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Methadone is a synthetic opioid agonist and N-methyl-D-aspartate (NMDA) receptor antagonist that is being increasingly used in pain management, particularly for pain that is resistant to conventional opioids. We describe two patients with neurotoxic side effects on escalating doses of parenteral hydromorphone with uncontrolled cancer pain who were successfully converted to oral methadone at a dose much smaller than predicted. The phenomenon of increasing pain despite opioid dose escalation is discussed and the rationale for the use of methadone in this situation is described. While methadone is useful for patients with unremitting pain on another opioid, existing conversion regimens do not specifically take into account the setting of dose escalation. Clinical guidelines for rotation to methadone after dose escalation of the previous opioid are needed to avoid toxicity including respiratory depression. A possible conversion method for rotation to methadone for patients with escalating pain and opioid use is suggested. [ABSTRACT FROM AUTHOR]

Context: Most survivors of cardiac arrest are comatose after resuscitation, and meaningful neurological recovery occurs in a small proportion of cases. Treatment can be lengthy, expensive, and often difficult for families and caregivers. Physical examination is potentially useful in this clinical scenario, and the information obtained may help physicians and families make accurate decisions about treatment and/or withdrawal of care.Objective: To determine the precision and accuracy of the clinical examination in predicting poor outcome in post-cardiac arrest coma.Data Sources and Study Selection: We searched MEDLINE for English-language articles (1966-2003) using the terms coma, cardiac arrest, prognosis, physical examination, sensitivity and specificity, and observer variation. Other sources came from bibliographies of retrieved articles and physical examination textbooks. Studies were included if they assessed the precision and accuracy of the clinical examination in prognosis of post-cardiac arrest coma in adults. Eleven studies, involving 1914 patients, met our inclusion criteria.Data Extraction: Two authors independently reviewed each study to determine eligibility, abstract data, and classify methodological quality using predetermined criteria. Disagreement was resolved by consensus.Data Synthesis: Summary likelihood ratios (LRs) were calculated from random effects models. Five clinical signs were found to strongly predict death or poor neurological outcome: absent corneal reflexes at 24 hours (LR, 12.9; 95% confidence interval [CI], 2.0-68.7), absent pupillary response at 24 hours (LR, 10.2; 95% CI, 1.8-48.6), absent withdrawal response to pain at 24 hours (LR, 4.7; 95% CI, 2.2-9.8), no motor response at 24 hours (LR, 4.9; 95% CI, 1.6-13.0), and no motor response at 72 hours (LR, 9.2; 95% CI, 2.1-49.4). The proportion of individuals' dying or having a poor neurological outcome was calculated by pooling the outcome data from the 11 studies (n = 1914) and used as an estimate of the pretest probability of poor outcome. The random effects estimate of poor outcome was 77% (95% CI, 72%-80%). The highest LR increases the pretest probability of 77% to a posttest probability of 97% (95% CI, 87%-100%). No clinical findings were found to have LRs that strongly predicted good neurological outcome.Conclusions: Simple physical examination maneuvers strongly predict death or poor outcome in comatose survivors of cardiac arrest. The most useful signs occur at 24 hours after cardiac arrest, and earlier prognosis should not be made by clinical examination alone. These data provide prognostic information, rather than treatment recommendations, which must be made on an individual basis incorporating many other variables. [ABSTRACT FROM AUTHOR]

Context: Severe acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in China in November 2002 and has subsequently spread worldwide.Objectives: To describe the clinical characteristics and short-term outcomes of SARS in the first large group of patients in North America; to describe how these patients were treated and the variables associated with poor outcome.Design, Setting, and Patients: Retrospective case series involving 144 adult patients admitted to 10 academic and community hospitals in the greater Toronto, Ontario, area between March 7 and April 10, 2003, with a diagnosis of suspected or probable SARS. Patients were included if they had fever, a known exposure to SARS, and respiratory symptoms or infiltrates observed on chest radiograph. Patients were excluded if an alternative diagnosis was determined.Main Outcome Measures: Location of exposure to SARS; features of the history, physical examination, and laboratory tests at admission to the hospital; and 21-day outcomes such as death or intensive care unit (ICU) admission with or without mechanical ventilation.Results: Of the 144 patients, 111 (77%) were exposed to SARS in the hospital setting. Features of the clinical examination most commonly found in these patients at admission were self-reported fever (99%), documented elevated temperature (85%), nonproductive cough (69%), myalgia (49%), and dyspnea (42%). Common laboratory features included elevated lactate dehydrogenase (87%), hypocalcemia (60%), and lymphopenia (54%). Only 2% of patients had rhinorrhea. A total of 126 patients (88%) were treated with ribavirin, although its use was associated with significant toxicity, including hemolysis (in 76%) and decrease in hemoglobin of 2 g/dL (in 49%). Twenty-nine patients (20%) were admitted to the ICU with or without mechanical ventilation, and 8 patients died (21-day mortality, 6.5%; 95% confidence interval [CI], 1.9%-11.8%). Multivariable analysis showed that the presence of diabetes (relative risk [RR], 3.1; 95% CI, 1.4-7.2; P =.01) or other comorbid conditions (RR, 2.5; 95% CI, 1.1-5.8; P =.03) were independently associated with poor outcome (death, ICU admission, or mechanical ventilation).Conclusions: The majority of cases in the SARS outbreak in the greater Toronto area were related to hospital exposure. In the event that contact history becomes unreliable, several features of the clinical presentation will be useful in raising the suspicion of SARS. Although SARS is associated with significant morbidity and mortality, especially in patients with diabetes or other comorbid conditions, the vast majority (93.5%) of patients in our cohort survived. [ABSTRACT FROM AUTHOR]

