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Background: Patients with resected oral cavity squamous cell carcinoma (OCSCC) are often treated with adjuvant radiation (RT) ± concomitant chemotherapy based on pathological findings. Standard RT volumes include all surgically dissected areas, including the tumour bed and dissected neck. RT has significant acute and long-term toxicities including odynophagia, dysphagia, dermatitis and fibrosis. The goal of this study is to assess the rate of regional failure with omission of radiation to the surgically dissected pathologically node negative (pN0) hemi-neck(s) compared to historical control, and to compare oncologic outcomes, toxicity, and quality of life (QoL) profiles between standard RT volumes and omission of RT to the pN0 neck., Methods: This is a multicentre phase II study randomizing 90 patients with T1-4 N0-2 OCSCC with at least one pN0 hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). Patients will be stratified based on overall nodal status (nodal involvement vs. no nodal involvement) and use of concurrent chemotherapy. The primary endpoint is regional failure in the pN0 hemi-neck(s); we hypothesize that a 2-year regional recurrence of 20% or less will be achieved. Secondary endpoints include overall and progression-free survival, local recurrence, rate of salvage therapy, toxicity and QoL., Discussion: This study will provide an assessment of omission of RT to the dissected pN0 hemi-neck(s) on oncologic outcomes, QoL and toxicity. Results will inform the design of future definitive phase III trials., Trial Registration: Clinicaltrials.gov identifier: NCT03997643 . Date of registration: June 25, 2019, Current version: 2.0 on July 11 2020.

Background: During coronavirus disease 2019 (COVID‐19)–related operating room closures, some multidisciplinary thoracic oncology teams adopted a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to surgery, an approach called SABR‐BRIDGE. This study presents the preliminary surgical and pathological results. Methods: Eligible participants from four institutions (three in Canada and one in the United States) had early‐stage presumed or biopsy‐proven lung malignancy that would normally be surgically resected. SABR was delivered using standard institutional guidelines, with surgery >3 months following SABR with standardized pathologic assessment. Pathological complete response (pCR) was defined as absence of viable cancer. Major pathologic response (MPR) was defined as ≤10% viable tissue. Results: Seventy‐two patients underwent SABR. Most common SABR regimens were 34 Gy/1 (29%, n = 21), 48 Gy/3–4 (26%, n = 19), and 50/55 Gy/5 (22%, n = 16). SABR was well‐tolerated, with one grade 5 toxicity (death 10 days after SABR with COVID‐19) and five grade 2–3 toxicities. Following SABR, 26 patients underwent resection thus far (13 pending surgery). Median time‐to‐surgery was 4.5 months post‐SABR (range, 2–17.5 months). Surgery was reported as being more difficult because of SABR in 38% (n = 10) of cases. Thirteen patients (50%) had pCR and 19 (73%) had MPR. Rates of pCR trended higher in patients operated on at earlier time points (75% if within 3 months, 50% if 3–6 months, and 33% if ≥6 months; p =.069). In the exploratory best‐case scenario analysis, pCR rate does not exceed 82%. Conclusions: The SABR‐BRIDGE approach allowed for delivery of treatment during a period of operating room closure and was well‐tolerated. Even in the best‐case scenario, pCR rate does not exceed 82%. During COVID‐19–related operating room closures, a paradigm of stereotactic ablative radiotherapy as a bridge to surgery >3 months later was well‐tolerated and allowed for curative treatment of early‐stage lung malignancy with delay. Pathological complete response (pCR) was 50%, with best‐case scenario sensitivity analysis demonstrating that maximal possibly achievable pCR rate is 82%. [ABSTRACT FROM AUTHOR]

Background: Palliative radiotherapy (PRT) is an effective treatment for managing symptoms of advanced cancer. At least half of all radiation treatments are delivered with palliative intent, aimed at relieving symptoms, such as pain or shortness of breath. Symptomatic patients must receive PRT quickly, therefore expeditious treatment planning is essential. Standard radiation planning requires a dedicated CT scan acquired at the cancer centre, called a 'CT simulation', which facilitates treatment planning (i.e. tumor delineation, placement of radiation beams and dose calculation). However, the CT simulation process creates a bottleneck and often leads to delays in starting treatment. Other researchers have indicated that CT simulation can be replaced by the use of standard diagnostic CT scans for target delineation and planning, which are normally acquired through the radiology department as part of standard patient workup. The goals of this feasibility study are to assess the efficacy, acceptability and scalability of diagnostic-CT-enabled planning, compared to conventional CT simulation planning, for patients receiving PRT to bone, soft tissue and lung disease. Methods: This is a randomized, phase II study, with 33 PRT patients to be randomized in a 1:2 ratio between conventional CT simulation (Arm 1), and the diagnostic CT enabled planning workflow (Arm 2). Patients will be stratified by treatment target volume (bone and soft tissue metastasis vs. primary or metastatic intrathoracic disease targets). The primary endpoint is the amount of time the patient spends at the cancer centre. Secondary endpoints include efficacy (rate of plan deliverability and rate of plan acceptability on blinded dose distribution review), stakeholder acceptability (based on patient and clinician perception of acceptability questionnaires) and scalability. Discussion: This study will investigate the efficacy, acceptability and scalability of a "sim-free" PRT pathway compared to conventional CT simulation. The workflow may provide opportunity for resource optimization by using pre-existing diagnostic imaging and requires minimal investment due to its similarity to current PRT models. It also offers potential benefit to patients by eliminating an imaging procedure, reducing the amount of time spent at the cancer centre, and expediting time to treatment. Trial registration: Clinicaltrials.gov identifier: NCT05233904. Date of registration: February 10, 2022; current version: 1.4 on April 29, 2022. [ABSTRACT FROM AUTHOR]

