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In a phase 3, placebo-controlled study, lenvatinib was associated with a significant increase in progression-free survival (18.3 months vs. 3.6 months). Toxic effects with lenvatinib were substantial and included hypertension, diarrhea, and unexplained death. The 10-year survival rate among patients with differentiated thyroid cancer that is refractory to radioiodine (iodine-131) therapy is 10% from the time of detection of metastasis. 1 – 3 Although treatment options have historically been limited, efforts have first targeted vascular endothelial growth factor (VEGF) and its receptor (VEGFR), since this signaling network has been associated with the aggressiveness and metastasis of thyroid cancer. 4 – 6 However, other molecular pathways of tumor growth and maintenance beyond VEGF-driven angiogenesis contribute to the pathogenesis of thyroid cancer, including BRAF, NRAS, HRAS, RET/PTC, fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR). 7 – 16 Because . . .

Purpose Cancer-related fatigue (CRF) is the most prevalent and distressing symptom among cancer patients and survivors. However, research on its prevalence and related disability in the post-treatment survivorship period remains limited. We sought to describe the occurrence of CRF within three time points in the post-treatment survivorship trajectory. Methods A self-administered mail-based questionnaire which included the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and the World Health Organisation Disability Assessment Schedule 2.0 was sent to three cohorts of disease-free breast, prostate or colorectal cancer survivors (6–18 months; 2–3 years; and 5–6 years post-treatment). Clinical information was extracted from chart review. Frequencies of significant fatigue by diagnostic group and time cohorts were studied and compared. Multivariate logistic regressions were conducted to examine the associations between CRF and demographic, clinical, and psychosocial variables. Results One thousand two hundred ninety-four questionnaire packages were returned (63 % response rate). A total of 29 % (95 % CI [27 % to 32 %]) of the sample reported significant fatigue (FACT-F ≤34), and this was associated with much higher levels of disability ( p  < 0.0001). Breast (40 % [35 % to 44 %]) and colorectal (33 % [27 % to 38 %]) cancer survivors had significantly higher rates of fatigue compared with the prostate group (17 % [14 % to 21 %]) ( p  < 0.0001). Fatigue levels did not differ between the three time cohorts. The main factors associated with CRF included physical symptom burden, depression, and co-morbidity (AUC, 0.919 [0.903 to 0.936]). Conclusions Clinically relevant levels of CRF are present in approximately 1/3 of cancer survivors up to 6 years post-treatment, and this is associated with high levels of disability. Implications for Cancer Survivors Clinicians need to be aware of the chronicity of CRF and assess for it routinely in medical practice. While there is no gold standard treatment, non-pharmacological interventions with established efficacy can reduce its severity and possibly minimize its disabling impact on patient functioning. Attention must be paid to the co-occurrence and need for possible treatment of depression and other co-occurring physical symptoms as contributing factors.

Background The clinical utility of molecular profiling of tumor tissue to guide treatment of patients with advanced solid tumors is unknown. Our objectives were to evaluate the frequency of genomic alterations, clinical “actionability” of somatic variants, enrollment in mutation-targeted or other clinical trials, and outcome of molecular profiling for advanced solid tumor patients at the Princess Margaret Cancer Centre (PM). Methods Patients with advanced solid tumors aged ≥18 years, good performance status, and archival tumor tissue available were prospectively consented. DNA from archival formalin-fixed paraffin-embedded tumor tissue was tested using a MALDI-TOF MS hotspot panel or a targeted next generation sequencing (NGS) panel. Somatic variants were classified according to clinical actionability and an annotated report included in the electronic medical record. Oncologists were provided with summary tables of their patients’ molecular profiling results and available mutation-specific clinical trials. Enrolment in genotype-matched versus genotype-unmatched clinical trials following release of profiling results and response by RECIST v1.1 criteria were evaluated. Results From March 2012 to July 2014, 1893 patients were enrolled and 1640 tested. After a median follow-up of 18 months, 245 patients (15 %) who were tested were subsequently treated on 277 therapeutic clinical trials, including 84 patients (5 %) on 89 genotype-matched trials. The overall response rate was higher in patients treated on genotype-matched trials (19 %) compared with genotype-unmatched trials (9 %; p  < 0.026). In a multi-variable model, trial matching by genotype ( p  = 0.021) and female gender ( p  = 0.034) were the only factors associated with increased likelihood of treatment response. Conclusions Few advanced solid tumor patients enrolled in a prospective institutional molecular profiling trial were treated subsequently on genotype-matched therapeutic trials. In this non-randomized comparison, genotype-enrichment of early phase clinical trials was associated with an increased objective tumor response rate. Trial registration NCT01505400 (date of registration 4 January 2012).

