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Purpose: A cross-sectional study was conducted to investigate the feasibility of implementing routine collection of the Euro-Qol 5 dimensions (EQ-5D) questionnaire, to inform drug and health technology reimbursement decision making., Methods: Women with breast cancer were recruited during scheduled clinic visits to an academic cancer centre. EQ-5D-5L was self-administered using electronic tablets. Diagnostic and treatment data were abstracted from patient charts. Feasibility was assessed primarily by the proportion of patients who fully completed EQ-5D-5L and by their willingness to complete the instrument at each clinic visit., Results: 588 women were approached for study participation, 341 were enrolled. Fully completed EQ-5D-5L questionnaires were obtained in 323 participants (95% of participants, 95% CI 92-97%). Median time for EQ-5D-5L completion was 1.5 minutes (range:0.35 to 14.7). Mean age of participants was 58 years old. Most women who completed EQ-5D were White, born outside Canada and presented a high education level; one-quarter had metastatic disease. Most participants reported "No problems" in all EQ-5D-5L dimensions. Mean EQ-5D-5L index and mean EQ-5D-5L VAS values for all participants were respectively 0.83 (SD 0.13) and 75.7 (SD 17.45), with patients with metastatic disease scoring the lowest values. Seventy-eight percent of participants were willing to complete EQ-5D-5L at each clinic visit; lower Charlson comorbidity index and higher education level were predictors of willingness to continue to answer EQ-5D-5L., Conclusions: Tablet-based collection of EQ-5D-5L in the context of routine clinical practice proved to be feasible. However, many patients declined study participation or reported being in full health, raising concerns about whether this method of collecting EQ-5D adequately represents the health status of all breast cancer patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Torres et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Many research studies have investigated the relationship between baseline factors or exposures, such as patient demographic and disease characteristics, and study outcomes such as toxicities or quality of life, but results from most of these studies may be problematic because of potential confounding effects (eg, the imbalance in baseline factors or exposures). It is important to study whether the baseline factors or exposures have causal effects on the clinical outcomes, so that clinicians can have better understanding of the diseases and develop personalized medicine. Mendelian randomization (MR) provides an efficient way to estimate the causal effects using genetic instrumental variables to handle confounders, but most of the existing studies focus on a single outcome at a time and ignores the correlation structure of multiple outcomes. Given that clinical outcomes like toxicities and quality of life are usually a mixture of different types of variables, and multiple datasets may be available for such outcomes, it may be much more beneficial to analyze them jointly instead of separately. Some well-established methods are available for building multivariate models on mixed outcomes, but they do not incorporate MR mechanism to deal with the confounders. To overcome these challenges, we propose a Bayesian-based two-stage multivariate MR method for mixed outcomes on multiple datasets, called BMRMO. Using simulation studies and clinical applications on the CO.17 and CO.20 studies, we demonstrate better performance of our approach compared to the commonly used univariate two-stage method., (© 2023 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Introduction: Analyzing longitudinal cancer quality-of-life (QoL) measurements and their impact on clinical outcomes may improve our understanding of patient trajectories during systemic therapy. We applied an unsupervised growth mixture modeling (GMM) approach to identify unobserved subpopulations ("patient clusters") in the CO.20 clinical trial longitudinal QoL data. Classes were then evaluated for differences in clinico-epidemiologic characteristics and overall survival (OS)., Methods and Materials: In CO.20, 750 chemotherapy-refractory metastatic colorectal cancer (CRC) patients were randomized to receive Brivanib+Cetuximab (n = 376, experimental arm) versus Cetuximab+Placebo (n = 374, standard arm) for 16 weeks. EORTC-QLQ-C30 QoL summary scores were calculated for each patient at seven time points, and GMM was applied to identify patient clusters (termed "classes"). Log-rank/Kaplan-Meier and multivariable Cox regression analyses were conducted to analyze the survival performance between classes. Cox analyses were used to explore the relationship between baseline QoL, individual slope, and the