Background: We compared the health‐related quality of life (HRQOL) in patients undergoing trimodality therapy for resectable stage I‐III esophageal cancer. Methods: A total of 96 patients were randomized to standard neoadjuvant cisplatin and 5‐fluorouracil chemotherapy plus radiotherapy (neoadjuvant) followed by surgical resection or adjuvant cisplatin, 5‐fluorouracil, and epirubicin chemotherapy with concurrent extended volume radiotherapy (adjuvant) following surgical resection. Results: There was no significant difference in the functional assessment of cancer therapy‐esophageal (FACT‐E) total scores between arms at 1 year (p = 0.759) with 36% versus 41% (neoadjuvant vs. adjuvant), respectively, showing an increase of ≥15 points compared to pre‐treatment (p = 0.638). The HRQOL was significantly inferior at 2 months in the neoadjuvant arm for FACT‐E, European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ‐OG25), and EuroQol 5‐D‐3 L in the dysphagia, reflux, pain, taste, and coughing domains (p < 0.05). Half of patients were able to complete the prescribed neoadjuvant arm chemotherapy without modification compared to only 14% in the adjuvant arm (p < 0.001). Chemotherapy related adverse events of grade ≥2 occurred significantly more frequently in the neoadjuvant arm (100% vs. 69%, p < 0.001). Surgery related adverse events of grade ≥2 were similar in both arms (72% vs. 86%, p = 0.107). There were no 30‐day mortalities and 2% vs. 10% 90‐day mortalities (p = 0.204). There were no significant differences in either overall survival (OS) (5‐year: 35% vs. 32%, p = 0.409) or disease‐free survival (DFS) (5‐year: 31% vs. 30%, p = 0.710). Conclusion: Trimodality therapy is challenging for patients with resectable esophageal cancer regardless of whether it is given before or after surgery. Newer and less toxic protocols are needed. [ABSTRACT FROM AUTHOR]

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Background: Stereotactic ablative radiation therapy (SABR) is effective in treating inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. This prospective study aimed to develop a predictive model for true pathologic complete response (pCR) to SABR using imaging-based biomarkers from dynamic [18F]FDG-PET and CT Perfusion (CTP).Methods: Twenty-six patients with early-stage NSCLC treated with SABR followed by surgical resection were included, as a pre-specified secondary analysis of a larger study. Dynamic [18F]FDG-PET and CTP were performed pre-SABR and 8-week post. Dynamic [18F]FDG-PET provided maximum and mean standardized uptake value (SUV) and kinetic parameters estimated using a previously developed flow-modified two-tissue compartment model while CTP measured blood flow, blood volume and vessel permeability surface product. Recursive partitioning analysis (RPA) was used to establish a predictive model with the measured PET and CTP imaging biomarkers for predicting pCR. The model was compared to current RECIST (Response Evaluation Criteria in Solid Tumours version 1.1) and PERCIST (PET Response Criteria in Solid Tumours version 1.0) criteria.Results: RPA identified three response groups based on tumour blood volume before SABR (BVpre-SABR) and change in SUVmax (ΔSUVmax), the thresholds being BVpre-SABR = 9.3 mL/100 g and ΔSUVmax = - 48.9%. The highest true pCR rate of 92% was observed in the group with BVpre-SABR < 9.3 mL/100 g and ΔSUVmax < - 48.9% after SABR while the worst was observed in the group with BVpre-SABR ≥ 9.3 mL/100 g (0%). RPA model achieved excellent pCR prediction (Concordance: 0.92; P = 0.03). RECIST and PERCIST showed poor pCR prediction (Concordance: 0.54 and 0.58, respectively).Conclusions: In this study, we developed a predictive model based on dynamic [18F]FDG-PET and CT Perfusion imaging that was significantly better than RECIST and PERCIST criteria to predict pCR of NSCLC to SABR. The model used BVpre-SABR and ΔSUVmax which correlates to tumour microvessel density and cell proliferation, respectively and warrants validation with larger sample size studies.Trial Registration: MISSILE-NSCLC, NCT02136355 (ClinicalTrials.gov). Registered May 8, 2014, https://clinicaltrials.gov/ct2/show/NCT02136355. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic ablative radiotherapy (SABR) is a guideline-recommended treatment for inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. The goal of this study was to evaluate imaging-based biomarkers of tumour response using dynamic 18 F-FDG-PET and CT perfusion (CTP).Methods: Thirty-one patients with early-stage NSCLC participated in this prospective correlative study. Each underwent dynamic 18 F-FDG-PET/CTP studies on a PET/CT scanner pre- and 8 weeks post-SABR. The dynamic 18 F-FDG-PET measured the tumour SUVmax , SUVmean and the following parameters: K1 , k2 , k3 , k4 and Ki , all using the Johnson-Wilson-Lee kinetic model. CTP quantitatively mapped BF, BV, MTT and PS in tumours and measured largest tumour diameter. Since free-breathing was allowed during CTP scanning, non-rigid image registration of CT images was applied to minimize misregistration before generating the CTP functional maps. Differences between pre- and post-SABR imaging-based parameters were compared.Results: Tumour size changed only slightly after SABR (median 26 mm pre-SABR vs. 23 mm post-SABR; P = 0.01). However, dynamic 18 F-FDG-PET and CTP study showed substantial and significant changes in SUVmax , SUVmean , k3 , k4 and Ki . Significant decreases were evident in SUVmax (median 6.1 vs. 2.6; P < 0.001), SUVmean (median 2.5 vs. 1.5; P < 0.001), k3 (relative decrease of 52%; P = 0.002), Ki (relative decrease of 27%; P = 0.03), whereas there was an increase in k4 (+367%; P < 0.001).Conclusions: Hybrid 18 F-FDG-PET/CTP allowed the response of NSCLC to SABR to be assessed regarding metabolic and functional parameters. Future studies are needed, with correlation with long-term outcomes, to evaluate these findings as potential imaging biomarkers of response. [ABSTRACT FROM AUTHOR]

Background: Intensity modulated radiotherapy (IMRT) is increasingly being used to treat gynaecological malignancies in the postoperative setting. The purpose of this study was to evaluate the use of image-guided radiotherapy (IGRT) using cone-beam computed tomography (CBCT) with fiducial markers for daily localization. Material and methods: A single institution study was performed of consecutive cervical or endometrial cancer patients receiving adjuvant external beam radiotherapy (n = 15). Patients were set up at treatment using daily CBCT and alignment of implanted fiducial markers. Image registration was retrospectively completed based on soft tissue matching and the resulting couch shifts from each IGRT method were compared (n = 122). Results: The median shift between IGRT methods was 2 mm, 1 mm and 1 mm in the anterior-posterior (A-P), superior-inferior (S-I), and lateral directions, respectively. The largest deviations were observed in the A-P direction; however, more than 90% were within 5 mm and 63.9% were within 2.5 mm. Conclusions: IGRT based on soft tissue match provides a noninvasive convenient method for daily localization and is accurate within treatment uncertainty for the majority of cases. [ABSTRACT FROM AUTHOR]

