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Racovitan V, Goodman E, Cheung WY, Nichols AC, Caulley L, Wurzba S
Abstract:
Oral human papillomavirus (HPV) infection is a risk for oropharyngeal cancer (OPC), now the leading HPV-related cancer in males in Canada. P16 positivity is a marker of HPV positivity. Since 2015, all major Canadian cancer centers perform routine p16 tumor marker testing of OPCs to define their HPV status but recent data on the HPV-attributable fraction for OPC in Canada do not exist. A retrospective chart review was conducted of all squamous cell OPC cases in patients 18 years and older diagnosed from 2016 to 2020 in 4 major Canadian hospital-based regional oncology centers to determine the HPV attributable fraction for OPC in Canada using p16 as a surrogate marker for HPV. 1154 OPC cases were identified. Most patients (85.4%) were male; about one-third 26 (31.4%) had never smoked. Most OPC (80.6%) were P16 positive. p16 positivity was 27 associated with younger age (mean age p16+ 61.6 vs. p16- 66.5 years, p < 0.0001), male sex 28 (p16+ males 84.0% vs p16+ females 60.9%, p < 0.0001), lower tumor stage (Stage 1 p16+ 29 88.1% vs Stage 4 p16+ 69.4%, p < 0.001), and non-smoking (never smoked 92.3% vs past 30 smoker 82.8% vs current smoker 65.0%, p < 0.001). Logistic regression confirmed these 31 associations. This study, the largest cohort of Canadian patients with OPC yet reported, demonstrates the high attributable fraction for HPV-related OPC. HPV-related OPC was more likely in men, younger individuals, and never smokers. These findings highlight the burden of HPV-related OPC in Canada and support gender-neutral HPV vaccination as an important public health strategy to prevent head and neck cancer.
Muñoz CE, Dai WF, Cheung WY, de Oliveira C, Pataky RE, Ding PQ, Tran DA, Aurangzeb Z, Nagamuthu C, Liu N, Lethbridge L, McClure C, Vriends K, Xiong H, Folkins C, Somayaji C, Peacock S, Alvi R, Turner D, O'Conaill C, McDonald T, Urquhart R, Kendell C, Dowden J, Strumpf E, Denburg A, Beca JM, Mercer RE, Tadrous M, Takhar P, Chan KKW, CanREValue Collaboration
Abstract:
We assessed the comparative effectiveness and safety of pertuzumab plus trastuzumab and chemotherapy versus trastuzumab and chemotherapy for patients with HER2+ metastatic breast cancer (mBC) in Canada. We conducted a population-based retrospective study of patients receiving first-line treatment for mBC across eight Canadian provinces. Patients receiving trastuzumab and chemotherapy were historical comparators, and patients receiving pertuzumab plus trastuzumab and chemotherapy were the treatment group. Patients were followed until death or up to 5 years following the start of treatment (maximum follow-up to December 31, 2019). The primary outcome was overall survival (OS). One-year cumulative incidence and RDs were calculated for safety outcomes including hospitalization, emergency department visits, febrile neutropenia, and cardiac-related events. Propensity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were applied within provinces. Individual provincial survival estimates were pooled using random effects meta-analysis. 3063 patients who received first-line treatment for mBC were identified. Median OS was higher among treatment patients compared to comparator patients in most provinces. Pertuzumab was associated with a statistically significantly lower risk of mortality (pooled HRs, PSM: 0.65, 95%CI: 0.57-0.74; IPTW: 0.65, 95% CI: 0.61-0.70). The treatment group had a lower risk of hospitalization compared to the comparator group (pooled RD: -0.05, 95% CI: [-0.09]-[-0.01]). No difference in 1-year cumulative incidence of cardiac-related events was identified between groups. Pertuzumab use in practice was associated with statistically significant improved survival without apparent safety concerns among patients with mBC. Real-world evaluations allow for assessments of publicly funded treatments to inform funding policies.
