BC Cancer Agency

Our systematic and comprehensive genomic and spatially resolved profiling of Hodgkin lymphoma revealed a paradigmatic link between a genetic disease subtype and TME composition and function. Insights into mutation-driven mechanisms of deregulated cytokine signaling will pave the way for therapeutic interventions that interfere with oncogenic signaling and cellular ecosystems in cancer.

Not available.

Exercise interventions improve quality of life and survival for individuals living with and beyond cancer (ILWBC), yet equitable access remains limited. Evidence on characteristics of who enrolls in exercise oncology programs is scarce, leaving gaps for equity-focused recruitment and scale-up, particularly in rural and underserved settings. The EXercise for Cancer to Enhance Living Well (EXCEL) study offers a unique opportunity to examine these issues across a Canada-wide cohort. EXCEL is an 8-12-week tailored exercise intervention delivered primarily to ILWBC in rural/remote communities, with additional enrollment of urban participants lacking exercise oncology resources. Adults with any cancer type or stage were eligible if pre-treatment, receiving treatment, or within 3 years post-treatment. This analysis describes baseline demographic, lifestyle, medical, and fitness factors by rural versus urban residence using descriptive statistics. Of 1495 participants enrolled in the EXCEL program (rural n = 1085; urban n = 400), baseline characteristics differed modestly by geography. Age did not differ significantly between rural and urban participants. Rural participants were more often male, had lower educational attainment, and demonstrated higher BMI than urban participants. Urban participants exhibited greater ethnic diversity and higher levels of education. Physical activity levels were similar with 78% classified as physically active at baseline. This Canada-wide baseline analysis reveals rural-urban variations in age, treatment status, disease burden, education, and lifestyle, yet comparable physical activity and functional capacity levels. These findings provide descriptive evidence to inform recruitment strategies and considerations for exercise oncology program delivery across geographic settings.

90 Background: Germline and somatic alterations in genes associated with DNA repair are common in patients with mPCa and have treatment implications. International guidelines uniformly recommend genomic testing for patients with mPCa however a variety of barriers influence uptake. In the Canadian province of British Columbia (population 5.7 million), publicly funded tumor and germline centralized genomic testing became available for all patients with mPCa in May 2022. We reviewed the program to understand uptake, utilization, clinical impact and identify areas for improvement. Methods: This multicenter, retrospective observational study included all patients in British Columbia with mPCa who underwent molecular tumor testing at the Cancer Genetics and Genomics Laboratory (CGL) of BC Cancer from initiation of the program on 24 May 2022 to 24 May 2024. Tumor tissue testing was prioritized with blood based circulating tumor DNA (ctDNA) serving as an alternative where tumor tissue testing failed or was not possible. Data were extracted from the CGL database and electronic medical records, and analysed using descriptive statistics. Results: Over the two-year period, 2119 individual patients underwent a total of 2253 tests; 2018 tissue tests and 235 ctDNA tests. Most tests (83.0%) were requested by medical oncologists. Median turnaround times from receipt of tissue by the laboratory to result date were 31 days, 44 days, and 66 days for ctDNA, tissue and germline tests, respectively. 235 (11.6%) tissue tests failed, and 153 (65.1%) ctDNA tests had undetectable ctDNA. An estimated 113 (73.9%) of the ctDNA tests with undetectable ctDNA could potentially have been avoided by limiting testing to patients with: 1) metastatic hormone-sensitive prostate cancer on androgen deprivation ≤14 days (46 avoidable tests), and 2) progressive metastatic castration-resistant prostate cancer with a predicted ctDNA fraction of ≥2% using the ctDNA.org tool (67 avoidable tests). Of 96 (4.5%) patients with a BRCA1/2 alteration detected, 47.9% received targeted PARP inhibitor treatment by February 2025, with a further 34.3% remaining eligible while responding to their current treatment. Conclusions: Population-wide tumor testing was rapidly adopted in British Columbia, resulting in identification of actionable alterations and facilitating access to targeted therapies in keeping with international guidelines. Education on optimal timing for cfDNA collection is needed to reduce unnecessary testing and improve test yield.

Associated normal tissue toxicity from current radiotherapy (RT) treatments limits effective dose escalation in the tumor to achieve nominal treatment results. Gold nanoparticles (GNPs) as radiosensitizing agents to locally increase photoelectron production have gained interest as a safe and viable method to improve therapeutic results. Among many other factors, the dose rate of the incident radiation has been shown to affect the radiosensitizing properties of GNPs significantly. To evaluate GNP-induced radiosensitization during variable dose rate delivery from the decay of a high dose rate brachytherapy 192-Ir source and a clinical 6MV linear accelerator (LINAC). HEC-1A endometrial cancer cells were seeded into 35mm petri dishes with or without 10µg/mL with spherical 11nm GNPs functionalized with polyethylene glycol and integrin binding domain RGD to improve intracellular uptake. Variable dose rate delivery from the 192-Ir source was achieved at two source strengths of 37.95 mGy m2/h and 18.97 mGy m2/h, corresponding to dose rates of 1.1 and 0.55Gy/min, respectively. For 6MV irradiations, dose rate variability was controlled by adjusting the distance to the target from 91cm to 129cm, yielding identical dose rates of 1.1 and 0.55Gy/min, respectively. Cellular viability was measured using a clonogenic assay after irradiations between 0 and 8Gy, and a DNA double-strand break assay after 2Gy irradiations. GNP-induced radiosensitization was significantly greater with higher dose rates than lower. Clonogenic loss with GNPs was increased from 1.00 to 1.19 (p<0.001) with higher dose rates from 192-Ir source and from 1.03 to 1.16 (p<0.001) with higher dose rate LINAC irradiations. DNA damage increase from GNPs was not significant at lower dose rates for both 192-Ir (p>0.05) and LINAC (p>0.05) irradiations; however, DNA damage was significantly increased at higher dose rates (192-Ir: p<0.01; 6MV: p<0.05). We have successfully demonstrated in vitro that clinically plausible GNP concentrations can induce variable radiosensitization based on the administered dose rate from both 192-Ir and LINAC irradiations. This work demands future research into the clinical translation of GNPs into high-dose-rate environments.