ABSTRACTBackgroundAlthough suspicions of cancer may be raised in patients who visit the emergency department, little is known about emergency department use before a cancer diagnosis. We sought to describe emergency department use among patients in Ontario within the 90 days before confirmed cancer diagnosis and to evaluate factors associated with this emergency department use. MethodsWe conducted a retrospective, population-based study of patients aged 18 years or older who had a confirmed cancer diagnosis in Ontario from 2014 to 2021 using linked administrative databases. The primary outcome was any emergency department visit within 90 days before the cancer diagnosis date. We used multivariable logistic regression to evaluate factors associated with emergency department use, such as demographics (e.g., age, sex, rurality, Ontario Health region, indicators of marginalization), comorbidities, previous emergency department visits and hospital admissions, continuity of primary care, type of cancer, and year of cancer diagnosis. ResultsWe included 651 071 patients with cancer. Of these, 229 683 (35.3%) had an emergency department visit within 90 days before diagnosis, 51.4% of whom were admitted to hospital from the emergency department. Factors associated with increased odds of emergency department use before cancer diagnosis included rurality (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.13–1.17), residence in northern Ontario (North East region OR 1.14, 95% CI 1.10–1.17 and North West region OR 1.27, 95% CI 1.21–1.32, v. Toronto region), and living in the most marginalized areas (material resources OR 1.37, 95% CI 1.35–1.40 and housing OR 1.09, 95% CI 1.06–1.11, v. least marginalized quintile). We observed significant variation in emergency department use by cancer type, with high odds of emergency department use among patients with intracranial, pancreatic, liver or gallbladder, or thoracic cancer. InterpretationEmergency department use is common before cancer diagnosis, with about one-third of patients with cancer in Ontario using the emergency department before diagnosis. Understanding why patients visit the emergency department before cancer diagnosis is important, particularly for patients who live in rural or marginalized areas, or those who have specific cancer types.

Virtual care is here to stay but there remains no comprehensive measurement framework to guide evaluation of its impacts, to inform policy decisions and optimization of practice. The aim of our study was to conduct a scoping review of reviews to synthesize measures related to virtual care evaluation across clinical conditions and contexts to identify gaps in current evaluation measures, and to inform the development of recommendations for future work. Citations published from 2015-2023 were retrieved from Medline, Cochrane Database of Systematic Reviews, Embase, Emcare, Scopus, CINAHL and Web of Science, utilizing search terms grouped by key concept (virtual care and evaluation/ quality measurement). Measures were defined as any quantitative or qualitative evaluation of performance or impact of virtual care on processes, outcomes or systems. Articles were excluded if they were not a literature review (primary results, commentaries, letters, protocols), dealt exclusively with pediatric populations, published in a language other than English, or were abstract only. Measures from retained articles (1,233) were thematically grouped against the Proctor Implementation Research Outcomes framework. The study was reported according to the PRISMA guideline extension for scoping reviews. There has been substantial growth in the virtual care literature, particularly since the start of the COVID-19 pandemic. The majority of articles (73.0%; 900/1233) evaluated client outcomes, including satisfaction with virtual care, usability or functionality of platforms, and/or clinical outcomes. Relative to the other domains of the Proctor framework, implementation measures were poorly defined, and many of the measures were proxy rather than direct measures. Despite the potential impacts of virtual care on health equity, most studies examining health equity were purely qualitative. Measures of safety, privacy and security of virtual care were sparse and poorly defined. Caregivers play an important role in facilitating virtual visits and providing informal technical support; however, few studies examined implementation or satisfaction with virtual care from the perspective of caregivers. Additionally, clinician experience and acceptance of virtual care has implications for availability and adoption; however, relative to patients, few articles examined the clinician perspective. Our study highlights gaps in current evaluations of virtual care. Work is needed to improve the quality and standardization of virtual care evaluation to ensure reproducibility, generalizability and comparability of findings. Additionally, better compliance with existing measure definitions and conventions should extend to virtual care. Finally, additional theoretical work is needed to standardize and conceptually frame future virtual care evaluations. Future studies should include both the caregiver and clinician as unique perspectives in evaluations, and should embed systematic evaluations of the impact of social determinants of health on virtual care access, adoption, and perspectives of care.

