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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 (IThese 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.

No population-based study exists to demonstrate the full-spectrum impact of COVID-19 on hindering incident cancer detection in a large cancer system. Building upon our previous publication in JNCCN, we conducted an updated analysis using 12 months of new data accrued in the pandemic era (extending the study period from September 26, 2020, to October 2, 2021) to demonstrate how multiple COVID-19 waves affected the weekly cancer incidence volume in Ontario, Canada, and if we have fully cleared the backlog at the end of each wave.

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.

Purpose: Molecular testing is critical to guiding treatment decisions in vulnerable patients with metastatic non-small cell lung cancer (mNSCLC), with testing delays associated with prolonged treatment times and higher mortality. Here, we evaluated 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 stage IV NSCLC 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, pvs. 3 days, pvs. 8 days, pvs.74% send-out, pvs. 52% send-out, pvs. 86% send-out, p=0.57). Conclusion: Our results demonstrate the advantages of in-house biomarker testing for mNSCLC at high-volume oncology centres. Incorporation of in-house testing may reduce barriers to offering personalized medicine by improving the time to optimal systemic therapy decision.

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.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.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 of0.05 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).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.

The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration was established to develop a framework for generating and using real-world evidence (RWE) to inform the reassessment of cancer drugs following initial health technology assessment (HTA). The Reassessment and Uptake Working Group (RWG) is one of the five established CanREValue Working Groups. The RWG aims to develop considerations for incorporating RWE for HTA reassessment and strategies for using RWE to reassess drug funding decisions. Between February 2018 and December 2019, the RWG attended four teleconferences (with follow-up surveys) and two in-person meetings to discuss recommendations for the development of a reassessment process and potential barriers and facilitators. Modified Delphi methods were used to gather input. A draft report of recommendations (to December 2018) was shared for public consultation (December 2019 to January 2020). Initial considerations for developing a reassessment process were proposed. Specifically, reassessment can be initiated by diverse stakeholders, including decision makers from public drug plans or industry stakeholders. The reassessment process should be modelled after existing deliberation and recommendation frameworks used by HTA agencies. Proposed reassessment outcome categories include maintaining status quo, revisiting funding criteria, renegotiating price, or disinvesting. Overall, these initial considerations will serve as the basis for future advancements by the Collaboration.

The National Institutes of Health's policy for the inclusion of females in clinical research was a pivotal step towards the consideration of sex as a biological variable, which is of particular importance in oncology, given differential incidence and outcomes of cancer between the sexes, and known pharmacodynamic, pharmacokinetic, and immunological differences. Therefore, we aim to investigate if such biological sex-based differences translate to clinically meaningful outcome differences from recently approved systemic oncology therapies.A systematic review of randomized control trials (RCTs) cited in Food and Drug Administration, European Medicines Agency, and Health Canada approvals was conducted. Chemotherapy, targeted agents, and immunotherapy RCTs reporting sex-based sub-group analyses for overall/progression-free survival (OS/PFS) were considered. Hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized. Sensitivity analyses for survival endpoints, drug type, and cancer site were conducted.Ninety-nine RCTs were included, representing 62,384 patients (23,574 (38%) female). Pooled OS HRs [95% CIs] were 0.77 [0.72-0.81] and 0.76 [0.72-0.79] for females and males, respectively (P = 0.73), and 0.51 [0.47-0.56] and 0.57 [0.53-0.61] (P = 0.08) for PFS. Sensitivity analyses yielded similar results. No RCTs reported sex-based toxicity or quality-of-life (QOL) data.Female and male patients appear to derive comparable benefits from recently approved systemic oncology therapies. Future RCTs are encouraged to report sex-based toxicity and QOL data.

