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Abstract: Background: Different jurisdictions report different breast cancer treatment rates. Evidence-based utilization models may be specific to derived populations. We compared predicted optimal with actual radiotherapy utilization in British Columbia, Canada; Dundee, Scotland; and Perth, Western Australia. Design: Data were analyzed for differences in demography, tumor, and treatment. Epidemiological data were fitted to published Australian optimal radiotherapy utilization trees and region-specific optimal treatment rates were calculated. Optimal and actual surgery/radiotherapy rates from 2 population-based and 1 institution-based registries were compared for patients diagnosed with breast cancer between 2000 and 2004, and 2002 for British Columbia. Results: Mastectomy rates differed between British Columbia (40%), Western Australia (44%), and Dundee (47%, p <0.01). Radiotherapy rates differed between British Columbia (60%), Western Australia (52%), and Dundee (49%, p <0.01). Actual radiotherapy utilization rates were lower than optimal estimates. Region-specific optimal utilization rates at diagnosis varied from 57% to 71% for radiotherapy and 62% to 64% when taking into account patient preference. Variation was attributed to local differences in demography and tumor stage. Conclusions: Actual treatment rates varied, and were associated with patterns of care and guideline differences. Actual radiotherapy rates were lower than optimal rates. Differences between optimal and actual utilization may be due to access shortfalls, and patient preference. [Copyright &y& Elsevier]

Background: We compared outcomes after breast-conserving therapy (BCT) and mastectomy in multicentric (MC)/multifocal (MF) versus unifocal breast cancer. Patients and methods: Women with stage I–II disease were classified as having unifocal or MC/MF disease. MC/MF and other prognostic factors were compared using binary logistic regression analysis. Univariate and multivariate analyses (MVAs) for relapse were carried out using cumulative incidence curves and Fine and Gray regression models. For the BCT group, matched analysis was added. Results: Median follow-up was 7.9 years, 11 983 having BCT (unifocal: 11 683, MC/MF: 300) and 7771 having mastectomy (unifocal: 6884, MC/MF: 887). MC/MF patients treated with BCT were 50–69 years old, free of extensive ductal carcinoma in situ (DCIS), and had smaller tumors. The cumulative 10-year local recurrence rates among unifocal and MC/MF disease were 4.6% [95% confidence interval (CI) 4.1% to 5.0%] versus 5.5% (95% CI 2.6% to 9.9%) for the BCT group, P = 0.76 and 5.8% (95% CI 5.2% to 6.5%) versus 6.5% (95% CI 4.7% to 8.7%) for the mastectomy group, P = 0.77. MC/MF was not a significant factor for relapse or survival on MVA. In the matched analysis, relapse rates were similar in the unifocal and MC/MF groups, P = 0.60. Conclusion: BCT is a reasonable option in selected MC/MF cases, particularly those women aged 50–69 years old with small (<1 cm) MF tumors and without an extensive DCIS component. [ABSTRACT FROM PUBLISHER]

Background: Little is known about the correlations between tumor markers (TMs), breast cancer subtypes, site(s) of metastasis and prognosis. Methods: Women diagnosed with metastatic breast cancer were included. Breast cancer subtypes were defined as LuminalA, LuminalB, LuminalHer2, Her2, Basal and non-Basal triple negative (TN). Levels of elevation of TM values [cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA 125)] among the subtypes were analyzed. Site(s) of metastasis and outcomes were captured. Results: Eight hundred and ten patients were included. Luminal subtypes were associated with an elevation in at least one TM: 90.8% of LuminalHer2+, 90% of LuminalB and 88.6% of LuminalA. TMs were less frequently elevated in Basal (74.1%) and non-Basal TN (71.4%) cases (P < 0.001). CA 15-3 was the most frequently elevated TM. The incidence of TM elevation did not differ between patients with solitary versus multiple metastatic sites. Breast cancer-specific survival (BCSS) was significantly worse for patients with elevated TMs (P = 0.001). Conclusions: TM elevation of CA 15-3, CEA and/or CA 125 was documented in the majority of patients with metastatic breast cancer with CA 15-3 occurring most commonly. Luminal subtypes expressed elevated TMs significantly more frequently compared with the non-Luminal groups. TM elevation was not different between the different sites of metastasis. Overall, elevated TMs predicted a worse BCSS. [ABSTRACT FROM PUBLISHER]

