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Background and Purpose: Stereotactic ablative radiotherapy (SABR) for oligometastases may improve survival, however concerns about safety remain. To mitigate risk of toxicity, target coverage was sacrificed to prioritize organs-at-risk (OARs) during SABR planning in the population-based SABR-5 trial. This study evaluated the effect of this practice on dosimetry, local recurrence (LR), and progression-free survival (PFS)., Methods: This single-arm phase II trial included patients with up to 5 oligometastases between November 2016 and July 2020. Theprotocol-specified planning objective was to cover 95 % of the planning target volume (PTV) with 100 % of the prescribed dose, however PTV coverage was reduced as needed to meet OAR constraints. This trade-off was measured using the coverage compromise index (CCI), computed as minimum dose received by the hottest 99 % of the PTV (D99) divided by the prescription dose. Under-coverage was defined as CCI < 0.90. The potential association between CCI and outcomes was evaluated., Results: 549 lesions from 381 patients were assessed. Mean CCI was 0.88 (95 % confidence interval [CI], 0.86-0.89), and 196 (36 %) lesions were under-covered. The highest mean CCI (0.95; 95 %CI, 0.93-0.97) was in non-spine bone lesions (n = 116), while the lowest mean CCI (0.71; 95 % CI, 0.69-0.73) was in spine lesions (n = 104). On multivariable analysis, under-coverage did not predict for worse LR (HR 0.48, p = 0.37) or PFS (HR 1.24, p = 0.38). Largest lesion diameter, colorectal and 'other' (non-prostate, breast, or lung) primary predicted for worse LR. Largest lesion diameter, synchronous tumor treatment, short disease free interval, state of oligoprogression, initiation or change in systemic treatment, and a high PTV Dmax were significantly associated with PFS., Conclusion: PTV under-coverage was not associated with worse LR or PFS in this large, population-based phase II trial. Combined with low toxicity rates, this study supports the practice of prioritizing OAR constraints during oligometastatic SABR planning., 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: A subset of patients with oligometastatic cancer experience early widespread cancer dissemination and do not benefit from metastasis-directed therapy such as SABR. This study aimed to identify factors associated with early polymetastatic relapse (PMR)., Methods and Materials: The SABR-5 trial was a single arm phase 2 study conducted at all 6 regional cancer centers across British Columbia (BC), Canada. SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastatic lesions (total, progressing, or induced) received SABR to all lesions. Patients were 18 years of age or older, Eastern Cooperative Oncology Group 0 to 2 and life expectancy ≥6 months. This secondary analysis evaluated factors associated with early PMR, defined as disease recurrence within 6 months of SABR, which is not amenable to further local treatment. Univariable and multivariable analyses were performed using binary logistic regression. The Kaplan-Meier method and log-rank tests assessed PMR-free survival and differences between risk groups, respectively., Results: Between November 2016 and July 2020, 381 patients underwent treatment on SABR-5. A total of 16% of patients experienced PMR. Worse performance status (Eastern Cooperative Oncology Group 1-2 vs 0; hazard ratio [HR] = 2.01, P = .018), nonprostate/breast histology (HR = 3.64, P <.001), and oligoprogression (HR = 3.84, P <.001) were independent predictors for early PMR. Risk groups were identified with median PMR-free survival ranging from 5 months to not yet reached at the time of analysis. Rates of 3-year overall survival were 0%, 53% (95% confidence interval [CI], 48-58), 77% (95% CI, 73-81), and 93% (95% CI, 90-96) in groups 1 to 4, respectively (P <.001)., Conclusions: Four distinct risk groups for early PMR are identified, which differ significantly in PMR-free survival and overall survival. The group with all 3 risk factors had a median PMR-free survival of 5 months and may not benefit from local ablative therapy alone. This model should be externally validated with data from other prospective trials., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: After the publication of the landmark SABR-COMET trial, concerns arose regarding high-grade toxic effects of treatment with stereotactic ablative body radiotherapy (SABR) for oligometastases., Objective: To document toxic effects of treatment with SABR in a large cohort from a population-based, provincial cancer program., Design, Setting, and Participants: From November 2016 to July 2020, 381 patients across all 6 cancer centers in British Columbia were treated in this single-arm, phase 2 trial of treatment with SABR for patients with oligometastatic or oligoprogressive disease. During this period, patients were only eligible to receive treatment with SABR in these settings in trials within British Columbia; therefore, this analysis is population based, with resultant minimal selection bias