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Aim: To evaluate acute toxicity at 6 months after stereotactic body radiotherapy (SBRT) in patients with oligometastatic cancer within the OligoCare cohort., Material and Methods: OligoCare is a prospective, registry-based, single-arm, observational study that aims to report prospective real-world data of patients with oligometastases from solid cancer treated with SBRT (NCT03818503). Primary tumor included non-small cell lung cancer (NSCLC), breast cancer (BC), colorectal cancer (CRC), and prostate cancer (PC). This analysis addresses a secondary endpoint of the trial, acute toxicity within 6 months after SBRT., Results: Out of 1,597registered patients, 1'468 patients were evaluated for acute toxicity. Globally, 290 (20 %) had NSCLC primary disease, 227 (16 %) had BC, 293 (20 %) had CRC, and 658 (45 %) had PC. Concomitant systemic treatment was administered in 527 (35.9 %) patients. According to the EORTC/ESTRO oligometastatic disease (OMD) classification, 828 (56 %) patients had de novo OMD, 464 (32 %) repeat OMD, and 176 (12 %) induced OMD. Acute grade ≥ 3 SBRT related adverse events were reported in 8 (0.5 %) patients, including 2 (0.1 %) fatal AEs. In particular, 6 (0.4 %) grade 3 events were: 1 empyema, 1 pneumonia, 1 radiation pneumonitis, 1 radiation skin injury, 1 decreased appetite, and 1 bone pain. Among those 2 occurred in NSCLC patients, 2 in BC patients, and 1 in CRC and PC patients each. The two (0.1 %) grade 5 toxicity were represented by: pneumonitis and cerebral hemorrhage., Conclusion: OligoCare is the largest prospective registry cohort on oligometastatic disease. Acute toxicity within 6 months was low, confirming the safety of SBRT in the treatment of oligometastases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: We report the results of an international multi-institutional cohort of oligometastatic (OMD) head and neck cancer (HNC) patients treated with SBRT., Methods: Patients with OMD HNC (≤5 metastases) treated with SBRT between 2008 and 2016 at six institutions were included. Treated metastasis control (TMC), progression-free survival (PFS), and overall survival (OS) were analyzed by multivariable analysis (MVA)., Results: Forty-two patients with 84 HNC oligometastases were analyzed. The TMC rate at 1 and 2 years were 80% and 66%, with a median time to recurrence of 10.1 months. The median PFS and OS were 4.7 and 23.3 months. MVA identified a PTV point maximum (BED)10 > 100 Gy as a predictor of improved TMC (HR = 0.31, p = 0.034), and a cumulative PTV > 48 cc as having worse PFS (HR = 2.99, p < 0.001)., Conclusion: Favorable TMC and OS was observed in OMD HNCs treated with SBRT., (© 2023 Wiley Periodicals LLC.)

Purpose: We investigated the impact of local control (LC) on widespread progression (WSP) and overall survival (OS) in patients treated to all extracranial oligometastases (OMs) at presentation to SBRT in this retrospective review across 6 international centers., Materials/methods: Relationships between LC status of SBRT-directed OMs and OS and WSP (>5 new active/untreated lesions) were explored using Cox and Fine-Gray regression models, adjusting for radioresistant histology and pre-SBRT systemic therapy receipt. The association between LC and dosimetric predictors was analyzed with competing risk regression using death as a competing risk and across a wide range of simulated α/βratios., Results: In total, 1700 OMs in 1033 patients were analyzed, with 25.2% NSCLC, 22.7% colorectal, 12.8% prostate, and 8.1% breast histology. Patients who failed locally in any SBRT-directed OM within 6 mo were at 3.6-fold higher risk of death and 2.7-fold higher risk of WSP compared to those who remained locally-controlled (p < 0.001). Similar associations existed for each duration of LC investigated through 3 yrs post-SBRT. There was no significant difference in risk of WSP or death between patients who failed in a subset of SBRT-treated lesions vs. patients who failed in all lesions. Minimum dose (Dmin) to the GTV/ITV was most predictive of LC when compared to prescription dose, PTV Dmin, and PTV Dmax. Sensitivity analysis for achieving 1-yr LC > 95% found thresholds of 41.2 Gy and 55.2 Gy in 5 fractions for smaller (< 27.7 cc) and larger radioresistant lesions, respectively., Conclusion: This large multinational cohort suggests that the duration of LC following OM-directed SBRT strongly correlates with WSP and OS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: This joint guideline by American Society for Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) was initiated to review evidence and provide recommendations regarding the use of local therapy in the management of extracranial oligometastatic non-small cell lung cancer (NSCLC). Local therapy is defined as the comprehensive treatment of all known cancer-primary tumor, regional nodal metastases, and metastases-with definitive intent., Methods: ASTRO and ESTRO convened a task force to address 5 key questions focused on the use of local (radiation, surgery, other ablative methods) and systemic therapy in the management of oligometastatic NSCLC. The questions address clinical scenarios for using local therapy, sequencing and timing when integrating local with systemic therapies, radiation techniques critical for oligometastatic disease targeting and treatment delivery, and the role of local therapy for oligoprogression or recurrent disease. Recommendations were based on a systematic literature review and created using ASTRO guidelines methodology., Results: Based on the lack of significant randomized phase 3 trials, a patient-centered, multidisciplinary approach was strongly recommended for all decision-making regarding potential treatment. Integration of definitive local therapy was only relevant if technically feasible and clinically safe to all disease sites, defined as 5 or fewer distinct sites. Conditional recommendations were given for definitive local therapies in synchronous, metachronous, oligopersistent, and oligoprogressive conditions for extracranial disease. Radiation and surgery were the only primary definitive local therapy modalities recommended for use in the management of patients with oligometastatic disease, with indications provided for choosing one over the other. Sequencing recommendations were provided for systemic and local therapy integration. Finally, multiple recommendations were provided for the optimal technical use of hypofractionated radiation or stereotactic body radiation therapy as definitive local therapy, including dose and fractionation., Conclusions: Presently, data regarding clinical benefits of local therapy on overall and other survival outcomes is still sparse for oligometastatic NSCLC. However, with rapidly evolving data being generated supporting local therapy in oligometastatic NSCLC, this guideline attempted to frame recommendations as a function of the quality of data available to make decisions in a multidisciplinary approach incorporating patient goals and tolerances., Competing Interests: Disclosures All task force members’ disclosure statements were reviewed before being invited and were shared with other task force members throughout the guideline's development. Those disclosures are published within this guideline. Where potential conflicts were detected, remedial measures to address them were taken. Tom Boike: APEx reviewer (honoraria), Boston Scientific (speaker's bureau); Anne-Marie Dingemans: Amgen (advisory board, research), Bayer, Boehringer Ingelheim, Lilly, PharmaMar, Roche, Sanofi (all advisory boards), AstraZeneca, Chiesi, Janssen, Pfizer, Takeda (all honoraria), EORTC Lung Cancer Group (chair); Jill Feldman (patient representative): AstraZeneca, Blueprint Medicines, Janssen, Novartis (all honoraria), EGFR Resisters (cofounder), IASLC Patient Advocate Committee (chair); Daniel Gomez: AstraZeneca (consultant and research), GRAIL (consultant), Johnson & Johnson (consultant), Medtronic (advisory board), Medical Learning Group (honoraria–ended 8/2021), Varian (consultant and research); Matthias Guckenberger (co-chair): European Thoracic Oncology Platform (research), Varian (research-ended 12/2020), ViewRay (institutional research), ESTRO (president); Paul Hesketh (American Society of Clinical Oncology representative): UpToDate (consultant – editor); Puneeth Iyengar (co-chair): AstraZeneca (advisory board-ended 12/2020), National Cancer Institute/NRG Oncology (research – PI); Salma Jabbour: Advarra (consultant – DSMB), IMX Medical and Merck (consultant), Novocure (consultant-ended 4/2022), Beigene and Merck (institutional research grant), Syntactx (consultant – adjudication committee), International Journal of Radiation Oncology, Biology, and Physics (deputy editor), NCI Radiation Research Program, Upper GI Work Group (co-chair); Mirjana Josipovic: Danish National Research Center for Radiation Therapy (research), Varian (institutional research); Yolande Lievens: AstraZeneca (institutional research), Belgium College for Physicians in Radiation Oncology, (deputy chair-ended 10/2021), Belgium College of Oncology & AntiCancer Fund (board member), European Cancer Organization (Ex-officio executive committee member-ended 3/2022), ESTRO (former president), UGent Chair on ESTRO value-based health care (promotor, institutional research); Fiona McDonald: AstraZeneca (institutional research), Cancer Research United Kingdom (research – PI), Merck (institutional research), IASLC Advanced Radiotherapy Committee (chair), ESTRO ACROP Guidelines Committee (chair), UK SABR Consortium (chair); Bradford Perez: BMS (consultant, research-ended 12/2021), G1 Therapeutics (consultant–ended 4/2021); Umberto Ricardi: BrainLab (institutional research), ESTRO (past president); Enrico Ruffini: AstraZeneca (honoraria), European Society of Thoracic Surgeons (past president), IASLC (steering committee and chair, Thymic subcommittee); Dirk De Ruysscher: AstraZeneca and BMS (research and institutional advisory board), BeiGene (institutional research), Celgene, Merck/Pfizer, Roche/Genentech, Seattle Genetics (all institutional advisory boards), EORTC Lung Oligometastases committee (chair); Suresh Senan: AstraZeneca (advisory board – DSMB), BMS (consultant–ended 6/2022), BeiGene (advisory board-ended 3/2021), Merck (consultant), Varian and ViewRay (institutional research); Joachim Widder: Elekta and Raysearch (institutional research); Hina Saeed (Guideline Subcommittee representative),Clinical and Translational Radiation Oncology (editor); Bryan Schneider (American Society of Clinical Oncology representative), ASCO Guideline advisory group (co-chair), NCCN Immune Checkpoint Inhibitor-Related Toxicities guideline (vice chair). Sean All, Mark Berry, and Lisa Bradfield reported no disclosures., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Patients with oligometastatic disease (OMD) can experience durable disease control with ablative therapy to all sites of disease. Stereotactic body radiation therapy (SBRT) is an important modality in the management of OMD, although a validated prognostic model for OMD treated with SBRT is currently lacking. The purpose of this study was to develop a prognostic model for overall survival (OS) in patients with OMD treated with SBRT., Methods and Materials: A multi-institutional database of patients with extracranial OMD treated with SBRT was used for model development. The final prognostic model was generated in a training set using recursive partitioning analysis representing 75% of the population. Model performance was evaluated in the reserved test set., Results: The analysis included 1033 patients. The median OS for the entire cohort was 44.2 months (95% confidence interval [CI], 39.2-48.8 months). The variables used in the regression tree, in order of importance, were primary histology, lung-only OMD on presentation, the timing of OMD presentation, and age at the start of SBRT. A full 5-category risk stratification system based on the terminal nodes possessed fair to good discriminative power with a Harrell concordance statistic of 0.683 (95% CI, 0.634-0.731) and a time-dependent area under the receiver operating characteristic curve of 0.709 (95% CI, 0.706-0.711) in the test set, with good calibration. A simplified risk stratification system consisting of 3 risk categories was also proposed for greater ease of use with comparable performance., Conclusions: A clinical prognostic model for OS in patients with extracranial OMD treated with SBRT has been developed and validated., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Prolonged survivorship is increasingly observed in patients with oligometastases (OM) treated with stereotactic body radiation therapy (SBRT). The purpose of this study was to study the conditional survival of patients with OM, which can provide more detailed prognostic information over time by considering time already survived., Methods and Materials: A multi-institutional database consisting of 1033 patients with OM (≤5 metastases) treated with SBRT between 2006 and 2017 was analyzed. Conditional overall survival (OS) and progression-free survival (PFS) in 3 years were obtained at multiple time points for all patients and by primary cancer type. Cox regression was used to determine trends in conditional OS and PFS. Changes in the predictors of OS and PFS over time were also determined by multivariable Cox regression., Results: The median follow-up was 24 months (0.3-105 months). Three-year OS and PFS at baseline were 56.7% and 23.2%, respectively. The OS in 3 years conditional on having survived for 3, 6, 12, and 24 months did not significantly change over time (56.7%, 55.4%, 55.8%, and 50.6%, respectively; P = .60). In contrast, the probability of PFS in 3 years conditional on having survived progression-free for 3, 6, 12, and 24 months significantly increased over time (23.6%, 27.3%, 35.1%, and 48.8%, respectively; P < .001). When stratified by primary site, conditional PFS significantly increased over time for patients with colorectal, breast, or kidney cancer. Conditional OS remained stable for patients with non-small cell lung cancer or kidney cancer but significantly decreased over time for patients with prostate, breast, or colorectal cancer. Changes in significant prognostic factors of OS and PFS over time were also observed., Conclusions: Analysis of conditional survival among patients with OM showed that as patients survived longer, their prognosis for further survival remained stable or decreased. However, patients who survived longer without disease progression had increased probability of PFS over time., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: In recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for oligometastatic cancers. Here, we report radiation treatment parameters and clinical outcomes for patients with oligometastatic colorectal cancer (CRC) treated with SBRT using a large multi-institutional database., Methods: Patients with extra-cranial oligometastatic CRC (≤5 lesions) treated with SBRT at six large academic cancer centers were included. The primary outcome was local recurrence while secondary outcomes included overall survival (OS) progression free survival, oligo-progression, and widespread progression. Survival outcomes were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were performed to determine the relationship between patient and