ObjectivesTo assess the prevalence and drivers of distress, a composite of burnout, decreased meaning in work, severe fatigue, poor work–life integration and quality of life, and suicidal ideation, among nurses and physicians during the COVID-19 pandemic.DesignCross-sectional design to evaluate distress levels of nurses and physicians during the COVID-19 pandemic between June and August 2021.SettingCardiovascular and oncology care settings at a Canadian quaternary hospital network.Participants261 nurses and 167 physicians working in cardiovascular or oncology care. Response rate was 29% (428 of 1480).Outcome measuresSurvey tool to measure clinician distress using the Well-Being Index (WBI) and additional questions about workplace-related and COVID-19 pandemic-related factors.ResultsAmong 428 respondents, nurses (82%, 214 of 261) and physicians (62%, 104 of 167) reported high distress on the WBI survey. Higher WBI scores (≥2) in nurses were associated with perceived inadequate staffing (174 (86%) vs 28 (64%), p=0.003), unfair treatment, (105 (52%) vs 11 (25%), p=0.005), and pandemic-related impact at work (162 (80%) vs 22 (50%), p<0.001) and in their personal life (135 (67%) vs 11 (25%), p<0.001), interfering with job performance. Higher WBI scores (≥3) in physicians were associated with perceived inadequate staffing (81 (79%) vs 32 (52%), p=0.001), unfair treatment (44 (43%) vs 13 (21%), p=0.02), professional dissatisfaction (29 (28%) vs 5 (8%), p=0.008), and pandemic-related impact at work (84 (82%) vs 35 (56%), p=0.001) and in their personal life (56 (54%) vs 24 (39%), p=0.014), interfering with job performance.ConclusionHigh distress was common among nurses and physicians working in cardiovascular and oncology care settings during the pandemic and linked to factors within and beyond the workplace. These results underscore the complex and contextual aspects of clinician distress, and the need to develop targeted approaches to effectively address this problem.

Treatment with small molecule tyrosine kinase inhibitors (TKIs) has improved survival in many cancers, yet has been associated with an increased risk of adverse events. Warnings of cardiovascular events are common in drug labels of many TKIs. Despite these warnings, cardiovascular toxicity of patients treated with TKIs remains unclear. Here, we evaluate the cardiovascular outcomes of advanced cancer patients treated with small molecule tyrosine kinase inhibitors. A population based cohort study was undertaken involving adults aged >18 years in Ontario, Canada, diagnosed with any advanced malignancy between 2006 and 2012. Data were extracted from linked administrative governmental databases. Adults with advanced cancer receiving TKIs were identified and followed throughout the time period. The main outcomes of interest were rates of hospitalization for ischemic heart disease (acute myocardial infarction and angina) or cerebrovascular accidents and death. 1642 patients with a mean age of 62.5 years were studied; 1046 were treated with erlotinib, 166 with sorafenib and 430 with sunitinib. Over the 380 day median follow-up period (range 6-1970 days), 1.1% of all patients had ischemic heart events, 0.7% had cerebrovascular accidents and 72.1% died. Rates of cardiovascular events were similar to age and gender-matched individuals without cancer. In a subgroup analysis of treatment patients with a prior history of ischemic heart disease, 3.3% had ischemic heart events while 1.2% had cerebrovascular accidents. TKIs do not appear to increase the cause-specific hazard of ischemic heart disease and cerebrovascular accidents compared to age and gender-matched individuals without advanced cancer.