compared with previously published SABR series., Interventions: Stereotactic ablative body radiotherapy to up to 5 metastases., Main Outcomes and Measures: Rate of grade 2, 3, 4, and 5 toxic effects associated with SABR., Findings: Among 381 participants (122 women [32%]), the mean (SD; range) age was 68 (11.1; 30-97) years, and the median (range) follow-up was 25 (1-54) months. The most common histological findings were prostate cancer (123 [32%]), colorectal cancer (63 [17%]), breast cancer (42 [11%]), and lung cancer (33 [9%]). The number of SABR-treated sites were 1 (263 [69%]), 2 (82 [22%]), and 3 or more (36 [10%]). The most common sites of SABR were lung (188 [34%]), nonspine bone (136 [25%]), spine (85 [16%]), lymph nodes (78 [14%]), liver (29 [5%]), and adrenal (15 [3%]). Rates of grade 2, 3, 4, and 5 toxic effects associated with SABR (based on the highest-grade toxic effect per patient) were 14.2%; (95% CI, 10.7%-17.7%), 4.2% (95% CI, 2.2%-6.2%), 0%, and 0.3% (95% CI, 0%-0.8%), respectively. The cumulative incidence of grade 2 or higher toxic effects associated with SABR at year 2 by Kaplan-Meier analysis was 8%, and for grade 3 or higher, 4%., Conclusions and Relevance: This single-arm, phase 2 clinical trial found that the incidence of grade 3 or higher SABR toxic effects in this population-based study was less than 5%. Furthermore, the rates of grade 2 or higher toxic effects (18.6%) were lower than previously published for SABR-COMET (29%). These results suggest that SABR treatment for oligometastases has acceptable rates of toxic effects and potentially support further enrollment in randomized phase 3 clinical trials., Trial Registration: ClinicalTrials.gov Identifier: NCT02933242.

Purpose: To model and quantify the relationship between radiation therapy (RT) use and travel time to RT services., Methods and Materials: Population-based registries and databases were used to identify both incident cancer patient and patients receiving RT within 1 year of diagnosis (RT1y) in British Columbia, Canada, between 1992 and 2011. The effects of age, gender, diagnosis year, income, prevailing wait time, and travel duration for RT on RT1y were assessed. Significant factors from univariate analyses were included in a multivariable logistic regression model. The shape of the travel time-RT1y curve was represented by generalized additive and segmented regression models. Analyses were conducted for breast, lung, and genitourinary cancer separately and for all cancer sites combined., Results: After adjustment for age, gender, diagnosis year, income, and prevailing wait times, increasing travel time to the closest RT facility had a negative impact RT1y. The shape of the travel time-RT1y curve varied with cancer type. For breast cancer, the odds of RT1y were constant for the first 2 driving hours and decreased at 17% per hour thereafter. For lung cancer, the odds of RT1y decreased by 16% after 20 minutes and then decreased at 6% per hour. Genitourinary cancer RT1y was relatively independent of travel time. For all cancer sites combined, the odds of RT1y were constant within the first 2 driving hours and decreased at 7% per hour thereafter., Conclusions: Travel time to receive RT has a different impact on RT1y for different tumor sites. The results provide evidence-based insights for the configuration of catchment areas for new and existing cancer centers providing RT., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study was undertaken to determine whether there was an increased risk of second malignancies (SM), particularly lung cancer, in early stage breast cancer patients treated with the addition of nodal fields to breast and/or chest wall radiation therapy (RT)., Materials and Methods: Subjects were stage I/II female breast cancer patients 20 to 79 years of age, diagnosed between 1989 and 2005 and treated with adjuvant RT at our institution. Patients were included if they survived and did not have SM within 3 years of diagnosis. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to compare SM incidence to cancer incidence in the general sex- and age-matched populations. Secondary malignancy risks in patients treated with local RT (LRT) to the breast/chest wall were compared to those in patients treated with locoregional RT (LRRT) to the breast/chest wall and regional nodes, using multivariate regression analysis (MVA) to account for covariates., Results: The cohort included 12,836 patients with a median follow-up of 8.4 years. LRRT was used in 18% of patients. The SIR comparing patients treated with LRT to the general population was 1.29 (CI: 1.21-1.38). No statistically significant increased incidence of in-field malignancies (SIR, 1.04; CI: 0.87-1.23) and lung cancers (SIR, 1.06; CI: 0.88-1.26) was detected. The SIR comparing patients treated with LRRT to the general population was 1.39 (CI: 1.17-1.64). No statistically significant increased incidence of in-field malignancies (SIR, 1.26; CI: 0.77-1.94) and lung cancers (SIR, 1.27; CI: 0.76-1.98) was detected. On MVA comparing LRRT to LRT, the adjusted