treatment characteristics and clinical outcomes., Results: We identified 235 patients with a total of 381 oligometastatic CRC lesions. The 1- and 5-year local recurrence rate was 13.6% and 44.3% respectively. The median OS was 49 months with a 2-and 5-year OS of 76.1% and 35.9%, respectively. On multivariable analysis, a BED 10 of ≥120 Gy, and lung versus liver metastases were associated with a reduction in local recurrence. Larger total PTV size (≥17.5 cc) was associated with worse overall survival, progression free survival, and widespread progression., Conclusion: This large multi-institutional analysis found that the use of SBRT for oligometastatic colorectal cancer resulted in favorable overall survival. However, local recurrence is higher than expected for ablative radiation treatment. An increase in BED 10 should be considered if feasible and safe., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: There is a paucity of data on SBRT to non-spine bone (NSB) lesions compared to spine metastases. We report local recurrence (LR), widespread progression (WSP), and overall survival (OS) for oligometastatic patients treated to bone lesions with SBRT and investigate the hypothesis that outcomes are different between patients with spine and non-spine bone oligometastatic disease., Methods: Patients with oligometastatic disease (≤5 cumulative extracranial metastases) treated with bone SBRT at 6 international institutions from 2007 to 2016 were reviewed. Fine and Gray competing risks and Cox regressions were used to analyze univariable and multivariable relationships between disease/treatment factors and outcomes., Results: In total, 288 spine and 233 NSB lesions are reported in 356 patients. Cumulative incidence of LR across all bone lesions was 6.3%, 12.6% and 19.3% at 6 mo, 1 yr and 2 yrs. While univariable analysis suggested inferior LC and OS in spine patients, this did not hold true in multivariable analysis. The final regression model for LR in NSB lesions included PTV ≥ median of 31.8 cc (HR 5.02, p = 0.014) and primary histology, with RCC and NSCLC conferring a 10.8- and 6.5-fold increased risk of LR compared to prostate histology, respectively. The spine LR model included radioresistant histology (HR 2.11, p = 0.0051), PTV Dmin (BED10) ≥ median of 19.1 Gy (HR 0.46, p = 0.0085), and epidural disease (HR 1.99, p = 0.016)., Conclusion: This large multi-institutional series reports comparably excellent response to SBRT for a balanced distribution of oligometastatic NSB and spine lesions. Dose escalation for large and/or radioresistant NSB lesions should be explored, given the typical lack of an immediately adjacent dose-limiting critical structure., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The role of postoperative radiation therapy (PORT) in stage III N2 NSCLC is controversial. We analyzed decision-making for PORT among European radiation oncology experts in lung cancer., Methods: Twenty-two experts were asked before and after presentation of the results of the LungART trial to describe their decision criteria for PORT in the management of pN+ NSCLC patients. Treatment strategies were subsequently converted into decision trees and analyzed., Results: Following decision criteria were identified: extracapsular nodal extension, incomplete lymph node resection, multistation lymph nodes, high nodal tumor load, poor response to induction chemotherapy, ineligibility to receive adjuvant chemotherapy, performance status, resection margin, lung function and cardiopulmonary comorbidities. The LungART results had impact on decision-making and reduced the number of recommendations for PORT. The only clear indication for PORT was a R1/2 resection. Six experts out of ten who initially recommended PORT for all R0 resected pN2 patients no longer used PORT routinely for these patients, while four still recommended PORT for all patients with pN2. Fourteen experts used PORT only for patients with risk factors, compared to eleven before the presentation of the LungART trial. Four experts stated that PORT was never recommended in R0 resected pN2 patients regardless of risk factors., Conclusion: After presentation of the LungART trial results at ESMO 2020, 82% of our experts still used PORT for stage III pN2 NSCLC patients with risk factors. The recommendation for PORT decreased, especially for patients without risk factors. Cardiopulmonary comorbidities became more relevant in the decision-making for PORT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: To define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from non-small cell lung cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology)., Methods: NSCLC patients with BM receiving SRT + IT and treated in 19 Italian centers were analyzed and compared with a control group of patients treated with exclusive SRT., Results: One hundred patients treated with SRT + IT and 50 patients treated with SRT-alone were included. Patients receiving SRT + IT had a longer intracranial Local Progression-Free Survival (iLPFS) (propensity score-adjusted P = .007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n = 24), IT administration after SRT was shown to be related to a better overall survival (OS) (P = .037). A multivariate analysis, non-adenocarcinoma histology, KPS = 70 and use of HFSRT were associated with a significantly worse survival (P = .019, P = .017 and P = .007 respectively). Time interval between SRT and IT ≤7 days (n = 90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n = 10) (propensity score-adjusted P = .008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT + IT patients and SRT-alone patients was observed. The time interval between SRT and IT had no impact on the toxicity rate., Conclusions: Combined SRT + IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Stereotactic body radiotherapy (SBRT) is increasingly used to treat oligometastatic disease (OMD), but the effect of metastasis timing on patient outcomes remains uncertain., Methods: An international database of patients with OMD treated with SBRT was assembled with rigorous quality assurance. Early versus late metastases were defined as those diagnosed ≤24 versus >24 months from the primary tumor. Overall survival (OS), progression-free survival (PFS), and incidences of wide-spread progression (WSP) were estimated using multivariable Cox proportional hazard models stratified by primary tumor types., Results: The database consists of 1033 patients with median follow-up of 24.1 months (0.3-104.7). Late metastatic presentation (N = 427) was associated with improved OS compared to early metastasis (median survival 53.6 vs. 33.0 months, hazard ratio [HR] 0.59, 95% confidence interval [CI]: 0.47-0.72, p < 0.0001). Patients with non-small cell lung cancer (NSCLC, N = 255, HR 0.49, 95% CI: 0.33-0.74, p = 0.0005) and colorectal cancer (N = 235, HR 0.50, 95% CI: 0.30-0.84, p = 0.008) had better OS if presenting with late metastasis. Late metastasis correlated with longer PFS (median 17.1 vs. 9.0 months, HR 0.71, 95% CI: 0.61-0.83, p < 0.0001) and lower 2-year incidence of WSP (26.1% vs. 43.6%, HR 0.60, 95% CI: 0.49-0.74, p < 0.0001). Fewer WSP were observed in patients with NSCLC (HR 0.52, 95% CI: 0.33-0.83, p = 0.006) and kidney cancer (N = 63, HR 0.37, 95% CI: 0.14-0.97, p = 0.044) with late metastases. Across cancer types, greater SBRT target size was a significant predictor for worse OS., Conclusion: Late metastatic presentation is associated with improved survival and delayed progression in patients with OMD treated with SBRT., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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., (© 2021. Italian Society of Medical Radiology.)