Jimenez-Zepeda VH, Stephen MM, Chan H, Cheung WY
Abstract:
BACKGROUND: Proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs) are important backbones in early line treatments for patients with multiple myeloma (MM). This study examined real-world treatment patterns, clinical outcomes and healthcare resource utilization (HCRU) of double-class exposed (DCE) patients with MM after prior PI and IMiD-based treatment. METHODS: DCE patients were identified using integrated administrative databases in the province of Alberta, Canada. DCE patients who commenced subsequent lines of therapy (LOT) between January 2012 and December 2022 were included. RESULTS: Among 831 DCE patients identified to have initiated subsequent LOT during the study period, median age was 68.0 years. IMiD (61%) was the most commonly used therapeutic class after progressing on double-class exposure, followed by PI (39%) and monoclonal antibodies (26%). Attrition rates after first subsequent LOT, defined as death before receiving the next LOT, was 27%, and attrition from second to third subsequent LOT was 30%. Median time to next treatment or death was 12.1 months (95% confidence interval: 10.3-14.1) and median overall survival was 34.4 months (30.3-40.2) from the start of the next subsequent LOT after double-class exposure. healthcare resource utilization (HCRU) during the first year of starting subsequent LOT was high, with a median of 1 ED visit, 1 inpatient admission, 30 clinic visits, 3 infusion appointments, 56 unique healthcare encounters. On average, patients spent 42.2 days on laboratory tests. CONCLUSION: Clinical outcomes among patients with MM initiating postdouble-class exposure treatments remain suboptimal, with high attrition rates and significant healthcare use, highlighting the need for therapies that reduce patient burden.
Khan M, King WD, Brenner DR, Peters CE, O'Sullivan DE
Abstract:
BACKGROUND: The objective of this study was to examine the relationship of recreational and occupational exposure to solar ultraviolet radiation (UVR) with the risk of developing prostate cancer (PC). METHODS: Data from three provincial prospective cohorts in Canada (Ontario Health Study, Québec's CARTaGENE, and Alberta's Tomorrow Project) were used. A nested case-cohort approach was applied for the examination of occupational solar UVR and was based on longest held job at baseline. Cox proportional hazards models with age as the time-scale were used to estimate the risk of PC associated with self-reported time spent in the sun and occupational solar UVR (weighted model). Effect modification by body mass index (BMI) was explored. RESULTS: A total of 543 PC cases were included in the analysis of time spent in the sun and 1667 PC cases were included in the analysis of occupational solar UVR. Compared to < 1 h/day in the sun, 1-< 2 h (Hazard Ratio [HR] 0.96, 95 % CI: 0.81-1.13) and ≥ 2 h (HR 0.89, 95 % CI: 0.76-1.05) were not significantly associated with PC risk. Occupational solar UVR was also not significantly associated with PC risk (HR 1.08, 95 % CI: 0.90-1.30). Compared to < 1 h/day, individuals who spent 1-< 2 h in the sun were at a reduced risk of PC if they had a normal BMI (HR 0.64, 95 % CI: 0.44-0.92), but not if they were overweight (HR 0.99, 95 % CI: 0.76-1.30) or obese (HR 1.20, 95 % CI: 0.90-1.61). CONCLUSION: Overall, results do not support an association between solar UVR exposure and PC risk, but larger studies are needed to confirm these findings. There is some indication of effect modification by BMI that should be explored in future studies.
Owen C, Mojtabavi A, Buckland T, Dean M, Deschenes J, Peters A, Puckrin R, Scott A, Stewart DA
Abstract:
Rapid time to diagnosis and consultation are important parameters in cancer care for patient satisfaction and survival. Historically, most cancer centers only accepted patients with confirmed cancer diagnoses leading to diagnostic and treatment delays. We created a comprehensive Lymphoma Diagnosis Program (LDP) within the provincial cancer care service to expedite lymphoma diagnoses. The results of the first 2 years of the LDP are summarized. The LDP successfully identified patients at high likelihood of lymphoma with 70% of accepted patients having malignancy (57% lymphoma; 13% other cancers). The use of a minimum 2.0 cm short axis measure lymph node for entry into the program proved useful. The radiological core needle biopsy diagnostic approach reduced time to diagnosis compared to pre-LDP timelines. Hospitalizations during the diagnostic process were also reduced. A cancer-care based diagnostic program for lymphoma can successfully improve the time to diagnosis and consultation for lymphoma patients.