hazard ratio was 1.20 for in-field malignancies (CI: 0.68-2.16) and 1.26 for lung cancer (CI: 0.67-2.36). The excess attributable risk (EAR) to regional RT was 3.1 per 10,000 person years (CI: -8.7 to 9.9)., Conclusions: No statistically significant increased risk of second malignancy was detected after LRRT relative to that for LRT. The upper limit of the EAR was approximately 1% at 10 years., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Management of Stage III non-small-cell lung cancer (NSCLC) involves surgery, radiotherapy (RT), chemotherapy, and best supportive care. The aims were to describe the patterns of treatment in a population-based cohort of patients, and compare utilization of RT and chemotherapy to model estimates of need., Methods: Patients diagnosed with Stage III NSCLC between January 1, 2000, to December 31, 2007, were identified from the British Columbia Cancer Agency database. Patients who had prior or concomitant malignancy were excluded. Patient demographics, tumor characteristics, and initial treatment were extracted. Survival data were derived from the British Columbia Vital Statistics Death Listings., Results: 2365 patients with Stage III NSCLC were referred, of which 212 patients were excluded, leaving 2153 patients in the study population. Median age was 69 years. Disease stage was IIIA in 49% and IIIB in 51%. Histologies were squamous-cell carcinoma (31%), adenocarcinoma (27%), NSCLC not otherwise specified (31%), and other pathology (11%). Initial treatment included surgery in 12%, RT in 78%, and chemotherapy in 31%. Predicted RT utilization was 77% to 87% and chemotherapy 78%. From 2000 to 2007, curative-intent treatment increased from 21% to 35%, chemoradiotherapy from 8% to 18.6%, and concurrent chemoradiotherapy from 5.1% to 17.6%. Median survival was 30 months for patients who had curative surgery, 21 months for curative RT, 8 months for palliative treatment, and 5 months for best supportive care (p < 0.001)., Conclusion: RT utilization was similar to that predicted by models whereas chemotherapy utilization was less. During the study period, the proportion of patients receiving curative chemoradiotherapy doubled and of those receiving concurrent chemoradiotherapy trebled.

Purpose: Estimates of the need for radiotherapy (RT) using different methods (criterion based benchmarking [CBB] and the Canadian [C-EBEST] and Australian [A-EBEST] epidemiologically based estimates) exist for various cancer sites. We compared these model estimates to actual RT rates for lung, breast, and prostate cancers in British Columbia (BC)., Methods and Materials: All cases of lung, breast, and prostate cancers in BC from 1997 to 2004 and all patients receiving RT within 1 year (RT(1Y)) and within 5 years (RT(5Y)) of diagnosis were identified. The RT(1Y) and RT(5Y) proportions in health regions with a cancer center for the most recent year were then calculated. RT rates were compared with CBB and EBEST estimates of RT needs. Variation was assessed by time and region., Results: The RT(1Y) in regions with a cancer center for lung, breast, and prostate cancers were 51%, 58%, and 33% compared with 45%, 57%, and 32% for C-EBEST and 41%, 61%, and 37% for CBB models. The RT(5Y) rates in regions with a cancer center for lung, breast, and prostate cancers were 59%, 61%, and 40% compared with 61%, 66%, and 61% for C-EBEST and 75%, 83%, and 60% for A-EBEST models. The RT(1Y) rates increased for breast and prostate cancers., Conclusions: C-EBEST and CBB model estimates are closer to the actual RT rates than the A-EBEST estimates. Application of these model estimates by health care decision makers should be undertaken with an understanding of the methods used and the assumptions on which they were based., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aims: To compare the existing model estimates of the appropriate rates of radiotherapy for lung, breast and prostate cancers with actual radiotherapy rates in rural, semi-urban and urban areas, and in areas with short and long drive distances to cancer clinics in British Columbia., Materials and Methods: All registered cases of lung, breast and prostate cancer diagnosed in British Columbia between 1997 and 2007 were identified. The proportion of cancers treated within 1 (RT1Y) and 5 years (RT5Y) of diagnosis were calculated according to rural, semi-urban and urban area, and areas associated with short and long drive distances to cancer clinics in British Columbia., Results: RT1Y for lung, breast and prostate in urban and rural areas were 47/45%, 57/46% and 31/30%, and for short and long drive times were 47/44%, 56/50% and 31/31% compared with model estimates for initial radiotherapy needs of 41-45%, 57-61% and 32-37%, respectively. RT5Y for lung, breast and prostate in urban and rural areas were 52/47%, 59/48% and 42/39%, and for short and long drive times were 51/47%, 57/50% and 42/42% compared with model estimates for overall radiotherapy needs of 66-83%, 57-61% and 60-61%, respectively., Conclusions: Radiotherapy rates vary between and within