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"Parmar, Ambica"
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Stereotactic radiosurgery versus whole brain radiotherapy in patients with intracranial metastatic disease and small-cell lung cancer: a systematic review and meta-analysis
2022
Patients with small-cell lung cancer (SCLC) are at high risk for intracranial metastatic disease (IMD). Although stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as first-line treatment for IMD in most solid cancers, WBRT remains first-line treatment for IMD in patients with SCLC. We aimed to evaluate the efficacy of SRS in comparison with WBRT and assess treatment outcomes following SRS.
In this systematic review and meta-analysis, we searched MEDLINE, Embase, CENTRAL, and grey literature sources for controlled trials and cohort studies published in English reporting on SRS for IMD treatment in patients with SCLC from inception to March 23, 2022. Studies were excluded that did not report on SRS for IMD secondary to SCLC. Summary data were extracted. The primary outcome was overall survival, presented as pooled hazard ratios (HR) through random-effects meta-analysis for studies comparing SRS with WBRT with or without SRS boost, and as medians for single-arm SRS studies. This study is registered with the Open Science Framework, DOI 10.17605/OSF.IO/8M4HC, and PROSPERO, CRD42021258197.
Of 3823 identified records, 31 were eligible for inclusion; seven were included in the meta-analysis. Overall survival following SRS was longer than following WBRT with or without SRS boost (HR 0·85; 95% CI 0·75–0·97; n=7 studies; n=18 130 patients), or WBRT alone (0·77; 0·72–0·83; n=7 studies; n=16 961 patients), but not WBRT plus SRS boost (1·17, 0·78–1·75; n=4 studies; n=1167 patients). Using single-arm studies, pooled median overall survival from SRS was 8·99 months (95% CI 7·86–10·16; n=14 studies; n=1682 patients). Between-study heterogeneity was considerable when pooled among all comparative studies (I2=71·9%).
These results suggest survival outcomes are equitable following treatment with SRS compared with WBRT in patients with SCLC and IMD. Future prospective studies should focus on tumour burden and differences in local and distant intracranial progression between WBRT-treated and SRS-treated patients with SCLC.
None.
Journal Article
Safety and efficacy of POEM for treatment of achalasia: a systematic review of the literature
by
Shlomovitz, Eran
,
Parmar, Ambica
,
Jackson, Timothy D.
in
Abdominal Surgery
,
Endoscopy
,
Esophageal Achalasia - surgery
2017
Introduction
Peroral endoscopic myotomy (POEM) is a novel intervention for the treatment of achalasia, which combines the advantages of endoscopic access and myotomy. The purpose of this study was to perform a systematic review of the literature to evaluate the efficacy and safety of POEM.
Methods
The systematic review was conducted following the PRISMA guidelines. Evidence-Based Medicine Reviews, Cochrane Central Register of Controlled Trials, Ovid MEDLINE (R) including in-process and non-indexed citations were searched for POEM studies using the keywords: esophageal achalasia, POEM, endoscopy, natural orifice surgery, laparoscopic Heller myotomy (LHM), and related terms. Eckardt score, lower esophageal sphincter (LES) pressure, and reported complications were the main outcomes. Two authors reviewed the search result independently. A third reviewer resolved all disagreements. Data abstraction was pilot-tested and approved by all authors. Data were examined for clinical, methodological, and statistical heterogeneity with the aim of determining whether evidence synthesis using meta- analysis was possible.
Results
The search strategy retrieved 2894 citations. After removing duplicates and applying the exclusion criteria, 54 studies were selected for full-text review of which a total of 19 studies were considered eligible for further analysis. There were 10 retrospective and 9 prospective studies, including 1299 POEM procedures. No randomized control trial (RCT) was identified. Overall, the pre- and post-POEM Eckardt scores and LES pressure were significantly different. The most frequently reported complications were mucosal perforation, subcutaneous emphysema, pneumoperitoneum, pneumothorax, pneumomediastinum, pleural effusion, and pneumonia. The median follow-up was 13 months (range 3–24).
Conclusion
POEM is a safe and effective alternative for the treatment of achalasia. However, only short-term follow-up data compared with LHM are available. RCTs and long-term follow-up studies are needed to establish the efficacy and safety of POEM in the management of patients with achalasia.
Journal Article
Impact of cancer surgery slowdowns on patient survival during the COVID-19 pandemic: a microsimulation modelling study
2022
With the declaration of the global pandemic, surgical slowdowns were instituted to conserve health care resources for anticipated surges in patients with COVID-19. The long-term implications on survival of these slowdowns for patients with cancer in Canada is unknown.
