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Phillips WJ, Zhan LJ, Chowdhury D, Gill J, Sun A, Rittberg R, Cohen V, Gibson AJW, Yan M, Liwski D, Surapaneni S, D'Amours MF, Yu FPS, Kim Y, Qadeer RA, Dawe DE, Agulnik J, Navani V, Fung AS, Snow S, Kuruvilla S, Ho C, Lok BH, Liu G, Wheatley-Price P, Moore S
Abstract:
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Bista S, Khan M, Nambayan R, Vaska M, Ruan Y, Hilsden RJ, Brenner DR, O'Sullivan DE
Abstract:
INTRODUCTION: This study aimed to determine the prevalence of colorectal cancer (CRC) screening among cancer survivors and compare the likelihood of CRC screening among cancer survivors to that of the cancer-free general population. METHODS: A systematic search of MEDLINE (Ovid), EMBASE, PubMed, and CINAHL databases from inception through September 16, 2024 was conducted. Studies reporting CRC screening among cancer survivors or in both cancer survivors and cancer-free controls were included. Random effects meta-analyses were conducted to pool estimates. Analyses were performed across primary cancer sites where at least three studies were identified. RESULTS: Of the 2497 articles identified, 59 fulfilled the inclusion criteria. The overall pooled prevalence of CRC screening (up-to-date for screening or had been screened during a specific time period after non-CRC diagnosis) was 0.53 (95% CI: 0.46, 0.61), with estimates ranging from 0.72 (prostate) to 0.51 (breast) across primary cancer sites. Cancer survivors were more likely to participate in CRC screening than cancer-free controls (Odds Ratio: 1.39, 95%CI: 1.26, 1.52), but there was some evidence of publication bias (Egger's test p-value = 0.092). Study design, method of CRC screening ascertainment (self-report vs. medical records), and first primary cancer site were significant sources of heterogeneity. DISCUSSION: Cancer survivors were more likely to undergo CRC screening compared to cancer-free controls, but overall rates were well below generally recommended levels for population-based screening. Future studies should evaluate the predictors of non-adherence to CRC screening among cancer survivors to inform policymakers in targeting populations with lower screening rates.
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.
O'Sullivan DE, Blosser N, Crisp N, Randhawa B, Bista S, Beda G, Shafey M, Hay K, Puckrin R, Daly A, Storek J, Jamani K
Abstract:
Background Survivors of allogeneic hematopoietic cell transplantation (allo-HCT) are known to be at risk of late toxicities. The spectrum of late toxicities may be impacted by changing allo-HCT practices: In contemporary allo-HCT practice, conditioning with high-dose total body irradiation is infrequent, the incidence of chronic GVHD is declining, and older adults receive allo-HCT more frequently. Few studies have examined the burden of comorbidities and the quality of life (QoL) of recent long-term survivors of allo-HCT, and even fewer have included a biological sibling control group for comparison. Objectives We set out to quantify and compare the burden of comorbidities and the QoL of a largely contemporary group of survivors of allo-HCT versus their biological siblings. We further aimed to understand the association of transplant-related variables, demographic variables, and comorbidities, with QoL amongst recipients. Study Design We conducted a cross-sectional study comparing QoL and comorbidity burden between allo-HCT recipients and their biological siblings. In addition, we built multivariable models to understand predictors of physical health (PH) and mental health (MH)-related QoL amongst recipients. Recipients without active chronic GVHD or relapse were enrolled at one of two survivorship clinics alongside their siblings. We used PROMIS Global Health to assess QoL and the post-transplant multimorbidity index to evaluate comorbidities. Results In total, 391 recipients were enrolled. Of these, 106 recipients had a total of 154 siblings enrolled for comparison. The 106 recipients experienced significantly more comorbidities versus their siblings: 3 or more comorbidities were observed in 51.9% of recipients versus 33.1% of siblings (p = 0.002), while at least 1 severe comorbidity was observed in 24.5% vs. 13.0%, respectively (p = 0.02). In spite of this, PH and MH-related QoL of recipients was similar to that of siblings: PH QoL median T-score 49.9 (IQR 45.8-57.4) versus 50.7 (IQR 46.3-54.4), respectively (p = 0.77), and MH QoL median T-score 50.9 (IQR 44.8-54.6) versus 51.6 (IQR 45.3-55.1), respectively (p = 0.58). Social functioning was rated as very good or excellent by 65.1% of recipients versus 68.6% of siblings (p = 0.33). Amongst the entire cohort of 391 recipients, the number of comorbidities was strongly associated with MH and PH-related QoL as well as social functioning, whereas transplant-related variables such as prior cGVHD, receipt of low dose TBI, graft and donor type, were not. Conclusions Survivors of allo-HCT continue to experience excess comorbidities versus their biological siblings. Despite this, survivors enjoy QoL and social functioning that are comparable to their siblings and general population norms. Amongst survivors, the number of comorbidities is strongly associated with QoL and social functioning while transplant-related variables are not.