Background There are no randomized control trials (RCTs) comparing gemcitabine and nab-paclitaxel (Gem-Nab) and fluorouracil, folinic acid, irinotecan, oxaliplatin (FOLFIRINOX) for advanced pancreatic cancer (APC). Although it is well known that RCT-based efficacy often does not translate to real-world effectiveness, there is limited literature investigating comparative cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC. We aimed to examine the real-world cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC in Ontario, Canada. Methods This study compared patients treated with first-line Gem-Nab or FOLFIRINOX for APC in Ontario from April 2015 to March 2019. Patients were linked to administrative databases. Using propensity scores and a stabilizing weights method, an inverse probability of treatment weighted cohort was developed. Mean survival and total costs were calculated over a 5-year time horizon, adjusted for censoring, and discounted at 1.5%. Incremental cost-effectiveness ratio and net monetary benefit were computed to estimate cost-effectiveness from the public health-care payer’s perspective. Sensitivity analysis was conducted using the propensity score matching method. Results A total of 1988 patients were identified (Gem-Nab: n = 928; FOLFIRINOX: n = 1060). Mean survival was lower for patients in the Gem-Nab than the FOLFIRINOX group (0.98 vs 1.26 life-years; incremental effectiveness = −0.28 life-years [95% confidence interval = −0.47 to −0.13]). Patients in the Gem-Nab group incurred greater mean 5-year total costs (Gem-Nab: $103 884; FOLFIRINOX: $101 518). Key cost contributors include ambulatory cancer care, acute inpatient hospitalization, and systemic therapy drug acquisition. Gem-Nab was dominated by FOLFIRINOX, as it was less effective and more costly. Results from the sensitivity analysis were similar. Conclusions Gem-Nab is likely more costly and less effective than FOLFIRINOX and therefore not considered cost-effective at commonly accepted willingness-to-pay thresholds.

Background Although increasing evidence has suggested that an efficacy-effectiveness gap exists between clinical trial (CT) and real-world evidence (RWE), to the authors' knowledge, the magnitude of this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies. Methods Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population-based databases. The efficacy-effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1-year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan-Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates. Results Twenty-nine indications from 20 systemic therapies were included. Twenty-eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0-12.1 months). Lower effectiveness in RWE also was demonstrated through a meta-analysis of an OS hazard ratio of 1.58 (95% CI, 1.39-1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%-22%). Conclusions An efficacy-effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2-month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real-world decision making regarding the use of cancer systemic therapies.

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 .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.

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.

ImportanceThe impact of COVID-19 on the modality and timeliness of first-line cancer treatment is unclear yet critical to the planning of subsequent care.ObjectiveTo explore the association of the COVID-19 pandemic with modalities of and wait times for first cancer treatment.Design, Setting, and ParticipantsThis retrospective population-based cohort study using administrative data was conducted in Ontario, Canada, among adults newly diagnosed with cancer between January 3, 2016, and November 7, 2020. Participants were followed up from date of diagnosis for 1 year, until death, or until June 26, 2021, whichever occurred first, to ensure a minimum of 6-month follow-up time.ExposuresReceiving a cancer diagnosis in the pandemic vs prepandemic period, using March 15, 2020, the date when elective hospital procedures were halted.Main Outcomes and MeasuresThe main outcome was a time-to-event variable describing number of days from date of diagnosis to date of receiving first cancer treatment (surgery, chemotherapy, or radiation) or to being censored. For each treatment modality, a multivariable competing-risk regression model was used to assess the association between time to treatment and COVID-19 period. A secondary continuous outcome was defined for patients who were treated 6 months after diagnosis as the waiting time from date of diagnosis to date of treatment.ResultsAmong 313 499 patients, the mean (SD) age was 66.4 (14.1) years and 153 679 (49.0%) were male patients. Those who were diagnosed during the pandemic were less likely to receive surgery first (subdistribution hazard ratio [sHR], 0.97; 95% CI, 0.95-0.99) but were more likely to receive chemotherapy (sHR, 1.26; 95% CI, 1.23-1.30) or radiotherapy (sHR, 1.16; 95% CI, 1.13-1.20) first. Among patients who received treatment within 6 months from diagnosis (228 755 [73.0%]), their mean (SD) waiting time decreased from 35.1 (37.2) days to 29.5 (33.6) days for surgery, from 43.7 (34.1) days to 38.4 (30.6) days for chemotherapy, and from 55.8 (41.8) days to 49.0 (40.1) days for radiotherapy.Conclusions and RelevanceIn this cohort study, the pandemic was significantly associated with greater use of nonsurgical therapy as initial cancer treatment. Wait times were shorter in the pandemic period for those treated within 6 months of diagnosis. Future work needs to examine how these changes may have affected patient outcomes to inform future pandemic guideline development.