Background: Whole brain radiotherapy (WBRT) is a common treatment option for brain metastases secondary to non-small cell lung cancer (NSCLC). Data from the QUARTZ trial suggest that WBRT can be omitted in selected patients and treated with optimal supportive care alone. Nevertheless, WBRT is still widely used to treat brain metastases secondary to NSCLC. We analysed decision criteria influencing the selection for WBRT among European radiation oncology experts., Methods: Twenty-two European radiation oncology experts in lung cancer as selected by the European Society for Therapeutic Radiation Oncology (ESTRO) for previous projects and by the Advisory Committee on Radiation Oncology Practice (ACROP) for lung cancer were asked to describe their strategies in the management of brain metastases of NSCLC. Treatment strategies were subsequently converted into decision trees and analysed for agreement and discrepancies., Results: Eight decision criteria (suitability for SRS, performance status, symptoms, eligibility for targeted therapy, extra-cranial tumour control, age, prognostic scores and "Zugzwang" (the compulsion to treat)) were identified. WBRT was recommended by a majority of the European experts for symptomatic patients not suitable for radiosurgery or fractionated stereotactic radiotherapy. There was also a tendency to use WBRT in the ALK/EGFR/ROS1 negative NSCLC setting., Conclusion: Despite the results of the QUARTZ trial WBRT is still widely used among European radiation oncology experts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Importance: The outcomes and factors that influence survival in patients with oligometastasis (OM) are not well understood and have not been well described in large-scale studies., Objective: To evaluate overall progression-free survival (PFS), widespread progression (WSP) outcomes, and survival factors from a pooled data set of 1033 patients with OM treated with stereotactic body radiotherapy (SBRT)., Design, Setting, and Participants: Case series from January 1, 2008, to December 31, 2016. The dates of analysis were April 2019 to May 2020. The setting was multi-institutional tertiary care hospitals. Participants were consecutive patients with 5 or fewer extracranial OMs whose primary tumor was treated curatively., Exposure: Definitive SBRT., Main Outcomes and Measures: Overall survival (OS), progression-free survival, rate of WSP, patterns of failure, and factors altering OS., Results: In the largest international OM case series to date (1033 participants) (mean age, 68.0 years [range, 18.0-94.3 years]; 601 [58.2%] men), 1416 SBRT courses were delivered to patients with 1 OM (596 [57.7%]), 2 OMs (245 [23.7%]), 3 OMs (105 [10.2%]), 4 OMs (55 [5.3%]), and 5 OMs (32 [3.1%]). The median follow-up was 24.1 months (range, 0.3-104.7 months), and the median OS was 44.2 months (95% CI, 39.2-48.8 months). The median PFS was 12.9 months (95% CI, 11.6-14.2 months), and the median time to WSP was 42.5 months (95% CI, 36.8-53.5 months). The OS rates were 84.1% (95% CI, 81.7%-86.2%) at 1 year, 56.7% (95% CI, 53.0%-60.2%) at 3 years, and 35.2% (95% CI, 30.1%-40.3%) at 5 years. The 3-year OS, PFS, and WSP rates were 56.7% (95% CI, 53.0%-60.2%), 23.0% (95% CI, 20.2%-25.9%), and 45.2% (95% CI, 41.4%-48.9%), respectively. The 5-year OS, PFS, and WSP rates were 35.2% (95% CI, 30.1%-40.3%), 14.8% (95% CI, 11.9%-17.9%), and 54.5% (95% CI, 49.8%-59.2%), respectively. At the time of first progression, 342 patients (33.1%) had recurrence of OM disease, and 230 patients (22.3%) underwent subsequent ablative therapies to all known metastatic sites. Multivariable analyses identified primary tumor type (hazard ratio [HR], 3.73; 95% CI, 1.75-7.94; P < .001 for breast; 5.75; 95% CI, 2.88-11.46; P < .001 for colorectal; 4.67; 95% CI, 2.12-10.31; P < .001 for kidney; 10.61; 95% CI, 5.36-20.99; P < .001 for lung; and 12.00; 95% CI, 6.06-23.76; P < .001 for other [with prostate being the reference group]), metachronous OM presentation more than 24 months since initial diagnosis (HR, 0.63; 95% CI, 0.49-0.80; P < .001), metastases confined to the lung only (HR, 0.58; 95% CI, 0.48-0.72; P < .001), and nodal or soft-tissue metastases only (HR, 0.49; 95% CI, 0.26-0.90; P = .02) as survival factors. Sixty-six (6.4%) grade 3 or higher toxic effects were observed, including 1 (0.1%) grade 5 event., Conclusions and Relevance: This study found favorable long-term OS and WSP rates associated with extracranial OM ablated with SBRT; however, modest PFS rates were observed. A substantial proportion of patients with OM developed progressive disease and were treated with local ablation. Factors that can inform clinical decision-making and clinical trial design include primary tumor type, a metachronous presentation more than 24 months since diagnosis, and the site of OM presentation.

Radiotherapy (RT) plays a major role in the treatment of small cell lung cancer (SCLC). Therefore, the ACROP committee was asked by ESTRO to provide recommendations on target volume delineation for standard clinical scenarios in definitive (chemo)-radiotherapy (CRT), adjuvant RT for stages I-III SCLC and consolidation thoracic RT for stage IV disease. The aim of these guidelines is to standardise and optimise the process of RT treatment planning for clinical practice and prospective studies. The process for the development of the guidelines included the evaluation of a structured questionnaire followed by a consensus discussion, voting and writing process within the committee. Firstly, we provide recommendations for both the imaging to be performed as part of the diagnostic work-up and for the RT planning process. Secondly, recommendations are made for target volume delineation including delineation of the primary gross tumour volume (GTV) and lymph node GTV and clinical tumour volume (CTV) expansion in the context of definitive and adjuvant RT. With regard to internal target volume (ITV) and planning target volume (PTV) definitions, we make recommendations about the management of geometric uncertainties and target motion. Finally, we provide our opinions on organ at risk (OAR) delineation and organisational issues to be considered., (Copyright © 2020. Published by Elsevier B.V.)

The prognosis of lung cancer patients has improved in the last few years. Despite definitive therapy, local recurrence or a second primary tumour can occur in many patients within previously irradiated areas. Recent developement of more accurate techniques in radiation oncology allows delivery of high radiation dose to the tumor with the aim of improving local control, delaying disease progression and in some cases even curing. Nevertheless, the use of high dose in the reirradiation setting is not without risks, especially when treatment volumes overlap with previously irradiated tissues. The risk of adverse effects must be balanced with the choice of an effective treatment by selecting suitable candidates and the best radiation technique. In this systemic review efficacy and toxicity of reirradiation in locoregionally recurrent non-small-cell lung cancer is extensively discussed. Results indicate that reirradiation might be beneficial in well-selected patients. Prospective and high quality studies are necessary in this field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic., Methods: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC., Results: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided., Conclusion: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Concurrent chemotherapy and radiotherapy (cCRT) is considered the standard treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Unfortunately, management is still heterogeneous across different specialists. A multidisciplinary approach is needed in this setting due to recent, promising results obtained by consolidative immunotherapy. The aim of this survey is to assess current LA-NSCLC management in Italy. From January to April 2018, a 15-question survey focusing on diagnostic/therapeutic LA-NSCLC management was sent to 1,478 e-mail addresses that belonged to pneumologists, thoracic surgeons, and radiation and medical oncologists. 421 answers were analyzed: 176 radiation oncologists, 86 medical oncologists, 92 pneumologists, 64 thoracic surgeons and 3 other specialists. More than a half of the respondents had been practicing for >10 years after completing residency training. Some discrepancies were observed in clinical LA-NSCLC management: the lack of a regularly planned multidisciplinary tumor board, the use of upfront surgery in multistation stage IIIA, and territorial diffusion of cCRT in unresectable LA-NSCLC. Our analysis demonstrated good compliance with international guidelines in the diagnostic workup of LA-NSCLC. We observed a relationship between high clinical experience and good clinical practice. A multidisciplinary approach is mandatory for managing LA-NSCLC., Competing Interests: A pharma company (Astra Zeneca Italy, principal site in Basiglio, Milano, Italy) gave the unconditional support to develop a web platform for data entry. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No patents or products needs to be declared related to the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The treatment landscape of metastatic non-small cell lung cancer (NSCLC) has dramatically evolved in recent years, since the recognition of several clinical-biological entities requiring personalized treatment approaches, leading to significant improvements in patients' survival outcomes. In particular, targeted therapies acting against EGFR, ALK , and ROS1 , and immunotherapeutic agents modulating the PD-1/PD-L1 axis, represent new milestones in the treatment of advanced disease, supporting a chemotherapy backbone within a multidisciplinary model. The Italian Association of Medical Oncology (AIOM) has developed evidence-based guidelines for the management of lung tumors. Given the epidemiologic relevance, this report is dedicated to the treatment of advanced/metastatic NSCLC. These guidelines serve as a practical tool for oncologists, physicians, and other healthcare professionals to easily embrace the updated key points of NSCLC treatment strategies. Considering the upcoming introduction of potential new standards of care in several disease settings, these guidelines represent a benchmark from which to move forward.

