PURPOSE: There is strong interest from patients, researchers, the pharmaceutical industry, medical journal editors, funders of research, and regulators in sharing clinical trial data for secondary analysis. However, data access remains a challenge because of concerns about patient privacy. It has been argued that synthetic data generation (SDG) is an effective way to address these privacy concerns. There is a dearth of evidence supporting this on oncology clinical trial data sets, and on the utility of privacy-preserving synthetic data. The objective of the proposed study is to validate the utility and privacy risks of synthetic clinical trial data sets across multiple SDG techniques. METHODS: We synthesized data sets from eight breast cancer clinical trial data sets using three types of generative models: sequential synthesis, conditional generative adversarial network, and variational autoencoder. Synthetic data utility was evaluated by replicating the published analyses on the synthetic data and assessing concordance of effect estimates and CIs between real and synthetic data. Privacy was evaluated by measuring attribution disclosure risk and membership disclosure risk. RESULTS: Utility was highest using the sequential synthesis method where all results were replicable and the CI overlap most similar or higher for seven of eight data sets. Both types of privacy risks were low across all three types of generative models. DISCUSSION: Synthetic data using sequential synthesis methods can act as a proxy for real clinical trial data sets, and simultaneously have low privacy risks. This type of generative model can be one way to enable broader sharing of clinical trial data.

Follow-up care of early breast cancer (EBC) patients usually includes routinely scheduled physical examinations. While ASCO guidelines recommend a physical exam every three to six months for the first three years, little evidence supports this schedule. We evaluated recurrence detection of patients transferred into a single centre survivorship program that follows ASCO recommendations. Patients with EBC referred to the Wellness Beyond Cancer Program (WBCP) who had breast cancer recurrence between February 1, 2013, and January 1, 2019 were reviewed. Descriptive analyses were used to present patient and disease characteristics stratified by type of recurrence and mode of cancer detection. Of 206 recurrences, 135 were distant recurrences (65.5%), 41 were ipsilateral breast recurrences (19.9%), and 30 were contralateral breast primaries (14.6%). Distant recurrences were primarily detected via patient-reported symptoms (125/135, 92.6%). 53.7% (22/41) of ipsilateral breast recurrences were detected by patients and 41.5% (17/41) by routine imaging. Contralateral breast primaries were primarily detected by imaging 83.3% (25/30) and patient-reported symptoms 16.7% (5/30). Only 2/206 (1.14%) recurrences/new primaries were detected by healthcare providers at routinely scheduled follow-up visits. Despite following ASCO guidelines, healthcare providers rarely detect recurrences at routinely scheduled follow-up appointments. Our data suggests that approximately 35, 000 follow-up visits were required for healthcare providers to detect these 2 recurrences. While reduced in-person visits may affect other aspects of follow-up care (e.g. toxicity management), it appears unlikely, provided patients attend regular screening tests, that less frequent in-person follow-up is associated with worse breast cancer-related outcomes.

Background: Ipilimumab and nivolumab (ipi/nivo) improved overall survival (OS) compared to sunitinib in the pivotal Checkmate 214 trial of metastatic renal cell carcinoma (mRCC) with International Metastatic RCC Database Consortium (IMDC) intermediate/poor risk disease. We evaluated the efficacy and toxicity of ipi/nivo in older and frailer populations in a real-world mRCC cohort. Methods: Analysis was conducted on a real-world cohort with mRCC (N = 551) treated with first-line ipi/nivo from the Canadian Kidney Cancer information system (CKCis) database from January 2014 to December 2021. A comparison was made between outcomes and toxicity in patients 1. <70 versus (vs.) ≥70 yo, 2. <75 vs. ≥75 yo, and 3. KPS ≥70 vs. 70 yo and >75 yo when controlled for IMDC. However, when comparing patients with KPS > 70 vs. KPS < 70, patients with a poor performance status had decreased median OS at 54.5 m vs. 10.8 m (p-value < 0.0001) and PFS at 11.6 vs. 3.1 m (p-value < 0.0001). Conclusions: The use of ipi/nivo in mRCC demonstrated similar survival outcomes and toxicity in an older patient population. In patients with a poor performance status, it was associated with inferior OS and PFS. We believe that ipi/nivo is a reasonable treatment option for these patient populations, particularly in older patients.

Treatment for early-stage breast cancer is complex, requiring multidisciplinary care with a multitude of treatment options available for each patient. Coupled with the rising importance of shared decision-making, patient-physician conversations are progressively more complicated. These conversations require frank disclosure of risks and benefits of the different treatment modalities in a way that is individualized for each patient and simple to understand. In most patients, breast conserving therapy with radiation should be presented as the gold-standard local treatment given similar long-term and improved quality of life outcomes. De-escalation is currently at the forefront of research in loco-regional treatments, and further investigations are required to best determine the optimal patient populations for reduced sentinel lymph node sampling, omission of sentinel lymph node biopsy altogether and omission of radiation treatment. For future trials, better endpoints need to be established considering patient-centered outcomes as well as recurrence.

Background: Non-compliance and non-persistence with endocrine therapy for breast cancer is common and usually related to treatment-induced side effects. There are anecdotal reports that simply changing the time of day when taking endocrine therapy (i.e., changing morning dosing to evening dosing or vice versa) can reduce side effects. Literature review: We conducted a literature review to evaluate whether changing the timing of tamoxifen and/or aromatase inhibitor administration impacted patient outcomes. No randomized control trials or prospective cohort studies that looked at time of day of endocrine therapy were identified through our review of literature from 1947 until August 2020. Conclusions: Given the rates of endocrine therapy non-compliance and non-persistence reported in the literature, ranging from 41–72% and 31–73%, respectively, simply changing the time of day when medications are taken could be an important strategy. We could identify no trials evaluating the effect of changes in timing of administration of endocrine therapy on breast cancer patient outcomes. Randomized control trials are clearly indicated for this simple and cost-effective intervention.

For early-stage hormone receptor (HR)-positive and HER2-negative breast cancer, tools to estimate treatment benefit include free and publicly available algorithms (e.g., PREDICT 2.1) and expensive molecular assays (e.g., Oncotype DX). There remains a need to identify patients who de-rive the most benefit from molecular assays and where this test may be of poor value. In this multicenter prospective cohort study, we evaluated whether use of PREDICT 2.1 would impact physician decision making. For the first 6 months of the study, data on physician use of both PREDICT 2.1 and Oncotype DX ordering were collected on all newly diagnosed patients eligible for molecular testing. After 6 months, an educational intervention was undertaken to see if providing physicians with PREDICT 2.1 results affects the frequency of Oncotype DX requests. A total of 602 patients across six cancer centers in Ontario, Canada were recruited between March 2020 and November 2021. Providing PREDICT 2.1 results and an educational intervention did not alter the ordering of an Oncotype DX. For patients with low clinical risk, either by clinico-pathologic features or by PREDICT 2.1, the probability of obtaining a high Oncotype DX recurrence score was substantially lower compared to patients with high-clinical-risk disease. The introduction of an educational intervention had no impact on molecular assay requests. However, routine ordering of molecular assays for patients with low-clinical-risk disease is of poor value.