Background: The 2003 global outbreak of severe acute respiratory syndrome (SARS) provided numerous challenges to the delivery of critical care. The Toronto critical care community has learned important lessons from SARS, which will help in preparation for future disease outbreaks.Objectives: The objectives of this study were to review the epidemiology and clinical characteristics of the Toronto SARS outbreak, the challenges SARS provided to the delivery of critical care, and how we would like to be better organized for a similar challenge in the future.Findings: SARS manifests clinically as atypical pneumonia and ranges in severity from minor nonspecific symptoms to adult respiratory distress syndrome (ARDS). Approximately 20% of patients with SARS will become critically ill and require admission to the intensive care unit. ARDS develops in the majority of these patients. Mortality from ARDS in SARS is high, and outcome is associated with the presence of comorbid disease and the severity of illness at presentation. The influx of critically ill patients and the transmission of SARS to front line workers created a tremendous strain on Toronto's healthcare system. From a critical care perspective, the most important limitation in the response to SARS was the absence of a coordinated leadership and communication infrastructure. Other challenges encountered during SARS include the following: closure of intensive care unit beds and loss of staff through quarantine and illness, implementing novel infection control protocols, educating staff, conducting research to learn about SARS, system planning, and maintaining staff morale during this very difficult period.Conclusions: Communication and leadership strategies were key components in the critical care response to SARS. Ideally, centers should have systems in place to allow for the rapid expansion and modification of critical care services in the event of a disease outbreak. Other critical care communities should consider their crisis response strategies in advance of similar events. [ABSTRACT FROM AUTHOR]

Background: Effective techniques for eliciting patients' preferences regarding their own care, when treatment options offer marginal gains and different risks, is an important clinical need. We sought to evaluate the association between patients' considerations of the time burdens of care ("time toxicity") with decisions about hypothetical treatment options., Methods: We conducted a secondary analysis of a multicenter, mixed-methods study that evaluated patients' attitudes and preferences toward palliative-intent cancer treatments that delayed imaging progression-free survival (PFS) but did not improve overall survival (OS). We classified participants based on if they spontaneously volunteered one or more consideration of time burdens during qualitative interviews after treatment trade-off exercises. We compared the percentage of participants who opted for treatments with no PFS gain, some PFS gain, or who declined treatment regardless of PFS gain (in the absence of OS benefit). We conducted narrative analysis of themes related to time burdens., Results: The study cohort included 100 participants with advanced cancer (55% women, 63% age > 60 years, 38% with gastrointestinal cancer, and 80% currently receiving cancer-directed treatment. Forty-six percent (46/100) spontaneously described time burdens as a factor they considered in making treatment decisions. Participants who mentioned time (vs not) had higher thresholds for PFS gains required for choosing additional treatments (P value .004). Participants who mentioned time were more likely to decline treatments with no OS benefit irrespective of the magnitude of PFS benefit (65%, vs 31%). On qualitative analysis, we found that time burdens are influenced by several treatment-related factors and have broad-ranging impact, and illustrate how patients' experiences with time burdens and their preferences regarding time influence their decisions., Conclusions: Almost half of participating patients spontaneously raised the issue of time burdens of cancer care when making hypothetical treatment decisions. These patients had notable differences in treatment preferences compared to those who did not mention considerations of time. Decision science researchers and clinicians should consider time burdens as an important attribute in research and in clinic., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Institutions providing care to individuals with cancer are organized based on available resources and treatments offered. It is presumed that increasing levels of care will result in improved quality of care and outcomes. The objective is to determine whether Cancer Level Designation is associated with guideline adherent care and/or survival., Methods: This is a retrospective study of individuals within the Ontario Rectal Cancer Cohort, a population-level database including all adults undergoing surgical resection for rectal cancer between 2010 - 2019 were included in Ontario, Canada. The primary exposure was Cancer Centre Level Designation as defined by Cancer Care Ontario (i.e., Level 1/2 = regional cancer center; Level 3 = affiliate cancer center; Level 4 = satellite cancer center). The primary outcomes were guideline adherent care and survival. Associations were determined using one-way analysis of variances and a multivariable Cox proportional hazards model., Results: 12,399 patients were included with 54 % from a Level 1/2 centre, 33 % from a Level 3 centre and 13 % from a Level 4+ centre. All assessed aspects of guideline adherent care were associated with cancer centre level designation. Unadjusted 5-year overall survival was associated with cancer