Background: In this article, we report the evolution of treatment with increased use of active surveillance for stage I disease as well as risk-adapted chemotherapy for disseminated disease and associated outcomes of testicular seminoma in a contemporary population-based cohort.Methods: All patients with histologically confirmed seminoma referred from 1999 to 2008 to the British Columbia Cancer Agency or Providence Cancer Center were retrospectively reviewed. Both institutions manage ∼90% of testicular cancers in their respective area.Results: A total of 649 patients were included. Clinical stage (CS) distribution: CSI/II/III n = 545/87/17. For CSI, there was a progressive and marked decrease in the utilization of prophylactic radiation (RT), and corresponding increase in the use of active surveillance. No deaths related to seminoma were reported in CSI patients. CSII or CSIII patients received RT or International Germ Cell Cancer Collaborative Group (IGCCCG) risk-appropriate chemotherapy with 101 of 104 patients being in long-term remission and 3 patients dying from treatment complications. For the entire seminoma population, <1% of patients died of seminoma or treatment after a median follow-up of 47 months (range 2–130 months).Conclusions: Progressive application of policies of active surveillance and earlier initiation of IGCCCG risk-adapted chemotherapy result in nearly universal control for all patients presenting with seminoma while reducing the burden of treatment. [ABSTRACT FROM PUBLISHER]

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 &y& Elsevier]

Summary: 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 were 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. [Copyright &y& Elsevier]

Purpose: The objective of the present study was to estimate the proportion of incident cases of breast cancer that should receive breast conserving surgery (BCS), using an evidence-based approach.Methods: An extensive search of the literature was undertaken to identify eligibility criteria for BCS. The eligibility criteria for BCS were combined with the information about case mix and patient preference to estimate the need for BCS. An epidemiological approach was then used to estimate the incidence of each eligibility criterion for BCS in a typical North American population of breast cancer patients. The effect of sampling error on the estimated appropriate rate of BCS was calculated, and the effect of systematic error using alternative sources of information, was estimated by sensitivity analysis.Results: The analysis showed that 69.6% of breast cancer cases are eligible for BCS, and that 48.0±6.0% of breast cancer patients are both eligible for BCS and prefer it to mastectomy. Based on sensitivity analysis, the plausible range of the appropriate rate was 42.1% to 49.43%. The proportion of breast cancer cases in which BCS was appropriate was stage dependent; 63.0±11.5% in ductal carcinoma in-situ; 57.0±9.9% in stage I; 52.2±9.4% in stage II, and 27.2±5.2% in stage III.Conclusions: This model suggests that BCS is appropriate in 48% of all breast cancer patients. This information may be useful in auditing surgical practice, and may serve as a basis for planning of ancillary services, including radiotherapy. Copyright 2003 The Royal College of Radiologists. Published by Elsevier Science Ltd. All rights reserved. [Copyright &y& Elsevier]