quadratic terms from the GMM output with OS., Results: In univariable analysis, the linear mixed effect model (LMM) identified sex and ECOG Performance Status as strongly associated with the longitudinal QoL score (p < 0.01). The patients within each treatment arm were clustered into three distinct QoL-based classes by GMM, respectively. The three classes identified in the experimental (log-rank p-value = 0.00058) and in the control arms (p < 0.0001) each showed significantly different survival performance. The GMM's baseline, slope, and quadratic terms were each significantly associated with OS (p < 0.001)., Conclusion: GMM can be used to analyze longitudinal QoL data in cancer studies, by identifying unobserved subpopulations (patient clusters). As demonstrated by CO.20 data, these classes can have important implications, including clinical prognostication., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Recent advances in small cell lung cancer (SCLC) treatments necessitate a better understanding of real-world health utility scores (HUS) in patients treated under current standards to facilitate robust pharmaco-economic assessments., Methods: In this single institution cohort observational study, HUS were evaluated in patients with SCLC through EQ-5D questionnaires at outpatient visits (encounters). In addition, patients completed questionnaires relating to treatment toxicities and cancer symptoms. Clinical and pathological variables were abstracted from electronic medical records and disease status at each patient visit was documented. The impact of these variables on HUS were explored., Results: There were 282 clinical encounters (12% newly diagnosed; 37% stable on treatment; 22% progressing on treatment; 29% stable off therapy/other) in 111 SCLC patients (58% male; 64% extensive stage (ES) SCLC). At the first encounter 29% of patients had an ECOG performance status (PS) ≥ 2. ES-SCLC, bone metastases, female sex, progressive disease and/or PS were each significantly associated with decreased HUS in multivariable analyses. Patients clinically stable on first line therapy had generally steady HUS longitudinally, with differences in HUS between limited disease (LD) and ES patients emerging as treatment progressed. Decreased HUS were associated with increased severity of the majority of measured symptoms (fatigue/tiredness, loss of appetite, pain, drowsiness, shortness of breath, anxiety, depression, and overall well-being; each p<0.001), supporting the value of EQ-5D-derived HUS in assessing health utility., Conclusion: Our HUS values in chemotherapy-treated SCLC are clinically relevant and are associated with specific clinico-demographic, symptom and toxicity factors., (Copyright © 2021. Published by Elsevier Inc.)

Background: Routine early palliative care (EPC) improves quality of life (QoL) for patients with advanced cancer, but it may not be necessary for all patients. We assessed the feasibility of Symptom screening with Targeted Early Palliative care (STEP) in a phase II trial., Methods: Patients with advanced cancer were recruited from medical oncology clinics. Symptoms were screened at each visit using the Edmonton Symptom Assessment System-revised (ESAS-r); moderate to severe scores (screen-positive) triggered an email to a palliative care nurse, who called the patient and offered EPC. Patient-reported outcomes of QoL, depression, symptom control, and satisfaction with care were measured at baseline and at 2, 4, and 6 months. The primary aim was to determine feasibility, according to predefined criteria. Secondary aims were to assess whether STEP identified patients with worse patient-reported outcomes and whether screen-positive patients who accepted and received EPC had better outcomes over time than those who did not receive EPC., Results: In total, 116 patients were enrolled, of which 89 (77%) completed screening for ≥70% of visits. Of the 70 screen-positive patients, 39 (56%) received EPC during the 6-month study and 4 (6%) received EPC after the study end. Measure completion was 76% at 2 months, 68% at 4 months, and 63% at 6 months. Among screen-negative patients, QoL, depression, and symptom control were substantially better than for screen-positive patients at baseline (all P<.0001) and remained stable over time. Among screen-positive patients, mood and symptom control improved over time for those who accepted and received EPC and worsened for those who did not receive EPC (P<.01 for trend over time), with no difference in QoL or satisfaction with care., Conclusions: STEP is feasible in ambulatory patients with advanced cancer and distinguishes between patients who remain stable without EPC and those who benefit from targeted EPC. Acceptance of the triggered EPC visit should be encouraged., Clinicaltrials: gov identifier: NCT04044040.