centre level designation (Level 1/2 79.5 % vs. Level 3 79.1 % vs. Level 4/non-designated 75.4 %, P = 0.003). Adjusted Cox Proportional Hazard Analysis for overall survival found the following: Level 4/5 HR 1.11 (95 %CI 0.99 - 1.25); Level 3 HR 1.01 (95 % CI 0.93 - 1.11); Level 1/2 1 [Referent group]., Conclusions: Increasing Cancer Centre Level Designation was associated with higher likelihood of receiving the appropriate investigations and treatments in those with rectal cancer and may also be associated with survival., Policy Summary: Future work should consider the centralization of complex rectal cancer care as well as quality improvement initiatives aimed at enhancing guideline adherent care across all centres managing rectal cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Exercise plays many important roles across the entire cancer continuum that have been described in previous frameworks. These frameworks, however, have generally provided a simplified description of the roles of exercise postdiagnosis. The modern cancer treatment landscape has become complex and often consists of multiple lines of multimodal treatments combined concurrently and/or sequentially and delivered over many months or years. This complexity requires a more multifaceted and targeted approach to the study of exercise after a cancer diagnosis. Here, we propose a new integrated framework-Exercise Across the Postdiagnosis Cancer Continuum (EPiCC)-that highlights the distinct roles of exercise for disease treatment and supportive care from diagnosis until death. We also propose new terminology to clarify the distinct roles of exercise that emerge in the context of the modern cancer treatment landscape. The EPiCC Framework is structured around multiple sequential cancer treatments that highlight six distinct cancer treatment-related time periods for exercise-before treatments, during treatments, between treatments, immediately after successful treatments, during longer term survivorship after successful treatments, and during end of life after unsuccessful treatments. The EPiCC Framework proposes that the specific roles of exercise as a disease treatment and supportive care intervention will vary depending on its positioning within different cancer treatment combinations. As a cancer treatment, exercise may serve as a "priming therapy", primary therapy, neoadjuvant therapy, induction therapy, "bridging therapy", adjuvant therapy, consolidation therapy, maintenance therapy, and/or salvage therapy. As a supportive care intervention, exercise may serve as prehabilitation, intrahabilitation, interhabilitation, rehabilitation, "perihabilitation", health promotion/disease prevention, and/or palliation. To date, exercise has been studied during all of the cancer treatment-related time periods but only in relation to some cancer treatments and combinations. Moreover, fewer studies have examined exercise across multiple cancer treatment-related time periods within any cancer treatment combination. Future research is needed to study exercise as a disease treatment and supportive care intervention within and across the distinct cancer treatment-related time periods contained within different cancer treatment combinations. The aim of the EPiCC Framework is to stimulate a more targeted, integrated, and clinically-informed approach to the study of exercise after a cancer diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Courneya, McNeely, Booth and Friedenreich.)

Despite major biomedical advancements in various realms of oncology, the benefits of these developments are not equitably distributed, particularly in underresourced settings. Although much work has described the challenges and systemic barriers in global cancer control, in this article we focus on success stories. This article describes clinical care delivered at Rwanda's Butaro Cancer Center of Excellence, the cancer research collaborations under India's National Cancer Grid, and the efforts of Latin America's Institute of Cancer of São Paulo in advancing cancer care and training. These examples highlight the potential of strategic collaborations and resource allocation strategies in improving cancer care globally. We emphasize the critical role of partnerships between physicians and allied health professionals, funders, and policy makers in enhancing access to treatment and infrastructure, advancing contextualized research and national guidelines, and establishing regional and global collaborations. We also draw attention to challenges faced in diverse global settings and outline benchmarks to measure success in the fight against cancer., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Although contact days-days with health-care contact outside home-are increasingly adopted as a measure of time toxicity and treatment burden, they could also serve as a surrogate of treatment-related harm. We sought to assess the association between contact days and patient-reported outcomes and the prognostic ability of contact days., Methods: We conducted a secondary analysis of CO.17 that evaluated cetuximab vs supportive care in patients with advanced colorectal cancer. CO.17 collected European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 instrument data. We assessed the association between number of contact days in a window and changes in physical function and global health status and the association between number of contact days in the first 4 weeks with overall survival., Results: There was a negative association between the number of contact days and change in physical function (per each additional contact day: at 4 weeks, 1.50-point decrease; 8 weeks, 1.06-point decrease; P < .0001 for both) but not with global health status. This negative association was seen in patients receiving cetuximab but not supportive care. More contact days in the first 4 weeks was associated with worse overall survival for all participants and patients receiving cetuximab (per each additional contact day: all participants, adjusted hazard ratio [HR] = 1.07, 95% confidence interval [CI] = 1.05 to 1.10; and cetuximab, adjusted HR = 