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External Validation of the FLIPI Risk Score Measured at Diagnosis and POD24 Among Individuals With Follicular Lymphoma at the Time of Subsequent Relapse

Boyne DJ,
Chua N,
Owen C,
Joe-Uzuegbu O,
Shakir H,
Gogna P,
Jarada TN,
Brenner DR,
Elia-Pacitti J,
Ewara EM,
Cheung WY

Clin Lymphoma Myeloma Leuk. 2023 Sep 29; 23(9):e277-e285.


BACKGROUND: The Follicular lymphoma international prognostic index (FLIPI) risk score and POD24 have previously been shown to have prognostic value in follicular lymphoma (FL), but the extent to which they can inform prognosis at the time of subsequent relapse is uncertain. PATIENTS AND METHODS: We conducted a longitudinal cohort study of individuals diagnosed with FL between 2004 and 2010 in Alberta, Canada who received front-line therapy and subsequently relapsed. FLIPI covariates were measured prior to the initiation of front-line therapy. Median overall survival (OS), progression-free survival (PFS2), and time to next treatment (TTNT2) were estimated from the time of relapse. RESULTS: A total of 216 individuals were included. The FLIPI risk score was highly prognostic at the time of relapse for OS (c-statistic = 0.70; HR[High vs. Low] = 7.38; 95% CI: 3.05-17.88), PFS2 (c-statistic = 0.68; HR[High vs. Low] = 5.84; 95% CI: 2.93-11.62) and TTNT2 (c-statistic = 0.68; HR[High vs. Low] = 5.72; 95% CI: 2.87-11.41). POD24 was not prognostic at the time of relapse for either OS, PFS2, or TTNT2 (c-statistic = 0.55). CONCLUSION: The FLIPI score measured at diagnosis may help with the risk stratification of individuals with relapsed FL.

The Choosing Wisely Oncology Canada Cancer List: An Update

Karim S,
Doll CM,
Dingley B,
Merchant SJ,
de Moraes FY,
Booth CM

J Cancer Policy. 2023 Sep 28; 37:100431.


BACKGROUND: Choosing Wisely (CW) Canada is a national campaign to identify unnecessary or harmful services that are frequently used in Canada. The original CW Oncology Canada Cancer list was developed in 2014. A CW Oncology Canada working group was established to review new evidence and guidelines and to update the current CW Oncology Canada Cancer List. METHODS: Between January and March 2022, we conducted a survey of members of the Canadian Association of Medical Oncology (CAMO), Canadian Association of Radiation Oncology (CARO) and the Canadian Society of Surgical Oncology (CSSO). We took the feedback from the survey, including potential new recommendations as well as those that were thought to be no longer relevant and up to date, and conducted a literature review with the assistance of the Canadian Agency for Drugs and Technology in Health (CADTH). The final updated list of recommendations was made by the CW Oncology Canada working group based on a consensus process. RESULTS: We reviewed two potential recommendations to add and two potential recommendations to remove from the existing CW Oncology Canada Cancer List. The recommendation "Do not prescribe whole brain radiation over stereotactic radiosurgery for patient with limited brain metastases (≤4 lesions)" was supported by several evidence-based guidelines with the strength of recommendations ranging from strong to moderate and the quality of evidence ranging from level 1 to level 3. After reviewing the evidence, the working group felt that the other potential recommendation to add and the two potential recommendations to remove did not have sufficient strength and quality of evidence at this time to be added or removed from the list. CONCLUSION: The updated Choosing Wisely Oncology Canada Cancer List consists of 11 items that oncologists should question in the treatment of patients with cancer. This list can be used to design specific interventions to reduce low value care.

American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: methodology and review of evidence

Al-Haddad MA,
Elhanafi SE,
Forbes N,
Thosani NC,
Draganov PV,
Othman MO,
Ceppa EP,
Kaul V,
Feely MM,
Sahin I,
Ruan Y,
Sadeghirad B,
Morgan RL,
Buxbaum JL,
Calderwood AH,
Chalhoub JM,
Coelho-Prabhu N,
Desai M,
Fujii-Lau LL,
Kohli DR,
Kwon RS,
Machicado JD,
Marya NB,
Pawa S,
Ruan W,
Sheth SG,
Storm AC,
Thiruvengadam NR,
Qumseya BJ,
(ASGE Standards of Practice Committee Chair)

Gastrointest Endosc. 2023 Sep 25; 98(3):285-305.e38.


