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Purpose: In a learning health system (LHS), data gathered from clinical practice informs care and scientific investigation. To demonstrate how a novel data and analytics platform can enable an LHS at a regional cancer center by characterizing the care provided to breast cancer patients. Methods: Socioeconomic information, tumor characteristics, treatments and outcomes were extracted from the platform and combined to characterize the patient population and their clinical course. Oncologists were asked to identify examples where clinical practice guidelines (CPGs) or policy changes had varying impacts on practice. These constructs were evaluated by extracting the corresponding data. Results: Breast cancer patients (5768) seen at the Juravinski Cancer Centre between January 2014 and June 2022 were included. The average age was 62.5 years. The commonest histology was invasive ductal carcinoma (74.6%); 77% were estrogen receptor‐positive and 15.5% were HER2 Neu positive. Breast‐conserving surgery (BCS) occurred in 56%. For the 4294 patients who received systemic therapy, the initial indications were adjuvant (3096), neoadjuvant (828) and palliative (370). Metastases occurred in 531 patients and 495 patients died. Lowest‐income patients had a higher mortality rate. For the adoption of CPGs, the uptake for adjuvant bisphosphonate was very low, 8% as predicted, compared to 64% for pertuzumab, a HER2 targeted agent and 40.2% for CD4/6 inhibitors in metastases. During COVID‐19, the provincial cancer agency issued a policy to shorten the duration of radiation after BCS. There was a significant reduction in the average number of fractions to the breast by five fractions. Conclusion: Our platform characterized care and the clinical course of breast cancer patients. Practice changes in response to regulatory developments and policy changes were measured. Establishing a data platform is important for an LHS. The next step is for the data to feedback and change practice, that is, close the loop. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies suggest that external-beam partial breast irradiation (PBI) delivered twice a day can lead to increased adverse cosmesis (AC). The objective of our trial was to determine whether two regimens for PBI given once daily over 1 week resulted in acceptable AC to inform a phase III trial., Methods: Patients age ≥50 years with invasive breast cancer or ductal carcinoma in situ, ≤3 cm in size treated by lumpectomy with negative axillary nodes were randomly assigned to external-beam PBI of 30 Gy or 27.5 Gy, each given in five fractions once daily. The primary outcome was AC (fair or poor) by photographic assessment at 2 years. Secondary outcomes included AC assessed by nurse at 2 years, by patient self-assessment at 3 years, and late toxicity. On the basis of a 17% risk of AC with whole-breast irradiation, the upper bound of a two-sided 90% CI, 23% was set as the tolerance margin (OPAR, ClinicalTrials.gov identifier: NCT02637024)., Results: In total, 142 patients were randomly assigned to 30 Gy and 139 to 27.5 Gy. The median follow-up was 5 years. The mean age was 65 years, and the mean tumor size was 1.2 cm. Both schedules met acceptability criteria by photographic assessment (AC, 12.1% [90% CI, 8.2 to 17.6] for 30 Gy and 15.2% [90% CI, 10.8 to 21.1] for 27.5 Gy) and by nurse assessment. AC by patient self-assessment exceeded the 90% CI for the 30 Gy regimen. At 5 years, 16 (11.3%, 90% CI, 7.6 to 16.4) patients treated with 30 Gy and eight (5.8%, 90% CI, 3.3 to 9.9) patients treated with 27.5 Gy were observed to have grade 2 or more late toxicity., Conclusion: According to the study design, 30 Gy and 27.5 Gy resulted in acceptable cosmetic outcomes. In light of recent studies, a lower dose was chosen for the phase III trial.