Purpose The aims of this study were to examine the relationship between negative attitudes towards expressing emotion following patient death and burnout in oncologists and to explore oncologists’ preferences for institutional interventions to deal with patient death. Methods The participants included a convenience sample of 177 oncologists from Israel and Canada. Oncologists completed a questionnaire package that included a sociodemographic survey, a burnout measure, a survey assessing negative attitudes towards expressing emotion, and a survey assessing desired interventions to cope with patient death. To examine the association between burnout and negative attitudes while controlling for the effect of sociodemographic variables, a hierarchical linear regression was computed. Results Higher burnout scores were related to higher negative attitudes towards perceived expressed emotion (partial r  = .25, p  < .01) of those who viewed this affect as a weakness and as a sign of unprofessionalism. Approximately half of the oncologists found each of the five categories of institutional interventions (pedagogical strategies, emotional support, group/peer support, taking time off, and research and training) helpful in coping with patient death. Conclusions Our findings suggest that high burnout scores are associated with negative attitudes towards expressing emotion and that there is a wide variation in oncologist preferences in coping with patient death. Institutions should promote interventions that are varied and that focus on the needs of oncologists in order to reduce burnout. Interventions that legitimize expression of emotion about patient death may be useful. Another way to reduce stigma would be to require oncologists to “opt out” rather than “opt in” to accessing a selection of social and/or individual interventions.

Patients with cancer have complex care requirements and frequently use the emergency department. The purpose of this study was to determine whether continuity of care, cancer expertise of an institution or both affect outcomes in patients with cancer in the emergency setting. We conducted a retrospective cohort study using administrative databases from Ontario, Canada, involving records of patients aged 20 years and older who received chemotherapy or radiation in the 30 days before a cancer-related visit to the emergency department between 2006 and 2011. Patients seen in an emergency department at an alternative hospital (not the site where cancer treatment was given) were matched based on propensity score to patients who visited their original hospital (site where cancer treatment was given). Next, patients seen at an alternative emergency department that was in a general hospital (i.e., not a cancer centre) were matched to patients who visited their original hospital or a cancer centre. Outcomes were admission to hospital at the index visit to the emergency department, 30-day mortality, having imaging with computed tomography and return visits to the emergency department. We found 42 820 patients who were eligible for our study. Patients seen in the emergency departments at alternative hospitals were less likely to be admitted to hospital (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.74–0.83) and had higher hazards of return visits to the emergency department than matched patients at original hospitals (hazard ratio [HR] 1.06, 95% CI 1.03–1.11). In comparison, patients at alternative general hospitals also had lower odds of admission to hospital (OR 0.83, 95% CI 0.79–0.88) and higher hazards of return visits to the emergency department (HR 1.07, 95% CI 1.03–1.11) compared with matched counterparts; however, these patients had higher 30-day mortality (OR 1.13, 95% CI 1.05–1.22) and lower odds of having CT imaging (OR 0.74, 95% CI 0.69–0.80). Cancer expertise of an institution rather than continuity of care may be an important predictor of outcomes following emergency treatment of patients with cancer.

Background There is a paucity of real-world data regarding lenvatinib for locally-recurrent, metastatic and RAI-refractory thyroid cancer. Here we examined the efficacy of first-line lenvatinib in a genomically-characterized cohort and identified clinicopathological/molecular correlates of drug response. Methods Patients with advanced follicular cell-derived thyroid cancer who underwent NGS at Princess Margaret Cancer Centre and commenced first-line lenvatinib monotherapy between 2015-2023 were included. Kaplan-Meier method, log-rank tests and univariable/multivariable proportional hazard models were employed. Results In total, 77 patients were included (48% female, majority papillary (52%), poorly differentiated (17%) or invasive encapsulated follicular variant papillary (16%)). Most (79%) underwent total thyroidectomy and adjuvant RAI (median cumulative dose 231 mCi). At lenvatinib initiation, median age was 62.9 years, 68% were ECOG performance status ≥2, 81% had lung metastases, 53% had bone metastases and 8% had liver metastases. Most patients started with ≤ 14 mg of lenvatinib daily. Median time to treatment discontinuation was 33 months. Older age, ECOG ≥ 2, liver metastases and TP53 mutation(s) were associated with shorter time to treatment discontinuation; ECOG ≥ 2 and TP53 mutation(s) remained significant on multivariable analysis. Conclusion Our findings reinforce the clinical efficacy of lenvatinib in advanced thyroid cancer patients with heterogenous clinicopathologic/molecular features and highlight variables for future treatment stratification.