in metastatic hormone sensitive prostate cancer. Nonetheless, oligometastatic patients may benefit from local treatment approaches such as stereotactic body radiotherapy (SBRT). Aiming to explore the benefit of SBRT in this scenario, we designed this trial to specifically test the hypothesis that SBRT will improve clinical outcomes in select population affected by metachronous oligometastatic HSPC treated with androgen deprivation therapy + apalutamide. Enrolled patients will be randomized to receive the standard systemic treatment alone or in combination with SBRT on all metastatic sites of disease. Here we report the protocol design and an overview of the ongoing trials testing different integration strategies between RT and systemic therapies. [ABSTRACT FROM AUTHOR]

Purpose: Given the absence of standardized planning approach for clinically node-positive (cN1) prostate cancer (PCa), we collected data about the use of prophylactic pelvic irradiation and nodal boost. The aim of the present series is to retrospectively assess clinical outcomes after this approach to compare different multimodal treatment strategies in this scenario. Methods: Data from clinical records of patients affected by cN1 PCa and treated in six different Italian institutes with prophylactic pelvic irradiation and boost on pathologic pelvic lymph nodes detected with CT, MRI or choline PET/CT were retrospectively reviewed and collected. Clinical outcomes in terms of overall survival (OS) and biochemical relapse-free survival (b-RFS) were explored. The correlation between outcomes and baseline features (International Society of Urological Pathology-ISUP pattern, total dose to positive pelvic nodes ≤ / > 60 Gy, sequential or simultaneous integrated boost (SIB) administration and definitive vs postoperative treatment) was explored. Results: ISUP pattern < 2 was a significant predictor of improved b-RFS (HR = 0.3, 95% CI 0.1220–0.7647, P = 0.0113), while total dose < 60 Gy to positive pelvic nodes was associated with worse b-RFS (HR = 3.59, 95% CI 1.3245–9.741, P = 0.01). Conversely, treatment setting (postoperative vs definitive) and treatment delivery technique (SIB vs sequential boost) were not associated with significant differences in terms of b-RFS (HR = 0.85, 95% CI 0.338–2.169, P = 0.743, and HR = 2.39, 95% CI 0.93–6.111, P = 0.067, respectively). Conclusion: Results from the current analysis are in keeping with data from literature showing that pelvic irradiation and boost on positive nodes are effective approaches. Upfront surgical approach was not associated with better clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively estimate the impact of radiotherapy as a progression-directed therapy (PDT) in oligoprogressive metastatic castration-resistant prostate cancer (mCRPC) patients under androgen receptor-target therapy (ARTT). Materials and methods: mCRPC patients are treated with PDT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events v4.0. Survival analysis was performed using the Kaplan–Meier method; univariate and multivariate analyses were performed. Results: Fifty-seven patients were analyzed. The median follow-up after PDT was 25.2 months (interquartile, 17.1–44.5). One-year NEST-free survival, r-PFS and OS were 49.8%, 50.4% and 82.1%, respectively. At multivariate analysis, polymetastatic condition at diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) (HR 2.82, p = 0.004) and PSA doubling time at diagnosis of mCRPC (HR 2.76, p = 0.006) were associated with NEST-free survival. The same variables were associated with r-PFS (HR 2.32, p = 0.021; HR 2.24, p = 0.021). One patient developed late grade ≥ 2 toxicity. Conclusion: Our study shows that radiotherapy in oligoprogressive mCRPC is safe, is effective and seems to prolong the efficacy of ARTT in patients who otherwise would have gone systemic treatment switch, positively affecting disease progression. Prospective trials are needed. [ABSTRACT FROM AUTHOR]