Introduction: Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) improves overall survival, but pathological response rates are low. Predictive biomarkers could select those patients most likely to benefit from NAC. Radiomics technology offers a novel, non-invasive method to identify predictive biomarkers. Our study aimed to develop a predictive radiomics signature for response to NAC in MIBC. Methods: An institutional bladder cancer database was used to identify MIBC patients who were treated with NAC followed by radical cystectomy. Patients were classified into responders and non-responders based on pathological response. Bladder lesions on computed tomography images taken prior to NAC were contoured. Extracted radiomics features were used train a radial basis function support vector machine classifier to learn a prediction rule to distinguish responders from non-responders. The discriminative accuracy of the classifier was then tested using a nested 10-fold cross-validation protocol. Results: Nineteen patients who underwent NAC followed by radical cystectomy were found to be eligible for analysis. Of these, nine (48%) patients were classified as responders and 10 (52%) as non-responders. Nineteen bladder lesions were contoured. The sensitivity, specificity and discriminative accuracy were 52.9±9.4%, 69.4±8.6%, and 62.1±6.1%, respectively. This corresponded to an area under the curve of 0.63±0.08 (p=0.20). Conclusions: Our developed radiomics signature demonstrated modest discriminative accuracy; however, these results may have been influenced by small sample size and heterogeneity in image acquisition. Future research using novel methods for computer-based image analysis on a larger cohort of patients is warranted.

Introduction: Earlier application of oral androgen receptor-axis-targeted therapies in patients with metastatic castration-sensitive prostate cancer (mCSPC) has established improvements in overall survival, as compared to androgen deprivation therapy (ADT) alone. Recently, the use of apalutamide plus ADT has demonstrated improvement in mCSPC-related mortality, vs. ADT alone, with an acceptable toxicity profile. However, the cost-effectiveness of this therapeutic option remains unknown. Methods: We used a state-transition model with probabilistic analysis to compare apalutamide + ADT, as compared to ADT alone for mCSPC patients over a time horizon of 20 years. Primary outcomes included expected life-years (LY), quality-adjusted life-years (QALY), lifetime cost (2020 Canadian dollars), and incremental cost-effectiveness ratio (ICER). Parameter and model uncertainties were assessed through scenario analyses. Health outcomes and cost were discounted at 1.5%, as per Canadian guidelines. Results: For the base-case analysis, expected LY for ADT and apalutamide plus ADT were 4.11 and 5.56, respectively (incremental LY 1.45). Expected QALYs were 3.51 for ADT and 4.84 for apalutamide plus ADT (incremental QALYs 1.33); expected lifetime cost was $36 582 and $255 633, respectively (incremental cost $219,051). ICER for apalutamide plus ADT, as compared to ADT alone, was $164 700/QALY. Through scenario analysis, price reductions >50% were required for apalutamide in combination with ADT to be considered cost-effective, at a cost-effectiveness threshold of $100 000/QALY. Conclusions: Apalutamide plus ADT is unlikely to be cost-effective from the Canadian healthcare perspective unless there are substantial reductions in the price of apalutamide treatment.