The European Organisation for Research and Treatment of Cancer (EORTC) 22,881–10,882 trial showed significant benefit of a radiotherapy boost (RTB) in women ≤40 years in a pre-hormone therapy (HT) era. We determined how the use of HT and RTB changed in response to clinical guidelines and whether the benefit of routine RTB was still observed in the HT era. Between 1996 and 2004, a provincial database identified all women ≤40 years with breast cancer who met the inclusion criteria of the EORTC trial. In total, 411 patients were classified into three eras defined by the guidelines: era 1 (discretionary HT, discretionary RTB); era 2 (routine HT, discretionary RTB); era 3 (routine HT, routine RTB). HT use, RTB use and cumulative incidence of local recurrence were calculated and compared across eras. HT use increased after the first policy change from 13% to 75% for oestrogen receptor-positive patients (P < 0.01). RTB use also increased from 33% to 76% following the second policy change (P < 0.01). At 10 years, the cumulative incidence of local recurrence was 12% in era 1, 6% in era 2 and 6% in era 3 (era 2 versus era 3, P = 0.92). For patients in the routine HT era (eras 2 and 3 combined) there was no significant difference in local recurrence between RTB and 'no RTB' patients (6% versus 7%, P = 0.81). The routine use of HT and RTB increased significantly after new practice guidelines. Introduction of the HT guideline was associated with a 6% improvement in local recurrence at 10 years. No improvement in local recurrence was associated with the introduction of the RTB guideline in the HT era. The routine use of a boost in unselected young women with negative margins should be re-evaluated in the current HT era. • Prior to routine hormone therapy (HT) use, a boost (RTB) reduced breast cancer local recurrence in women ≤ 40 years. • The use of HT and RTB increased significantly after the introduction of new practice guidelines. • Local recurrence was halved after introduction of the HT guideline. • No improvement in local recurrence was associated with the introduction of the RTB guideline in the HT era. • The routine use of RTB in unselected young women with negative margins should be re-evaluated in the current HT era. [ABSTRACT FROM AUTHOR]

Abstract Aims To evaluate the prevalence, patterns of care and outcome of pathologically node-positive (pN+) prostate cancer (P-Ca) after radical prostatectomy from a provincial population database. Patients and methods Patients were identified from a provincial cancer registry and a genitourinary cancer outcomes unit (2005–2014). Of a total of 4723 patients who underwent radical prostatectomy, 167 patients with pN+ P-Ca were identified (28/2181 from 2005–2007 and 139/2542 from 2010–2014). Persistently elevated postoperative prostate-specific antigen (PSA) ≥ 0.2 ng/ml was noted in 52 (31%) patients, 23 (44.2%) of whom had salvage androgen deprivation therapy plus radiotherapy (ADT + RT), 25 (48%) were managed with ADT alone and four (7.8%) had no treatment. Of 115 patients with postoperative PSA <0.2 ng/ml, 47 (41%) had ADT alone and 50 (43.5%) had ADT + RT. Survival estimation was carried out using the Kaplan–Meier method. The association of prognostic factors with survival was evaluated using univariate and multivariate analysis and was limited to the newer cohort (2010–2014). Results The median age was 64 years; the median baseline PSA was 12.5 ng/mL (range 2.5–108.4). After a median follow-up of 48 months, overall survival at 5 and 10 years for the entire cohort were 89% and 81%, respectively, and distant metastasis-free survival (DMFS) at the same time points were 77% and 58%, respectively. For the newer cohort, 5-year overall survival and DMFS were 91.5% and 76%, respectively. On univariate analysis, persistently elevated postoperative PSA ≥0.2 ng/ml (P = 0.0003), seminal vesicle involvement (P = 0.027), ≥2 nodes (P = 0.035) and ADT alone (P = 0.054) had a poor prognostic impact on DMFS, whereas margin involvement had a marginally negative influence on overall survival (P = 0.06). On multivariate analysis, postoperative PSA ≥0.2 ng/ml (hazard ratio 4.4, 95% confidence interval 1.7–11.4; P = 0.002) continued to have a significant association with DMFS. On a sensitivity analysis, postoperative PSA ≥0.1 also had a significant association with DMFS on univariate and multivariate analysis (hazard ratio 3.69, 95% confidence interval 1.32–10.29; P = 0.01). Similarly, postoperative PSA ≥0.4 ng/ml had a significant association with DMFS (hazard ratio 3.87, 95% confidence interval 1.58–9.46, P = 0.003). Conclusion This study showed a notable difference in the proportion of pN+ P-Ca patients between two different time cohorts. A significant association of persistently elevated postoperative PSA with DMFS was noted in our study. This must be accounted for while tailoring postoperative treatment in pN+ P-Ca. Highlights • The study shows rising incidence of pathologically node-positive prostate cancer. • Persistently elevated postoperative PSA >0.2 ng/ml is predictive of poor prognosis. • No additional benefit of ADT + RT over ADT alone was noted in pN+ prostate cancer. [ABSTRACT FROM AUTHOR]