1.08, 95% CI = 1.05 to 1.11; P < .0001 for both)., Conclusions: In this secondary analysis of a clinical trial, more contact days early in the course were associated with declines in physical function and worse survival in all participants and in participants receiving cancer-directed treatment., Trial Registration: ClinicalTrials.gov number, NCT00079066., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Prior systematic reviews addressing the impact of diet on cancer outcomes have focused on specific dietary interventions. In this systematic review, we assessed all randomized controlled trials (RCTs) investigating dietary interventions for cancer patients, examining the range of interventions, endpoints, patient populations, and results., Methods: This systematic review identified all RCTs conducted before January 2023 testing dietary interventions in patients with cancer. Assessed outcomes included quality of life, functional outcomes, clinical cancer measurements (eg, progression-free survival, response rates), overall survival, and translational endpoints (eg, inflammatory markers)., Results: In total, 252 RCTs were identified involving 31 067 patients. The median sample size was 71 (interquartile range 41 to 118), and 80 (32%) studies had a sample size greater than 100. Most trials (n = 184, 73%) were conducted in the adjuvant setting. Weight or body composition and translational endpoints were the most common primary endpoints (n = 64, 25%; n = 52, 21%, respectively). Direct cancer measurements and overall survival were primary endpoints in 20 (8%) and 7 (3%) studies, respectively. Eight trials with a primary endpoint of cancer measurement (40%) met their endpoint. Large trials in colon (n = 1429), breast (n = 3088), and prostate cancer (n = 478) each showed no effect of dietary interventions on endpoints measuring cancer., Conclusion: Most RCTs of dietary interventions in cancer are small and measure nonclinical endpoints. Although only a small number of large RCTs have been conducted to date, these trials have not shown an improvement in cancer outcomes. Currently, there is limited evidence to support dietary interventions as a therapeutic tool in cancer care., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: Health care contact days-days spent receiving health care outside the home-represent an intuitive, practical, and person-centered measure of time consumed by health care., Methods: We linked 2019 Medicare Current Beneficiary Survey and traditional Medicare claims data for community-dwelling older adults with a history of cancer. We identified contact days (ie, spent in a hospital, emergency department, skilled nursing facility, or inpatient hospice or receiving ambulatory care including an office visit, procedure, treatment, imaging, or test) and described patterns of total and ambulatory contact days. Using weighted Poisson regression models, we identified factors associated with contact days., Results: We included 1,168 older adults representing 4.51 million cancer survivors (median age, 76.4 years, 52.8% women). The median (IQR) time from cancer diagnosis was 65 (27-126) months. In 2019, these adults had mean (standard deviation) total contact days of 28.4 (27.6) and ambulatory contact days of 24.2 (23.6). These included days for tests (8.0 [8.8]), imaging (3.6 [4.1]), visits with any clinicians (12.4 [11.5]), and visits with primary care clinicians (4.4 [4.7]), and nononcology specialists (7.1 [9.4]) specifically. Sixty-four percent of days with a nonvisit ambulatory service (eg, a test) were not on the same day as a clinician visit. Factors associated with more total contact days included younger age, lower income, more chronic conditions, poor self-rated health, and tendency to "go to doctor as soon as feel bad.", Conclusion: Older adult cancer survivors spent nearly 1 month of the year receiving health care outside the home. This care was largely ambulatory, often delivered by nononcologists, and varied by factors beyond clinical characteristics. These results highlight the need to recognize patient burdens and improve survivorship care delivery, including through care coordination.

While some recent drug treatments have been transformative for patients with cancer, many treatments offer small benefits despite high clinical toxicity, time toxicity and financial toxicity. Moreover, treatments that do provide substantial clinical benefits are not available to many patients globally due to issues with availability and affordability. The Common Sense Oncology's vision is that patients will have access to treatments that provide meaningful improvements in outcomes that matter, regardless of where they live. In recognition of the growing challenges in the field of oncology, Common Sense Oncology seeks to achieve this vision by improving evidence generation, evidence interpretation and evidence communication.

Objectives: The addition of bevacizumab to chemotherapy for platinum-resistant (PL-R) ovarian cancer (OC) improved progression-free (PFS) but not overall survival (OS) in clinical trials. We explored real-world outcomes in Ontario, Canada, and compared survival in the pre- and post-bevacizumab era., Methods: Administrative databases were utilized to identify all patients treated with bevacizumab for PL-R OC. Time on treatment (ToT) was used as surrogate for PFS. Median OS was determined using the Kaplan-Meier method. Factors associated with ToT/OS were identified using a Cox proportional hazard model. A before and after comparative effectiveness analysis was performed to determine mOS for patients treated pre- and post-bevacizumab approval., Results: From 2017 to 2019, 176 patients received bevacizumab. Median ToT was 3 months and OS was 11 months. Sixty-four percent received liposomal doxorubicin and 34% received paclitaxel. ToT (6 vs 3 months; HR 0.44; p < 0.0001) and OS (14 vs 9 months; HR 0.45; p = 0.0089) were longer with bevacizumab/paclitaxel. OS was not significantly different pre- and post-bevacizumab funding (8 vs 9 months; HR 1.01; 0.937). Median OS increased for those receiving paclitaxel (6 vs 11 months), but