Radiotherapy (RT) plays a major role in the curative treatment of locally advanced non-small cell lung cancer (NSCLC). Therefore, the ACROP committee was asked by the ESTRO to provide recommendations on target volume delineation for standard clinical scenarios in definitive (chemo)radiotherapy (RT) and adjuvant RT for locally advanced NSCLC. The guidelines given here are a result of the evaluation of a structured questionnaire followed by a consensus discussion, voting and writing procedure within the committee. Hence, we provide advice for methods and time-points of diagnostics and imaging before the start of treatment planning and for the mandatory and optional imaging to be used for planning itself. Concerning target volumes, recommendations are given for GTV delineation of primary tumour and lymph nodes followed by issues related to the delineation of CTVs for definitive and adjuvant radiotherapy. In the context of PTV delineation, recommendations about the management of geometric uncertainties and target motion are given. We further provide our opinions on normal tissue delineation and organisational and responsibility questions in the process of target volume delineation. This guideline intends to contribute to the standardisation and optimisation of the process of RT treatment planning for clinical practice and prospective studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Stereotactic Body Radiotherapy (SBRT) is a well established therapeutic option for patients affected with peripheral early stage non-small cell lung cancer (NSCLC), given the positive clinical evidence accumulated so far on its efficacy and safety. SBRT is regarded as the best choice for inoperable patients, and could also be offered as an alternative to surgery to selected operable patients. More recently, its use for lung metastases progressively increased, and SBRT is now regarded as a low toxic and highly effective local therapy for lung oligometastases from different primary tumors, especially colorectal cancer. Improved planning and delivery techniques have facilitated over the years its use on large and/or centrally located primary tumors, and multiple nodules. Given the successful applications and the current wide dissemination of this technique, clinicians are now faced with an increasingly complex and multi-variable decision process. Some clinically relevant factors are still uncertain, and strategies are needed to reduce the risk of both local and distant failures. Secondly, aspects related to target delineation, dose prescription, image guidance and treatment planning still need to be fully addressed; this may hamper, at least for now, the standardization of SBRT procedures through different Institutions making any kind of direct outcomes comparison difficult. We here aim to provide a perspective on the current role of lung SBRT and its critical aspects, highlighting the potential future developments., (Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare patterns of acute and late radiological lung injury following either 3D conformal or image-guided volumetric modulated arc therapy stereotactic radiotherapy for Stage I non-small-cell lung cancer., Methods: We included 148 patients from a prospective mono-institutional stereotactic body radiation therapy (SBRT) series (time interval 2004-2014), treated with prescription BED 10 Gy (at 80%) in the range 100-120 Gy. The first 95 patients (2004-2010) were planned with 3D-CRT, with a stereotactic body frame. The second cohort (2010-2014) included 53 patients, planned with volumetric IMRT on a smaller planning target volume generated from a patient's specific internal target volume, with a frameless approach through cone-beam CT guidance. Acute and late radiological modifications were scored based on modified Kimura's and Koenig's classifications, respectively., Results: Median follow-up time was 20.5 months. The incidence of acute radiological changes was superimposable between the groups: increased density was observed in 68.4 and 64.2% of patients for 3D-CRT and VMAT, respectively, and patchy ground glass opacity in 23.7 and 24.5%, respectively; diffuse ground glass opacity was 2.6 vs 9.4%, respectively, and patchy consolidation 2.6 vs 1.9%, respectively. Late changes occurred in approximately 60% of patients: modified conventional pattern was the most frequent modification (25 vs 32.6%, respectively); other patterns were less common (mass-like 19.6 vs 17.4%, and scar-like 13 vs 10.9%, respectively)., Conclusion: Results of the present study indicate that the pattern of radiological lung changes following SBRT for peripheral early stage non-small-cell lung cancer is not influenced by the different techniques used for planning and delivery. Advances in knowledge: This comparative observational study shows that smaller margins, image guidance and most importantly dose distribution do not change the pattern of radiological injury after lung SBRT; the same scoring system can be used, and expected incidence is similar.

Background: The gross tumor volume (GTV) definition for malignant pleural mesothelioma (MPM) is ill-defined. We therefore investigated which imaging modality is optimal: computed tomography (CT) with intravenous contrast (IVC), positron emission tomography-CT (PET/CT) or magnetic resonance imaging (MRI)., Material and Methods: Sixteen consecutive patients with untreated stage I-IV MPM were included. Patients with prior pleurodesis were excluded. CT with IVC, 18FDG-PET/CT and MRI (T2 and contrast-enhanced T1) were obtained. CT was rigidly co-registered with PET/CT and with MRI. Three sets of pleural GTVs were defined: GTV CT , GTV CT+PET/CT and GTV CT+MRI . Quantitative and qualitative evaluations of the contoured GTVs were performed., Results: Compared to CT-based GTV definition, PET/CT identified additional tumor sites (defined as either separate nodules or greater extent of a known tumor) in 12/16 patients. Compared to either CT or PET/CT, MRI identified additional tumor sites in 15/16 patients (p = .7). The mean GTV CT , GTV CT+PET/CT and GTV CT+MRI [±standard deviation (SD)] were 630.1 cm 3 (±302.81), 640.23 cm 3 (±302.83) and 660.8 cm 3 (±290.8), respectively. Differences in mean volumes were not significant. The mean Jaccard Index was significantly lower in MRI-based contours versus all the others., Conclusion: As MRI identified additional pleural disease sites in the majority of patients, it may play a role in optimal target volume definition.