Aims This study describes the proportion of men who experienced hot flashes (flashes), and the testosterone level at onset, peak frequency and cessation of flashes after 12 months of androgen deprivation therapy (ADT) in men undergoing curative-intent external beam radiation therapy (± brachytherapy boost). We also aimed to characterise testosterone recovery in this population. Materials and methods This was a pre-specified secondary analysis of the ASCENDE-RT clinical trial. Three hundred and ninety-eight men were randomised. All received 12 months of ADT. The presence and frequency of flashes were patient reported. Cessation of flashes was defined as the first date a patient reported resolution of this symptom. Testosterone recovery was defined as any single serum testosterone above the threshold of 5, 7.5 or 10 nmol/l. Results The median age and follow-up were 68 years and 6.1 years. Flashes were reported in 93% of men. Flashes began and reached peak frequency at a median time of 4.0 months from the first luteinizing hormone-releasing hormone injection when testosterone levels had fallen to castrate. The median time to cessation of flashes was 7.6 months after the cessation of ADT (last injection + 3 months), when the median testosterone had risen to 5.7 nmol/l. A resolution of flashes was reported in 99% of patients. Baseline testosterone was available in 338 patients (85%). The median baseline testosterone was 13.2 nmol/l. The median (95% confidence interval) time of testosterone recovery to thresholds of 5 nmol/l, 7.5 nmol/l and 10 nmol/l were 9 (9–10) months, 13 (10–15) months and 18 (17–19) months from the cessation of ADT. At the time of censor, 96, 94 and 91% of patients had recovered testosterone to thresholds of 5, 7.5 and 10 nmol/l. Conclusion Flashes occur at castrate levels of testosterone, with cessation of hot flashes antedating full recovery of testosterone in most patients. Rates of testosterone recovery after 12 months of ADT exceed 90%, although it can be delayed. [ABSTRACT FROM AUTHOR]

While estimation of prognosis for patients with oligometastatic cancer is important to aid in treatment decision making, at present, prognostication tools are lacking. The purpose of this study was to develop predictive models for polymetastatic progression free survival (PPFS) and overall survival (OS), based on patient outcomes on the SABR-5 clinical trial. In the SABR-5 trial (a multi-center, single arm, phase II clinical trial), 381 patients with 1-5 oligometastases or oligoprogressing lesions were treated with stereotactic ablative radiotherapy (SABR). Prostate cancer was the most common histology (32%), followed by colorectal (16%), breast (11%), lung (9%), and renal (9%). Most patients (91%) were treated for 1-2 metastases. PPFS was defined as time from SABR until polymetastatic failure (≥ 6 metastases, or malignant pleural effusion/malignant ascites) or death. We trained separate Cox models for PPFS and OS. An elastic net penalty was used to select from candidate covariates. The model was internally validated using 10-fold cross validation with three repetitions and evaluated using partial likelihood. The proportional hazards and linearity assumptions were tested by examination of scaled Schoenfold Residuals and Martingale Residuals, respectively. After a median follow-up time of 28.0 months (interquartile range [IQR]19.1 – 39.1), median PPFS was 34.3 months (95% confidence interval [CI] 28.8 – 39.9), and median OS was 50.5 months (95% CI 45.2 – 58.9). The resulting PPFS model contained four covariates: primary tumor type (prostate, colorectal, lung, breast, renal, other), ECOG (1-2 vs 0), oligoprogression (yes vs no), number of organs with metastases (single vs multiple). The cross-validated C-Index was 0.66 [95% CI 0.64 – 0.68]. The OS model had five covariates: age (continuous), primary tumor type (prostate, colorectal, lung, breast, renal, other), ECOG (1-2 vs 0), number of organs with metastases (single vs multiple), presence of brain metastasis (yes vs no) and had a corresponding C-Index of 0.67 [95% CI 0.64 – 0.700]. These nomograms can be a useful guiding tool for clinicians in predicting PPFS and OS in patients treated with SABR in oligometastatic or oligoprogressive setting. These models should be externally validated. [ABSTRACT FROM AUTHOR]