In the past decade, literature has called attention to financial toxicities experienced by cancer patients. Though studies have addressed research questions in high-income countries, there remains a paucity of in-depth reviews regarding low- and middle-income countries (LMICs). Our scoping review provides an overview of treatment-related financial toxicities experienced by cancer patients in LMICs.A systematic search was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. English peer-reviewed articles that (a) explored patients' experience with financial toxicity due to cancer treatment (b) were specific to LMICs as defined by the World Bank and (c) focused on qualitative data were included. Details regarding participants and main findings were extracted and synthesized.The search yielded 6290 citations, and 42 studies across 3 low-income, 9 lower-middle-income and 8 upper-middle-income countries. Main themes identified included cancer patients encountered various material hardships, managed costs with different coping behaviours and experienced negative psychological responses to their financial burden. Higher levels of financial toxicities were associated with patient characteristics such as lower socio-economic status and lack of insurance, as well as patient outcomes such as lower quality of life.Cancer patients in LMIC experience deleterious financial toxicities as a result of treatment. This comprehensive characterization of financial toxicities will better allow health systems to adopt evidence-based mitigation strategies to reduce the financial burden on patients.

Background: Resource restrictions were established in many jurisdictions to maintain health system capacity during the COVID-19 pandemic. Disrupted healthcare access likely impacted early cancer detection. The objective of this study was to assess the impact of the pandemic on weekly reported cancer incidence. Patients and Methods: This was a population-based study involving individuals diagnosed with cancer from September 25, 2016, to September 26, 2020, in Ontario, Canada. Weekly cancer incidence counts were examined using segmented negative binomial regression models. The weekly estimated backlog during the pandemic was calculated by subtracting the observed volume from the projected/expected volume in that week. Results: The cohort consisted of 358,487 adult patients with cancer. At the start of the pandemic, there was an immediate 34.3% decline in the estimated mean cancer incidence volume (relative rate, 0.66; 95% CI, 0.57–0.75), followed by a 1% increase in cancer incidence volume in each subsequent week (relative rate, 1.009; 95% CI, 1.001–1.017). Similar trends were found for both screening and nonscreening cancers. The largest immediate declines were seen for melanoma and cervical, endocrinologic, and prostate cancers. For hepatobiliary and lung cancers, there continued to be a weekly decline in incidence during the COVID-19 period. Between March 15 and September 26, 2020, 12,601 fewer individuals were diagnosed with cancer, with an estimated weekly backlog of 450. Conclusions: We estimate that there is a large volume of undetected cancer cases related to the COVID-19 pandemic. Incidence rates have not yet returned to prepandemic levels.

In response to an increase in COVID-19 infection rates in Ontario, several systemic treatment (ST) regimens delivered in the adjuvant setting for breast cancer were temporarily permitted for neoadjuvant-intent to defer nonurgent breast cancer surgical procedures.To examine the use and compare short-term outcomes of neoadjuvant-intent vs adjuvant ST in the COVID-19 era compared with the pre-COVID-19 era.This was a retrospective population-based cohort study in Ontario, Canada. Patients with cancer starting selected ST regimens in the COVID-19 era (March 11, 2020, to September 30, 2020) were compared to those in the pre-COVID-19 era (March 11, 2019, to March 10, 2020). Patients were diagnosed with breast cancer within 6 months of starting systemic therapy.Estimates were calculated for the use of neoadjuvant vs adjuvant ST, the likelihood of receiving a surgical procedure, the rate of emergency department visits, hospital admissions, COVID-19 infections, and all-cause mortality between treatment groups over time.Among a total of 10 920 patients included, 7990 (73.2%) started treatment in the pre-COVID-19 era and 7344 (67.3%) received adjuvant ST; the mean (SD) age was 61.6 (13.1) years. Neoadjuvant-intent ST was more common in the COVID-19 era (1404 of 2930 patients [47.9%]) than the pre-COVID-19 era (2172 of 7990 patients [27.2%]), with an odds ratio of 2.46 (95% CI, 2.26-2.69; P .001). This trend was consistent across a range of ST regimens, but differed according to patient age and geography. The likelihood of receiving surgery following neoadjuvant-intent chemotherapy was similar in the COVID-19 era compared with the pre-COVID-19 era (log-rank P = .06). However, patients with breast cancer receiving neoadjuvant-intent hormonal therapy were significantly more likely to receive surgery in the COVID-19 era (log-rank P .001). After adjustment, there were no significant changes in the rate of emergency department visits over time between patients receiving neoadjuvant ST, adjuvant ST, or ST only during the ST treatment period or postoperative period. Hospital admissions decreased in the COVID-19 era for patients who received neoadjuvant ST compared with adjuvant ST or ST alone (P for interaction = .01 for both) in either setting.In this cohort study, patients were more likely to start neoadjuvant ST in the COVID-19 era, which varied across the province and by indication. There was limited evidence to suggest any substantial impact on short-term outcomes.