Purpose: Small cell lung cancer (SCLC) is a highly fatal disease associated with significant morbidity, with a need for real-world symptom and health utility score (HUS) data. HUS can be measured using an EQ-5D-5L questionnaire, however most captured data is available in non-SCLC (NSCLC) only. As new treatment regimens become available in SCLC it becomes important to understand factors which influence health-related quality of life and health utility., Methods: A prospective observational cohort study (2012-2017) of ambulatory histologically confirmed SCLC evaluated patient-reported EQ-5D-5L-derived HUS, toxicity and symptoms. A set of NSCLC patients was used to compare differential factors affecting HUS. Clinical and demographic factors were evaluated for differential interactions between lung cancer types. Comorbidity scores were documented for each patient., Results: In 75 SCLC and 150 NSCLC patients, those with SCLC had lower mean HUS ((SCLC vs NSCLC: mean 0.69 vs 0.79); (p < 0.001)) when clinically stable and with progressive disease: ((SCLC mean HUS = 0.60 vs NSCLC mean HUS = 0.77), (p = 0.04)). SCLC patients also had higher comorbidity scores ((1.11 vs 0.73); (p < 0.015)). In multivariable analyses, increased symptom severity and comorbidity scores decreased HUS in both SCLC and NSCLC (p < 0.001); however, only comorbidity scores differentially affected HUS (p < 0.0001), with a greater reduction of HUS adjusted per unit of comorbidity in SCLC., Conclusion: Patients with advanced SCLC had significantly lower HUS than NSCLC. Both patient cohorts are impacted by symptoms and comorbidity, however, comorbidity had a greater negative effect in SCLC patients.

Importance: Treatment options for platinum-refractory metastatic urothelial cancer (mUC) are limited, and outcomes remain poor. Nab-paclitaxel is an albumin-bound formulation of paclitaxel showing promising activity and tolerability in a prior single-arm trial., Objectives: To evaluate the efficacy and safety of nab-paclitaxel vs paclitaxel in platinum-refractory mUC., Design, Setting, and Participants: In this investigator-initiated, open-label, phase 2 randomized clinical trial conducted across Canada and Australia from January 2014 to April 2017, eligible patients had histologically confirmed, radiologically evident mUC of the urinary tract. Mixed histologic findings, except small cell, were permitted provided UC was the predominant histologic finding. All patients had received platinum-based chemotherapy either in the metastatic setting or were within 12 months of perioperative chemotherapy. Patients with prior taxane chemotherapy were not included. Patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 to 2 and adequate organ function., Interventions: Patients were randomized to nab-paclitaxel, 260 mg/m2, or paclitaxel, 175 mg/m2, every 3 weeks., Main Outcomes and Measures: The primary end point was progression-free survival (PFS)., Results: Among 199 patients, median age was 67 (range, 24-88) years; 144 (72%) were men; 167 (84%) were ECOG PS 0-1; 59 (30%) had liver metastases; and 110 (55%) were within 6 months of prior platinum-based chemotherapy. At a median follow-up of 16.4 months, there was no significant difference between nab-paclitaxel vs paclitaxel for median PFS (3.4 months vs 3.0 months; hazard ratio [HR], 0.92; 90% CI, 0.68-1.23; 1-sided P = .31). Median overall survival was 7.5 months for nab-paclitaxel vs 8.8 months for paclitaxel (HR, 0.95; 90% CI, 0.70-1.30; 1-sided P = .40); and objective response rate (ORR) was 22% for nab-paclitaxel vs 25% for paclitaxel (P = .97). Grade 3/4 adverse events were more frequent with nab-paclitaxel (64/97 [66%]) compared with paclitaxel (45/97 [46%]), P = .009; but peripheral sensory neuropathy was similar (all grades, 72/97 [74%] vs 64/97 [66%]; grade 3/4, 7/97 [7%] vs 3/97 [3%]; P = .27). There were no apparent differences in scores for health-related quality of life., Conclusions and Relevance: In this open-label, phase 2 randomized clinical trial of patients with platinum-refractory mUC, nab-paclitaxel had similar efficacy to paclitaxel; but worse toxic effects. The ORR with either taxane, however, was higher than previously reported and similar to those reported for the immune checkpoint inhibitors, suggesting that the taxanes remain a reasonable option in this setting., Trial Registration: ClinicalTrials.gov Identifier: NCT02033993.