Despite advancements in stereotactic ablative radiotherapy (SABR) for non-spine bone metastases (NSBMs), uncertainty remains surrounding target volumes. While expert consensus guidelines recommend a clinical target volume (CTV), patterns of failure analyses are lacking, and larger treatment volumes may be associated with higher toxicity. This study aims to compare local failure, marginal failure, and toxicity in NSBMs treated with versus without a CTV in a population-based cohort. A retrospective review was conducted on all patients in British Columbia treated with SABR for NSBMs on the single-arm phase II SABR-5 trial (November 2016 – July 2020) and on the BC Oligometastases Registry (August 2020 - October 2022). Use of a CTV was optional for both SABR-5 and the Registry. NSBMs were stratified based on CTV use for treatment planning. A total of 158 patients (113 on SABR-5 and 45 on Registry) with 200 NSBMs were included. One hundred fifty-nine (80%) NSBMs were treated with a CTV and 41 (21%) without a CTV. The most common histologies were prostate (60%), breast (17%) and lung cancer (6%), and lesions received 35 Gy in 5 fractions (81%) or 24 Gy in 2 fractions (14%). Rib (34%) and pelvis (47%) were the most common lesion sites. Groups with vs without a CTV did not differ in baseline patient or tumor characteristics. After a median follow-up time of 33.7 months (interquartile range [IQR] = 19.5-48.9), local failure rates did not differ, with 2-year local failure 9.3% (95% confidence interval [CI] = 4.4 – 14.2) in lesions treated with a CTV and 7.6% (95% CI = 0 – 15.8) without a CTV (P = 0.39). Marginal failure, defined as disease recurrence outside of the GTV but within 1 cm of the PTV, occurred in 15 (8%) of lesions and 2-year cumulative incidence did not differ between groups (6.2% [95% CI = 2.3 – 10.1] and 2.6%, [95% CI = 0 – 7.5], respectively [ P = 0.16]). Overall survival (OS) was also similar (2-year OS = 84.6%, 95% CI = 78.1 – 91.1, and 90.3%, 95% CI = 79.9 – 100, respectively; P = 0.64). The most common grade ≥ 2 toxicities were pain (n = 18, 9%) and fracture (n = 8, 4%). There were no grade 4 or 5 toxicities. The 2-year cumulative incidence of grade ≥ 2 toxicity did not differ between groups (14.9%, 95% CI = 3.9-25.9 and 15.6%, 95% CI = 9.9-21.3, respectively; P = 0.78). Due to low number of events, local and marginal failure events were collated for a multivariable regression analysis. On multivariable regression, use of a CTV was not associated with the risk of local-marginal failure (hazard ratio [HR] = 2.41, 95% CI = 0.81 – 7.18, P = 0.11). Extraosseous extension (HR = 2.62, 95% CI = 1.07-6.38, P = 0.035) and lack of receipt of systemic therapy (HR = 3.03, 95% CI = 1.40-6.67, P = 0.005) were associated with higher risk. Use of a CTV was not associated with local or marginal failure or toxicity. Extraosseous extension and lack of receipt of systemic therapy were associated with higher risk of local-marginal failure. This may assist in informing future approaches to treatment planning in this patient population. [ABSTRACT FROM AUTHOR]

Purpose: The recently developed European Society for Radiotherapy and Oncology (ESTRO)/European Organization for Research and Treatment of Cancer (EORTC) oligometastatic disease (OMD) classification has not been validated in terms of its prognostic significance. This study stratified patients from the phase II SABR-5 trial based on ESTRO/EORTC criteria and compared progression-free survival (PFS) and overall survival (OS) to determine the prognostic significance of the classification scheme.Methods and Materials: The SABR-5 trial was a single arm phase II study conducted at the 6 regional cancer centers across British Columbia (BC), Canada, where SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced OMD) underwent SABR to all lesions. Patients were 18 years of age or older, Eastern Cooperative Oncology Group 0 to 2, and life expectancy ≥6 months. PFS and OS were calculated using the Kaplan-Meier method and differences between OMD groups were assessed with log-rank tests. Univariable and multivariable analyses were performed using Cox regression modeling.Results: Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). The most frequent OMD group was de novo OMD (69%), followed by repeat (16%) and induced (13%). OMD groups differed significantly in PFS (P < .001) but not OS (P = .069). The OMD classification was an independent predictor of both PFS (P = .005) and OS (P = .002). Of the 5 classification factors, only chronicity (synchronous, hazard ratio, 0.52; P = .027) and oligoprogression (hazard ratio, 2.05; P = .004) were independently prognostic for OS.Conclusions: In this large prospective cohort, the ESTRO/EORTC classification was an independent predictor of PFS and OS and should be used to identify specific patient groups for clinical trials. In this trial population, the prognostic power is largely attributable to chronicity and oligoprogression. Simplification of the framework may be possible in the future and allow for greater ease of use; however, further data on underrepresented OMD groups and histologies will be required. [ABSTRACT FROM AUTHOR]