Jimenez-Zepeda VH, Cheung WY, Stephen MM, Chan H
Abstract:
AIM: Immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies (MAbs) alone or in combination form the backbone of multiple myeloma (MM) treatment, yet MM remains incurable requiring further lines of therapy (LOT). This study investigated real-world treatment patterns, clinical outcomes, and healthcare utilization among triple-class exposed (TCE) patients initiating subsequent LOTs. METHODS: TCE patients receiving additional LOTs (January 2012-December 2022) in the Alberta Health System databases were included. RESULTS: Median age among 221 TCE patients requiring subsequent LOT was 70 years. MAbs (42%) and IMiDs (51%) were the most common drug classes incorporated as first and second LOT, respectively. After first LOT, attrition rate was 32%. From first LOT, median time to next treatment or death (TTNT-D) was 10.1 (95% confidence interval: 8.4-13.3) months, median TTNT was 18.1 (15.6-22.4) months and overall survival was 18.7 (16.0-24.3) months. Within first year of subsequent LOT, patients had a median of 1 emergency department visit, 1 hospitalization, 33 clinic visits, 4 infusion appointments, 37 unique healthcare encounters, and a mean of 32 days spent on laboratory tests. CONCLUSION: Treatment for TCE patients has limited effectiveness and a high healthcare system burden, emphasizing the unmet need for therapies with novel mechanisms of action.
Phillips WJ, Zhan LJ, Chowdhury D, Gill J, Sun A, Rittberg R, Cohen V, Gibson AJW, Yan M, Liwski D, Surapaneni S, D'Amours MF, Yu FPS, Kim Y, Qadeer RA, Dawe DE, Agulnik J, Navani V, Fung AS, Snow S, Kuruvilla S, Ho C, Lok BH, Liu G, Wheatley-Price P, Moore S
Abstract:
INTRODUCTION: There have been minimal advances in the systemic treatment of limited stage small cell lung cancer (LS-SCLC) for decades. With the publication of the ADRIATIC trial, consolidation durvalumab is a new standard of care. This study evaluated real-world treatments and clinical outcomes prior to the era of immunotherapy for LS-SCLC. METHODS: The Canadian Small Cell Lung Cancer Database (CASCADE) is a Canadian multi-institutional federated database that includes patients with SCLC from 9 academic institutions. This analysis included patients with pathologically confirmed LS-SCLC treated curatively between January 2001 and December 2022. Baseline characteristics and treatment patterns were obtained from medical records and assessed descriptively. The primary outcome was overall survival (OS) assessed using Kaplan Meier (KM) methods. OS was also assessed among patients who received treatment eligible for participation in the ADRIATIC trial. RESULTS: A total of 1,024 patients were included. Median age was 66 years old and 52 % of patients were female. Concurrent chemoradiation therapy (cCRT) was the most common treatment modality (76 %), followed by surgery (11 %) and sequential CRT (10 %). Median OS was 24.9 months (95 % confidence interval [CI] = 23.4-27.4). Only 36 % of patients treated with cCRT received treatment meeting eligibility criteria for the ADRIATIC trial. The most common reason for ineligibility was due to the radiation therapy (RT) dose/schedule used. Median OS of eligible and ineligible patients was 30.3 months (95 % CI = 26.4-36.4) versus 21.7 months (95 % CI = 19.7-24.9). CONCLUSIONS: Survival outcomes for LS-SCLC remain poor despite curative-intent multimodality treatment. Immunotherapy represents a promising advance but a high proportion of patients in the real-world receive treatment that was not represented in the ADRIATIC trial. Future work evaluating the outcomes of patients treated with immunotherapy is critical to assess its real-world impact.