We constructed a microsimulation model based on real-world population data on cancer care from Ontario, Canada, from 2019 and 2020. Our model estimated wait times for cancer surgery over a 6-month period during the pandemic by simulating a slowdown in operating room capacity (60% operating room resources in month 1, 70% in month 2, 85% in months 3–6), as compared with simulated prepandemic conditions with 100% resources. We used incremental differences in simulated wait times to model survival using per-day hazard ratios for risk of death. Primary outcomes included life-years lost per patient and per cancer population. We conducted scenario analyses to evaluate alternative, hypothetical scenarios of different levels of surgical slowdowns on risk of death.
The simulated model population comprised 22 799 patients waiting for cancer surgery before the pandemic and 20 177 patients during the pandemic. Mean wait time to surgery prepandemic was 25 days and during the pandemic was 32 days. Excess wait time led to 0.01–0.07 life-years lost per patient across cancer sites, translating to 843 (95% credible interval 646–950) life-years lost among patients with cancer in Ontario.
Pandemic-related slowdowns of cancer surgeries were projected to result in decreased long-term survival for many patients with cancer. Measures to preserve surgical resources and health care capacity for affected patients are critical to mitigate unintended consequences.
Journal Article
Socioeconomic disparity trends in diagnostic imaging, treatments, and survival for non‐small cell lung cancer 2007‐2016
by
Chan, Kelvin K. W.
,
Shah, Monica
,
Parmar, Ambica
in
Ambulatory care
,
cancer stage
,
Cancer therapies
2020
Socioeconomic status (SES) has led to treatment and survival disparities; however, limited data exist for non‐small cell lung cancer (NSCLC). This study investigates the impact of SES on NSCLC diagnostic imaging, treatment, and overall survival (OS), and describes temporal disparity trends. The Ontario Cancer Registry was used to identify NSCLC patients diagnosed between 2007 and 2016. Through linkage to administrative datasets, patients’ demographics, imaging, treatment, and survival were obtained. Based on median household neighborhood income, the Ontario population was divided into five income quintiles (Q1‐Q5; Q1 = lowest income). Multivariable regressions assessed SES association with OS, imaging, treatment receipt, and treatment delay, and their interaction with year of diagnosis to understand temporal trends. Endpoints were adjusted for demographics, stage and comorbidities, along with treatments and imaging for OS. A total of 50 542 patients were identified. Higher SES patients (Q5 vs. Q1) showed improved 5‐year OS (hazard ratio, 0.89; 95% confidence interval [CI], 0.87‐0.92; P < .0001) and underwent greater magnetic resonance imaging head (stages IA‐IV; odds ratio [OR], 1.24; 95% CI, 1.16‐1.32; P < .0001), lung resection (IA‐IIIA; OR, 1.58; 95% CI, 1.43‐1.74; P < .0001), platinum‐based vinorelbine adjuvant chemotherapy (IB‐IIIA; OR, 1.63; 95% CI, 1.39‐1.92; P < .0001), palliative radiation (IV; OR, 1.14; 95% CI, 1.05‐1.25; P = .023), and intravenous chemotherapy (IV; OR, 1.45; 95% CI, 1.32‐1.60; P < .0001). Lower SES patients underwent greater thoracic radiation (IA‐IIIB; OR, 0.86; 95% CI, 0.79‐0.94; P = .0003). Across 2007‐2016, socioeconomic disparities remain largely unchanged (interaction P > .05) despite widening income inequality. Longstanding socioeconomic disparities in non‐small cell lung cancer imaging, treatments, and survival persist without improvement despite a universal health care system. Although these socioeconomic disparities remain largely unchanged over time, further exploratory research is necessary to better understand their causal pathways in efforts to reduce these inequalities.
Journal Article
Health technology assessment methodology in metastatic renal cell carcinoma
by
Chan Kelvin K W
,
Parmar Ambica
in
Decision making
,
Health technology assessment
,
Kidney cancer
2020
Cancer care is currently experiencing rapid development in novel therapeutics, with an associated rise in treatment costs. These changes not only create a critical challenge for therapeutic decision-making but also highlight the need to prioritize therapies of high clinical and economic value. Health technology assessment methodology is a novel approach that could help guide value-based decision-making.