This document from the American Society for Gastrointestinal Endoscopy (ASGE) provides a full description of the methodology used in the review of the evidence used to inform the final guidance outlined in the accompanying Summary and Recommendations document regarding the role of endoscopic submucosal dissection (ESD) in the management of early esophageal and gastric cancers. This guideline used the Grading of Recommendations, Assessment, Development and Evaluation framework and specifically addresses the role of ESD versus EMR and/or surgery, where applicable, for the management of early esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC) and their corresponding precursor lesions. For ESCC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >15 mm, whereas in patients with similar lesions ≤15 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for such patients with ESCC, whenever possible. For EAC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >20 mm, whereas in patients with similar lesions measuring ≤20 mm, the ASGE suggests either ESD or EMR. For GAC, the ASGE suggests ESD over EMR for patients with early-stage, well or moderately differentiated, nonulcerated intestinal type cancer measuring 20 to 30 mm, whereas for patients with similar lesions <20 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for patients with such lesions measuring ≤30 mm, whereas for lesions that are poorly differentiated, regardless of size, the ASGE suggests surgical evaluation over endosic approaches.

Comparative Effectiveness of Lurbinectedin for the Treatment of Relapsed Small Cell Lung Cancer in the Post-Platinum Setting: A Real-World Canadian Synthetic Control Arm Analysis

Boyne DJ,
Dawe DE,
Shakir H,
Joe-Uzuegbu O,
Farah E,
Pabani A,
Baratta C,
Brenner DR,
Cheung WY

Target Oncol. 2023 Sep 01:10.1007/s11523-023-00995-1.


BACKGROUND: Based on findings from a single-arm, phase 2 basket trial (NCT02454972), lurbinectedin may be an effective treatment for individuals with small cell lung cancer (SCLC) who progressed on or after platinum-based chemotherapy. OBJECTIVE: To estimate the comparative effectiveness of lurbinectedin versus the historical standard of care for relapsed SCLC in Canada. METHODS: A synthetic control arm (SCA) analysis was conducted using real-world data. Population-level data were obtained from real-world databases in Alberta, Canada. Individuals diagnosed with SCLC who initiated post-platinum systemic therapy and met approximated eligibility criteria from the lurbinectedin trial were included in the SCA. Median overall survival (OS) in the SCA was estimated after adjusting for chemotherapy-free interval (CTFI; < 90 versus ≥ 90 days) and stage at initial diagnosis (extensive versus limited). The CTFI-adjusted hazard ratio was estimated using a Cox proportional hazards model. RESULTS: One hundred seventy-four individuals were included in the SCA and 105 in the lurbinectedin trial. The adjusted median OS in the SCA was 6.1 months (95% CI 5.4-7.7 months; unadjusted: 6.7 months, 95% CI 6.0-7.7 months) versus 9.3 months (95% CI 6.3-11.8 months) in the lurbinectedin trial. The adjusted hazard ratio comparing lurbinectedin with the historical standard of care (referent group) was 0.61 (95% CI 0.45-0.82; unadjusted HR: 0.72; 95% CI 0.54-0.97). The hazard ratio was more pronounced among individuals with CTFI ≥ 90 days (HR: 0.49, 95% CI 0.33-0.73). CONCLUSION:  These findings suggest improved OS with lurbinectedin monotherapy versus the historical standard of care in Alberta, Canada.

Time spent in the sun and the risk of developing non-Hodgkin lymphoma: a Canadian cohort study

O'Sullivan DE,
Hillier TWR,
Brenner DR,
Peters CE,
King WD

Cancer Causes Control. 2023 Sep 01; 34(9):791-799.


PURPOSE: The objective was to explore the relationship of sun behavior patterns with the risk of developing non-Hodgkin lymphoma (NHL). METHODS: Sun behavior information from Alberta's Tomorrow Project, CARTaGENE, and Ontario Health Study were utilized. The relationship between time in the sun during summer months and risk of NHL was assessed using Cox proportional hazard models with age as the time scale and adjustment for confounders. Cohorts were analyzed separately and hazard ratios (HR) pooled with random effects meta-analysis. Joint effects of time in the sun and use of sun protection were examined. Patterns of exposure were explored via combinations of weekday and weekend time in the sun. RESULTS: During an average follow-up of 7.6 years, 205 NHL cases occurred among study participants (n = 79,803). Compared to < 30 min daily in the sun, we observed HRs of 0.84 (95% CI 0.55-1.28) for 30-59 min, 0.63 (95% CI 0.40-0.98) for 1-2 h, and 0.91 (95% CI 0.61-1.36) for > 2 h. There was suggestive evidence that > 2 h was protective against NHL with use of sun protection, but not without it. Compared to < 30 min daily, moderate exposure (30 min to 2 h on weekdays or weekend) was associated with a lower risk of NHL (HR 0.63, 95% CI 0.43-0.92), while intermittent (< 30 min on weekdays and > 2 h on weekends) and chronic (> 2 h daily) were not. CONCLUSION: This study provides evidence of a protective effect of moderate time spent in the sun on NHL risk.