Importance: Stereotactic body radiotherapy (SBRT) is widely used for stage I medically inoperable non-small cell lung cancer (NSCLC), yet varied results from randomized clinical trials (RCTs) and concerns in treating centrally located tumors persist., Objective: To examine whether SBRT would improve local control (LC) compared with hypofractionated conventional radiotherapy (CRT)., Design, Setting, and Participants: This phase 3 RCT was conducted in 16 Canadian centers. Patients with medically inoperable stage I (≤5 cm) NSCLC were randomized 2:1 to SBRT of 48 Gy in 4 fractions (peripheral NSCLC) or 60 Gy in 8 fractions (central NSCLC) vs CRT of 60 Gy in 15 fractions. Data were collected from May 2014 to January 2020, and data were analyzed from July 2022 to July 2023., Interventions: SBRT or CRT., Main Outcomes and Measures: The primary objective was to determine the effectiveness of SBRT compared with CRT based on LC at 3 years. Secondary outcomes included event-free survival, overall survival, and toxic effects. All radiation plans were subject to real-time/final review. Local failures were centrally adjudicated. The study was designed to detect a 3-year LC improvement of SBRT from 75% to 87.5%. The target sample size was 324 patients., Results: Of 233 included patients, 119 (51.1%) were male, and the mean (SD) age was 75.4 (7.7) years; the median (IQR) follow-up was 36.1 (26.4-52.8) months. A total of 154 patients received SBRT and 79 received CRT. The 3-year LC was 87.6% (95% CI, 81.9%-93.4%) for SBRT and 81.2% (95% CI, 71.9%-90.5%) for CRT (hazard ratio [HR], 0.61; 95% CI, 0.31-1.20; P = .15). The HR was 1.02 (95% CI, 0.72-1.45; P = .87) for event-free survival and 1.18 (95% CI, 0.80-1.76; P = .40) for overall survival. Minimal acute toxic effects were observed. Among those randomized to SBRT, late grade 3 or 4 toxic effects occurred in 5 of 45 (11%) with central NSCLC and 2 of 109 (1.8%) with peripheral NSCLC; among those randomized to CRT, in 1 of 19 (5%) with central NSCLC and 1 of 60 (2%) with peripheral NSCLC. One patient who received SBRT for an ultracentral lesion (target overlapping proximal bronchus) experienced a possible treatment-related grade 5 event (hemoptysis)., Conclusions and Relevance: This RCT compared lung SBRT with hypofractionated CRT that included central/ultracentral tumors. No difference was detected in LC between groups. Severe toxic effects were limited, including patients with central tumors. The trial provides important prospective data evaluating SBRT; however, further research is necessary to determine if SBRT is more effective than CRT for peripheral and central NSCLC., Trial Registration: ClinicalTrials.gov Identifier: NCT03924869.

Purpose: Accurate IHC biomarkers incorporating nestin positivity or inositol polyphosphate-4-phosphate (INPP4B) loss have recently been optimized to identify the basal-like intrinsic breast cancer subtype regardless of estrogen, progesterone, or Her2 status. We examined the predictive capacity of these basal biomarkers in the CCTG MA.5 chemotherapy and MA.12 endocrine therapy trials., Experimental Design: Formalin-fixed paraffin embedded blocks of primary tumors from patients randomized in the two trials were used to build tissue microarrays. IHC staining for nestin and INPP4B followed published methods and REMARK criteria. A prespecified statistical plan tested the hypothesis that patients with basal breast cancer (nestin + or INPP4B - ) would not benefit from anthracycline substitution in MA.5 or from tamoxifen in MA.12., Results: Nestin positivity or INPP4B loss was observed in 110/453 (24%) interpretable samples from MA.5 and 47/366 (13%) from MA.12, and was associated with high grade, younger age, estrogen receptor negativity, triple-negative, core basal, and PAM50 basal-like subtypes. In the MA.5 trial, patients assigned as basal experienced lower benefit from anthracycline versus nonanthracycline adjuvant chemotherapy [HR, 1.49; 95% confidence interval (CI), 0.72-3.10] when compared with non-basal (nestin - and INPP4B + ) cases where there was a higher benefit from anthracyclines (HR, 0.75; 95% CI, 0.54-1.04; P interaction = 0.01). In the MA.12 trial, patients assigned as basal did not demonstrate a benefit from adjuvant tamoxifen versus placebo (HR, 0.48; 95% CI, 0.12-1.86; P = 0.29), whereas nonbasal cases displayed significant benefit (HR, 0.66; 95% CI, 0.45-0.98; P = 0.04), although the interaction test was not significant., Conclusions: The nestin/INPP4B IHC panel identifies women with basal breast cancers who benefit from nonanthracycline chemotherapy but not endocrine adjuvant treatments., (©2021 American Association for Cancer Research.)