Pulmonary metastases are common in patients with cancer for which surgery is considered a standard approach in appropriately selected patients. A number of patients are not candidates for surgery due to a medical comorbidities or the extent of surgery required. For these patients, noninvasive or minimally invasive approaches to ablate pulmonary metastases are potential treatment strategies. This article summarizes the rationale and outcomes for non-surgical treatment approaches, including radiotherapy, radiofrequency and microwave ablation, for pulmonary metastases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Stereotactic Body Radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated over the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow up. In early stage lung cancer, clinicians are now faced with a decision-making process that should take into account different factors. The need of pathological diagnosis and accurate nodal staging still represents a challenge, as well as the interpretation of radiological findings after SBRT, often confusing du to the difficulties in distinguishing between radiation-induced changes and local relapse. Aim of this review is to summarize and discuss the major studies on SBRT for early stage lung cancer, providing data on its efficacy and toxicity and discussing the still open issues on its role. Quality of life, pulmonary function and risk of secondary cancers are also discussed, as well as future perspectives and current research topics., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To analyze changes in pulmonary function and quality of life (QoL) at different time points after Stereotactic Ablative Radiotherapy (SABR) for early stage inoperable lung cancer, and potential correlations between radiation dose-volume parameters and pulmonary toxicity or changes in pulmonary function tests (PFT) and QoL., Materials and Methods: From July 2012 to October 2013, 30 patients were enrolled in this prospective observational study. Complete PFT were performed and Lung Cancer Symptoms Scale (LCSS) questionnaire administered prior to SABR; all patients then underwent Computed Tomography (CT) scan and PFT at 45, 135, 225 and 315 days after SABR, together with LCSS questionnaire. Clinical lung toxicity and radiological toxicity (acute and late) were prospectively recorded by using the Radiation Therapy Oncology Group (RTOG) scoring system., Results: A decline in Slow Vital Capacity (SVC), Forced Expiratory Volume in 1s (FEV1), Single-breath lung diffusing capacity (DLCO) and blood partial pressure of oxygen (PaO2) was seen at 135 days post-SABR. PaO2 values rescued to normal levels at 315 days. None of the baseline PFT parameters resulted to be associated with the occurrence of pulmonary toxicity or with late radiological changes. Mean V5, V10, and V20 and MLD2Gy were higher in patients who developed radiation pneumonitis, even if not significantly associated at Cox regression analysis. LCSS QoL showed a significant worsening of the single item fatigue at 135 days after SABR., Conclusions: A small (mean 10%) but significant decline in lung volumes and DLCO was recorded after SABR, with clinical impact of such change difficult to estimate in individual patients. Global QoL was not significantly impaired. Dose-volume parameters did not emerge as significantly predictive of any clinical, radiological or functional toxicity., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This single-arm multicenter Phase II study investigated the efficacy and safety of pemetrexed (Pem) and cisplatin (Cis) induction chemotherapy (CT) followed by full-dose Pem-Cis plus concurrent radiotherapy (RT) in patients with locally advanced non-squamous NSCLC., Materials and Methods: Patients with unresectable Stage III non-squamous NSCLC received two 21-day cycles of Pem 500 mg/m(2) (vitamin/folic acid supplementation and dexamethasone prophylaxis per Pem-label)+Cis 75 mg/m(2) on Day 1. Eligible patients who had not progressed continued with 2 further cycles of full-dose Pem-Cis plus concurrent RT (2 Gy/fraction, 5 days/week, 66 Gy total). Primary endpoint was the 1-year progression-free survival (PFS) rate., Results: Of 90 patients enrolled (all treated; median age 61 years, male/female 57%/43%, ECOG performance status 0/1 66%/34%, adenocarcinoma 90%, Stage III 36%/62%), 75 (83%) completed induction CT and started concurrent CT+RT. 64 (71%) patients received all 4 CT cycles and an RT dose ≥60 Gy. The 1-year PFS rate was 51.3% (95%CI: 42.0, 60.5). Median PFS was 10.6 months (95%CI: 8.6, 17.3), median OS was 26.2 months (95%CI: 16.7, not estimable). One patient died from enteritis (treatment-related) during Cycle 4. Four patients discontinued due to treatment-related adverse events, 1 on induction CT (renal failure), 3 on concurrent CT+RT (1 hypoacusis, 2 acute esophagitis). During induction CT, 18.9% of patients reported Grade 3/4 CTCAEs, only neutropenia (2.2%) and syncope (2.2%) were reported by >1 patient. During concurrent CT+RT, 41.3% of patients reported G3/4 CTCAEs, mainly esophagitis (12.0%), neutropenia (10.7%), and leukopenia (9.3%)., Conclusion: In this study of Pem-Cis induction CT followed by full-dose Pem-Cis with concurrent RT, median PFS was 10.6 months and toxicity was manageable, in line with previous data on Pem-Cis plus RT., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Purpose: To estimate stereotactic ablative radiation therapy (SABR) efficacy and its potential role as an alternative to surgery for the treatment of lung metastases from colorectal cancer., Methods and Materials: Forty consecutive patients who received SABR as first local therapy at the time of lung progression were included, from 2004 to 2014. The primary study endpoint was overall survival. Secondary endpoints were progression-free survival and safety., Results: A single nodule was treated in 26 patients (65%), 2 nodules in 10 patients (25%), 3 in 3 patients (7.5%), and 4 in 1 patient (2.5%), for a total of 59 lesions. The median delivered biological effective dose was 96 Gy, in 1 to 8 daily fractions. Median follow-up time was 20 months (range, 3-72 months). Overall survival rates at 1, 2, and 5 years were, respectively, 84%, 73%, and 39%, with 14 patients (35%) dead. Median overall survival was 46 months. Progression occurred in 25 patients (62.5%), at a median interval of 8 months; failure at SABR site was observed in 3 patients (7.5%). Progression-free survival rates were 49% and 27% at 1 and 2 years, respectively., Discussion: The results of this retrospective exploratory analysis suggest safety and efficacy of SABR in patients affected with colorectal cancer lung oligometastases and urge inclusion of SABR in prospective clinical trials., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Thoracic surgery for a newly diagnosed primary lung tumor following a previous pneumonectomy is rarely indicated. Stereotactic ablative radiotherapy (SABR) might represent a curative option. This report focuses on outcomes, toxicity and quality of life (QoL) after SABR., Methods: Nine patients were treated with SABR between 2004 and 2011; median time since surgery was 8.4 years. In 4 cases, a histological confirmation was possible with bronchoscopy. In 5 cases, the clinical proof of malignancy was based on radiological criteria. Forced expiratory volume in 1 second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) were tested in all patients. A SABR biologically equivalent dose of &gt;100 Gy was prescribed in all cases. QoL questionnaire forms were administered before SABR and during follow-up., Results: Median follow-up was 41.8 months. We did not observe grade ≥3 acute toxicity, and concerning late toxicity, we registered 2 cases. QoL was decreased during the first 12 months of follow-up, followed by a progressive improvement after this time. One patient had a local relapse at 7.4 years; 1 developed a new nodule at 5.5 years, associated with metastases; and 1 developed a new nodule without any systemic disease at 3 years. There were 2 cancer-related deaths (18.2%) at 3 and 12 months after progression., Conclusions: Data support efficacy and safety of SABR in patients with a new primary lung cancer following previous pneumonectomy, with acceptable acute, late toxicity profile and without significant impairment of QoL. Our results were comparable to those in the literature.

An increasing body of experience suggests that oligometastasis represents a minimal metastatic state with the potential for cure or prolonged survival in selected patients treated with radical local therapy to all identified sites of disease. The main clinical scenarios managed by thoracic oncology specialists are pulmonary oligometastases from primary malignancies of other anatomic sites and primary lung cancer with oligometastases to lung or other organs. Surgery has been a mainstay of treatment in these situations, with remarkably favorable outcomes following pulmonary metastasectomy in well-selected patient cohorts. As with early stage lung cancer in patients who are medically inoperable, stereotactic ablative radiotherapy is emerging as a prominent local treatment option for oligometastatic disease. We review the role and clinical experience of stereotactic ablative radiotherapy for pulmonary oligometastases and oligometastatic lung cancer.