Adjuvant Systemic Therapies for Resected Stages III and IV Melanoma: A Multi-Center Retrospective Clinical Study

Rigo R,
Ding PQ,
Batuyong E,
Cheung WY,
Walker J,
Monzon JG,
Cheng T

Oncologist. 2023 Aug 30:7256067.


BACKGROUND: Adjuvant therapies have been approved for resected melanoma based on improved recurrence-free survival. We present early findings from a real-world study on adjuvant treatments for melanoma. METHODS: A comprehensive chart review was conducted for patients receiving adjuvant systemic therapy for resected high-risk stages III and IV melanoma. Statistical analysis was performed to assess recurrence-free survival and subgroup differences. RESULTS: A total of 149 patients (median age = 58.0 years, 61.1% men, 49.7% with BRAF V600E/K genotypes) were included, with 94.6% having resected stage III melanoma. Anti-PD-1 immunotherapy was received by 86.5% of patients, while 13.4% received BRAF-targeted therapy. At a median follow-up of 22.4 months, the recurrence rate was 31.5%, with 1-year and 2-year recurrence-free survival rates of 79% and 62%, respectively. Similar recurrence rates were observed between anti-PD-1 immunotherapy and BRAF-targeted therapy. Long-term toxicity affected 27.4% of patients, with endocrinopathies and late-emergent immune-related adverse events being common. CONCLUSIONS: Real-world adjuvant systemic therapy aligns with clinical trial practice. Recurrence rates remain high despite treatment, and long-term toxicities, including endocrinopathies and chronic inflammatory conditions, are not uncommon.

Impact of Oncology Drug Review Times on Public Funding Recommendations

Hussain M,
Wong C,
Taguedong E,
Verma S,
Mahsin M,
Karim S,
Lee-Ying R,
Ezeife DA

Curr Oncol. 2023 Aug 18; 30(8):7706-7712.


New oncology drugs undergo detailed review prior to public funding in a single-payer healthcare system. The aim of this study was to assess how cancer drug review times impact funding recommendations. Drugs reviewed by the pan-Canadian Oncology Drug Review (pCODR) between the years 2012 and 2020 were included. Data were collected including Health Canada approval dates, initial and final funding recommendations, treatment intent, drug class, clinical indications, and incremental cost-effectiveness ratios (ICER). Univariable and multivariable analyses were used to determine the association between funding recommendations and review times. Of the 164 applications submitted, 130 received a positive final recommendation. Median time from Health Canada (HC) approval to final recommendation was longer for drugs indicated for the treatment of gastrointestinal (GI) and lung cancer compared to breast, genitourinary (GU), and other tumours (205 vs. 198 vs. 111 vs. 129 vs. 181 days, respectively; Kruskal-Wallis p = 0.0312). Drugs with longer review times were more likely to receive a negative pCODR recommendation, even when adjusting for tumour type, drug class, and intent of therapy (157 vs. 298 days; Wilcoxon p = 0.0003, OR 1.002 95% CI [1.000-1.004].). There was no association between funding recommendation and tumour type or class of drug. The exploration of factors associated with variance in review times will be important in ensuring timely patient access to cancer drugs.

Cost-Effectiveness of Surveillance after Metastasectomy of Stage IV Colorectal Cancer

Ding PQ,
Au F,
Cheung WY,
Heitman SJ,
Lee-Ying R

Cancers (Basel). 2023 Aug 16; 15(16).


Surveillance of stage IV colorectal cancer (CRC) after curative-intent metastasectomy can be effective for detecting asymptomatic recurrence. Guidelines for various forms of surveillance exist but are supported by limited evidence. We aimed to determine the most cost-effective strategy for surveillance following curative-intent metastasectomy of stage IV CRC. We performed a decision analysis to compare four active surveillance strategies involving clinic visits and investigations elicited from National Comprehensive Cancer Network (NCCN) recommendations. Markov model inputs included data from a population-based cohort and literature-derived costs, utilities, and probabilities. The primary outcomes were costs (2021 Canadian dollars) and quality-adjusted life years (QALYs) gained. Over a 10-year base-case time horizon, surveillance with follow-ups every 12 months for 5 years was most economically favourable at a willingness-to-pay threshold of CAD 50,000 per QALY. These patterns were generally robust in the sensitivity analysis. A more intensive surveillance strategy was only favourable with a much higher willingness-to-pay threshold of approximately CAD 425,000 per QALY, with follow-ups every 3 months for 2 years then every 12 months for 3 additional years. Our findings are consistent with NCCN guidelines and justify the need for additional research to determine the impact of surveillance on CRC outcomes.