Key Points Question Are oncology therapies recently approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) associated with clinically meaningful improvements in quality of life (QOL)? Findings In this systematic review of approved oncology therapies, 40% of FDA-approved and 58% of EMA-approved indications had published QOL evidence. However, only 6% and 11% of FDA- and EMA-approved indications, respectively, had clinically meaningful improvements in QOL beyond minimal clinically important differences. Meaning These findings suggest that oncology therapies are often approved without evidence of QOL improvement, despite the importance to patients., This systematic review of US Food and Drug Administration and European Medicines Agency approvals for oncology therapies examines the prevalence of trials showing clinically meaningful improvements in quality of life as evidence in the approval process., Importance For patients with cancer treated with palliative intent, quality of life (QOL) is a critical aspect of treatment decision-making, alongside survival. However, regulatory approval can be based solely on survival measures or antitumor activities, without QOL evidence. Objective To investigate whether recently approved oncology therapies demonstrate clinically meaningful improvements in QOL. Evidence Review This systematic review study identified oncology drug indications approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) from January 2006 to December 2017 and supporting clinical trials (QOL publications identified to October 2019). Indications were evaluated for the presence of published QOL evidence; QOL benefits according to the American Society of Clinical Oncology Value Framework version 2.0 (ASCO-VF) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) QOL bonus criteria; and clinically meaningful improvements in QOL beyond minimal clinically important differences. Hematology trials were not evaluated by ESMO-MCBS. Associations between QOL evidence and approval year were examined using logistic regression models. Findings In total, 214 FDA-approved (77 [36%] hematological) and 170 EMA-approved (52 [31%] hematological) indications were included. QOL evidence was published for 40% and 58% of FDA- and EMA-approved indications, respectively. QOL bonus criterion for ASCO-VF and ESMO-MCBS was met in 13% and 17% of FDA-approved and 21% and 24% of EMA-approved indications, respectively. Clinically meaningful improvements in QOL beyond minimal clinically important differences were noted in 6% and 11% of FDA- and EMA-approved indications, respectively. Availability of published QOL evidence at the time of approval increased over time for EMA (odds ratio [OR], 1.13; P = .03), however not for FDA (OR, 1.10; P = .12). Over time, no increase in awarded QOL bonuses or clinically meaningful improvements in QOL were found. Conclusions and Relevance The findings of this systematic review suggest that approved systemic oncology therapies often do not have published evidence to suggest QOL improvement, despite its recognized importance. Of indications with evidence of statistical improvement, few have demonstrated clinically meaningful improvements.

Pembrolizumab monotherapy has replaced chemotherapy as first-line treatment for patients with metastatic non-small-cell lung cancer with tumor programmed death-ligand 1 expression ≥ 50%. The benefit of chemotherapy combined with pembrolizumab, as compared to pembrolizumab monotherapy, remains uncertain. This systematic review and network meta-analysis aimed to compare these therapies through a network of randomized controlled trials. Endpoints evaluated were progression-free survival (PFS) and overall survival (OS) expressed as hazard ratio (HR) and restricted mean survival time (RMST) through reconstruction of individual patient data from Kaplan-Meier curves, and objective response rate and adverse events. Four trials were included. Through HR and RMST, combination therapy demonstrated longer PFS and similar OS as compared to pembrolizumab monotherapy. Combination therapy was associated with an increase in response rate and adverse events. Thus, combination therapy can be considered when rapid response or prevention of rapid progression is needed. Further evidence to directly compare these therapies is required.