Introduction/background: An individual patient data metaanalysis was performed to determine clinical outcomes, and to propose a risk stratification system, related to the comprehensive treatment of patients with oligometastatic NSCLC., Materials and Methods: After a systematic review of the literature, data were obtained on 757 NSCLC patients with 1 to 5 synchronous or metachronous metastases treated with surgical metastectomy, stereotactic radiotherapy/radiosurgery, or radical external-beam radiotherapy, and curative treatment of the primary lung cancer, from hospitals worldwide. Factors predictive of overall survival (OS) and progression-free survival were evaluated using Cox regression. Risk groups were defined using recursive partitioning analysis (RPA). Analyses were conducted on training and validating sets (two-thirds and one-third of patients, respectively)., Results: Median OS was 26 months, 1-year OS 70.2%, and 5-year OS 29.4%. Surgery was the most commonly used treatment for the primary tumor (635 patients [83.9%]) and metastases (339 patients [62.3%]). Factors predictive of OS were: synchronous versus metachronous metastases (P < .001), N-stage (P = .002), and adenocarcinoma histology (P = .036); the model remained predictive in the validation set (c-statistic = 0.682). In RPA, 3 risk groups were identified: low-risk, metachronous metastases (5-year OS, 47.8%); intermediate risk, synchronous metastases and N0 disease (5-year OS, 36.2%); and high risk, synchronous metastases and N1/N2 disease (5-year OS, 13.8%)., Conclusion: Significant OS differences were observed in oligometastatic patients stratified according to type of metastatic presentation, and N status. Long-term survival is common in selected patients with metachronous oligometastases. We propose this risk classification scheme be used in guiding selection of patients for clinical trials of ablative treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Aim of this retrospective multicenter observational study was to provide data on outcomes and prognostic factors in patients affected with stage I histologically confirmed NSCLC treated with Stereotactic Ablative Radiotherapy (SABR, or Stereotactic Body Radiotherapy, SBRT) outside clinical trials., Materials and Methods: We analyzed a cohort of 196 patients with histological/cytological diagnosis of NSCLC. Median age at treatment was 75 years old; median tumor diameter was 2.48 cm, and median GTV 13.3 cc. One hundred fifty-five patients had stage IA disease (79.1%) and 41 patients stage IB disease (20.9%). Total doses ranged from 48 to 60 Gy in 3-8 fractions. Primary endpoints of the study were safety (acute and late toxicity) and efficacy (Local Control, Disease-Free Survival, Overall and Cancer-Specific Survival)., Results: Median follow-up time was 30 months. The percentage of grade ≥2 pulmonary toxicity was 3%, and the 30 and 60 days mortality rate was 0%. Local Recurrence-Free Survival was 89.7% at 3 years. Fifty-nine patients (30.1%) had at least one failure (local and/or nodal and/or distant), with a Disease-Free Survival (DFS) rate at 3 years of 65.5%. Overall Survival (OS) and Cancer-Specific Survival (CSS) rates were 68% and 82.1% at 3 years, respectively. Median time to any recurrence was 15 months, while median overall survival time was 54 months. At multivariate analysis, stage IB was the only variable associated to a decrease in DFS, OS and CSS (HR 2.77, p = 0.006; HR 2.38, p = 0.009; HR 4.06, p ≤ 0.001, respectively). A difference in survival according to stage was also evident at the log-rank test (p ≤ 0.0001 for CSS and OS)., Conclusion: The results of the present study support the routine use of SABR for stage I NSCLC in a daily practice environment. The only prognostic factor that has been confirmed by our analysis was tumor stage (IA vs. IB)., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Stereotactic Ablative Radiotherapy (SABR) has been previously investigated as an alternative to thoracic surgery in patients with a limited number of pulmonary nodules from different primary tumors. We here report the clinical outcomes of a series of consecutive patients homogeneously selected and treated with single dose SABR in our Institution. Eligibility criteria were: 1-5 lung metastases, maximum tumor diameter <50 mm, absent or controlled extra-thoracic disease, adequate pulmonary function, no prior radiotherapy, performance status ECOG 0-1. All patients were treated with a single dose of 26 Gy prescribed to the 80% isodose, by 3D-CRT or by IGRT-VMAT. Follow-up consisted of clinical evaluation and periodic CT scans. Primary endpoints were Local Control (LC), toxicity and Progression-Free Survival (PFS). Secondary endpoints were Cancer-Specific Survival (CSS) and Overall Survival (OS). Out of 102 patients treated with SABR between october 2003 and october 2011, we selected 67 patients for a total of 90 lesions. Main primary tumor sites were lung and colon-rectum (37.3% and 43.3% of lesions, respectively). Median follow up time was 24 months. Treated metastasis progression at SABR site was observed in 10 lesions (11.1%), and actuarial LC rates at 1 and 2 years were respectively 93.4% and 88.1%. Systemic failure occurred in 37 patients (55.2%) at a median interval of 8 months after SABR. PFS rates were 72% and 55.4% at 1 and 2 year. Seven patients had grade 1 (10.4%) and 8 grade 2-3 late radiological toxicity (11.9%), while 6 experienced late chest wall toxicity (2 rib fractures, 4 chronic chest pain, 8.9%). CSS rates at 1 and 2 years were 90% and 76%, while OS rates were 85.1% and 70.5%, respectively. Median survival time was 40 months. On multivariate analysis, a disease-free interval longer than 24 months was close to significance for a benefit in CSS (p = 0.07; HR 0.34 [95% CI 0.1-1.12]). The study includes a cohort of patients treated with single fraction 26 Gy SABR followed for a prolonged time interval. Single fraction SABR appears to be an effective treatment option, with little observed acute toxicity and limited late toxicity (<15%); its advantages also include a high patients' compliance, a short overall treatment time and an easy combination with systemic therapies. These results might provide supportive evidence to the use of single fraction SABR as a valid and acceptable alternative to surgery for pulmonary metastases from different primary tumors.