Brufsky A, Cheung W, Ryan JC
Abstract:
Real-world studies have become more common in clinical literature in recent years, but many clinicians remain unfamiliar with real-world study design and statistical approaches. This vodcast intends to be a practical guide for clinicians by clarifying aspects of real-world study methodology. As both practicing oncologists and researchers with extensive real-world data experience, the hosts discuss types of study designs and real-world data source considerations. An overview of statistical techniques for mitigating treatment-selection bias is also provided, including propensity score matching, inverse probability of treatment weighting, and multivariable analysis. By combining high-quality data sources, careful sample size considerations, and rigorous statistical techniques, real-world studies can offer valuable insights into therapeutic effectiveness in routine clinical practice that supplement learnings from randomized clinical trials. This vodcast is designed to equip clinicians with the knowledge to critically evaluate real-world evidence and potentially apply it to their practice.Vodcast and infographic available for this article. Vodcast (MP4 1207725 KB) INFOGRAPHIC.
Lemelin A, Maj D, Takemura K, Boyne DJ, Warkentin MT, Brenner DR, Cheung WY, Wells C, Labaki C, McGregor BA, Contreras LM, Pal SK, Beuselinck B, McKay RR, Szabados B, Powles T, Yuasa T, Ludwig L, Choueiri TK, Heng DYC
Abstract:
BACKGROUND AND OBJECTIVE: While the benefit of cabozantinib in metastatic renal cell carcinoma (mRCC) is well established post-tyrosine kinase inhibitor therapy, its comparative effectiveness versus sunitinib after first-line (1L) nivolumab-ipilimumab is uncertain. METHODS: A target trial emulation was designed using data from the IMDC to estimate the effect of second-line (2L) cabozantinib versus sunitinib within 18 months of discontinuing 1L nivolumab-ipilimumab on overall survival (OS). Patients diagnosed after January 1, 2017 were followed from initiation of 2L until death or last known contact. Inverse-probability of treatment weighting was used to adjust for hemoglobin, calcium, platelets, and neutrophils at 2L, Karnofsky performance score (KPS) at 2L, time from diagnosis to initiation of 2L, and response to 1L nivolumab-ipilimumab. Treatments were compared using adjusted Kaplan-Meier curves and adjusted hazard ratios (HR) from a Cox regression model. Missing data were addressed with multiple imputation by chained equations. E-values were used to assess the likelihood findings could be explained by residual confounding. KEY FINDINGS AND LIMITATIONS: A total of 120 and 121 patients who received cabozantinib or sunitinib after 1L nivolumab-ipilimumab were included. The proportion with a KPS < 80% at 2L (21% vs. 46% P = .001) and the overall response rate to first line therapy (12.7% vs. 17.9% P = .002) differed significantly between cabozantinib and sunitinib. The objective response was 27% for cabozantinib versus 20% for sunitinib with a median time to treatment failure of 8.5 (95% CI: 6.9-12.9) and 4.5 (95% CI: 3.7-5.8) months. Median OS was 21.4 (95% CI: 17.9-NA) months from initiation of cabozantinib and 10.1 (95% CI: 7.6-17.7) months for sunitinib (Adjusted HR 0.44 (95% CI: 0.22-0.86)). The E-value was 2.92, suggesting a low likelihood of findings being due to residual confounding alone. CONCLUSIONS: These data provide real-world evidence supporting cabozantinib as a second-line treatment option in mRCC following 1L nivolumab-ipilimumab.