Purpose: Randomized clinical trials (RCTs) are essential to evidence-based medicine, yet a significant proportion fail to be completed. In radiation oncology, factors contributing to trial failure are not well understood. We sought to compare completed and incomplete clinical trials involving radiation therapy (RT) to identify predictors of trial failure.Methods and Materials: We undertook a review of ClinicalTrials.gov to identify RCTs involving RT. Eligible trials mandated external beam RT in ≥1 arm of the study and were registered between September 27, 2007, and December 31, 2010. Univariate and multivariate logistic regression analyses were performed to determine factors predictive of trial failure.Results: We included 134 eligible studies, of which 94 (70.1%) were successful and 40 (29.9%) failed. The reasons for trial failure were categorized as follows: lack of accrual (57.5%), inadequate funding (15.0%), drug unavailability (7.5%), interim data-monitoring report recommendations (7.5%), and other (12.5%). Over time, significantly more trials were failing to be completed (P = .010), with rates increasing from 11.8% (before 2007) to 34.0% (2007-2008) to 39.5% (2009-2012). On univariate analysis, predictors of failure were trials with a surgical comparator (odds ratio [OR], 8.12; P = .013), government sponsorship (vs non-government; OR, 3.67; P = .025), inclusion of a safety endpoint (OR, 2.85; P = .022), and studies starting after 2006 (P = .033). On multivariate analysis, surgical trials were strongly predictive of failure (OR, 12.30; P = .025) while behavioral trials were associated with success (OR, 0.11; P = .045).Conclusions: RT RCTs involving ≥1 surgical arms are at a very high risk of failure, with 75% failing to be completed. In contrast, behavioral studies are associated with study completion, with 94% of studies being successful. Future RT trials involving surgical interventions should consider novel methods to reduce the risk of trial failure. [ABSTRACT FROM AUTHOR]

Background:Volumetric-modulated arc therapy (VMAT) delivery for stereotactic ablative radiotherapy (SABR) of multiple lung tumors allows for faster treatments. We report on clinical outcomes and describe a general approach for treatment planning. Material and methods:Patients undergoing multi iso-center VMAT-based SABR for ≥2 lung lesions between 2009 and 2014 were identified from the VU University Medical Center and London Health Sciences Centre. Patients were eligible if the start date of the SABR treatment for the different lesions was within a time range of 30 days. SABR was delivered using separate iso-centers for lesions at a substantial distance from each other. Tumors were either treated with a single fraction of 34 Gy, or using three risk-adapted dose-fractionation schemes, namely three fractions of 18 Gy, five fractions of 11 Gy, or eight fractions of 7.5 Gy, depending on the tumor size and the location. Multivariable analysis was performed to assess factors predictive of clinical outcomes. Results:Of 84 patients (188 lesions) identified, 46% were treated for multiple metastases and 54% for multiple primary NSCLC. About 97% were treated for two or three lesions, and 56% had bilateral disease. After a median follow-up of 28 months, median overall survival (OS) for primary tumors was 27.6 months, and not reached for metastatic lesions (p = .028). Grade ≥3 toxicity was observed in 2% of patients. Multivariable analysis showed that grade 2 or higher radiation pneumonitis (n = 9) was best predicted by a total lung V35Gyof ≥6.5% (in 2Gy/fraction equivalent) (p = .007). Conclusion:Severe toxicity was uncommon following SABR using VMAT for up to three lung tumors. Further investigations of planning parameters are needed in patients presenting with more lesions. [ABSTRACT FROM PUBLISHER]

Background Assessment of nodal response after radiotherapy ( RT) for head and neck squamous cell carcinoma is difficult, as both CT and positron emission tomography scanning have limited predictive value for residual disease. We sought to measure changes in nodal volume during RT to determine whether such changes are predictive of nodal disease control. Methods Patients with locally advanced head and neck squamous cell carcinoma treated with 70 Gy of radical RT (±chemotherapy or anti-epidermal growth factor receptor ( EGFR) antibodies) were eligible. Baseline pre- RT scans and cone-beam CT scans done at the outset of treatment and at weeks 3, 5 and 7 (cone-beam CTs # 1, 2, 3 and 4, respectively) were deformably coregistered, and 3 D nodal volumes were measured. Results Thirty-eight eligible patients were identified. The main primary tumour site was oropharyngeal; most patients had stage IVa disease. Twenty-seven patients received concurrent platinum-based chemotherapy, 10 received only an EGFR inhibitor with RT and one received RT alone. Twelve patients had a failure in the neck. After week 1 of treatment, a 4% mean decrease in nodal volume was observed, increasing to 40% at week 7. Platinum-based chemotherapy achieved significantly greater decreases in nodal volume than EGFR inhibitors (44 vs. 25%; P = 0.026). Advanced tumour stage predicted neck failure ( P = 0.002), but nodal volumes did not correlate with neck control. Conclusions Changes in nodal volume are minimal initially during RT but accelerate during the latter weeks of therapy. This study suggests that chemotherapy achieves a greater decrease in nodal volume than EGFR inhibitors and that nodal changes do not predict disease control in the neck. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Our objective was to assess the effect of 18F-DCFPyL prostate-specific membrane antigen (PSMA) positron emission tomography (PET) on the management and outcomes of patients receiving salvage radiotherapy following biochemical failure (BF) postradical prostatectomy (RP) using a matched cohort analysis. METHODS: A PSMA-PET cohort of patients with BF post-RP was identified through a prospective registry. Patients from this registry were included if they did not have disease outside of the pelvis and underwent salvage radiotherapy to the prostate and/or pelvis. Casecontrol matching was performed with a contemporary cohort of patients with BF post-RP without PSMA-PET information. RESULTS: Forty-four patients were included in the PSMA-PET cohort and 80 were analyzed in the non-PSMA-PET cohort. The PSMA-PET cohort had a significantly higher pre-radiotherapy median prostate-specific antigen (PSA) of 0.48 ng/mL compared to 0.20 ng/mL in the non-PSMAPET cohort (p<0.001), but these levels were similar after matching. The PSMA-PET cohort had a higher proportion of patients receiving radiotherapy to pelvic lymph nodes (n=27 [61.4%] vs. n=16 [20.0%], p<0.001). Median followup was 26 months (interquartile range 18.8-33) for both cohorts. BF-free survival and event-free survival were not significantly different between the two cohorts for all (p=0.662 and >0.99) and matched patients (p=0.808 and 0.808), respectively. Metastasis-free survival was significantly higher in the matched PSMA-PET cohort compared to the matched non-PSMA-PET cohort (p=0.046), although a higher proportion of patients in the non-PSMA-PET cohort underwent PSMA-PET restaging after BF (52% vs. 20%, p=0.08726). CONCLUSIONS: Our study showed that patients undergoing PSMA-PET scans after BF post-RP had a higher likelihood of pelvic nodal treatment at the time of salvage RT. Despite higher PSA levels at salvage, we identified no recurrence or survival differences. [ABSTRACT FROM AUTHOR]