Introduction: Almost 30% of non-small cell lung cancer (NSCLC) patients have locally advanced-stage disease. In this setting, definitive radiotherapy concurrent to chemotherapy plus adjuvant immunotherapy (cCRT + IO) is the standard of care, although only 40% of these patients are eligible for this approach. Aims: A comparison between cCRT and hypofractionated radiotherapy regimens (hypo-fx RT) with the addition of sequential chemotherapy (sCHT) could be useful for future combinations with immunotherapy. We developed a recommendation about the clinical question of whether CHT and moderately hypo-fx RT are comparable to cCRT for locally advanced NSCLC Materials and methods: The panel used GRADE methodology and the Evidence to Decision (EtD) framework. After a systematic literature search, five studies were eligible. We identified the following outcomes: progression-free survival (PFS), overall survival (OS), freedom from locoregional recurrence (FFLR), deterioration of quality of life (QoL), treatment-related deaths, severe G3–G4 toxicity, late pulmonary toxicity G3–G4, and acute esophageal toxicity G3–G4. Results: The probability of OS and G3–G4 late lung toxicity seems to be worse in patients submitted to sCHT and hypo-fx RT. The panel judged unfavorable the balance benefits/harms. Conclusions: The final recommendation was that sCHT followed by moderately hypo-fx RT should not be considered as an alternative to cCRT in unresectable stage III NSCLC patients. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the potential impact of upfront metastases-directed therapy (MDT) in terms of prolongation of castration-sensitive phase in a series of oligorecurrent castration-sensitive prostate cancer (PC) patients. The present article is a multicenter retrospective study. The population of interest was castrate-sensitive oligorecurrent PC, defined as the presence of 1-3 uptakes in non-visceral sites such as bones or nodes detected by means of 18F-Choline PET/CT or 68-Gallium PSMA PET/CT. Primary endpoint was the time to castration resistance. Secondary endpoints were ADT-free survival, local progression-free survival, and overall survival. Eighty-two patients and 118 lesions were analyzed. The median time to castration resistance for the entire population of the study was 49 months (95% CI 43.6-54.4 months). The 1- and 2-year TTCR-free survival rates were 94% and 82%, respectively. At the time of analysis, 52 patients were still in the castration-sensitive phase of the disease. In this cohort of patients, the median ADT-free survival was 20 months (range 3-69 months). On the other hand, during follow-up 30 patients switched to the castration-resistant phase of disease. In this last group of patients, the median ADT-free survival was 20 months (range 4-50 months). After the ADT administration, the median castration-sensitive phase was 29 months (range 5-71 months). Castration resistance generally occurs at a median follow-up of 24-36 months following ADT. In the current study, upfront MDT does not decrease the time from initiation of ADT to castration resistance. [ABSTRACT FROM AUTHOR]

Background: Elderly breast cancer patients are frequently affected by significant comorbidities that make sophisticated radiotherapy treatments particularly challenging. Aims: We dosimetrically analyzed two different simple free-breathing external beam radiotherapy (EBRT) techniques for the hypofractionated treatment of the left breast in elderly patients with a low compliance, to compare target coverage, and heart and left anterior descending coronary artery (LADCA) sparing. Methods: We developed radiation plans for 24 elderly patients using 3D conformal (3DCRT) field-in-field tangential technique and intensity-modulated (IMRT) tangential beam technique. Dose-Volume-Histograms (DVHs) were used to provide a quantitative comparison between plans. Results: The median breast volume was 645 cm3. IMRT and 3DCRT plans comparison demonstrated no significant differences in terms of organ sparing for the heart. Regarding LADCA, mean dose (10.3 ± 9.5 Gy vs 11.9 ± 9.6 Gy, p = 0.0003), maximum dose (26.1 ± 16.1 Gy vs 29.1 ± 16.1 Gy, p = 0.004) and V17 Gy (21.5% ± 26.9% vs 25.0% ± 27.2%, p = 0.002) significantly decreased using IMRT compared with 3DCRT. IMRT plans showed a better target coverage compared with 3DCRT (0.91 ± 0.05 vs 0.93 ± 0.04, p = 0.05). Discussion: Comparing the two different EBRT techniques, we demonstrated few, although substantial, dosimetric differences in terms of doses to the organs at risk characterized by a statistically significant dose reduction of LADCA in the IMRT plans. Conclusions: Elderly patients with a low compliance to treatment might benefit from 3DCRT with field-in-field tangential arrangement or from a simple IMRT approach. IMRT should be preferred. [ABSTRACT FROM AUTHOR]

Purpose: To report criticisms and barriers to the "real-life" application of international guidelines and recent developments in the management of locally advanced non-small cell lung cancer (NSCLC) in Italy. Methods: Three 2-day courses were organized. During the first day, experts in different fields of thoracic oncology gave their lecture on diagnosis and therapy for locally advanced NSCLC. During the second day, all participants were divided into four groups to discuss on a clinical case as a multidisciplinary team (MDT). The aim was to stimulate the discussion on practical issues in the management of NSCLC patients in the real-life practice. Results: A total of 196 physicians were involved in the courses as learners. Invasive diagnosis of nodal disease for staging purposes, a priori definition of "surgical resectability" and a regular MDT with all crucial participants available were the three main key points identified for a good management of these patients. The main barriers to the clinical application of a good diagnostic and therapeutic approach to the patient were the absence of a regular and complete MDT in the South and Centre of Italy, while in the North of Italy, time for discussion of clinical cases in the MDT and waiting lists for staging and therapeutic interventions were deemed as the major concerns. Conclusion: The meetings showed that diagnosis and treatment of locally advanced NSCLC are still extremely variable between different Italian regions. Logistic issues, waiting lists, paucity of well-trained staff and expertise seem to be the main barriers to international guidelines application. [ABSTRACT FROM AUTHOR]