urban and rural areas in British Columbia. Radiotherapy rates for breast and lung cancer patients are higher, and closer to model estimates of need, in urban areas and short drive time areas. Radiotherapy rates do not vary with drive time or rural versus urban classification for patients with prostate cancer., (Copyright (c) 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Introduction: Curative treatment of stage I non-small cell lung cancer (NSCLC) in elderly patients represents a therapeutic challenge. Data examining outcomes for the elderly after radical radiotherapy (RT) or surgery in the same geographic population are limited., Methods: Using prospective databases from British Columbia, patients with stage I NSCLC treated curatively with either surgery or RT between 2000 and 2006 were identified. Kaplan-Meier, Cox regression, and competing risk analyses were used to assess overall survival (OS) and disease-specific survival in the elderly, and the relationship between age and survival outcomes., Results: Of a total of 558 patients with stage I disease, 310 (56%) received surgery and 248 (44%) received RT. Elderly patients (age > or =75 years) were less likely to undergo resection than their younger counterparts (43% versus 72%, p < 0.0001). Actuarial OS after surgery for elderly patients was 87% at 2 years and 69% at 5 years. On multivariate analysis, OS after surgery was dependent on tumor stage (p = 0.034) and performance status (p = 0.03), but not age (p = 0.87). After RT, actuarial OS for elderly patients was 53% at 2 years and 23% at 5 years. On multivariate analysis, age did not predict for OS after RT (p = 0.43), whereas tumor stage (p = 0.033), sex (p = 0.044), and dose (p = 0.01) were significant predictors., Conclusions: Survival after radical treatment for stage I NSCLC is dependent on factors such as tumor stage, performance status, sex, and RT dose, but not age. Elderly patients who are sufficiently fit should not be considered ineligible for radical treatment based on age alone.

Background: Stage, weight loss, and performance status (PS) are important prognostic factors and eligibility factors for curative intent therapy for lung cancer patients. Details of stage, weight loss, and PS are often not collected until referral to a cancer specialist, and since not all patients are referred to cancer specialists these important variables are not well defined at a population level., Patients and Methods: Data on stage, weight loss, PS and referral pattern were requested from general practitioners (GPs) on all lung cancer patients diagnosed between May and June of 2002 in the province of British Columbia, Canada. Outcomes were analyzed in relation to survival and referral to a cancer centre., Results: 395 patients were identified, and GP questionnaires were returned on 85% of the cases. Patients referred to a cancer centre shortly after diagnosis differed from those who were not referred. Patients who were not referred to a cancer centre consisted of two groups-patients with localized disease and good PS who tended to have a better survival than those who were referred, and patients with advanced disease and poor performance status who tended to have a worse survival than those who were referred. GP assessed stage and PS are prognostic factors for survival., Conclusions: GP assessed stage and PS are prognostic factors for survival in lung cancer patients. The case mix of patients who are not referred to a cancer centre shortly after their diagnosis differs from those that are referred.

Purpose: To estimate the benefit and cost of using radiotherapy (RT) in the initial management of lung cancer in the general population., Methods: We identified indications for RT in the initial management of small cell and non-small cell lung cancer through a review of the literature. The proportion of patients with each specific indication for treatment was determined using epidemiological observations from cancer registry data and from the literature. We estimated the benefit gained from RT use for each indication in the model using values published in the literature. We estimated the cost of RT for each indication using published Canadian data. The total benefit and cost was calculated for all indications combined. Results are reported in 2001 Canadian dollars., Results: The mean benefit was 7 months of survival for each lung cancer patient treated with curative intent and 3 months of symptom control for each patient treated with palliative intent. The average cost was 9881 dollars per life year gained and 13,938 dollars per year of symptom control gained. Sensitivity analysis revealed values between 7905 dollars and 19,762 dollars per year of survival gain and between 10,368 dollars and 27,875 dollars per year of symptom control gained., Conclusions: Using RT in the initial management of lung cancer can provide considerable gains in survival and symptom control. The cost of RT for the initial management of lung cancer is inexpensive compared with a common cut off of 50,000 dollars per life year gained.

