Stereotactic Radiation for the Comprehensive Treatment of Oligometastases (SABR-COMET): Extended Long-Term Outcomes.

PURPOSE: Long-term randomized data assessing the effect of ablative therapies in patients with oligometastases are lacking. The Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastases (SABR-COMET) randomized phase 2 trial was originally designed with 5 years of follow-up, but the trial was amended in 2016 to extend follow-up to 10 years. Herein we report oncologic outcomes beyond 5 years. METHODS AND MATERIALS: Patients were eligible if they had a controlled primary tumor and 1 to 5 metastases, with all metastases amenable to SABR. Patients were randomized in a 1:2 ratio between palliative standard-of-care treatment (control arm) versus SABR to all metastases plus standard of care (SABR arm). The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), toxicity, quality of life (using the Functional Assessment of Cancer Therapy: General [FACT-G]), and time to new metastases. RESULTS: Ninety-nine patients were randomized between 2012 and 2016 (n = 33 in arm 1 vs n = 66 in arm 2). Primary tumor sites included lung (n = 18), breast (n = 18), colon (n = 18), prostate (n = 16), and other (n = 29). Eight-year OS was 27.2% in the SABR arm versus 13.6% in the control arm (hazard ratio, 0.50; 95% confidence interval, 0.30-0.84; P = .008). Eight-year PFS estimates were 21.3% versus 0.0%, respectively (hazard ratio, 0.45; 95% confidence interval, 0.28-0.72; P < .001). Rates of grade ≥ 2 acute or late toxic effects were 30.3% versus 9.1% (P = .019), with no new grade 3 to 5 toxic effects. FACT-G quality of life scores declined over time in both arms, but there were no differences in quality of life scores between arms. The use of systemic therapy overall was similar between arms, but patients in the SABR arm were less likely to require cytotoxic chemotherapy (33.3% vs 54.6%, respectively, P = .043). CONCLUSIONS: SABR achieved durable improvements in OS and PFS, with no new major toxicity signals with extended follow-up. A minority of patients randomized to the SABR arm (21.3%) achieved > 5 years of survival without recurrence.

Ninety-day mortality after radiotherapy for head and neck cancer: Population-based comparison between rural and urban patients.

BACKGROUND: This study assesses whether 90-day mortality differs between patients living in rural and urban areas, as lower access to supportive care services in rural areas could result in higher mortality. METHODS: All patients with head and neck cancer (HNC) treated between 1998 and 2014 with radiotherapy in British Columbia were included. Patients were divided into rurality areas according to the Modified Statistics Canada (mSC) definition, which classifies a population <30 000 as rural and ≥30 000 as urban. RESULTS: Five thousand five hundred and fifty-four patients were included in this study, of which 68% lived in urban centers. The 90-day mortality for rural versus urban patients were 3.0% and 3.9% (p = 0.09), respectively. Univariate and multivariate analyses showed no association with 90-day mortality and rurality. CONCLUSION: After controlling for potentially confounding factors, we did not find a significant association between 90-day mortality and rurality in patients who were treated with radiotherapy for HNC in British Columbia.

Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial.

PURPOSE: The oligometastatic paradigm hypothesizes that patients with a limited number of metastases may achieve long-term disease control, or even cure, if all sites of disease can be ablated. However, long-term randomized data that test this paradigm are lacking. METHODS: We enrolled patients with a controlled primary malignancy and 1-5 metastatic lesions, with all metastases amenable to stereotactic ablative radiotherapy (SABR). We stratified by the number of metastases (1-3 v 4-5) and randomized in a 1:2 ratio between palliative standard-of-care (SOC) treatments (arm 1) and SOC plus SABR (arm 2). We used a randomized phase II screening design with a primary end point of overall survival (OS), using an α of .20 (wherein P < .20 indicates a positive trial). Secondary end points included progression-free survival (PFS), toxicity, and quality of life (QOL). Herein, we present long-term outcomes from the trial. RESULTS: Between 2012 and 2016, 99 patients were randomly assigned at 10 centers internationally. The most common primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18), and prostate (n = 16). Median follow-up was 51 months. The 5-year OS rate was 17.7% in arm 1 (95% CI, 6% to 34%) versus 42.3% in arm 2 (95% CI, 28% to 56%; stratified log-rank P = .006). The 5-year PFS rate was not reached in arm 1 (3.2%; 95% CI, 0% to 14% at 4 years with last patient censored) and 17.3% in arm 2 (95% CI, 8% to 30%; P = .001). There were no new grade 2-5 adverse events and no differences in QOL between arms. CONCLUSION: With extended follow-up, the impact of SABR on OS was larger in magnitude than in the initial analysis and durable over time. There were no new safety signals, and SABR had no detrimental impact on QOL.