Purpose: Herein, we report the clinical outcomes of a multicenter study evaluating the role of SBRT in a cohort of patients affected by oligoprogressive castration-resistant prostate cancer (CRPC). Materials and methods: This is a retrospective multicenter observational study including eleven centers. Inclusion criteria of the current study were: (a) Karnofsky performance status > 80, (b) histologically proven diagnosis of PC, (c) 1–5 oligoprogressive metastases, defined as progressive disease at bone or nodes levels (detected by means of choline PET/CT or CT plus bone scan) during ADT, (d) serum testosterone level under 50 ng/ml during ADT, (e) controlled primary tumor, (f) patients treated with SBRT with a dose of at least 5 Gy per fraction to a biologically effective dose (BED) of at least 80 Gy using an alpha-to-beta ratio of 3 Gy, (g) at least 6 months of follow-up post-SBRT. Results: Eighty-six patients for a total of 117 lesions were treated with SBRT. The median follow-up was 30.7 months (range 4–91 months). The median new metastasis-free survival after SBRT was 12.3 months (95% CI 5.5–19.1 months). One- and two-year distant progression-free survival was 52.3% and 33.7%, respectively. Twenty-six out of 86 patients underwent a second course of SBRT due to further oligoprogressive disease: This resulted in a median systemic treatment-free survival of 21.8 months (95% CI 17.8–25.8 months). One-year systemic treatment-free survival was 72.1%. Conclusion: SBRT appears to be a promising approach in oligoprogressive castration-resistant prostate cancer. Further investigations are warranted. [ABSTRACT FROM AUTHOR]

Introduction: In RPA V-VI glioblastoma patients both hypofractionated radiotherapy and exclusive temozolomide can be used; the purpose of this trial is to compare these treatment regimens in terms of survival and quality of life. Methods: Patients with histologic diagnosis of glioblastoma were randomized to hypofractionated radiotherapy (RT–30 Gy in 6 fractions) and exclusive chemotherapy (CHT–emozolomide 200 mg/m2/day 5 days every 28 days). Overall (OS) and progression free survival (PFS) were evaluated with Kaplan Maier curves and correlated with prognostic factors. Quality- adjusted survival (QaS) was evaluated according to the Murray model (Neurological Sign and Symptoms–NSS) Results: From 2010 to 2015, 31 pts were enrolled (CHT: 17 pts; RT: 14pts). Four pts were excluded from the analysis. RPA VI (p = 0.048) and absence of MGMT methylation (p = 0.001) worsened OS significantly. Biopsy (p = 0.048), RPA class VI (p = 0.04) and chemotherapy (p = 0.007) worsened PFS. In the two arms the initial NSS scores were overlapping (CHT: 12.23 and RT: 12.30) and progressively decreased in both group and became significantly worse after 5 months in CHT arm (p = 0.05). Median QaS was 104 days and was significantly better in RT arm (p = 0.01). Conclusions: The data obtained are limited by the poor accrual. Both treatments were well tolerated. Patients in RT arm have a better PFS and QaS, without significant differences in OS. The deterioration of the NSS score would seem an important parameter and coincide with disease progression rather than with the toxicity of the treatment. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the role of radiotherapy (RT) in the management of EGFR- or ALK-mutated metastatic non-small cell lung cancer (NSCLC) treated with TKI. Materials and methods: Clinical data of 106 patients (pts) from five Institutions treated with RT concomitant to TKI were retrospectively revised. Overall survival (OS) and toxicities were analyzed as endpoints of the study. Results: Median age of pts was 65 years. TKIs were given for EGFR (81%)- or ALK (19%)-mutated metastatic NSCLC. Stereotactic RT (SRT) was delivered to 49 pts (46%). Patients with four or less metastasis were defined as oligometastatic/oligoprogressive (OM/OP); sites of RT were brain, bone, lung or others in 46%, 27%, 14% and 13%, respectively. Median OS was 23 months. At univariate analysis SRT, ECOG PS 0–1, OM/OP disease, lung sites and a TKI duration longer than median favorably affected OS (all p < 0.001). Multivariate analysis confirmed SRT (HR 0.355, CI 95% 0.212–0.595; p < 0.001) and median duration of TKI > 14 months (HR 0.17, 95% CI 0.10–0.30; p < 0.001) as independent factors related to better OS. Toxicities were rare. Conclusions: SRT seems to positively affect OS with limited toxicity in selected patients. [ABSTRACT FROM AUTHOR]