Background: We have previously used an evidence-based, epidemiologic approach to estimate the proportion of incident cases that should be treated with radiotherapy (RT) for lung cancer. The first objective of the present study was to compare this evidence-based estimate of the appropriate rate of use of RT with the rates observed in selected "benchmark" communities where there are no barriers to the appropriate use of RT and no incentives to the unnecessary use of RT. The second objective of the study was to compare the rates of use of RT in the general populations in the United States and Canada with the estimated appropriate rate., Methods: We established benchmark rates for the use of RT for lung cancer in Ontario, Canada, where: 1) residents make no direct payments for RT; 2) all RT is provided by site-specialized radiation oncologists in multidisciplinary cancer centers, and 3) radiation oncologists receive a salary in lieu of technical fees. Communities located close to cancer centers without long waiting lists for RT were selected to serve as benchmarks. Prospectively gathered electronic treatment records from all RT cancer centers were linked to the provincial cancer registry to describe the rate of use of RT in Ontario. The public use file of Surveillance, Epidemiology and End Results Registries (SEER) was used to describe the use of RT in the United States., Results: Overall, 41.3% (95% confidence interval [CI], 39.9%, 42.7%) of incident cases of lung cancer received RT as part of their initial management in the benchmark communities compared with the evidence-based estimate of 41.6% (95% CI, 39.2%, 44.1%). The rate of use of RT in the initial management of nonsmall cell lung cancer (NSCLC) in the benchmark communities was 49.3% (95% CI, 47.5%, 51.1%) compared with the evidence-based estimate of 45.9% (95% CI, 41.6%, 50.2%). The use of RT in the initial management of small-cell lung cancer (SCLC) in the benchmark communities was 47.0% (95% CI, 43.3%, 50.7%) compared with the evidence-based estimate of 45.4% (95% CI, 42.4%, 48.4%). In many counties of Ontario, the observed rates of RT use in the initial management of lung cancer were significantly lower than either the benchmark rate or the evidence-based estimate of the appropriate rate. In contrast, rates of use of RT in most counties in the SEER regions of the United States were close to, or higher than, the estimated appropriate rate., Conclusions: The observed benchmark rate converged on the evidence-based estimate of the appropriate rate of use of RT for lung cancer, suggesting that either measure might reasonably be used as a "standard" against which to compare rates observed in similar populations elsewhere.

Background and Objectives: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to use an evidence-based approach to estimate the proportion of incident cases of lung cancer that will require RT at any point in the evolution of the illness., Methods: A systematic review of the literature was undertaken to identify indications for RT for lung cancer, and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of lung cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error, was estimated by sensitivity analysis., Results: It was shown that 53.6% +/- 3.3% of small-cell lung cancer (SCLC) cases develop one or more indications for RT at some point in the course of the illness, 45.4% +/- 4.3% in their initial treatment, and 8.2% +/- 1.5% later for recurrence of progression. Overall, 64.3% +/- 4.7% of non-small-cell lung cancer (NSCLC) cases require RT, 45.9% +/- 4.3% in their initial treatment, and 18.3% +/- 1.8% later in the course of the illness. The proportion of NSCLC cases that ever require RT is stage dependent; 41.0% +/- 5.5% in Stage I; 54.5% +/- 6.5% in Stage II; 83.5% +/- 10.6% in Stage III; and 65.7% +/- 7.6% in Stage IV. In total, 61.0% +/- 3.9% of all patients with lung cancer will develop one or more indications for RT at some point in the illness, 44.6% +/- 3.6% in their initial treatment, and 16.5% +/- 1.5% later for recurrence or progression., Conclusion: This method provides a rational starting point for the long-term planning of radiation services, and for the audit of access to RT at the population level. We now plan to extend this study to the other major cancer sites to enable us to estimate the appropriate RT treatment rate for the cancer population as a whole.