Real-world impact of patient-reported outcome measurement on overall survival, healthcare use and treatment discontinuation in cancer patients

Yan JT,
Boyne DJ,
Lo E,
Farah E,
O'Sullivan DE,
Cheung WY

J Comp Eff Res. 2023 Aug 09.


The purpose of this retrospective, population-based, observational cohort analysis was to assess whether routine patient-reported outcomes (PRO) monitoring alone has an impact on real-world overall survival (OS) and hospitalizations among individuals diagnosed with lung, breast or colorectal cancer. The importance of follow-up care in post-PRO data collection was also discussed. Administrative databases covering 17 cancer centers from Alberta, Canada were queried and individuals ≥18 years old and diagnosed with lung, breast or colorectal cancer from 1 January 2016 to 31 December 2019 were included and followed until 31 December 2020. Patients were stratified by whether they received routine PRO monitoring initiated within 120 days of diagnosis and matched 1:1 with use of propensity scores based on baseline characteristics. OS was assessed from the index date to death, and the respective Kaplan-Meier curves were estimated along with hazard ratios from Cox Proportional Hazard Models. Linear and logistic regression models were used to estimate mean differences and odds ratios (OR) respectively for healthcare resource utilization events including cancer physician visits, emergency department visits and outpatient ambulatory care encounters. 4800 patients were included in each matched cohort. There was no statistically significant difference between PRO monitoring and non-monitoring cohorts in OS (HR = 1.01; 95% CI: 0.93-1.09; p = 0.836) and treatment discontinuation (OR = 0.98; 95% CI: 0.85-1.12; p = 0.75). Median OS was 51.5 months for unmonitored cohort (95% CI: 47.5-NA) versus 50.6 months for monitored cohort (95% CI: 47.6-55.7). Compared with PRO-monitored patients, unmonitored patients were associated with lower hospitalization risks (OR = 1.12; 95% CI: 1.03-1.22; p = 0.01). However, PRO-monitored patients experienced significantly fewer physician visits in comparison to unmonitored patients (MD = -1.036; 95% CI: -1.288 to -0.784, p < 0.001). Our results show that capturing patient-reported symptoms alone reduced the number of physician visits but neither reduced hospitalizations nor improved OS in this real-world cancer population. To drive more meaningful clinical impact, PRO monitoring programs must be met with rigorous follow-up response to the identified symptoms.

Supply and Demand for Radiation Oncologists in Canada: Workforce Planning Projections from 2020 to 2040

Loewen SK,
Ruan Y,
David Wu CH,
Arifin A,
Kim M,
Bashir B,
Halperin R,
McKenzie M,
Archambault J,
Thompson R,
Ringash J,
Brundage M,
Brenner D,
Stuckless T

Int J Radiat Oncol Biol Phys. 2023 Aug 08:S0360-3016(23)07684-8.


PURPOSE: The number of Canadians diagnosed with cancer, and subsequent demand for radiotherapy, are expected to increase over time. This study aims to update our needs-based workforce planning model to ensure appropriate staffing levels in the future. METHODS AND MATERIALS: The supply of radiation oncologists, by age group, sex, and full-time equivalent (FTE) status, was projected from 2020 to 2040 using a recursive-aging, input-output model developed with seeding parameters derived from national sources. The demand for radiation oncologists until 2040 was estimated using referral patterns for radiotherapy and consultation workload metrics applied to projected annual cancer incident cases to calculate required FTE positions. Baseline model parameters were also applied to 2005-2019 workforce and incident case data to evaluate pre-projection supply and demand trends. RESULTS: Pre-projection trends for 2005-2019 revealed accelerated staffing growth that transitioned from a workforce shortage to a surplus state in 2014 followed by substantial growth slowdown in 2016. The model predicts a transient surplus of radiation oncologists until 2026 followed by a projected deficit in subsequent years. Sensitivity analyses using the plausible range for each parameter continued to favor an undersupply, suggesting a trainee shortage unable to meet workforce expansion needs. Considering possible future declining trends in radiotherapy utilization and workload, calculations to inform corrective efforts in resident numbers resulted in 25 entry positions per year, up from 21 per year currently. Geographic distribution of trainees, relative to workforce and cancer incidence distributions, could be improved with more residency positions in Canadian regions outside Ontario. CONCLUSIONS: Demand for radiotherapy and radiation oncologists in Canada are expected to grow more quickly than future expansion in staffing levels. Our workforce planning model provides evidence for more trainee requirements to inform stakeholders of possible corrective actions to training programs and recruitment. Further research is needed to explore additional strategies to expand capacity and high-quality delivery of radiotherapy that meet the foreseeable rise in Canadian cancer patients.

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