Background: Breathlessness in lung cancer negatively impacts on quality of life but often goes undetected and undertreated in clinical practice. There is a need for routine surveillance for early identification and proactive management of breathlessness using patient reported outcome measures (PROMs) in clinical care but it is unclear what PROMs should be used or are accurate for use in routine care., Methods: We used mixed-methods (quantitative surveys and qualitative interviews) to examine the predictors of breathlessness in 339 lung cancer participants and acceptability of PROMs. In addition to multivariate analysis to examine predictors of dyspnea, participants completed an acceptability survey and themes were derived for the qualitative data (n = 26) to explore patient experience of PROMs. We also tested the accuracy of PROMs using a Receiver Operating Characteristic and Area Under the Curve analysis., Results: A total of 339 patients completed the breathlessness PROMs and acceptability survey and 26 patients participated in an in-depth interview to investigate their experiences of breathlessness and its PROMs. Prevalence of breathlessness was 51.9 % (n = 176) and 70.5 % of patients preferred the Medical Research Council (MRC) scale followed by the Breathlessness Intensity (BI) scale (63.7 %) among the five measures for breathlessness- Modified Borg Scale (MBS), Cancer Dyspnea Scale (CDS), MRC, BI, and Breathlessness Distress (BD). The finding showed wide variation in the MRC grades across the BI rating even among patients with the same BI score. AUC scores for the Borg scale was 0.71 (using MRC cut-off score of < 2), for CDS, 0.72, for BD, 0.70, and for BI 0.79. For an MRC score of 2, the Borg score cut-off was 0.8 (optimal sensitivity, 50 %; specificity, 93.3 %); the cut-off score of CDS, BD, BI score was 1.4 (optimal sensitivity, 67.1 %; specificity, 70 %), 1.5 (optimal sensitivity, 57.5 %; specificity, 73.3 %), and 1.5 (optimal sensitivity, 72.6 %; specificity, 83.3 %) respectively. AUC by ROC analysis for breathlessness and modest concordance among five PROMs showed important gaps between the individuals' experience and PROMs data. Three main themes from qualitative data included 1) Making sense of symptom reporting, 2) Valuing the reported data, 3) Managing the symptom of breathlessness., Conclusion: This study examined measurement of breathlessness using PROMs for routine clinical care and showed that severity measures alone do not accurately detect this symptomnor the experiential dimensions of breathlessness that are critical to guide appropriate intervention., (Copyright © 2020. Published by Elsevier B.V.)

Background: Smoking cessation is an integral part of cancer survivorship. To help improve survivorship education, clinicians need an understanding of patient awareness of the harms of continued smoking., Methods: Cancer survivors from Princess Margaret Cancer Centre (Toronto, ON) were surveyed on their awareness of the harms of continued smoking on cancer-related outcomes. Multivariable logistic regression models assessed factors associated with awareness and whether awareness was associated with subsequent cessation among smokers at diagnosis., Results: Among 1118 patients, 23% were current smokers pre-diagnosis and 54% subsequently quit; 25% had lung and 30% head and neck cancers. Many patients reported being unaware that continued smoking results in greater cancer surgical complications (53%), increased radiation side effects (62%), decreased quality of life during chemotherapy (51%), decreased chemotherapy or radiation efficacy (57%), increased risk of death (40%), and increased development of second primaries (38%). Being a current smoker was associated with greater lack of awareness of some of these smoking harms (aORs = 1.53-2.20, P < 0.001-0.02), as was exposure to any second-hand smoke (aORs = 1.45-1.53, P = 0.006-0.04) and being diagnosed with early stage cancer (aORs = 1.38-2.31, P < 0.001-0.06). Among current smokers, those with fewer pack-years, being treated for cure, or had a non-tobacco-related cancer were more likely unaware. Awareness that continued tobacco use worsen quality of life after chemotherapy was associated with subsequent cessation (aOR = 2.26, P = 0.006)., Conclusions: Many cancer survivors are unaware that continued smoking can negatively impact cancer-related outcomes. The impact of educating patients about the potential harms of continued smoking when discussing treatment plans should be further evaluated.

