Princess Margaret Cancer Centre

Genomic and clinical landscape of RAS mutations in acute myeloid leukemia

RAS mutations are recurrent in acute myeloid leukemia (AML); yet, their genomic and clinical landscape remain poorly characterized. We analyzed centralized molecular profiling data in 8,553 patients with newly diagnosed AML. Of these, 1,775 (21%) harbored RAS mutations: NRAS in 1...

A Remotely Delivered Exercise-Based Rehabilitation Program for Patients with Persistent Chemotherapy-Induced Peripheral Neuropathy (EX-CIPN): A Phase I Feasibility Trial

Background: Chemotherapy-induced peripheral neuropathy (CIPN) affects two-thirds of patients who receive neurotoxic chemotherapy. In almost half of these patients, CIPN is persistent, with limited treatment options. Exercise-based rehabilitation shows promising results in improvi...

Development and Validation of a Tool to Measure Documented Health Care Encounter Time

Importance Time toxicity, defined as the time patients spend receiving cancer treatment and interacting with health care systems, is an emerging treatment-related burden. Existing studies typically quantify time toxicity using health care contact days, which may inadequately capt...

The HEADSpAcE Data Center: An international data and biospecimen resource for head and neck cancer translational research

Head and neck cancer (HNC) comprises a heterogeneous group of malignancies with substantial variation in incidence, risk factors, and outcomes across populations. Existing studies are often limited by regional scope or lack integration of epidemiological, clinical, and molecular...

Werner helicase inhibitor for advanced microsatellite instability solid tumors: a phase 1 trial

Abstract Werner syndrome helicase (WRN) is a synthetic lethal target for microsatellite instability (MSI) cancers. In part 1 of this ongoing first-in-human, phase 1 trial, escalating doses of RO7589831 (VVD-133214), a first-in-class, WRN covalent inhibitor, were evaluated in 88 p...

Allosteric inhibition of human mitochondrial ClpP by hijacking the dordaviprone (ONC201) binding site

ClpP protease maintains proteostasis in human mitochondria and is overexpressed in cancers such as acute myeloid leukemia (AML). While activators such as dordaviprone (ONC201) have reached the clinic, the development of ClpP inhibitors has been hampered by paradoxical activation...

Neuroradiological spectrum of sarcoma intracranial metastases: a single center study

Sarcomas are a heterogeneous group of rare tumors sharing a common origin from connective or other non-epithelial tissues. Although clinical case series of intracranial sarcoma metastases have already been published, their neuroradiological findings are poorly known. This study a...

Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study

Abstract Early cancer detection improves survival; however, most cancer types do not have guideline-recommended screening. We previously reported the first PATHFINDER study that established feasibility of cancer screening with a blood-based multi-cancer early detection (MCED) tes...

Antioxidant premedication reduces mitochondrial and nuclear DNA damage repair in interventional physicians performing X-ray-guided angiography procedures: a pilot clinical intervention study

Abstract Background To examine effects of naturally occurring antioxidants on DNA damage repair acute responses of ionizing radiation sustained by interventional physicians during angiography. Methods The study cohort included 20 interventional physicians (19 males, 1 female; mea...

Dyadic Coping in Patients With Hematologic Malignancies and Their Partners

Background: Patients and their partners coping with hematologic malignancies (HMs) experience significant psychological and relational challenges. Dyadic coping (DC) plays a critical role in couples’ adaptation under cancer treatments. Objective: To synthesize existing evidence o...

Management of Soft Tissue and Visceral Leiomyosarcomas

Importance Leiomyosarcoma is a rare and heterogeneous malignant mesenchymal neoplasm associated with substantial morbidity and mortality. Given recent advances in biologic understanding and the complexity of leiomyosarcoma, a consensus-driven approach is needed to harmonize manag...

Prognostic Role of Adverse Events in a Worldwide Population of Patients with Biliary Tract Cancer Treated with Chemo-Immunotherapy

Background: Biliary tract cancers (BTCs) are aggressive malignancies with limited treatment options. The addition of durvalumab or pembrolizumab to cisplatin–gemcitabine improves overall survival (OS), but validated biomarkers of benefit remain limited. Immune-mediated adverse ev...

Nonviral delivery of chemically modified tRNA rescues nonsense mutations in cystic fibrosis

Suppressor transfer RNAs (sup-tRNAs) can rescue disease-causing nonsense mutations by promoting readthrough of premature termination codons (PTCs). Their clinical translation is limited by suboptimal activity and inefficient in vivo delivery. In this work, we combined site-specif...

EphA4 Mediates Pro- and Antitumoral Effects Through Upstream Negative Regulation of AKT in Head and Neck Squamous Cell Carcinoma

Head and Neck Head and Neck Squamous Cell Carcinoma (HNSCC) is driven by an immunosuppressive tumor microenvironment (TME). We examined the immune-modulatory role of EphA4 in HNSCC using spatial analysis, multi-compartment RNA-sequencing from Oral Cavity Squamous Cell Carcinoma (...

P1.179. Association of Proximal Margin Length With Survival and Recurrence Following Esophageal Resection

Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer Background R0 resection is a mainstay in the curative resection of esophageal cancer. However, the optimal length of proximal margin (PM) remains debated, as operative approach is dependent on tumor locatio...

Time-dependent analysis of HUS change in older patients aged > 75 years with head and neck cancer

Previous longitudinal evidence has suggested that patients aged > 75 years may be associated with a poorer Health Utility Index Mark 3 (HUI-3) trajectory. We compared the longitudinal health utility scores (HUS) of older (>75 years) versus younger patients with head and neck canc...

CAR T Cells Targeting an Intracellular Leukemia Antigen Promiscuously Presented by Diverse HLA-II Alleles

Chimeric antigen receptor (CAR) technology has revolutionized B-cell malignancy treatment by enabling T cells to effectively recognize and target lineage-specific surface antigens. However, CAR T cells show limited efficacy against myeloid neoplasms and solid tumors due to challe...

Maintenance therapy after allogeneic stem cell transplantation for relapse prevention in myeloid malignancies

Purpose of review Relapse remains the leading cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), and outcomes after relapse are poor. This review summarizes and critically appr...

Immune checkpoint blockade sensitivity is linked to endogenous retroelement transcriptional changes in cancer

Abstract Endogenous retrotransposable elements (EREs) can modulate immune responses. We explored ERE transcription in relation to response to immune checkpoint inhibition in advanced solid tumors. ERE expression was measured in pre and on-treatment samples from patients treated i...

Patient-physician sex concordance and real-world disparities in cancer treatment practices and outcomes in medical oncology

The impact of sex inequities in healthcare may be magnified in medical oncology, where patients and physicians often navigate life-limiting illnesses and intensive treatments. We examined the associations among patient-physician sex concordance, treatment practices, and cancer ou...