those in the post group were younger, more likely to have undergone primary surgery and had less co-morbidities., Conclusion: Real-world outcomes with bevacizumab in PL-R OC are inferior to those in the pivotal clinical trial. Survival has not significantly improved since funding became publicly available, indicating a substantial efficacy-effectiveness gap between trial and real-world outcomes. Median OS and ToT were significantly better when bevacizumab was given with paclitaxel., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The financial impact of cancer medicines on health systems is not well known. We describe temporal trends in expenditure on cancer medicines within the single-payer health system of Ontario, Canada, and the extent of clinical benefit these treatments offer., Methods: In this cross-sectional study, we identified cancer medicines and expenditures from formularies and costing databases (the New Drug Funding Program, Ontario Drug Benefit Program, and The High-Cost Therapy Funding Program) during 10 consecutive years (April 1, 2012, to March 31, 2022) in Ontario, Canada. For intravenous medicines, we applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) to identify expenditures associated with substantial clinical benefit. We also identified treatments associated with improved overall survival or quality of life., Findings: 69 intravenous and 98 oral or injectable medicines were funded during 2012-22. Annual expenditure on cancer medicines increased by approximately 15% per year during 2012-22; the increase was more rapid in the most recent 4 years. Total expenditure on cancer medicines in the 2021-22 financial year was CA$1·7 billion. Immune checkpoint inhibitors were the single biggest expense by class ($284 million), representing 17% of the entire cancer medicine annual budget. Drugs with the highest individual costs were lenalidomide ($178 million) and pembrolizumab ($163 million), each accounting for around 10% of the entire budget. 29 (76%) of 38 indications eligible for ESMO-MCBS scoring met the threshold for substantial clinical benefit. Eight (21%) indications had no randomised trial evidence of improved overall survival, and only four (11%) were associated with improved QOL. $346 million (67% of the expenditure on intravenous cancer medicines) was spent on drugs that improved median overall survival by more than 6 months, $82 million (16%) was spent on medicines with overall survival gains of 3-6 months, and $32 million (6%) was spent on medicines with overall survival gains of less than 3 months. $53 million (10%) was spent on medicines with no established improvement in overall survival., Interpretation: Costs of cancer medicines to the Canadian health system are increasing rapidly. Most funded indications met thresholds for substantial clinical benefit and two-thirds of the expenditure were for medicines that improve survival by more than 6 months. Whether this cost trajectory can be maintained in a sustainable, equitable, high-quality health system is unclear. Efforts are needed to ensure the price of medicines with substantial benefit is affordable and funding of treatments with very modest benefit might need to be re-assessed, particularly when alternative supportive and palliative therapies are available., Funding: None., Competing Interests: Declaration of interests BG is a member of the ESMO task force designing the evolving ESMO-MCBS. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Importance: Patients with stage IV non-small cell lung cancer (NSCLC) experience substantial morbidity and mortality. Contact days (ie, the number of days with health care contact outside the home) measure how much of a person's life is consumed by health care, yet little is known about patterns of contact days for patients with NSCLC., Objective: To describe the trajectories of contact days in patients with stage IV NSCLC and how trajectories vary by receipt of cancer-directed treatment in routine practice., Design, Setting, and Participants: A retrospective, population-based decedent cohort study was conducted in Ontario, Canada. Participants included adults aged 20 years or older who were diagnosed with stage IV NSCLC (January 1, 2014, to December 31, 2017) and died (January 1, 2014, to December 31, 2019); there was a maximum 2-year follow-up. Data analysis was conducted from February 22 to August 16, 2023., Exposure: Systemic cancer-directed therapy (yes or no) and type of therapy (chemotherapy vs immunotherapy vs targeted therapy)., Main Outcomes and Measures: Contact days (days with health care contact, outpatient or institution-based, outside the home) were identified through administrative data. The weekly percentage of contact days and fitted models with cubic splines were quantified to describe trajectories from diagnosis until death., Results: A total of 5785 decedents with stage IV NSCLC were included (median age, 70 [IQR 62-77] years; 3108 [53.7%] were male, and 1985 [34.3%] received systemic therapy). The median overall survival was 108 (IQR, 49-426) days, median contact days were 36 (IQR, 21-62), and the median percentage that were contact days was 33.3%. A median of 5 (IQR, 2-10) days were spent with specialty palliative care. Patients who did not receive systemic therapy had a median overall survival of 66 (IQR, 34-130) days and median contact days of 28 (IQR, 17-44), of which a median of 5 (IQR, 2-9) days were spent with specialty palliative care. Overall and for subgroups, normalized trajectories followed a U-shaped distribution: contact days were most frequent immediately after diagnosis and before death. Patients who received targeted therapy had the lowest contact day rate during the trough (10.6%; vs immunotherapy, 15.4%; vs chemotherapy, 17.7%)., Conclusions and Relevance: In this cohort study, decedents with stage IV NSCLC had a median survival in the order of 3.5 months and spent 1 in every 3 days alive interacting with the health care system outside the home. These results highlight the need to better support patients and care partners, benchmark appropriateness, and improve care delivery.