While SABR is known for its overall low toxicity and safety, there remains a research gap regarding its combined use with specific systemic therapies. This study aims to evaluate the toxicity of SABR in combination with various systemic therapies. The hypothesis is that certain systemic therapies would significantly increase the risk of Grade 2+ and Grade 3+ radiation therapy-related toxicities when used concurrently with Stereotactic Ablative Radiotherapy (SABR). A secondary analysis of the SABR-5 trial compared grade 2+ and 3+ toxicities associated with SABR until the last follow-up in patients receiving high-risk or non-high-risk systemic therapy at intervals of 3 months, 2 weeks, 1 week, and concurrently with SABR. High-risk systemic therapy was a priori defined, based on previous literature, as drugs that, when given close to SABR, may increase treatment toxicity. This category encompasses cytotoxic chemotherapy drugs, multi-targeted tyrosine kinase inhibitors, cyclin-dependent kinase 4/6 inhibitors, epidermal growth factor receptor inhibitors, anti-vascular endothelial growth factor agents, and anti-cytotoxic T-lymphocyte-associated protein 4 agents. Among the 381 patients, the actuarial rates of grade 2+ and 3+ toxic effects were as follows: for patients not on systemic therapy 3 months prior to SABR (n = 202), the rates were 17.3% and 3.5%, respectively; for patients on non-high-risk systemic therapy concurrent with SABR (n = 102), the rates were 18.6% and 3.9%, respectively; and for patients on high-risk systemic therapy concurrent with SABR (n = 5), the rates were notably higher at 60% and 40%, respectively. On multivariable analysis, concurrent use of high-risk systemic therapy was associated with a higher risk of grade 2+ (OR = 7.15, P = 0.043) or 3+ toxic effects (OR = 13.9, P = 0.015). Significance was not observed when high-risk drugs were used only within 1 week, 2 weeks, or 3 months of SABR, nor with the use of any non-high-risk drugs. A second adverse factor included increased tumor diameter (per 1 cm increment; G2+ OR = 1.25, P < 0.001; G3+ OR = 1.27, P = 0.015). High-risk drugs have demonstrated a potential of increased SABR-related toxicity, warranting caution in their concurrent use with SABR. In contrast, the combination of non-high-risk drugs with SABR may be safe. Ongoing efforts are essential to identify potential risks and uncertainties associated with this therapeutic combination. [ABSTRACT FROM AUTHOR]