Using diagnostic computed tomography (dCT) scans instead of CT simulation (CTsim) scans can increase departmental efficiency and reduce patient burden. The goal of the DART trial was to assess the efficacy and acceptability of dCT-based planning workflows with a focus on patient experiences, plan deliverability and adequacy of target coverage, and workflows. Patients undergoing same-day CTsim and treatment for palliative radiation therapy to thoracic, abdominopelvic, or proximal limb targets with a recent dCT (within 28 days) in a reproducible position were eligible. After stratifying by target type (bone or soft tissue vs. visceral), participants were randomized (1:2 ratio) between CTsim-based (CTsim arm) vs. dCT-based planning (dCT arm). The primary endpoint was time in center (TIC), defined as total time spent in the cancer center on first day of treatment, from first radiation department appointment to first fraction completion. Secondary endpoints included plan deliverability, adequacy of target coverage, and stakeholder acceptability. Thirty-three patients (42 treatment sites) were enrolled between June 2022 and April 2023. The median age was 72 (interquartile range [IQR]: 67-78), 73% were male, and the most common primary cancers were lung (33%), prostate (24%), and breast (12%). The most common dose and fractionations were 8 Gy in 1 and 20 Gy in 5 fractions (50% and 43% of plans, respectively). TIC was 4.7 ± 1.1 hours (mean ± SD) in the CTsim arm vs. 0.41 ± 0.14 hours in the dCT arm (P <.001). All dCT plans were deliverable. All plans in both arms were rated as "acceptable" (80% CTsim; 81% dCT) or "acceptable with minor deviation" (20% CTsim; 19% dCT). Patient perception of acceptability was similar in both arms with the exception of time burden, which was rated as "acceptable" by 50% in the CTsim arm vs. 90% in the dCT arm (P =.025). dCT-based radiation planning substantially reduced TIC without detriment in plan deliverability or quality and had a tangible impact on patient experience with reduced patient-reported time burden. [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate the acute toxicity and quality-of-life (QOL) impact of ultrahypofractionated whole pelvis radiation therapy (WPRT) compared with conventional WPRT fractionation after high-dose-rate prostate brachytherapy (HDR-BT). The HOPE trial is a phase 2, multi-institutional randomized controlled trial of men with prostate-confined disease and National Comprehensive Cancer Network unfavorable intermediate-, high-, or very-high-risk prostate cancer. Patients were randomly assigned to receive conventionally fractionated WPRT (standard arm) or ultrahypofractionated WPRT (experimental arm) in a 1:1 ratio. All patients underwent radiation therapy with 15 Gy HDR-BT boost in a single fraction followed by WPRT delivered with conventional fractionation (45 Gy in 25 daily fractions or 46 Gy in 23 fractions) or ultrahypofractionation (25 Gy in 5 fractions delivered on alternate days). Acute toxicities measured during radiation therapy and at 6 weeks posttreatment were assessed using the clinician-reported Common Terminology Criteria for Adverse Events version 5.0, and QOL was measured using the Expanded Prostate Cancer Index Composite (EPIC-50) and International Prostate Symptom Score (IPSS). A total of 80 patients were enrolled and treated across 3 Canadian institutions, of whom 39 and 41 patients received external radiation therapy with conventionally fractionated and ultrahypofractionated WPRT, respectively. All patients received androgen deprivation therapy except for 2 patients treated in the ultrahypofractionated arm. The baseline clinical characteristics of the 2 arms were similar, with 51 (63.8%) patients having high or very-high-risk prostate cancer disease. Treatment was well tolerated with no significant differences in the rate of acute adverse events between arms. No grade 4 adverse events or treatment-related deaths were reported. Ultrahypofractionated WPRT had a less detrimental impact on the EPIC-50 bowel total, function, and bother domain scores compared with conventional WPRT in the acute setting. By contrast, more patients treated with ultrahypofractionated WPRT reached the minimum clinical important difference on the EPIC-50 urinary domains. No significant QOL differences between arms were noted in the sexual and hormonal domains. Ultrahypofractionated WPRT after HDR-BT is a well-tolerated treatment strategy in the acute setting that has less detrimental impact on bowel QOL domains compared with conventional WPRT. [ABSTRACT FROM AUTHOR]

Background: Heart-sparing techniques are time and resource intensive, although not all patients require the use of these strategies. This study evaluates the performance of different distance metrics in predicting the need for breath-hold radiotherapy in left-sided breast cancer patients receiving adjuvant radiotherapy.Methods: Fifty left-sided breast cancer patients treated with breast conserving surgery and adjuvant radiotherapy to the breast from a single institution were retrospectively studied. The left breast and organs at risk were contoured in accordance to guidelines and a plan with tangents was obtained using the free-breathing CT in supine position. Heart (mean heart dose (MHD), heart V25 Gy) and left anterior descending artery dosimetry were computed and compared against distance metrics under investigation (Contact Heart, 4th Arch and 5th Arch). Recursive partitioning analysis (RPA) was used to determine optimal cut-points for distance metrics for dosimetric end points. Receiver operating characteristic curves and Pearson correlation coefficients were used to evaluate the association between distance metrics and dosimetric endpoints. Univariable and multivariable logistic regression analysis was performed to identify significant predictors of dosimetric end points.Results: The mean MHD and heart V25 Gy were 2.3 Gy and 10.4 cm3, respectively. With tangents, constraints for MHD (< 1.7 Gy and V25 Gy < 10 cm3) were unattainable in 80% and 46% of patients, respectively. Optimal RPA thresholds included: Contact Heart (73 mm), 4th Arch (7 mm) and 5th Arch (41 mm). Of these, the 4th Arch had the highest overall accuracy, sensitivity, concordance index and correlation coefficient. All metrics were statistically significant predictors for MHD ≥ 1.7 Gy based on univariable logistic regression. Fifth Arch did not reach significance for heart V25 Gy ≥ 10 cm3. Fourth Arch was the only predictor to remain statistically significant after multivariable analysis.Conclusions: We propose a novel "4th Arch" metric as an accurate and practical tool to determine the need for breath-hold radiotherapy for left-sided breast cancer patients undergoing adjuvant radiotherapy with standard tangents. Further validation in an external cohort is necessary. [ABSTRACT FROM AUTHOR]