Background: In lung cancer, brain metastases (BM) and their treatment are associated with high economic burden and inferior health-related quality of life. In the era of targeted therapy, real world evidence through health utility scores (HUS) is critical for economic analyses., Materials and Methods: In a prospective observational cohort study (2014-2016), outpatients with stage IV lung cancer completed demographic and EQ-5D-3L surveys (to derive HUS). Health states and clinicopathologic variables were obtained from chart abstraction. Patients were categorized by the presence or absence of BM; regression analyses identified factors that were associated with HUS. A subset of patients prospectively completed neurocognitive function (NCF) tests and/or the FACT-brain (FACT-Br) questionnaire, which were then correlated with HUS (Spearman coefficients; regression analyses)., Results: Of 519 patients with 1,686 EQ-5D-3L-derived HUS, 94 (18%) completed NCF tests and 107 (21%) completed FACT-Br; 301 (58%) never developed BM, 24 (5%) developed first BM during study period, and 194 (37%) had BM at study entry. The sample was enriched (46%) for EGFR mutations ( EGFR m) and ALK -rearrangements ( ALK r). There were no HUS differences by BM status overall and in subsets by demographics. In multivariable analyses, superior HUS was associated with having EGFR m/ ALK r ( p < .0001), no prior radiation for extracranial disease ( p < .001), and both intracranial ( p = .002) and extracranial disease control ( p < .01). HUS correlated with multiple elements of the FACT-Br and tests of NCF., Conclusion: Having BM in lung cancer is not associated with inferior HUS in a population enriched for EGFR m and ALK r. Patients exhibiting disease control and those with oncogene-addicted tumors have superior HUS., Implications for Practice: In the setting of EGFR mutations or ALK rearrangement non-small cell lung cancer (NSCLC), a diagnosis of brain metastases no longer consigns the patient to an inferior health state suggesting that new economic analyses in NSCLC are needed in the era of targeted therapies. Additionally, the EQ-5D questionnaire is associated with measures of health-related quality of life and neurocognitive scores suggesting this tool should be further explored in prospective clinical studies., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Background: The safety and efficacy of targeted therapy in older patients (≥ 70 years) with metastatic colorectal cancer is not well evaluated., Patients and Methods: Outcomes of older patients (including overall survival [OS], progression-free survival [PFS], toxicity, and quality of life [QoL]) were compared to young patients using data from 2 large previously reported clinical trials, CO.17 (cetuximab vs. best supportive care) and CO.20 (cetuximab plus placebo vs. cetuximab plus brivanib). Only patients with wild-type KRAS tumors were included., Results: A total of 251 (26.3%) of 955 patients were ≥ 70 years old. No significant differences in OS, PFS, or grade 3/4 adverse events were observed between older and younger patients treated with cetuximab (or cetuximab with placebo) in either trial. Younger patients trended toward superior OS in both CO.17 (hazard ratio = 1.80; P = .16) and CO.20 (hazard ratio = 1.34; P = .07). QoL maintenance favored younger patients in CO.17 (3.6 vs. 5.7 months; P = .046) but no difference of QoL maintenance was observed in the larger CO.20 trial (1.7 vs. 1.8 months; P = .64). Combination therapy of cetuximab and brivanib was significantly more toxic in older adults (87% vs. 77%; P = .03)., Conclusion: OS, PFS, and toxicities were similar between older and younger patients with wild-type KRAS metastatic colorectal cancer when treated with cetuximab. Both age groups likely experience similar QoL maintenance with cetuximab. Dual targeted therapy was significantly more toxic in older patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: A patient's physical function is a critical outcome variable for measuring and improving chronic care management. However, patient-reported outcome measures of physical function are not routinely assessed in cancer outpatients, in part due to limitations of tools available. This study presents the development and evaluation of the Cancer Ambulatory Patient Physical Function Longitudinal Evaluation Tool (CAPLET) as an adaptive response tool for routinely screening for physical dysfunction in oncology clinical practice., Methods: In phase 1, 407 adult outpatients at Princess Margaret Cancer Centre completed the World Health Organization Disability Assessment Schedule (WHODAS) 2.0, Health Assessment Questionnaire Disability Index (HAQ-DI), EuroQuol-5D-3L ( EQ-5D-3L), and patient-reported outcome (PRO)-Eastern Cooperative Oncology Group (ECOG). CAPLET was developed based on a branching logic algorithm navigating patients to appropriate domains of HAQ-DI/WHOAS using their responses to the PRO-ECOG/EQ-5D-3L as screeners. Sensitivity/specificity of CAPLET screeners for HAQ-DI/WHODAS items were reported. In phase 2, CAPLET vs the WHODAS/HAQ-DI were alternatively administrated to 318 adult outpatients in a two-arm trial comparing time to completion and acceptability between the tools., Results: Using a patient's ECOG status and the sum of the mobility, self-care, and usual activity dimensions of the EQ-5D-3L to dichotomize patients as with or without difficulty, CAPLET achieved a sensitivity > 90% against recommended WHODAS and HAQ-DI cutoffs for significant dysfunction. Sensitivity of screeners for capturing dysfunction in individual WHODAS/HAQ-DI items ranged from 85 to 100%. Compared to the HAQ-DI/WHODAS, CAPLET was associated with a 50% reduction in administration times and improved patient acceptability, while reducing question burden by 84% for half the sample population., Conclusions: CAPLET improves the feasibility of capturing detailed assessments of patient-reported physical function in cancer outpatients.