Clinical Practice Points • Patients with interstitial lung disease are at increased risk for lung cancer, have worse outcomes compared with patients with non–interstitial lung disease lung cancer, and are at higher risk for treatment-related toxicity. • Here, we report a patient with interstitial lung disease who initially presented with early stage non–small cell lung cancer, who was not a surgical candidate and refused stereotactic ablative body radiotherapy owing to a heightened risk of complications. • He progressed on surveillance to have metastatic non–small cell lung cancer, which was found to have ultra-high programmed death ligand-1 expression (>99%). He was started on first-line pembrolizumab, which has been well-tolerated and resulted in an excellent response. • Our case highlights important considerations when treating lung cancer in patients with interstitial lung disease and reviews the pertinent literature regarding the use of stereotactic ablative body radiotherapy and immunotherapy in these patients.

Graphical abstract, Highlights • COVID-19 resource constraints have resulted in treatment delays for oral cancer. • Non-surgical treatment may be necessary to provide timely access to care. • Definitive CCRT is associated with an increased rate of death in early oral cancer. • Neoadjuvant regimens have not shown survival benefit in resectable oral cancer., Objective Surgery is the preferred treatment modality for oral squamous cell carcinoma (OSCC). However, due to limited resources, re-assessment of treatment paradigms in the wake of the Coronavirus Disease 2019 (COVID-19) pandemic is urgently required. In this rapid review, we described contemporary oncological outcomes for OSCC using non-surgical modalities. Methods A systematic literature search was conducted for articles published between January 1, 2010 and April 1, 2020 on MEDLINE and Cochrane CENTRAL. Studies were included if they contained patients with OSCC treated with either neoadjuvant, induction, or definitive radiotherapy, chemotherapy, immunotherapy, or combination thereof, and an outcome of overall survival. Results In total, 36 articles were identified. Definitive radiotherapy or chemoradiotherapy were the focus of 18 articles and neoadjuvant chemotherapy or chemoradiotherapy were the focus of the other 18 articles. In early stage OSCC, definitive radiotherapy, with or without concurrent chemotherapy, was associated with a significantly increased hazard of death compared to definitive surgery (HR: 2.39, 95% CI: 1.56 - 3.67, I2: 63%). The hazard of death was non-significantly increased with definitive chemoradiotherapy in studies excluding early disease (HR: 1.98, 95% CI: 0.85 - 4.64, I2: 84%). Two recent randomized control trials have been conducted, demonstrating no survival advantage to neoadjuvant chemotherapy. Conclusion This review suggests that primary radiotherapy and chemoradiotherapy are inferior to surgical management for OSCC. Strategies for surgical delay warranting consideration are sparse, but may include several neoadjuvant regimens, recognizing these regimens may not offer a survival benefit over definitive surgery alone.

Background: Despite initial promising results, the IMvigor211 clinical trial failed to demonstrate an overall survival (OS) benefit for atezolizumab compared with chemotherapy as second-line treatment for metastatic bladder cancer (mBC). However, given lessened adverse events (AES) and preserved quality of life (QOL) with atezolizumab, there might still be investment value. To evaluate that potential value, we conducted a cost–utility analysis (CUA) of atezolizumab compared with chemotherapy from the perspective of the Canadian health care payer. Methods: A partitioned survival model was used to evaluate atezolizumab compared with chemotherapy over a lifetime horizon (5 years). The base-case analysis was conducted for the intention-to-treat (ITT) population, with additional scenario analyses for subgroups by IMvigor-defined PD-L1 status. Health outcomes were evaluated through life–year gains and quality-adjusted life–years (QALYS). Cost estimates in 2018 Canadian dollars for systemic treatment, AES, and end-of-life care were incorporated. The incremental cost-effectiveness ratio (ICER) was used to compare treatment strategies. Parameter and model uncertainty were assessed through sensitivity and scenario analyses. Per Canadian guidelines, cost and effectiveness were discounted at 1.5%. Results: For the ITT population, the expected qalys for atezolizumab and chemotherapy were 0.75 and 0.56, with expected costs of $90,290 and $8,466 respectively. The resultant ICER for atezolizumab compared with chemotherapy was $430,652 per QALY. Scenario analysis of patients with PD-L1 expression levels of 5% or greater led to a lower ICER ($334,387 per QALY). Scenario analysis of observed compared with expected benefits demonstrated a higher icer, with a shorter time horizon ($928,950 per QALY). Conclusions: Despite lessened aes and preserved QOL, atezolizumab is not considered cost-effective for the second-line treatment of mbc.