• Short-term ADT increased BFFS in UIR patients treated with HDT-BT boost. • CRFS and MFS were not impacted by ADT use. • UIR patients treated with ADT had similar BFFS to favourable intermediate risk (FIR). To investigate the role of androgen deprivation therapy (ADT) in unfavorable intermediate risk (UIR) prostate cancer patients treated with high-dose rate (HDR) brachytherapy (BT) boost. Data from 326 consecutive NCCN UIR prostate cancer patients treated in a single institution from 2009 to 2016 with 15 Gy HDR-BT boost plus 37.5 Gy external beam radiotherapy (EBRT) in 15 fractions to prostate and proximal seminal vesicles were retrospectively collected. Baseline information was collected and patients receiving vs. not receiving ADT were matched using a propensity-score model. Primary endpoint was biochemical-failure-free survival (BFFS). Kaplan–Meier estimates and stratified log-rank tests (adjusting for matched design) were used to compare BFFS, castration-resistance (CRFS) and metastasis free survival (MFS) outcomes between both groups. A total of 326 patients were included in the analysis of which 52 ADT patients were matched to 104 non-ADT patients in a 1:2 ratio. Median follow-up was 3.4 years and 5.5 years for ADT and non-ADT respectively. No significant baseline differences were observed. ADT was used for a median total time of 6 months (interquartile range [IQR]: 4–6) and delivered a median time of 2.7 months (IQR: 1.7–4.3) prior to HDR-BT. BFFS was significantly improved in the ADT group (stratified log-rank: p = 0.043) with 3-year and 6-year BFFS of 98% and 90% for the ADT group and 92% and 82% for the non-ADT group, respectively. No significant differences were detected for CRFS or MFS. Short-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT. [ABSTRACT FROM AUTHOR]

Background: Cancer patients frequently search the Internet for treatment options, and hospital websites are seen as reliable sources of knowledge. Guidelines support the use of proton radiotherapy in specific disease sites or on clinical trials. This study aims to evaluate direct-to-consumer advertising content and claims made by proton therapy centre (PTC) websites worldwide.Methods: Operational PTC websites in English were identified through the Particle Therapy Co-Operative Group website. Data abstraction of website content was performed independently by two investigators. Eight international guidelines were consulted to determine guideline-based indications for proton radiotherapy. Univariate and multivariate logistic regression models were used to determine the characteristics of PTC websites that indicated proton radiotherapy offered greater disease control or cure rates.Results: Forty-eight PTCs with 46 English websites were identified. 60·9% of PTC websites claimed proton therapy provided improved disease control or cure. U.S. websites listed more indications than international websites (15·5 ± 5·4 vs. 10·4 ± 5·8, p = 0·004). The most common disease sites advertised were prostate (87·0%), head and neck (87·0%) and pediatrics (82·6%), all of which were indicated in least one international guideline. Several disease sites advertised were not present in any consensus guidelines, including pancreatobiliary (52·2%), breast (50·0%), and esophageal (43·5%) cancers. Multivariate analysis found increasing number of disease sites and claiming their centre was a local or regional leader in proton radiotherapy was associated with indicating proton radiotherapy offers greater disease control or cure.Conclusions: Information from PTC websites often differs from recommendations found in international consensus guidelines. As online marketing information may have significant influence on patient decision-making, alignment of such information with accepted guidelines and consensus opinion should be adopted by PTC providers. [ABSTRACT FROM AUTHOR]