Patterns of Radiotherapy Utilization for Lung Cancer Patients with Brain Metastases: A Population-based Analysis.

INTRODUCTION: Brain metastases occur in 15%-20% of lung cancer patients. Recently, studies have suggested that whole-brain radiotherapy (WBRT) may not prolong survival for a subset of patients, and is associated with significant side-effects. Furthermore, it is hypothesized that radiotherapy is often given near the end-of-life when the potential for benefit is minimal. Therefore, this study investigates how frequently radiotherapy for brain metastases is given near the end-of-life in a population-based cohort. MATERIALS AND METHODS: All lung cancer patients who received radiotherapy in British Columbia for brain metastases in 2014-2015 were identified. Patient and treatment characteristics were collected and analyzed to assess associations with death within 90 days of first radiation treatment. RESULTS: In total, 740 patients were identified, with a total of 826 courses of brain radiation. The 90-day mortality rate was 40% (n=330). Multivariable analysis demonstrated higher odds for age (odds ratio (OR) = 1.04, 95% confidence interval (CI) 1.02-1.05), Eastern Cooperative Oncology Group (ECOG) performance score of 2 or higher (OR = 1.59, 95% CI 1.09-2.31) and squamous cell carcinoma (OR = 2.10, 95% CI 1.13-3.90) and lower odds for initial systemic therapy (OR = 0.48, 95% CI 0.34-0.68), more than five fractions of radiotherapy (OR = 0.25, 95% CI 0.16-0.39) and stereotactic radiation (OR = 0.29, 95% CI 0.13-0.65). CONCLUSION: In our population-based study, WBRT is given in 86% of radiotherapy courses for brain metastases from lung cancer. Of these patients, 40% received treatment near the end-of-life. We identified several factors associated with shortened survival. Using these factors and already established prognostic tools, WBRT utilization should be decreased in the future, improving individualized treatment for patients with brain metastases from lung cancer.

SUPR-3D: A randomized phase iii trial comparing simple unplanned palliative radiotherapy versus 3d conformal radiotherapy for patients with bone metastases: study protocol.

BACKGROUND: Bone metastases in the lower spine and pelvis are effectively palliated with radiotherapy (RT), though this can come with side effects such as radiation induced nausea and vomiting (RINV). We hypothesize that high rates of RINV occur in part because of the widespread use of inexpensive simple unplanned palliative radiotherapy (SUPR), over more complex and resource intensive 3D conformal RT, such as volumetric modulated arc therapy (VMAT). METHODS: This is a randomized, multi-centre phase III trial of SUPR versus VMAT. We will accrue 250 patients to assess the difference in patient-reported RINV. This study is powered to detect a difference in quality of life between patients treated with VMAT vs. SUPR. DISCUSSION: This trial will determine if VMAT reduces early toxicity compared to SUPR and may provide justification for this more resource-intensive and costly form of RT. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03694015 . Date of registration: October 3, 2018.

What to choose as radical local treatment for lung metastases from colo-rectal cancer: surgery or radiofrequency ablation?

BACKGROUND: Long-term survival can be obtained with local treatment of lung metastases from colorectal cancer. However, it is unclear as to what the optimal local therapy is: surgery, radiofrequency ablation (RFA) or stereotactic radiotherapy (SBRT). METHODS: A systematic review included 27 studies matching with the a priori selection criteria, the most important being ≥50 patients and a follow-up period of ≥24months. No SBRT studies were eligible. The review was therefore conducted on 4 RFA and 23 surgical series. RESULTS: Four of the surgical studies were prospective, all others were retrospective. No randomized trial was found. The reporting of data differed between the studies, which led to difficulties in the analyses. Treatment-related mortality rates for RFA and surgery were 0% and 1.4-2.4%, respectively, whereas morbidity rates were reported inconsistently but seemed the lowest for surgery. CONCLUSION: Due to the lack of phase III trials, no firm conclusions can be drawn, although most evidence supports surgery as the most effective treatment option. High-quality trials comparing currently used treatment modalities such as SBRT, RFA and surgery are needed to inform treatment decisions.