Aims: Clinical practice guidelines recommend palliative chemotherapy for most patients with metastatic colorectal cancer. However, outcomes observed in the real world compared with patients enrolled in clinical trials have not been sufficiently described. The objective of this study was to evaluate the delivery and outcomes of first-line palliative chemotherapy administered to patients with colorectal cancer in routine clinical practice compared with clinical trials., Materials and Methods: Using linked health administrative data, we carried out a retrospective population-level cohort study on patients diagnosed with colorectal cancer in Ontario, Canada from 2010 to 2019. Patient, disease and treatment characteristics were summarised. The primary outcome was median overall survival, stratified by treatment prescribed and age. Demographics and outcomes in this real-world population were compared with those from pivotal clinical trials. A multivariable Cox regression model reporting hazard ratios and 95% confidence intervals was used to determine factors associated with survival in patients receiving systemic treatment., Results: We identified 70 987 patients with a new diagnosis of colorectal cancer, of which 4613 received first-line chemotherapy for unresectable locally advanced or metastatic disease and formed the study cohort. Fifty-eight per cent were male and the mean age was 63 years. Most had colon cancer (69%), at least one comorbidity (73%) and lived in an urban location (79%). Less than half (47%) had surgery after diagnosis. The most common regimen prescribed was folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) with bevacizumab or epidermal growth factor receptor inhibitors (EGFRi; n = 2784, 60%). Among all treated patients, the median overall survival was 17.1 months, with survival difference by regimen [median overall survival 18.3 for FOLFIRI with bevacizumab or EGFRi, 19.6 for folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX)/capecitabine, oxaliplatin (XELOX) with bevacizumab or EGFRi, 13.6 for FOLFIRI alone and 7.8 for 5-fluorouracil or capecitabine]. Patients aged >80 years were most likely to have received single-agent 5-fluorouracil or capecitabine, and had inferior overall survival compared with their younger counterparts. Compared with pivotal clinical trials, patients in the real world had inferior overall survival outcomes despite similar demographic characteristics (including age and sex)., Conclusions: In this real-world population-based analysis of patients receiving first-line chemotherapy for unresectable locally advanced or metastatic colorectal cancer, survival outcomes were inferior to those reported in randomised trials despite similarities in age and sex. This information can be used when counselling patients in routine practice about expected outcomes., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Cancer is a major public health problem in Rwanda and other low- and middle-income countries (LMICs). While there have been some improvements in access to cancer treatment, the cost of care has increased, leading to financial toxicity and treatment barriers for many patients. This study explores the financial toxicity of cancer care in Rwanda., Methods: This prospective cross-sectional study was conducted at 3 referral hospitals in Rwanda, which deliver most of the country's cancer care. Data were collected over 6 months from June 1 to December 1, 2022 by trained research assistants (RAs) using a modified validated data collection tool. RAs interviewed consecutive eligible patients with breast cancer, cervical cancer, colorectal cancer, Hodgkin's and non-Hodgkin's lymphoma who were on active systemic therapy. The study aimed to identify sources of financial burden. Data were analyzed using descriptive statistics., Results: 239 patients were included; 75% (n = 180/239) were female and mean age was 51 years. Breast, cervix, and colorectal cancers were the most common diagnoses (42%, 100/239; 24%, 58/239; and 24%, 57/239, respectively) and 54% (n = 129/239) were diagnosed with advanced stage (stages III-IV). Financial burden was high; 44% (n = 106/239) of respondents sold property, 29% (n = 70/239) asked for charity from public, family, or friends, and 16% (n = 37/239) took loans with interest to fund cancer treatment., Conclusion: Despite health insurance which covers many elements of cancer care, a substantial proportion of patients on anti-cancer treatment in Rwanda experience major financial toxicity. Novel health financing solutions are needed to ensure accessible and affordable cancer care., (© The Author(s) 2023. Published by Oxford University Press.)

Background: In 2012, the Brazilian government launched a radiotherapy (RT) expansion plan (PER-SUS) to install 100 linear accelerators. This study assesses the development of this program after eight years., Methods: Official reports from the Ministry of Health (MoH) were reviewed. RT centres projects status, timeframes, and cost data (all converted to US dollars) were extracted. The time analysis was divided into seven phases, and for cost evaluation, there were five stages. The initial predicted project time (IPPT) and costs (estimated by the MoH) for each phase were compared between the 18 operational RT centres (able to treat patients) and 30 non-operational RT centres using t-tests, ANOVA, and the Mann-Whitney U. A p-value < 0.05 indicates statistical significance., Results: A significant delay was observed when comparing the IPPT with the overall time to conclude each 48 RT centres project (p < 0.001), with considerable delays in the first five phases (p < 0.001 for all). Moreover, the median time to conclude the first 18 operational RT centres (77.4 months) was shorter compared with the 30 non-operational RT centres (94.0 months), p < 0.001. The total cost of 48 RT services was USD 82,84 