Background: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for primary renal cell carcinoma, for which long-term data are awaited. The primary aim of this study was to report on long-term efficacy and safety of SABR for localised renal cell carcinoma.Methods: This study was an individual patient data meta-analysis, for which patients undergoing SABR for primary renal cell carcinoma across 12 institutions in five countries (Australia, Canada, Germany, Japan, and the USA) were eligible. Eligible patients had at least 2 years of follow-up, were aged 18 years or older, had any performance status, and had no previous local therapy. Patients with metastatic renal cell carcinoma or upper-tract urothelial carcinoma were excluded. SABR was delivered as a single or multiple fractions of greater than 5 Gy. The primary endpoint was investigator-assessed local failure per the Response Evaluation Criteria in Solid Tumours version 1.1, and was evaluated using cumulative incidence functions.Findings: 190 patients received SABR between March 23, 2007, and Sept 20, 2018. Single-fraction SABR was delivered in 81 (43%) patients and multifraction SABR was delivered in 109 (57%) patients. Median follow-up was 5·0 years (IQR 3·4-6·8). 139 (73%) patients were men, and 51 (27%) were women. Median age was 73·6 years (IQR 66·2-82·0). Median tumour diameter was 4·0 cm (IQR 2·8-4·9). 96 (75%) of 128 patients with available operability details were deemed inoperable by the referring urologist. 56 (29%) of 190 patients had a solitary kidney. Median baseline estimated glomerular filtration rate (eGFR) was 60·0 mL/min per 1·73 m2 (IQR 42·0-76·0) and decreased by 14·2 mL/min per 1·73 m2 (IQR 5·4-22·5) by 5 years post-SABR. Seven (4%) patients required dialysis post-SABR. The cumulative incidence of local failure at 5 years was 5·5% (95% CI 2·8-9·5) overall, with single-fraction SABR yielding fewer local failures than multifraction (Gray's p=0·020). There were no grade 3 toxic effects or treatment-related deaths. One (1%) patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis.Interpretation: SABR is effective and safe in the long term for patients with primary renal cell carcinoma. Single-fraction SABR might yield less local failure than multifraction, but further evidence from randomised trials is needed to elucidate optimal treatment schedules. These mature data lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery.Funding: None. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether functional lung avoidance based on 3He magnetic resonance imaging (MRI) improves quality of life (QOL) for patients undergoing concurrent chemoradiotherapy (CCRT) for advanced non-small cell lung cancer.Methods and Materials: Patients with stage III non-small cell lung cancer (or oligometastatic disease treated with curative intent) undergoing CCRT with at least a 10 pack-year smoking history were eligible. Patients underwent pretreatment 3He MRI to measure lung ventilation and had 2 radiation therapy (RT) plans created before randomization: a standard plan, which did not make use of the 3He MRI, and an avoidance plan, preferentially sparing well-ventilated lung. All participants were masked to assignment except the physicist responsible for exporting the selected plan. The primary end point was patient-reported QOL measured at 3-months post-RT by the FACT-L lung cancer subscale (LCS); secondary end points included other QOL metrics, toxicity, and survival outcomes. Target accrual was 64.Results: Twenty-seven patients were randomized before the trial was closed due to slower-than-expected accrual, with 11 randomized to the standard arm and 16 to the avoidance arm. Baseline patient characteristics were well-balanced. At 3 months post-RT, the mean ± SD LCS scores were 17.4 ± 2.8 versus 17.3 ± 6.1 for the standard and avoidance arms, respectively (P = .485). A clinically meaningful, prespecified decline of ≥3 points in the LCS score was observed in 50% (4/8) in the standard arm and 33% (4/12) in the avoidance arm (P = .648). Two patients in each arm developed grade ≥2 radiation pneumonitis, with no grade ≥4 toxicities.Conclusions: Although this trial did not reach full accrual, QOL scores were very similar between arms. Due to the scarcity of 3He MRI, other, more commonly available methods to measure functional lung, such as 4-dimensional computed tomography ventilation mapping, may be considered in the assessment of functional lung avoidance RT, and a larger, multicenter approach would be needed to accrue sufficient patients to test such approaches. [ABSTRACT FROM AUTHOR]

Purpose: The Anatomy and Radiology Contouring (ARC) Bootcamp was a face-to-face (F2F) intervention providing integrated education for radiation oncology (RO) residents and medical physicists. To increase access, we launched an online offering in 2019. We evaluated the effect of the online course on participants' knowledge acquisition, contouring skills, and self-confidence by comparing it with the F2F course.Methods and Materials: Using modules, the online course offers content similar to that of the F2F comparator. Participants from the 2019 F2F and the 2019-2020 online course completed pre- and postevaluations assessing anatomy and radiology knowledge, contouring skills, self-confidence, and course satisfaction.Results: There were 180 individuals enrolled (F2F: n = 40; online: n = 140); 57 participants (F2F: n = 30; online: n = 27) completed both evaluations. The online course had a wider geographic participation (19 countries) than F2F (4 countries). F2F had primarily RO resident participation (80%), compared with online (41%). Both cohorts demonstrated similar improvements in self-confidence pertaining to anatomy and radiology knowledge, contouring skills, and interpreting radiology images (all P < .001). Both the online (mean ± SD improvement: 6.6 ± 6.7 on a 40-point scale; P < .001) and F2F (3.7 ± 5.7; P = .002) groups showed anatomy and radiology knowledge improvement. Only the F2F group demonstrated improvement with the contouring assessment (F2F: 0.10 ± 0.17 on a 1-point Dice scale; P = .004; online: 0.07 ± 0.16; P = .076). Both cohorts perceived the course as a positive experience (F2F: 4.8 ± 0.4 on a 5-point scale; online: 4.5 ± 0.6), stated it would improve their professional practice (F2F: 4.6 ± 0.5; online: 4.2 ± 0.8), and said they would recommend it to others (F2F: 4.8 ± 0.4; online: 4.4 ± 0.6).Conclusions: The online ARC Bootcamp demonstrated improved self-confidence, knowledge scores, and high satisfaction levels among participants. The offering had lower completion rates but was more accessible to geographic regions, provided a flexible learning experience, and allowed for ongoing education during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Purpose: Simulation-based medical education is an effective tool for medical teaching, but simulation-based medical education deployment in radiation oncology (RO) is limited. Flexible nasopharyngoscopy (FNP), an essential skill for RO residents, requires practice that typically occurs on volunteer patients, introducing the potential for stress and discomfort. We sought to develop a high-fidelity simulator and intervention that provides RO residents the opportunity to develop FNP skills in a low-pressure environment.Methods and Materials: Computed tomography images were used to create an anatomically accurate 3-dimensional-printed model of the head and neck region. An intervention incorporating didactic instruction, multimedia content, and FNP practice on the model was designed and administered to RO residents attending the Anatomy and Radiology Contouring Bootcamp. Participants completed pre- and postintervention evaluations of the training session and model fidelity, and self-assessments of FNP skill and confidence performing FNP. Participants were video recorded performing FNP pre- and postintervention. Videos were scored by a blinded observer on a predefined rubric. Changes in scores were evaluated using the Wilcoxon signed-rank test.Results: Twenty-four participants from 17 institutions and 4 countries completed the intervention, 50% were women, and most were senior residents. Postintervention, FNP confidence and FNP performance improved significantly (mean ± standard deviation on a 10-point scale: 1.8 ± 1.8, P < .001; 2.2 ± 2.0, P < .001, respectively). Participants felt the model was helpful (mean ± standard deviation on a 5-point scale: 4.2 ± 0.6), anatomically correct (4.1 ± 0.9), and aided in spatial comprehension (4.3 ± 0.8). Overall satisfaction for the intervention was high (4.3 ± 0.8). Participants strongly agreed the intervention should be integrated into RO training programs (4.3 ± 0.8).Conclusions: A 3-dimensional-printed model and associated intervention were effective at improving FNP performance and the teaching method was rated highly by participants. RO residents may benefit from broader dissemination of this technique to improve trainee performance. [ABSTRACT FROM AUTHOR]