To determine polymetastatic recurrence-free survival (PMRFS) in patients with repeat oligometastases (OM) on the SABR-5 trial. SABR-5 is a prospective, multi-center trial that evaluated the safety of stereotactic ablative radiotherapy (SABR) in patients with 1-5 OM or oligoprogressive lesions. On SABR-5, patients were followed post-SABR according to standardized protocols. Patients with repeat extra-cranial OM after metastasis-directed therapy (MDT; SABR, surgery, or thermoablation) to all initial OM (including those treated before enrolment on SABR-5) were identified. Exclusion criteria included history of multiple primary malignancies and incomplete re-staging. PMRFS was defined as time from presentation of repeat oligometastases to death or presentation of 6 or more progressing metastases, leptomeningeal metastases, lymphangitic carcinomatosis, malignant ascites, or malignant pleural effusion. PMRFS, overall survival (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Seventy-six patients with repeat OM were included, of which 44 (58%) received second MDT to all OM. The most common histology in patients who received second MDT was colorectal cancer (10/44 [23%]) and in those who did not was prostate cancer (17/32 [53%]). Patients who did vs. did not receive second MDT had fewer metastases at repeat OM (mean 1.3 vs 2.2; p<0.001) and no difference in time between initial OM and repeat OM (16 vs. 17 months; p = 0.74). For patients who received second MDT, median follow-up from presentation of repeat OM was 2.6 years. Median PFS after first and second MDT were 15 months (95% CI 11-18) and 11 months (95% CI 7-17), respectively. At last follow-up, 22/44 patients (50%) were alive without polymetastatic recurrence. 3-year PMRFS and OS from presentation of repeat OM were 51% (95% CI 33-66%) and 66% (95% CI 47-79%), respectively. Patients presenting with repeat OM after MDT may still have favorable 3-year PMRFS and OS, which may justify exploring aggressive local treatments in this subpopulation. Further randomized trials in this space are needed. [ABSTRACT FROM AUTHOR]

Despite increasing utilization of stereotactic ablative radiotherapy (SABR), there is a lack of large population-based outcomes data. This study was designed to examine, as the primary end point, side effects and quality of life, which were reported elsewhere. This analysis focuses on overall survival as a secondary endpoint. From November 2016 to July 2020, 401 patients across 6 regional cancer centers in British Columbia, Canada were screened for eligibility in this single arm, phase II trial of SABR in patients with 5 or fewer oligometastatic or oligo-progressive lesions. During this time period, such patients were eligible for SABR only on trial. Of those screened, 385 patients were enrolled, with 381 completing SABR. This analysis was by intention to treat. The median follow up was 26.7 months (range 0-57 months). 68% of the patients were male, the mean age was 68 years old (SD 11 years, range 30-97 years). Median Charlson Comorbidity Index (CCI) was 9 (range 6-15). 60% had ECOG 0, 36% ECOG 1, and 4% ECOG 2. Prostate cancer was the most common histology (32%), followed by colorectal (16%), breast (11%), lung (9%), renal (9%), and others (22%). SABR was given to 1 site in 69% of patients, 2 sites for 22%, 3 sites for 7%, and 4-5 sites for 3%. The most common sites treated with SABR were lung (35%), non-spine bone (25%), spine (16%), lymph node (14%), liver (5%), adrenal (3%), and others (3%). 20% had synchronous disease, and 16% had oligoprogressive disease. Median survival was not reached. At 2 years, the overall survival was 79.8% (75.5-84.1%), and at 4 years, 58.0% (49.6-66.4%). In univariate analysis, age (p=0.023), ECOG (p<0.001), decline in ECOG 6 months before SABR (p=0.001), systemic therapy use after SABR (p=0.001), histology (p<0.001), Synchronous disease (p=0.050), and disease-free interval > 18 months (p<0.001) were significant predictors for overall survival. CCI (p=0.054), gender, oligometastatic disease, and number of lesions treated with SABR were not significant. Multi-variate analysis showed histology (Breast, ref; Lung, HR 9.91 (2.21-44.48), p=0.003; Colorectal, HR 5.09 (1.12-23.09), p=0.035; Renal, HR 5.20 (1.09-24.82), p=0.039; Prostate, p>0.05; Others HR 8.97 (2.07-38.77), p=0.003), ECOG (ECOG 1 vs 0, HR 1.69 (1.10-2.60), p=0.017; ECOG 2 vs 0, HR 3.00 (1.24-7.24), p=0.015), synchronous disease (HR 0.48 (0.27-0.85), p=0.012), and disease-free interval >18 months (HR 2.36 (1.52-3.66), p<0.001) predicted overall survival. Sensitivity analysis of only the patients who completed SABR showed similar results. Analyzing oligometastatic disease only, synchronous disease was not a significant predictor in univariate and multivariate analysis. The 2 years overall survival (80%) was similar to another population-based study in the UK by Chalkidou et al. We recommend continuing to stratify by favorable histology, performance status, and disease-free interval in ongoing randomized phase III trials on the efficacy of SABR. [ABSTRACT FROM AUTHOR]