Journal Article
Referred molecular testing as a barrier to optimal treatment decision making in metastatic non‐small cell lung cancer: Experience at a tertiary academic institution in Canada
2024
Background Molecular testing is critical to guiding treatment approaches in patients with metastatic non‐small cell lung cancer (mNSCLC), with testing delays adversely impacting the timeliness of treatment decisions. Here, we aimed to evaluate the time from initial mNSCLC diagnosis to treatment decision (TTD) following implementation of in‐house EGFR, ALK, and PD‐L1 testing at our institution. Methods We conducted a retrospective chart review of 165 patients (send‐out testing, n = 92; in‐house testing, n = 73) with newly diagnosed mNSCLC treated at our institution. Data were compared during the send‐out (March 2017–May 2019) and in‐house (July 2019–March 2021) testing periods. We performed a detailed workflow analysis to provide insight on the pre‐analytic, analytic, and post‐analytic intervals that constituted the total TTD. Results TTD was significantly shorter with in‐house testing (10 days vs. 18 days, p < 0.0001), driven largely by decreased internal handling and specimen transit times (2 days vs. 3 days, p < 0.0001) and laboratory turnaround times (TAT, 3 days vs. 8 days, p < 0.0001), with 96% of in‐house cases meeting the international guideline of a ≤ 10‐day intra‐laboratory TAT (vs. 74% send‐out, p < 0.001). Eighty‐eight percent of patients with in‐house testing had results available at their first oncology consultation (vs. 52% send‐out, p < 0.0001), and all patients with in‐house testing had results available at the time of treatment decision (vs. 86% send‐out, p = 0.57). Conclusion Our results demonstrate the advantages of in‐house biomarker testing for mNSCLC at a tertiary oncology center. Incorporation of in‐house testing may reduce barriers to offering personalized medicine by improving the time to optimal systemic therapy decision. Timely biomarker testing enables efficient initiation of optimal targeted treatments in metastatic non‐small cell lung cancer (mNSCLC) patients. We retrospectively compared time to treatment decision between mNSCLC patients with biomarkers tested in‐house (n = 73) and those sent‐out to an external laboratory (n = 92). We found that in‐house testing significantly decreased treatment decision times, resulting in a reduction in missed/suboptimal treatment opportunities.
Journal Article
Value‐based pricing: Toward achieving a balance between individual and population gains in health benefits
by
Chan, Kelvin K. W.
,
Jiao, Tina
,
Saluja, Ronak
in
Antineoplastic Agents - economics
,
Antineoplastic Agents - therapeutic use
,
Cancer therapies
2020
Objectives Value‐based pricing of oncology drugs provides a best estimate for the price of a drug, as it relates to the benefits it provides for individual patients. To date, the impact of value‐based pricing to reference cost‐effectiveness thresholds (λ) on individual and population‐level health benefits remains uncharacterized. The current study examined the potential benefits of value‐based pricing by quantifying the incremental net health benefit (INHB) of publicly funded oncology drugs, if funding occurred at manufacturer‐submitted price without value‐based pricing. Methods Pan‐Canadian Oncology Drug Review (pCODR) submissions were reviewed to identify eligible drug indications from which final economic guidance panel reports were reviewed for incremental costs (ΔC) and quality‐adjusted life‐years (ΔQALY) from manufacturer‐submitted, pCODR lower‐limit (pCODR‐LL) and upper‐limit (pCODR‐UL) re‐analyzed estimates. Annual number of cases in Ontario for each drug indication was obtained from population databases. Annual QALY gain per drug indication was determined by (ΔQALY × cases). Population QALY gain/loss in the absence of value‐based pricing to reference λ was estimated by the INHB: (INHB = [ΔQALY − (ΔC/λ)] × cases). Results In total, 34 drug indications (4629 cases) were identified. Annual gain in QALYs for the funded drug indications using manufacturer, pCODR‐LL, and pCODR‐UL estimates was 1851, 1617, and 1301, respectively. At a λ $100 000/QALY, funding in the absence of value‐based pricing resulted in loss of 2311, 2519, and 2604 QALYs. This would result in a provincial net annual loss of 460, 902, and 1303 QALYs. Conclusions Despite an annual gain in QALY per funded drug indication, a net loss in QALY for the province, in the absence of value‐based pricing, was demonstrated. Supportive evidence exists for value‐based pricing toward the promotion of health benefits for the greater population. Value‐based pricing allows for more accurate estimates of the generated value for a novel therapeutic. However, the impact of drug funding at value‐based prices, as compared to manufacturer‐submitted prices, for contemporary cancer therapeutics remains under‐characterized. By quantifying the incremental net health benefit and incremental net monetary benefit, this study revealed overall population‐level net gains with drug funding at value‐based pricing to various reference cost‐effectiveness thresholds.