Purpose: Various radiation schedules are used in concurrent chemoradiation therapy for limited-stage small cell lung cancer (LS-SCLC). Since there is currently no randomized evidence comparing hypofractionated radiation therapy (HFRT) and conventionally fractionated radiation therapy (CFRT), the aim of this study was to compare overall survival (OS), progression-free survival (PFS), and toxicity of HFRT and CFRT in LS-SCLC.Methods and Materials: Patients with LS-SCLC treated between 2000 and 2013 with HFRT (40 Gy/15 fractions, 45 Gy/15 fractions, 45 Gy/20 fractions) or CFRT (60 Gy/30 or 66 Gy/33 fractions) were included. Propensity scores were generated using a multivariable logistic regression model. Patients were matched on a 1:1 ratio with a caliper distance of 0.20. OS and PFS were estimated by the Kaplan-Meier method and compared using log-rank tests. As a sensitivity analysis, univariable and multivariable Cox regression was performed including all patients without matching. Logistic regression was performed to identify predictors of pulmonary and esophageal adverse events.Results: In the overall group of 117 patients, there were significant baseline differences between the HFRT and CFRT cohorts. Patients who received CFRT were older, more often smoked concurrently with treatment, had higher Eastern Cooperative Oncology Group performance status, different T and N stage patterns, and more commonly received concurrent chemoradiation therapy and prophylactic cranial irradiation. After propensity score matching for these differences, 72 patients were included, 36 in the HFRT and CFRT cohorts, respectively. There was no difference in OS (P = .724), PFS (P = .862), or any pulmonary (P = .350) or esophageal (P = .097) adverse events between cohorts. Skin adverse events were significantly higher for CFRT (41.7%) compared with HFRT (16.7%, P = .020). Multivariable Cox regression also revealed no differences in OS (P = .886) or PFS (P = .717) between all HFRT and CFRT patients, without matching. No grade 5 adverse events were observed.Conclusions: In LS-SCLC patients, HFRT was associated with comparable survival and toxicity outcomes and may be considered as an alternative to CFRT, should its efficacy be confirmed in prospective studies. [ABSTRACT FROM AUTHOR]

Objective As the optimal adjuvant management of stage IA serous or clear cell endometrial cancer is controversial, a multi-institutional review was conducted with the objective of evaluating the appropriateness of various strategies including observation. Methods Retrospective chart reviews for 414 consecutive patients who underwent hysterectomy for FIGO stage IA endometrial cancer with serous, clear cell or mixed histology between 2004 and 2015 were conducted in 6 North American centers. Time-to-event outcomes were analyzed by Kaplan-Meier estimates, log-rank test, univariable and multivariable cox proportional hazard regression models. Results Post-operative management included observation (50%), chemotherapy and radiotherapy (RT) (27%), RT only (16%) and chemotherapy only (7%). The 178 RT patients received external beam (EBRT, 16%), vaginal vault brachytherapy (VVB, 56%) or both (28%). Among patients without any adjuvant treatment, 5-year local control (LC), disease free survival (DFS) and cancer-specific survival (CSS) were 82% (95% confidence interval: 74–88), 70% (62–78) and 90% (82–94), respectively. CSS in patients without adjuvant treatment was improved with adequate surgical staging (100% vs. 87% (77–92), log-rank p = 0.022). Adjuvant VVB was associated with improved LC (5-year 96% (91–99) vs. 84% (76–89), log-rank p = 0.007) and DFS (5-year 79% (66–88) vs. 71% (63–77), log-rank p = 0.033). Adjuvant chemotherapy was associated with better LC (5-year 96% (90–98) vs. 84% (77–89), log-rank p = 0.014) and DFS (5-year 84% (74–91) vs. 69% (61–76), log-rank p = 0.009). On multivariable analysis, adjuvant chemotherapy and VVB were associated with improved LC while adjuvant chemotherapy and age were significant for DFS. Conclusions In stage IA serous or clear cell uterine cancer, adjuvant RT and chemotherapy were associated with better LC and DFS. Observation may be appropriate in patients who have had adequate surgical staging. [ABSTRACT FROM AUTHOR]

Purpose: Peer review is a recommended component of quality assurance in radiation oncology; however, it is resource-intensive and its effect on patient care is not well understood. We conducted a systematic review of the published data to assess the reported clinical impact of peer review on radiation treatment plans.Methods and Materials: A systematic review of published English studies was performed in accordance with the PRISMA guidelines using the MEDLINE and EMBASE databases and abstracts published from major radiation oncology scientific meeting proceedings. For inclusion, the studies were required to report the effect of peer review on ≥1 element of treatment planning (eg, target volume or organ-at-risk delineation, dose prescription or dosimetry).Results: The initial search strategy identified 882 potentially eligible studies, with 11 meeting the inclusion criteria for full-text review and final analysis. Across a total of 11,491 patient cases, peer review programs led to modifications in a weighted mean of 10.8% of radiation treatment plans. Five studies differentiated between major and minor changes and reported weighted mean rates of change of 1.8% and 7.3%, respectively. The most common changes were related to target volume delineation (45.2% of changed plans), dose prescription or written directives (24.4%), and non-target volume delineation or normal tissue sparing (7.5%).Conclusions: Our findings suggest that peer review leads to changes in clinical care in approximately 1 of every 9 cases overall. This is similar to the reported rates of change in peer review studies from other oncology-related specialties, such as radiology and pathology. [ABSTRACT FROM AUTHOR]

Purpose: Despite the rising costs in radiation oncology, the impact of health economics research on radiation therapy practice analysis patterns is unclear. We performed a systematic review of cost-effectiveness analyses (CEAs) and cost-utility analyses (CUAs) to identify trends in reporting quality in the radiation oncology literature over time.Methods and Materials: A systematic review of radiation oncology economic evaluations up to 2014 was performed, using MEDLINE and EMBASE databases. The Consolidated Health Economic Evaluation Reporting Standards guideline informed data abstraction variables including study demographics, economic parameters, and methodological details. Tufts Medical Center CEA registry quality scores provided a basis for qualitative assessment of included studies. Studies were stratified by 3 time periods (1995-2004, 2005-2009, and 2010-2014). The Cochran-Armitage trend test and linear trend test were used to identify trends over time.Results: In total, 102 articles were selected for final review. Most studies were in the context of a model (61%) or clinical trial (28%). Many studies lacked a conflict of interest (COI) statement (67%), a sponsorship statement (48%), a reported study time horizon (35%), and the use of discounting (29%). There was a significant increase over time in the reporting of a COI statement (P<.001), health care payer perspective (P=.019), sensitivity analyses using multivariate (P=.043) or probabilistic methods (P=.011), incremental cost-effectiveness threshold (P<.001), secondary source utility weights (P=.010), and cost effectiveness acceptability curves (P=.049). There was a trend toward improvement in Tuft scores over time (P=.065).Conclusions: Recent reports demonstrate improved reporting rates in economic evaluations; however, there remains significant room for improvement as reporting rates are still suboptimal. As fiscal pressures rise, we will rely on economic assessments to guide our practice decisions and policies. We recommend improved adherence to published guidelines and further research to determine the clinical implications of our findings. [ABSTRACT FROM AUTHOR]