Sabrie N, Minhas G, Vaska M, Meng ZW, Brenner DR, Forbes N
Abstract:
OBJECTIVES: Pancreatitis is common following endoscopic retrograde cholangiopancreatography (ERCP). Despite increased vigilance of post-ERCP pancreatitis (PEP), both its incidence and associated mortality are rising. Risk prediction models may provide more accurate stratification of patient risk and proactive mitigation of PEP incidence and/or severe associated outcomes. METHODS: We conducted an electronic search of MEDLINE, PubMEd, Cochrane, and CINAHL from inception through April 9, 2024 for studies evaluating the details and performances of available PEP prediction models. Studies were eligible if they used statistical measures to quantify their model's predictive ability. Risk of bias was determined using the PROBAST tool. RESULTS: Nineteen studies met eligibility criteria and were included. Logistic regression models were used in 15 studies, with machine learning models representing the second most commonly used approach. Ten studies reported the performance of their risk prediction models using derivation data, with areas under the receiver operating curve (AUC) ranging from 0.68 to 0.86. Fifteen studies reported the performance of their risk prediction models on internally validated data, with AUCs ranging from 0.66 to 0.97. Eight studies reported on the performance of their risk prediction models on external validation data, with AUCs ranging from 0.67 to 0.98. DISCUSSION: Numerous PEP clinical prediction models exist with variable performances. The use of PEP prediction tools can support the management of patients following ERCP. Implementation studies assessing the optimal usability of these tools, followed by prospective evaluations, are needed to evaluate their potential impacts on reducing PEP in real-world practice.
Oedingen C, MacDonald KV, Stein BD, Batist G, Cheung WY, Gill S, Goldenberg BA, Ko YJ, Marshall DA, Colorectal Cancer Canada’s Patient Values Project
Abstract:
BACKGROUND: Treatment decisions for metastatic colorectal cancer (mCRC) require patients to balance survival benefits, health-related quality of life (HRQoL), and potential risks of side effects while also factoring in their own preferences for different treatment options. Despite growing interest, quantitative patient preferences are not yet integrated into health technology assessments (HTAs) for drug reimbursement recommendations. OBJECTIVES: The Colorectal Cancer Canada's Patient Values Project aims to explore approaches to incorporate quantitative patient preferences into cancer treatment HTA decision-making processes. As a first step, we elicited the treatment preferences and risk tolerance of patients with mCRC in Canada using a multi-method approach. METHODS: We developed a preference survey that included two discrete choice experiments (DCEs) and case 1 best-worst scaling (BWS-1) to estimate preferences for mCRC treatments. DCE1 included change in HRQoL and overall survival as attributes, and treatment attributes in DCE2 were administration and frequency, side effects (nausea, pain, diarrhea), and progression-free survival. The BWS-1 included 25 attributes of potential mCRC treatment side effects based on the cancer-specific quality-of-life questionnaire. The survey was administered across Canada to patients with mCRC aged ≥ 18 years with a self-reported diagnosis of mCRC through patient organizations, cancer centers, and an online panel. Data were analyzed using mixed logit and latent class models (DCEs) and count-based analysis (BWS-1). RESULTS: Overall, 127 patients with mCRC completed the full survey (n = 143 fully completed DCE1, n = 108 fully completed DCE2, n = 127 fully completed BWS-1). Relative preferences for the treatment attributes in the study were consistent with the expectation that better clinical outcomes were preferred over worse clinical outcomes. In DCE1, patients valued both overall survival (24 vs. 12 months) and HRQoL (improvement to 90 vs. worsens to 50 out of 100) as almost equally important. In DCE2, patients preferred better outcomes (longer progression-free survival and no side effects) over worse outcomes, with a disutility for oral capsules/pills compared with intravenous infusions. Significant preference heterogeneity was observed depending on experiences with CRC treatments, treatment side effects, and health status. In the BWS-1, "need help with eating, dressing, washing yourself or using the toilet", "vomiting", and "pain" were ranked as the least and "need to rest", "trouble doing strenuous activities", and "feel tired" as the most tolerable side effects. CONCLUSIONS: This study highlights the value of a multi-method approach in comprehensively assessing treatment preferences and risk tolerance in mCRC. By triangulating multiple preference-elicitation methods, our findings offer a more robust foundation for integrating patient perspectives into Canada's HTA framework. These results will inform the next step of the Colorectal Cancer Canada's Patient Values Project, which aims to explore approaches to explicitly incorporate patient preferences alongside clinical and economic evidence into the cancer treatment HTA decision-making process in Canada.