Gambaro K, Rachedi K, Basik M, Saad F, Mes-Masson AM, Hassan S, Orimoto A, Boudreau D, Vincent F, St-Hilaire E, Mackay H, Abdelsalam M, Yip SM, Awan A, Hanel R, Guillemette S, Leite R, Caron MA, Patel C, Batist G, Marques M
Abstract:
BACKGROUND: Breast cancer is the most prevalent cancer and second leading cause of cancer-related mortality among Canadian women. Most of cases belong to the HR+/HER2- subtype, representing approximately two-thirds of all instances. OBJECTIVES: This real-world evidence study aims to comprehensively analyze the treatment pattern, and clinical outcomes of Canadian patients diagnosed with early-stage HR+/HER2- breast cancer. DESIGN: This retrospective, longitudinal cohort study involved 541 patients enrolled in the pan-Canadian cancer patient registry PMT (Personalize My Treatment). METHODS: The cohort included patients with newly diagnosed or recurrent stage II or III HR+/HER2- breast cancer between January 1st, 1992, and May 31st, 2022. Summary statistic to describe treatment pattern and Kaplan Meir analysis for clinical outcome were used. RESULTS: In the adjuvant setting, our study found that ET was administered to 75.6% of the cohort, with a significant preference for combining ET with cytotoxic agents and, particularly in stage III patients. In addition, neoadjuvant therapy, primarily using cytotoxic agents, was higher in stage III patients, and those receiving neoadjuvant therapy were more likely to either continue with ET as adjuvant treatment. The median duration of adjuvant ET was 4.5 years. In the adjuvant patient population, recurrence rates progressively increased over time from 13.2% after 2 years, 21.4% after 3 years, 30.3% after 5 years, and peaking at 58.4% after 10 years. Median time to recurrence for the patient population on ET was 7.76 years. OS rate for patients on ET was 94.6% at 5 years and 78.3% at 10 years. CONCLUSIONS: This study highlights the high unmet need in stage II and stage III breast cancer, with 1 patient out of 3 recurring after 5 years, and more than half recurring after 10 years despite adjuvant treatment with ET alone. This highlights the need for more effective and tolerable treatment options to address disease recurrence in both the short and long term for eBC HR+/HER2- patients in Canada.
Alimohamed NS, Gotto G, Kulkarni GS, Black PC, Kassouf W, Sridhar SS, Kokorovic A, Eigl BJ, Blais N, Lalani AA, Cheung WY, Stephen M, Osborne BJW, Wallis CJD
Abstract:
INTRODUCTION: Approximately 25% of patients diagnosed with bladder cancer have muscle-invasive disease (MIBC). While real-world data have highlighted opportunities to improve curative-intent treatment rates, comprehensive population-level data in Canada are limited. This study aimed to assess patterns of care and outcomes in a real-world cohort of MIBC in Canada. METHODS: This retrospective, observational study describes baseline characteristics, treatment patterns, and overall survival (OS) of individuals with de novo MIBC diagnosed between 2010 and 2020 in Alberta, Canada. Data from adult patients with MIBC (T2-T4, N0/1, M0) were obtained from administrative databases and analyzed using basic statistics, multivariate regression analyses, and the Kaplan-Meier method. RESULTS: We identified 1292 patients with de novo MIBC. Of these, 76% were male with a median age of 73 years, 68% had cT2, and 76% had cN0 disease; approximately half had a Charlson comorbidity index (CCI) ≥1. Overall, 25% did not receive active treatment, while 58% received curative-intent treatment (49% underwent radical cystectomy [RC] and 9% received chemoradiotherapy), and 17% received some form of non-curative-intent treatment. Of those who underwent RC, 45% received neoadjuvant chemotherapy (NAC). Median overall survival (mOS) in the entire cohort was 2.1 years (95% confidence interval 1.9-2.4). Key predictors of inferior survival were age ≥76 years, CCI score of ≥1, T4 tumor stage, or not receiving NAC. CONCLUSIONS: This real-world analysis highlights opportunities to improve outcomes for patients with MIBC. Increasing access to curativeintent treatments, particularly in the elderly and those with comorbidities, is likely to enhance patient care and outcomes.
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