Journal Article
Early survival for patients newly diagnosed with cancer during COVID‐19 in Ontario, Canada: A population‐based cohort study
by
Chan, Kelvin K. W.
,
Coburn, Natalie
,
Mahar, Alyson
in
Cancer
,
cancer detection
,
cancer survivorship
2023
Background Little is known about the association between the COVID‐19 pandemic and early survival among newly diagnosed cancer patients. Methods This retrospective population‐based cohort study used linked administrative datasets from Ontario, Canada. Adults (≥18 years) who received a cancer diagnosis between March 15 and December 31, 2020, were included in a pandemic cohort, while those diagnosed during the same dates in 2018/2019 were included in a pre‐pandemic cohort. All patients were followed for one full year after the date of diagnosis. Cox proportional hazards regression models were used to assess survival in relation to the pandemic, patient characteristics at diagnosis, and the modality of first cancer treatment as a time‐varying covariate. Interaction terms were explored to measure the pandemic association with survival for each cancer type. Results Among 179,746 patients, 53,387 (29.7%) were in the pandemic cohort and 37,741 (21.0%) died over the first post‐diagnosis year. No association between the pandemic and survival was found when adjusting for patient characteristics at diagnosis (HR 0.99 [95% CI 0.96–1.01]), while marginally better survival was found for the pandemic cohort when the modality of treatment was additionally considered (HR 0.97 [95% CI 0.95–0.99]). When examining each cancer type, only a new melanoma diagnosis was associated with a worse survival in the pandemic cohort (HR 1.25 [95% CI 1.05–1.49]). Conclusions Among patients able to receive a cancer diagnosis during the pandemic, one‐year overall survival was not different than those diagnosed in the previous 2 years. This study highlights the complex nature of the COVID‐19 pandemic impact on cancer care. This population‐based cohort study in Ontario, Canada found no association between the pandemic and the 1‐year overall survival of adults newly diagnosed with cancer. These results highlight the complex nature of the pandemic impact on cancer care.
Journal Article
Evaluating the impact of early identification of asymptomatic brain metastases in metastatic renal cell carcinoma
by
Reaume, M. Neil
,
Graham, Jeffrey
,
Lalani, Aly‐Khan A.
in
Asymptomatic
,
brain metastases
,
Brain Neoplasms - diagnostic imaging
2023
Background Brain metastases (BM) in metastatic renal cell carcinoma (mRCC) have been reported to be present in up to 25% of patients diagnosed with mRCC. There is limited published literature evaluating the role of routine intra‐cranial imaging for the screening of asymptomatic BM in mRCC. Aims To evaluate the potential utility of routine intra‐cranial imaging, a retrospective cohort study was conducted to characterize the outcomes of mRCC patients who presented with asymptomatic BM, as compared to symptomatic BM. Methods and Results The Canadian Kidney Cancer Information System (CKCis) database was used to identify mRCC patients diagnosed with BM. This cohort was divided into two groups based on the presence or absence of BM symptoms. Details regarding patient demographics, disease characteristics, systemic treatments, BM characteristics and survival outcomes were extracted. Statistical analysis was through chi‐square tests, analysis of variance, and Kaplan–Meier method to characterize survival outcomes. A p‐value of <0.05 was considered statistically significant for all analyses. A total of 267 mRCC patients with BM were identified of which 106 (40%) presented with asymptomatic disease. The majority of patients presented with multiple (i.e., >1) BM (75%) with no significant differences noted in number of BM or BM‐directed therapy received in symptomatic, as compared to asymptomatic BM patients. Median [95% confidence interval (CI)] overall survival (OS) from mRCC diagnosis was 42 months (95% CI: 32–62) for patients with asymptomatic BM, and 39 months (95% CI: 29–48) with symptomatic BM (p = 0.10). OS from time of BM diagnosis was 28 months (95% CI: 18–42) for the asymptomatic BM group, as compared to 13 months (95% CI: 10–21) in the symptomatic BM group (p = 0.04). Conclusions Given a substantial proportion of patients may present with asymptomatic BM, limiting intra‐cranial imaging to patients with symptomatic BM, may be associated with a missed opportunity for timely diagnosis and treatment. The utility of routine intra‐cranial imaging in patients with renal cell carcinoma, warrants further prospective evaluation.
Journal Article
Prioritising research into cancer treatment delays
2020
Better data are essential for effective cancer care both during and after the covid-19 pandemic
Journal Article