Therapeutic options for chemorefractory metastatic colorectal cancer (mcrc) have significantly expanded since 2009. The oral targeted therapies regorafenib and trifluridine/tipiracil have been established to be efficacious and safe in patients with mcrc who have progressed beyond 2 or more lines of chemotherapy. Evidence for the use of immunotherapy in a subgroup of this patient population is also encouraging, particularly in patients with mcrc that exhibits high microsatellite instability or deficient mismatch repair. Those significant advances have led to Health Canada approval of 3 novel therapeutic options for the treatment of patients with chemorefractory mcrc. However, the limited clinical efficacy of those treatments underscores the need for ongoing development of systemic therapy options for this unique cohort of patients. Here, we review the current and emerging treatment landscape for chemorefractory mcrc.

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.

Summary Analyses suggest iron overload in red blood cell (RBC) transfusion-dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient-related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient-related factors. TD International Prognostic Scoring System (IPSS) low and intermediate-1 risk MDS, at RBC TD, were included. Predictive factors for OS were determined. A matched pair analysis considering age, revised IPSS, TD severity, time from MDS diagnosis to TD, and receipt of disease-modifying agents was conducted. Of 239 patients, 83 received ICT; frailty, comorbidity and disability did not differ from non-ICT patients. Median OS from TD was superior in ICT patients (5·2 vs. 2·1 years; P

Modern radiation techniques have led to significant improvements in intracranial disease control and overall survival (OS) for metastatic renal-cell carcinoma (mRCC) patients diagnosed with brain metastases (BM). The impact of systemic therapy in patients developing mRCC BM remains undercharacterized.We performed a retrospective cohort study of mRCC patients diagnosed with BM. Patients were grouped as having either metachronous BM (ie, ≥ 3 months from mRCC diagnosis) or synchronous BM (ie, 3 months from mRCC diagnosis). Details of patient demographics, BM, systemic therapy, and outcomes were extracted. Statistical analysis comprised chi-square tests, analysis of variance, and Kaplan-Meier method to characterize survival outcomes.Seventy-four patients were identified (40 at ≥ 3 months from mRCC diagnosis and 34 at 3 months from mRCC diagnosis) of which 72 (97%) received local therapy for their BM. Median (interquartile range [IQR]) duration while first line treatment was longer at 7.8 (3.6-17.0) versus 5.1 (3.3-12.6) in patients with metachronous BM versus patients with synchronous BM (P = 0.6), respectively. After BM diagnosis, the metachronous BM cohort continued to receive the same systemic therapy for a median (IQR) duration of 1.9 (0.4-5.5) months, with eventual change most commonly the result of extracranial disease progression. Median (IQR) OS from mRCC diagnosis favored metachronous BM patients versus synchronous BM patients, at 64.2 (31.4-not yet reached) versus 22.4 (9.7-34.1) months (P = .003), respectively. However, this was not significantly different from the time of BM diagnosis, with median (IQR) survival of 20.6 (9.2-31.2) versus 15.7 (11.6-not yet reached) months (P = .95), respectively.Prolonged OS was found for mRCC patients with BM that presented either metachronously or synchronously. For patients diagnosed with metachronous BM, the development of BM may be an early sign of systemic therapy failure.