A systematic literature was performed to assess the benefit in terms of effectiveness and feasibility of hypofractionated radiotherapy (HypoRT), with or without chemotherapy (CT), in the treatment of locally advanced non-small cell lung cancer (NSCLC). We have identified all studies, published from 2007 onwards, on patients with locally advanced NSCLC treated with HypoRT with radical intent, with a minimal dose per fraction of 2.4 Gy, with or without concurrent chemotherapy. Twenty-nine studies were identified, for a total of 2614 patients. Patients were divided in the concurrent chemo-radiation therapy group (CT-RT) and radiotherapy alone (RT). In RT group, the delivered dose ranged from 45 to 85.5 Gy, with a dose/fraction from 2.4 to 4 Gy. Actuarial 2-year PFS ranged from 13 to 57.8%, and 1, 2- and 3-year overall survival (OS) ranged from 51.3 to 95%, from 22 to 68.7%, and from 7 to 32%, respectively. Acute Grade ≥ 3 esophagitis occurred in 0-15%, while late esophageal toxicity was 0-16%. Acute pneumonitis occured in 0-44%, whereas late pneumonitis occured in 0-47%, most commonly grade ≤ G3. In CT-RT group, the delivered dose ranged from 52.5 to 75 Gy, with a dose/fraction ranging from 2.4 to 3.5 Gy. Actuarial 2-year PFS ranged from 19 to 57.8%, and OS at 1, 2 and 3 years ranged from 28 to 95%, 38.6 to 68.7%, and 31 to 44%, respectively. Acute Grade 2 and 3 esophagitis occurred in 3-41.7%, while late esophageal toxicity occurred in 0-8.3%. Acute pneumonitis ranged from 0 to 23%, whereas late pneumonitis occured 0-47%. HypoRT seems to be safe in patients with locally advanced NSCLC. The encouraging survival results of several studies analyzed suggest that hypofractionated radiation schemes should be further investigated in the future. [ABSTRACT FROM AUTHOR]

Introduction: Radiation therapy plays an important role in the management of SCLC both in curative and palliative setting, however, conflicting data from clinical trials incite debate over the appropriate use of radiation therapy regarding prophylactic cranial irradiation (PCI) and/or thoracic consolidative in extensive-stage SCLC (ES-SCLC). This survey is conducted to evaluate the current pattern of care among Italian radiation oncologists.Methods: In June 2016, all Italian radiation oncologists were invited to a web-based survey. The survey contained 34 questions regarding the role of RT in SCLC. Questions pertaining the role of RT in the clinical management of both limited-stage (LS) and ES-SCLC were included.Results: We received 48 responses from Italian radiation oncologists. More than half of respondents had been practicing for more than 10 years after completing residency training and 55% are subspecialists in lung cancer. Preferred management of LS-SCLC favored primary concurrent chemoradiotherapy (89%), even if the 36.9% usually delivered RT during or after the cycle 3 of chemotherapy, due to organizational issues. The most common dose and fractionation schedule in this setting was 60 Gy in 30 once-daily fractions. Furthermore, almost all respondents recommended PCI in patients with LS-SCLC. For ES-SCLC scenario, chemotherapy was defined the standard treatment by all respondents. PCI was recommended in ES-SCLC patients with thoracic complete remission (63% of respondents), with thoracic partial response (45%) and with thoracic stable disease (17%) after first-line chemotherapy. Lastly, the thoracic consolidative RT was recommended by 51% of respondents in patients with ES-SCLC in good response after first-line chemotherapy and a great variability was shown in clinical target volume definition, doses and fractionation schedules.Conclusions: Our analysis showed a high adherence to current guidelines among the respondents in regard to chemoradiation approach in LS-SCLC patients and to PCI indications and doses. The great variability in radiation therapy doses and volumes in the thoracic consolidative radiotherapy in ES-SCLC is concerning. Future clinical trials are needed to standardize these treatment approaches to improve treatment outcomes among patients with ES-SCLC. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC).Methods: Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1-3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients.Results: About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design.Conclusions: Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC. [ABSTRACT FROM AUTHOR]