millions (mi) with a significant difference in the per project median total cost between 18 operational RT centres, USD1,34 mi and 30 non-operational RT centres USD2,11 mi, p < 0.001. All phases had a higher cost when comparing 30 non-operational RT centres to 18 operational RT centres, p < 0.001. The median total cost for expanding existing RT centres was USD1,30 mi versus USD2,18 mi for new RT services, p < 0.0001., Conclusion: After eight years, the PER-SUS programs showed a substantial delay in most projects and their phases, with increased costs over time., Policy Summary: Our findings indicate a need to act to increase the success of this plan. This study may provide a benchmark for other developing countries trying to expand RT capacity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Importance: The COVID-19 pandemic had a profound impact on the delivery of cancer care, but less is known about its association with place of death and delivery of specialized palliative care (SPC) and potential disparities in these outcomes., Objective: To evaluate the association of the COVID-19 pandemic with death at home and SPC delivery at the end of life and to examine whether disparities in socioeconomic status exist for these outcomes., Design, Setting, and Participants: In this cohort study, an interrupted time series analysis was conducted using Ontario Cancer Registry data comprising adult patients aged 18 years or older who died with cancer between the pre-COVID-19 (March 16, 2015, to March 15, 2020) and COVID-19 (March 16, 2020, to March 15, 2021) periods. The data analysis was performed between March and November 2023., Exposure: COVID-19-related hospital restrictions starting March 16, 2020., Main Outcomes and Measures: Outcomes were death at home and SPC delivery at the end of life (last 30 days before death). Socioeconomic status was measured using Ontario Marginalization Index area-based material deprivation quintiles, with quintile 1 (Q1) indicating the least deprivation; Q3, intermediate deprivation; and Q5, the most deprivation. Segmented linear regression was used to estimate monthly trends in outcomes before, at the start of, and in the first year of the COVID-19 pandemic., Results: Of 173 915 patients in the study cohort (mean [SD] age, 72.1 [12.5] years; males, 54.1% [95% CI, 53.8%-54.3%]), 83.7% (95% CI, 83.6%-83.9%) died in the pre-COVID-19 period and 16.3% (95% CI, 16.1%-16.4%) died in the COVID-19 period, 54.5% (95% CI, 54.2%-54.7%) died at home during the entire study period, and 57.8% (95% CI, 57.5%-58.0%) received SPC at the end of life. In March 2020, home deaths increased by 8.3% (95% CI, 7.4%-9.1%); however, this increase was less marked in Q5 (6.1%; 95% CI, 4.4%-7.8%) than in Q1 (11.4%; 95% CI, 9.6%-13.2%) and Q3 (10.0%; 95% CI, 9.0%-11.1%). There was a simultaneous decrease of 5.3% (95% CI, -6.3% to -4.4%) in the rate of SPC at the end of life, with no significant difference among quintiles. Patients who received SPC at the end of life (vs no SPC) were more likely to die at home before and during the pandemic. However, there was a larger immediate increase in home deaths among those who received no SPC at the end of life vs those who received SPC (Q1, 17.5% [95% CI, 15.2%-19.8%] vs 7.6% [95% CI, 5.4%-9.7%]; Q3, 12.7% [95% CI, 10.8%-14.5%] vs 9.0% [95% CI, 7.2%-10.7%]). For Q5, the increase in home deaths was significant only for patients who did not receive SPC (13.9% [95% CI, 11.9%-15.8%] vs 1.2% [95% CI, -1.0% to 3.5%])., Conclusions and Relevance: These findings suggest that the COVID-19 pandemic was associated with amplified socioeconomic disparities in death at home and SPC delivery at the end of life. Future research should focus on the mechanisms of these disparities and on developing interventions to ensure equitable and consistent SPC access.

Financial toxicity (FT) describes either objective or perceived excess financial strain due to a cancer diagnosis on the well-being of patients, families, and society. The consequences of FT have been shown to span countries of varied economic tiers and diverse healthcare models. This study attempts to describe FT and its effects in a lower- to middle-income country delivering predominantly public nonfee-levying healthcare. This was a cross-sectional study involving 210 patients with breast cancer of any stage (I to IV), interviewed between 6 and 18 months from the date of diagnosis. Financial toxicity was highly prevalent with 81% reporting 3 or more on a scale of 1 to 5. Costs incurred for travelling (94%), out-of-hospital investigations (87%), and consultation fees outside the public system (81%) were the most common contributors to FT. Daily compromises for food and education were made by 30% and 20%, respectively, with loss of work seen in over one-third. Greater FT was seen with advanced cancer stage and increasing distance to the nearest radiotherapy unit (P = .008 and .01, respectively). Family and relatives were the most common form of financial support (77.6%). In conclusion, FT is substantial in our group, with many having to make daily compromises for basic needs. Many opt to visit the fee-levying private sector for at least some part of their care, despite the availability of an established public nonfee-levying healthcare., (© The Author(s) 2023. Published by Oxford University Press.)

Competing Interests: BG receives salary support from the Ontario Institute for Cancer Research funded by the Government of Ontario. The views expressed in the publication are the views of the authors and do not necessarily reflect those of the Government of Ontario. BG has received consulting fees from Vivio Health, unrelated to the manuscript. CMB declares no competing interests. We gratefully acknowledge Rachel Koven (patient advocate) for her input on an early draft of this Essay; she was not compensated for her contributions.

