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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]

For patients with biologically low-risk, N1 breast cancer, the benefit of regional nodal irradiation (RNI) and post-mastectomy radiotherapy (PMRT) is unclear and is the subject of ongoing clinical trials. Population-level data of rates of RNI receipt is lacking in this cohort, and may be increasing despite its uncertain benefit. The purpose of this study was to determine if there was increasing use of RNI and PMRT for low-risk, N1 breast cancer. This was a population-based study of all patients diagnosed between 2005 to 2014 in the [state/province] of [blinded], who underwent breast conserving surgery (BCS) or mastectomy for breast cancer. We based our definition of low-risk on the original inclusion criteria of MA.39/TAILOR RT trial, which is a non-inferiority clinical trial examining whether the omission of RNI is non-inferior. We included: pT1-2 pN1 (macroscopically node-positive) breast cancer. To define a biologically low-risk population, we included patients with a Luminal A subtype. This was approximated by: ER Allred 6-8/8, PR Allred 6-8/8, HER2-negative, and Grade 1-2. Patients who underwent a BCS and mastectomy were analyzed separately. The primary outcome was RNI receipt for patients who had a BCS, and PMRT receipt for those who had a mastectomy. We performed a multivariate, logistic regression to see whether year of diagnosis predicted for receipt of radiation. Other variables included in the multivariate model were defined a priori, based on factors known to influence RNI and PMRT receipt in the literature. There were 637 women who had BCS and 532 who had mastectomy in this cohort. For patients who had BCS, the rates of RNI receipt by years were: 2005-2008 68%, 2009-2011 79%, 2012-2014 89%. For patients who had a mastectomy, the rates of PMRT receipt by years were: 2005-2008 67%, 2009-2011 68%, 2012-2014 80%. During this time period, decreasing rates of ALND were observed: 2005-2008: 92%, 2009-2011 74%, 2012-2014 42%. On multivariate analysis of patients who had a BCS, RNI receipt was associated with number of involved macroscopic nodes (p=0.002) and date of diagnosis (p<0.001), but not age (p=0.2), presence of LVI (p=0.2), ALND (p=0.08), or chemotherapy receipt (p=0.9). For patients who had a mastectomy, PMRT receipt on multivariate analysis was associated with number of involved macroscopic nodes (p=0.02) and chemotherapy receipt (p=0.004), but not age (p=0.09), LVI (p=0.3), or diagnosis date (p=0.1). There was an increased rate of RNI receipt, and a trend for increased receipt of PMRT for patients with low-risk, node-positive breast cancer between 2005 to 2014. This population-level data shows the large proportion of women who may be spared RNI if the MA.39 non-inferiority trial determines that omission of RNI is safe. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The benefit of regional nodal irradiation (RNI) for node-positive, low-risk breast cancer is controversial. The ongoing TAILOR RT trial is enrolling breast cancer patients with 1-3 involved macroscopic nodes and a low risk Oncotype DX Recurrence Score (< 18) to determine the breast cancer recurrence-free interval (BCRFI) with and without RNI. The objective of this study was to determine if RNI was associated with improved BCRFI in a population of patients similar to those enrolling on TAILOR RT.Materials/methods: We interrogated a population-based database, which included all women treated for breast cancer in the province. Inclusion criteria were: age 40-79, pT1-2 pN1 (macroscopically node-positive) breast cancer, and diagnosis between 2005 and 2014. To reproduce the inclusion criteria of TAILOR RT, patients could have had breast-conserving surgery (BCS) or mastectomy & axillary lymph node dissection (ALND) with 1-3 positive nodes, BCS & sentinel lymph node biopsy (SLNB) with 1-2 positive nodes or mastectomy & SLNB with 1 positive node. To select a cohort of patients likely to have Recurrence Score < 18, we only included Luminal A breast cancers. Luminal A was approximated based on the tumor being: ER positive (Allred 6-8/8), PR positive (Allred 6-8/8), HER2-negative, and Grade 1-2. All patients were started on hormonal treatment. The primary endpoint of BCRFI, which was the time to any breast cancer recurrence or breast cancer-related death, was analyzed using multivariate competing risks analysis. Secondary outcomes of locoregional recurrence and distant metastasis were analyzed with multivariate competing risks models, and overall survival was analyzed with multivariate cox analysis.Results: We identified 1,169 eligible women. Median follow-up was 9.2 years. There were 885 patients who received RNI and 284 who did not undergo RNI. The RNI group was younger (median 62 versus 58 years), had a higher rate of nodal involvement, and were more likely to have received chemotherapy (all P < 0.05). The 10-year estimate of BCRFI was 90% in the no-RNI group versus 90% in the RNI group (P = 0.5). On multivariable analysis, RNI was not a significant predictor of BCRFI (HR = 1.0, P = 0.9). At 10-years, locoregional recurrence was 3.3% in the no-RNI group and 1.7% in the RNI group (P = 0.2). Distant metastasis at 10-years was 7.0% for the no-RNI group versus 8.8% for the RNI group (P = 0.5). Finally, overall survival at 10-years was 85% for the no-RNI group and 85% for the RNI group (P = 0.2). All secondary outcomes were analyzed in multivariate models, and, in all cases, RNI receipt was not associated with improved outcomes (all P > 0.05).Conclusion: RNI was not associated with improved outcomes in node-positive, low-risk breast cancers. This work underscores the importance of continued accrual onto the ongoing non-inferiority trial of RNI, TAILOR RT. [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]