Ding PQ, Tam VC, Ramjeesingh R, Asselah J, Sheffield BS, Mitchell T, Gaudreau AJ, Knox JJ, Cheung WY
Abstract:
BACKGROUND: In September 2021, pemigatinib received Health Canada approval for previously treated locally advanced/metastatic cholangiocarcinoma (CCA) with FGFR2 rearrangements/fusions. This retrospective study aimed to characterize the real-world management and outcomes of patients with CCA receiving pemigatinib through a Canadian patient support program (PSP). METHODS: We evaluated a multi-centre case series of Canadian patients who were prescribed pemigatinib between September 2021 and January 2023 for eligible CCA diagnoses and enrolled in the PSP. The retrospective study data included demographic and disease-, treatment-, and outcome-related information, and these were collected using a survey of prescribing physicians. RESULTS: Of the 26 patients who initiated pemigatinib in the PSP, we received survey responses for 18 (69%). Their median age was 57 years, 67% were female, 61% had stage IV disease, and 83% had intrahepatic CCA. Prior to pemigatinib, a partial hepatectomy was performed in 44% of the patients, and 66% of the patients received 2-4 prior lines of systemic therapy. All patients were treated with platinum-based regimens as the first-line treatment for unresectable/metastatic disease. The median follow-up time on pemigatinib was 12.6 (range: 2.3-28.4) months, and their median real-world progression-free survival (rwPFS) was 12.1 months (95% CI 7.2-NR). The physician-assessed objective response and disease control rates were 56% and 89%, respectively. For the nine patients who discontinued pemigatinib, the median treatment duration was 10.6 months (range: 0.8-21.7). Disease progression was the most common reason for discontinuation (89%). None discontinued due to adverse events. CONCLUSIONS: Objective response rates, disease control rates, and a PFS comparable to that in the phase 2 FIGHT-202 trial was reported with pemigatinib use in this Canadian PSP cohort.
Chan A, Nixon N, Al-Khaifi M, Bestavros A, Blyth C, Cheung WY, Hamm C, Joly-Mischlich T, Manna M, McFarlane T, Minard LV, Naujokaitis S, Peragine C, Railton C, Edwards S
Abstract:
The adjuvant treatment landscape for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (EBC) is rapidly evolving, with a diverse range of therapeutic options-including endocrine therapies, bisphosphonates, ovarian function suppression, olaparib, CDK4/6 inhibitors, and emerging agents such as immunotherapy. While these advances have markedly improved patient outcomes, they also introduce challenges related to implementation, monitoring, and resource allocation. Notably, therapies like CDK4/6 inhibitors require particularly close monitoring, creating logistical and capacity challenges for medical oncologists, whose workloads are already stretched due to rising cancer incidence and treatment complexities. These challenges underscore the need for innovative care delivery solutions to ensure patients with EBC continue to receive optimal care. This paper offers a comprehensive guide-a playbook-of multidisciplinary-team-based care models designed to optimize adjuvant treatment delivery in EBC. Drawing on real-world evidence and successful applications across Canadian centers, we explore models led by nurses, nurse practitioners (NPs), general practitioners in oncology (GPO), and pharmacists. Each model leverages the unique expertise of its team to manage treatment toxicities, facilitate adherence, and enhance patient education, thereby promoting effective and sustainable care delivery. Importantly, these models are not intended to compete with one another, but rather to serve as a flexible recipe book from which breast cancer care teams can draw strategies tailored to their local resources and patient needs. By detailing implementation strategies, benefits, and challenges-in many instances supported by quantitative metrics and economic evaluations-this work aims to inspire care teams nationwide to optimize the adjuvant management of patients with HR+, HER2- EBC.
Walker SR, Abdelsalam RA, Ghosh S, Livingstone J, Palanisamy N, Boutros PC, Yip SM, Lees-Miller SP, Bismar TA
Abstract:
[This corrects the article DOI: 10.1016/j.euros.2021.05.004.].
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