The efficacy-effectiveness (EE) gap describes the differences in survival seen in clinical trials and routine clinical practice, where patients in real-world practice often have inferior outcomes compared to trial populations. However, EE gaps may exist beyond survival outcomes, including gaps in quality of life, toxicity, cost-effectiveness, and patient time, and these EE gaps should also influence patient and clinician treatment decisions. Failure to clearly acknowledge these EE gaps may cause patients, clinicians, and health care systems to have unrealistic expectations of the benefits of therapy across a range of important clinical and economic domains. In this commentary, the authors review the evidence supporting the existence of EE gaps in quality of life, time toxicity, cost and toxicities, and urge for further research into this important topic., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: The lack of sociodemographic diversity in clinical trials limits the generalizability of results. The authors examined participation rates and effect modification by sex and race in oncology trials., Methods: The authors extracted outcome data stratified by sex and race for registration trials supporting US Food and Drug Administration (FDA) approval (2010-2021). Effect modification by race and sex was examined using quantitative and qualitative methods. A random-effects meta-analysis and pairwise comparison of progression-free survival (PFS) and overall survival (OS) outcomes was conducted by sex and race., Results: Ninety-five trials with 123 end points and 54,365 patients provided information on sex. Trial patients were more often male (n = 35,482; 65% vs. 56% male patients in US Surveillance, Epidemiology, and End Results [SEER] data), although the proportion of male patients was similar after adjusting by tumor type (60% in FDA data vs. 58% in SEER data). There was no difference in pooled outcomes among male versus female patients (PFS: hazard ratio, 0.99; 95% confidence interval, 0.92-1.07; p = .89; OS: hazard ratio, 0.99; 95% confidence interval, 0.93-1.07; p = .90). In total, 111 trials including 74,217 patients provided information on race, and 68% of patients identified as White, compared with 72.3% in US SEER incidence data. Black patients were under-represented compared with US SEER incidence data, although ethnicity was poorly reported throughout the data set. In the authors' network meta-analysis by race, there were no statistically significant differences in PFS or OS outcomes., Conclusions: No significant differences in PFS or OS outcomes were identified when the analyses were stratified by sex or race. Certain racial minorities remain under-represented, and clearer reporting of race and ethnicity is needed. Representation of female patients in FDA trials is similar to that in SEER data after adjusting for tumor type., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Cancer patients' attitudes toward progression-free survival (PFS) gains offered by treatment are not well understood, particularly in the absence of overall survival (OS) gains. The objectives were to describe patients' willingness to accept treatment that offers PFS gains without OS gains, to compare these findings with treatments offering OS gains, and to qualitatively summarize patients' reasons for their preferences., Methods: A multicenter, cross-sectional, convergent mixed-methods study design recruited patients who had received at least 3 months of systemic therapy for incurable solid tumors. A treatment trade-off exercise determined the gains in imaging PFS that patients require to prefer additional systemic treatment for a scenario of a newly diagnosed, asymptomatic, incurable abdominal tumor. A qualitative, descriptive, thematic analysis explored factors influencing patients' decisions, and a narrative method integrated the quantitative and qualitative findings., Results: In total, 100 patients participated (63% were older than 60 years of age). If additional treatment with added toxicity offered no OS advantage, 17% would prefer it for no PFS benefit; 26% for some PFS benefit (range, 3-9 months), whereas 51% would decline it regardless of PFS benefit. Similarly, 71% preferred additional treatment offering a 6-month OS advantage dependent on described toxicity levels (P = .03). A spectrum of reasons for these preferences reflected the complexity of participants' attitudes and values., Conclusions: Prolongation of time to progression was not universally valued. Most patients did not prefer treatments that negatively affect quality of life for PFS gains alone. Implications for individual decision making, policy, and trials research are discussed., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: The number of systemic anticancer therapy (SACT) regimens has expanded rapidly over the last decade. There is a need to ensure quality of SACT delivery across cancer services and systems in different resource settings to reduce morbidity, mortality, and detrimental economic impact at individual and systems level. Existing literature on SACT focuses on treatment efficacy with few studies on quality or how SACT is delivered within routine care in comparison to radiation and surgical oncology., Methods: Systematic review was conducted following PRISMA guidelines. EMBASE and MEDLINE were searched and handsearching was undertaken to identify literature on existing quality indicators (QIs) that detect meaningful variations in the quality of SACT delivery across different healthcare facilities, regions, or countries. Data extraction was undertaken by two independent reviewers., Results: This review identified 63 distinct QIs from 15 papers. The majority were process QIs (n = 55, 87.3%) relating to appropriateness of treatment and guideline adherence (n = 28, 44.4%). There were few outcome QIs (n = 7, 11.1%) and only one structural QI (n = 1, 1.6%). Included studies solely focused on breast, colorectal, lung, and skin cancer. All but one studies were conducted in high-income countries., Conclusions: The results of this review highlight a significant lack of research on SACT QIs particularly those appropriate for resource-constrained settings in low- and middle-income countries. This review should form the basis for future work in transforming performance measurement of SACT provision, through context-specific QI SACT development, validation, and implementation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: Frequent visits to health care facilities can be time intensive and all-consuming for people with cancer. We measured health care contact days (days with healthcare contact outside the home) among decedents with advanced GI cancer and examined sources of contact days, their associations with demographic and clinical factors, and their temporal patterns over the course of illness., Methods: We conducted a retrospective cohort study using a tumor registry and electronic medical record data for decedents with stage IV GI cancer between 2011 and 2019 in a large health care network in MN. We determined contact days from diagnosis to death using chart review. Using multivariable beta regression adjusted for sociodemographic and clinical characteristics offset by survival, we calculated adjusted estimates of contact days and determined patient-level factors associated with percentage of contact days., Results: We identified 809 patients eligible for analysis (median [IQR] age at diagnosis, 65 [56-73] years). The median (IQR) overall survival was 175 (56-459) days. Patients spent a median (IQR) of 25.8% (17.4%-39.1%) of these as contact days. Of these days, 83.6% were spent on outpatient visits. In the multivariable analysis, older age, Black race, and never receiving systemic cancer-directed treatment were associated with a higher percentage of contact days. The percentage of contact days was highest in the first month after diagnosis (39.6%) and before death (32.2%), with a more moderate middle phase (U-shaped curve)., Conclusion: Decedents with advanced GI cancer spend 1 in 4 days alive with health care contact, despite a median survival of under 6 months. This is even higher immediately postdiagnosis and near death. These findings highlight the need to understand sources of variation, benchmark appropriate care, and deliver more efficient care for this vulnerable population with limited time.