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]

Purpose/objective(s): After the publication of the landmark SABR-COMET trial, concerns were raised over toxicity of SABR for oligometastases. This population-based study was designed as a bridge from phase II to phase III trials, while assessing the toxicity profile of SABR in a larger cohort from a provincial cancer program.Materials/methods: From November 2016 to July 2020, 399 patients were enrolled in this single arm, phase II trial of SABR in patients with oligometastatic or oligo-progressive disease. During this period, patients were only eligible for SABR in these settings on trial within our province, and therefore this analysis is population-based, with resultant minimal selection bias in comparison to previously published SABR series. The primary endpoint was toxicity and we hypothesized grade 4 toxicity < 5%. Grade 2 or higher toxicities were prospectively collected, and were rated as unrelated, unlikely, possibly, probably, or definitely related to SABR. Toxicities rated as possibly, probably, or definitely related to SABR were analyzed in this study. The radiotherapy details are previously published in the protocol; because of previously published high grade toxicity in this setting, all cases underwent individual peer review and organs at risk were prioritized over the planning target volumes.Results: The mean age was 68 years (SD 10.9, range 30-97). The participants were mostly male (69%). The most common histologies were prostate cancer (33%), colorectal cancer (14%), breast cancer (11%), and lung cancer (9%). The number of SABR treated sites were one (69%), two (22%), and three or more (9%). The most common sites of SABR were lung (33%), non-spine bone (28%), spine (14%), lymph nodes (13%), liver (5%) and adrenal (3%). Grade 2, 3, and 4 toxicity cumulative incidences were 11.4%, 4.6%, and 0.5%, respectively. There were no grade 5 toxicities. Grade 2 or higher specific toxicity included 4.8% pain, 1.3% pneumonitis, and 0.8% neuropathy. There were no reported gastrointestinal fistula, perforation, or hemorrhage. Cumulative incidence and prevalence of toxicity at 1 & 3 years will be updated and presented.Conclusion: The incidence of grade 2+ SABR toxicity on this population-based study was 16.5%, which is lower than that reported on SABR-COMET (29%). Importantly, there were no grade 5 toxicities attributed to SABR in this study to date. Severe (grade 3 or higher) toxicities were uncommon (5.0%). These results are encouraging that, in a population-based program with rigorous peer review quality assurance, SABR treatment for oligometastases has acceptable rates of toxicity. This supports further enrollment in randomized phase III trials. [ABSTRACT FROM AUTHOR]