Better data are essential for effective cancer care both during and after the covid-19 pandemic

The treatment landscape for metastatic renal cell carcinoma (mRCC) has undergone a substantial evolution in the past decade, with a dramatic increase in the number of available systemic therapies. Although this offers promise for improved patient outcomes, this rapid pace in development has led to new challenges in therapeutic choice. For instance, the absence of direct comparative evidence across all therapeutic options has led to a critical gap in evidence to clearly define preferred systemic therapy choice. Additionally, the rising cost of systemic therapies being evaluated for mRCC necessitates demonstration of cost-effectiveness prior to widespread adoption. This review provides an overview of the current treatment landscape in mRCC to highlight the emerging challenges faced by clinicians and health policy-makers. In addition, this review summarizes the currently available evidence that aims to address the above challenges.

Adjuvant chemotherapy has significantly improved outcomes following surgical resection for pancreatic adenocarcinoma; however, the optimal adjuvant strategy remains unclear. This systematic review and network meta-analysis was conducted to provide indirect comparative evidence across adjuvant chemotherapies. Electronic searches of EMBASE, MEDLINE, Cochrane and ASCO databases were conducted to identify eligible randomized controlled trials (RCT). Direct pairwise meta-analysis was conducted for disease-free survival (DFS), overall-survival (OS) and adverse events (AE). Network meta-analysis of DFS and OS was conducted to evaluate indirect comparisons. Ten publications of eleven RCT met eligibility criteria. Indirect DFS comparison demonstrated superiority of mFOLFIRINOX versus gemcitabine-capecitabine, gemcitabine-erlotinib and gemcitabine-nab-paclitaxel. S-1 demonstrated a DFS benefit versus gemcitabine-capecitabine, gemcitabine-erlotinib, gemcitabine-nab-paclitaxel. OS benefits were demonstrated for mFOLFIRINOX verus gemcitabine-erlotinib and for S-1 versus gemcitabine-based combination with erlotinib, capecitabine and nab-paclitaxel. In conclusion, mFOLFIRINOX is the preferred approach for adjuvant therapy. For mFOLFIRINOX-ineligible patients no additional benefit is seen with gemcitabine-nab-paclitaxel.

Patients with acute myeloid leukemia (AML) are at risk for sudden clinical deterioration. We aimed to describe the incidence of medical emergency team (MET) activation, intensive care unit (ICU) admissions and outcomes for patients with AML. We performed a 5-year retrospective cohort study of patients hospitalized with AML. One hundred and seventy patients were divided into three groups: (1) MET activated (n = 34); (2) MET criteria present but MET not activated (n = 17); and (3) all other patients with AML (n = 119). MET activation incidence was 200 calls/1000 admissions (95% confidence interval [CI], 138-279), compared with a hospital-wide rate of 29.3 calls/1000 admissions (95% CI, 28.2-30.4) (relative risk 6.90; 95% CI, 4.77-9.67, p0.0001). Some 77% (n = 26) were triaged to the ICU. Hospital mortality was higher in MET activated and MET fulfilled without activation groups compared with all others (27% vs. 12% vs. 7%, p = 0.007). Changes to goals of care were more common with MET activation. Patients with AML commonly receive MET activation. Approximately one in 10 fulfill MET criteria, however do not receive MET activation.

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. 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. 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). 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.

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) in which neuropathic pain is now recognized as a major symptom. To date, few studies have examined the underlying mechanisms of neuropathic pain in MS. Recently we showed that in a chronic-relapsing animal model of MS, experimental autoimmune encephalomyelitis (EAE), characteristic neuropathic behaviours develop. However, responses to persistent noxious stimuli in EAE remain unexplored. We, therefore set out to characterize the changes in pain sensitivity in our EAE model to subcutaneous injection of formalin. We show here that female C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG(35-55)) display a significant decrease in elicited pain behaviours in response to formalin injection. These effects were found to involve dysregulation of the glutamatergic system in EAE. We show here that these effects are mediated by decreased glutamate transporter expression associated with EAE. Our findings demonstrate that dysregulation of glutamate transporter function in EAE mice is an important mechanism underlying the abnormal pain sensitivity in response to persistent noxious stimulation of mice with EAE and also sheds light on a potential mechanism underlying neuropathic pain behaviours in this model.