Purpose: To identify dosimetric factors that predict development of radiation pneumonitis (RP) following stereotactic or hypofractionated radiotherapy for lung tumors., Methods: Seventy-nine consecutive patients with either a planning target volume (PTV)>100 cm(3) (n=69) or prior pneumonectomy or bi-lobectomy (n=13) were identified. Radiation doses (range: 5-50 Gy, with 5 Gy increments) were converted to equivalent doses (EQD(2 Gy)) (α/β=3). Total lung (TL), ipsilateral (IL) and contralateral lung (CL) volumes minus PTV, receiving 5 Gy (V5) up to 50 Gy (V50) and mean lung dose (MLD) were analyzed. Predictors of grade ≥3 RP (CTCAEv4.03) were identified with concordance-statistics (C-statistic) and p-values used to quantify the performance of the model. Factors found to be significant were entered into a recursive partitioning analysis (RPA)., Results: Median PTV was 150 cm(3). Grade ≥3 RP was observed in 8 patients (10%). In univariable analysis, CL-MLD, CL-V5-15, TL-MLD, TL-V5-V10 and ITV size were predictive of RP (p<0.05). In multivariable analysis, contralateral MLD (p=.007) and ITV (p=.063) were the strongest predictors of grade ≥3 RP, with excellent discrimination (C-statistic: 0.868)., Conclusion: Contralateral MLD and ITV size are both strong predictors of grade ≥3 RP post treatment. Planning constraints should aim to keep contralateral MLD below 3.6 Gy., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Adjuvant radiotherapy in non-small-cell lung cancer (NSCLC) is still controversial. The purpose of this retrospective study was to evaluate the role of postoperative radiotherapy (PORT) in terms of local control and survival in pathologic N2 NSCLC., Patients and Methods: From January 2003 to December 2008, 66 patients with pathologic N2 NSCLC received PORT. Mediastinal lymph node metastases were classified into single (12 patients) or multiple (54 patients) stations. All patients received conformal radiation therapy, with a median total dose of 50.4 Gy. Target volumes included the bronchial stump, ipsilateral hilum, all pathologically involved lymph node regions, and all the lymph nodes between 2 noncontiguous pathologic nodal stations. The pattern of failure was considered as locoregional or systemic, or a combination of both. Locoregional failure was defined as in field or out of field., Results: Median follow-up time was 34.9 months (range 3.5-62.8 months). Local control was 80% at 12 months, 77.2% at both 24 and 36 months, and 72.1% at 60 months. The pattern of failure was locoregional in 3 patients (1 out of field and 2 in field) and systemic in 25 patients, with 12 patients presenting both locoregional and distant disease. Overall survival at 12, 36, and 60 months was 77%, 44%, and 37%, respectively. Median survival time was 34 months. The number of pathologically involved lymph node stations was a prognostic factor for local control (P = .05), cancer-specific survival (CSS) (P = .04), and disease-free survival (DFS) (P = .04)., Conclusion: Despite the limitations of the present study, mainly represented by its retrospective nature, our data support the role of PORT in terms of locoregional control and overall survival benefit; the number of involved mediastinal lymph nodes represents a significant prognostic factor in patients with pathologic N2 NSCLC., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: Stereotactic body radiation therapy (SBRT) has an emerging role in patients affected with pulmonary metastases. Purpose of this study was to evaluate efficacy and tolerability of SBRT in a cohort of patients treated between 2003 and 2009 at our institution., Methods: A total of 61 patients with oligometastatic lung tumors (single pulmonary nodules in 73.7%) were included in the study. SBRT was performed with a stereotactic body frame and a 3D-conformal technique. Fifty-one patients received 26 Gy in 1 fraction, 22 a dose of 45 Gy in 3 fractions and 3 a dose of 36 Gy in 4 fractions. Primary tumor was lung cancer in 45.7% of patients, colorectal cancer in 21.3% and a variety of other origins in 33%. The primary endpoint was local control, secondary endpoints were survival and toxicity., Results: After a median follow-up interval of 20.4 months, local control rates at 2 and 3 years were 89% and 83.5%, overall survival 66.5% and 52.5%, cancer-specific survival 75.4% and 67%, progression-free survival 32.4% and 22.3%. Tumor volume was significantly associated to survival, with highest rates in patients with single small tumors. Median survival time was 42.8 months, while median progression-free survival time was 11.9 months. Toxicity profiles were good, with just one case of grade III toxicity (pneumonitis)., Conclusion: This study shows that SBRT is an effective and safe local treatment option for patients with lung metastases. Definitive results are strictly correlated to clinical selection of patients., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

In patients with proven distant metastases from solid tumors, it has been a notion that the condition is incurable, warranting palliative care only. The term "oligometastases" was coined to refer to isolated sites of metastasis, whereby the entire burden of disease can be recognized as a finite number of discrete lesions that can be potentially cured with local therapies. Stereotactic body radiation therapy (SBRT) is a novel treatment modality in radiation oncology that delivers a very high dose of radiation to the tumor target with high precision using single or a small number of fractions. SBRT is the result of technological advances in patient and tumor immobilization, image guidance, and treatment planning and delivery. A number of studies, both retrospective and prospective, showed promising results in terms of local tumor control and, in a limited subset of patients, of survival. This article reviews the radiobiologic, technical, and clinical aspects of SBRT for various anatomical sites.

Patients affected with early stage (IA-IB) non-small cell lung cancer (NSCLC), deemed medically inoperable, are usually treated by conventional 3D-CRT, with poor results in terms of local tumour control and survival. Hypofractionated stereotactic body radiation therapy (SBRT) appears to be a valid alternative option, with high rates of local control and promising survival rates according to recent reported series. We herein report the final results of a prospective phase II trial of SBRT in 62 stage I NSCLC patients, homogeneously treated with three fractions of 15Gy each, given every other day during a 1 week time, up to a total dose of 45Gy; dose was prescribed to the 80%-isodose encompassing planning target volume. Patients were immobilized in a dedicated stereotactic body frame; margins around gross tumour volume were 5mm in the axial plane and 10mm in the longitudinal direction. Median age was 73.7 years. A pathologic confirmation of NSCLC was obtained in 64.5% of patients. Forty-three patients had stage IA and 19 stage IB disease. The majority of patients did not experience any toxicity; mild skin reactions, fatigue, dyspnea/cough or transient thoracic pain were recorded in approximately 10% of patients. With a median follow-up time of 28 months, 2 patients experienced an isolated local relapse, 4 an isolated nodal relapse and 15 a systemic failure. At 3 years, local control rate was 87.8%, cancer-specific survival 72.5%, overall survival 57.1%, with 8 out of 20 non-cancer related deaths. In multivariate analysis, tumour volume was associated with a better outcome. In our series, SBRT was well tolerated and confirmed its efficacy, with local control and survival rates globally superior to those reported using conventional radiotherapy. A longer follow-up is needed in order to establish a correct comparison with surgical series, and to fully ascertain a potential negative impact of SBRT on comorbidities of such a fragile patients population., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Materials and Methods: The aim was to retrospectively investigate correlations between potential predictive parameters and the occurrence of radiation-induced lung injury in patients with primary or secondary lung tumours treated with stereotactic body radiation therapy (SBRT). Sixty patients (63 tumours) underwent SBRT, with a dose of 45 Gy in 3 fractions over 5 days or 26 Gy in single fraction. The following parameters were tested for correlation with Radiation Therapy Oncology Group (RTOG) lung toxicity score: planning target volume (PTV), tumour location, primary vs. metastatic tumour, and Mean Lung Dose (in 2 Gy fractions, MLD2). Normal Tissue Complication Probability (NTCP) values were then estimated., Results: The median follow-up time was 30.9 months (range 6.7-56.7). RTOG grade 0-1 toxicity was observed in 54/63 (85.7%) and grade 2-3 in 9/63 (14.3%) cases. Mean values of MLD(2) for RTOG grade 0-1 and 2-3 were respectively 11.2 Gy (95% Confidence Interval (CI) 10.1-12.3 Gy) and 20.3 Gy (95% CI 16.6-23.9 Gy). NTCP mean values for RTOG grade 0-1 and 2-3 were respectively 4% (95% CI 2-5.9%) and 37% (95% CI 11.6-62.3%). Univariate analysis, performed with t-Student test, showed a statistically significant difference between MLD(2) values in the two groups (t=5.93 and p < or = 0.001). Logistic regression analysis showed a good correlation between MLD(2) and toxicity scores 2-3 (p=0.008, odds ratio 1.5). From logistic regression relationship between the observed rates of grade 2-3 and MLD(2), a D(50)=19.8 Gy and a gamma50= 2.2 were obtained. From the sigmoid-shaped dose-response relationship between NTCP and MLD(2), a D(50)=22.4 Gy and gamma(50)= 2.2 were derived., Discussion: MLD(2) is strongly associated to the risk of lung injury. Higher NTCP values are associated with a higher risk, but when comparing the expected to the observed toxicity rate, NTCP seems to underestimate the risk.

BackgroundThe COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic.MethodsFor this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC.ResultsIn a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided.ConclusionThis joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.