Purpose To compare, in a retrospective study, biochemical failure-free survival (bFFS) and overall survival (OS) in low-risk and intermediate-risk prostate cancer patients who received brachytherapy (BT) (either low-dose-rate brachytherapy [LDR-BT] or high-dose-rate brachytherapy with external beam radiation therapy [HDR-BT+EBRT]) versus external beam radiation therapy (EBRT) alone. Methods and Materials Patient data were obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated with primary radiation therapy at four Canadian cancer institutions from 1994 to 2010. Propensity score matching was used to obtain the following 3 matched cohorts with balanced baseline prognostic factors: ( 1 ) low-risk LDR-BT versus EBRT; ( 2 ) intermediate-risk LDR-BT versus EBRT; and ( 3 ) intermediate-risk HDR-BT+EBRT versus EBRT. Kaplan-Meier survival analysis was performed to compare differences in bFFS (primary endpoint) and OS in the 3 matched groups. Results Propensity score matching created acceptable balance in the baseline prognostic factors in all matches. Final matches included 2 1:1 matches in the intermediate-risk cohorts, LDR-BT versus EBRT (total n=254) and HDR-BT+EBRT versus EBRT (total n=388), and one 4:1 match in the low-risk cohort (LDR-BT:EBRT, total n=400). Median follow-up ranged from 2.7 to 7.3 years for the 3 matched cohorts. Kaplan-Meier survival analysis showed that all BT treatment options were associated with statistically significant improvements in bFFS when compared with EBRT in all cohorts (intermediate-risk EBRT vs LDR-BT hazard ratio [HR] 4.58, P =.001; intermediate-risk EBRT vs HDR-BT+EBRT HR 2.08, P =.007; low-risk EBRT vs LDR-BT HR 2.90, P =.004). No significant difference in OS was found in all comparisons (intermediate-risk EBRT vs LDR-BT HR 1.27, P =.687; intermediate-risk EBRT vs HDR-BT+EBRT HR 1.55, P =.470; low-risk LDR-BT vs EBRT HR 1.41, P =.500). Conclusions Propensity score matched analysis showed that BT options led to statistically significant improvements in bFFS in low- and intermediate-risk prostate cancer patient populations. [ABSTRACT FROM AUTHOR]

Abstract: Background: The Genitourinary Radiation Oncologists of Canada (GUROC) published a three-group risk stratification (RS) system to assist prostate cancer decision-making in 2001. The objective of this project is to use the ProCaRS database to statistically model the predictive accuracy and clinical utility of a proposed new multi-group RS schema. Methods: The RS analyses utilized the ProCaRS database that consists of 7974 patients from four Canadian institutions. Recursive partitioning analysis (RPA) was utilized to explore the sub-stratification of groups defined by the existing three-group GUROC scheme. 10-fold cross-validated C-indices and the Net Reclassification Index were both used to assess multivariable models and compare the predictive accuracy of existing and proposed RS systems, respectively. Results: The recursive partitioning analysis has suggested that the existing GUROC classification system could be altered to accommodate as many as six separate and statistical unique groups based on differences in BFFS (C-index 0.67 and AUC 0.70). GUROC low-risk patients would be divided into new favorable-low and low-risk groups based on PSA ⩽6 and PSA >6. GUROC intermediate-risk patients can be subclassified into low-intermediate and high-intermediate groups. GUROC high-intermediate-risk is defined as existing GUROC intermediate-risk with PSA >=10 AND either T2b/c disease or T1T2a disease with Gleason 7. GUROC high-risk patients would be subclassified into an additional extreme-risk group (GUROC high-risk AND (positive cores ⩾87.5% OR PSA >30). Conclusions: Proposed RS subcategories have been identified by a RPA of the ProCaRS database. [Copyright &y& Elsevier]

Abstract: Objectives: Metastatic non-small cell lung carcinoma (NSCLC) generally carries a poor prognosis, and systemic therapy is the mainstay of treatment. However, extended survival has been reported in patients presenting with a limited number of metastases, termed oligometastatic disease. We retrospectively reviewed the outcomes of such patients treated at two centers. Materials and methods: From September 1999–July 2012, a total of 61 patients with 1–3 synchronous metastases, who were treated with radical intent to all sites of disease, were identified from records of two cancer centers. Treatment was considered radical if it involved surgical resection and/or delivery of radiation doses ≥13×3Gy. Results: Besides the primary tumor, 50 patients had a solitary metastasis, 9 had two metastases, and 2 had three metastases. Locations of metastases included the brain (n =36), bone (n =11), adrenal (n =4), contralateral lung (n =4), extra-thoracic lymph nodes (n =4), skin (n =2) and colon (n =1). Only one patient had metastases in two different organs. Median follow-up was 26.1 months (m), median overall survival (OS) was 13.5m, median progression free survival (PFS) was 6.6m and median survival after first progression (SAFP) was 8.3m. The 1- and 2-year OS were, 54% and 38%, respectively. Significant predictors of improved OS were: smaller radiotherapy planning target volume (PTV) (p =0.004) and surgery for the primary lung tumor (p <0.001). Factors associated with improved SAFP included surgery for the primary lung tumor, presence of brain metastases, and absence of bone metastases. No significant differences in outcomes were observed between the two centers. Conclusion: Radical treatment of selected NSCLC patients presenting with 1–3 synchronous metastases can result in favorable 2-year survivals. Favorable outcomes were associated with intra-thoracic disease status: patients with small radiotherapy treatment volumes or resected disease had the best OS. Future prospective clinical trials, ideally randomized, should evaluate radical treatment strategies in such patients. [Copyright &y& Elsevier]