Objectives: The management of patients with locally advanced thymic malignancies remains controversial. Differing combinations of surgical resection, chemotherapy and radiation are used in the management of initial and relapsed disease. Treatment-related toxicities and quality of life could inform therapeutic options. This study describes health utility scores (HUS) in survivors with locally advanced thymic malignancies and investigates the impact of multimodality regimens on HUS., Methods: In a cross-sectional study (2014-2017), patients with Masaoka Stage II-IVa thymic malignancies completed various self-reported questionnaires, including EuroQol-5-Dimensions with visual analogue scale (VAS), Eastern Cooperative Oncology Group (ECOG) and Edmonton Symptom Assessment Scale tools. Trimodality versus uni- or bimodality regimens and aggressive versus non-aggressive management of recurrent disease were compared using regression analyses., Results: Of the 72 patients, 43 (60%) were male with a median age of 58 years, 65 (90%) had thymoma while 7 (10%) had thymic carcinomas; and median time since diagnosis was 50.5 months (range: 3-266). Median HUS and VAS did not differ between groups (trimodality n = 24 vs uni- or bimodality n = 48: HUS = 0.77 vs 0.80, P = 0.29; VAS = 80 vs 75, P = 0.79, respectively). The distributions of patient-reported ECOG were also similar (P = 0.86). Edmonton Symptom Assessment Scale scores for every assessed symptom were similar for different modalities of therapy. Median scores on these tools were also similar regardless of recurrence status or management of relapsed disease (aggressive versus non-aggressive)., Conclusion: Survivors with Stage II-IVa thymic malignancies report favourable HUS, VAS and self-reported ECOG with minimal symptom burden. These outcomes may be independent of number and type of initial treatment modalities or management of recurrence.

Objectives: The impact of lung cancer screening with low-dose chest CT (LDCT) on participants' anxiety levels and health-related quality of life (HRQoL) is an important consideration in the implementation of such programmes. We aimed to describe changes in anxiety and HRQoL in a high-risk Canadian cohort undergoing LDCT lung cancer screening., Methods: 2537 subjects who had 2% or greater lung cancer risk over 6 years using a risk prediction tool were recruited from eight centres across Canada in the Pan-Canadian Early Detection of Lung Cancer Study (2008-2010). We compared HRQoL and anxiety levels before and after screening of 1237 participants with LDCT (excluding a subset of 1300 participants who also underwent autofluorescence bronchoscopy screening), as well as after investigations performed because of a positive screening examination. The 12-item short-form Physical and Mental Component Scales (SF-12), EQ-5D-3L scores and State Trait Anxiety Inventory-State anxiety were used at each assessment., Results: Overall, there were no clinically significant differences in HRQoL outcomes between baseline and each of the survey time points following initial screening. No mean change in anxiety in the overall cohort was noted following baseline LDCT, but more participants had clinically significant increase in anxiety versus decrease after baseline screening (increase >minimal clinically important difference (MCID) (n=180) vs decrease >MCID (n=50), p<0.001). This finding persisted but to a lesser degree at the 12 month time point (increase >MCID (n=146) vs decrease >MCID (n=87), p<0.001)., Conclusions: CT screening for lung cancer has no major overall impact on HRQoL among participants, although a minority of participants (number-needed-to-harm=7 after baseline screening and 18 at 1 year) demonstrated clinically significant increased anxiety levels., Trialregistration Number: NCT00751660; Results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Continued consumption of alcohol after a cancer diagnosis is associated with poorer outcomes. We evaluated whether perceptions of the effects of continued alcohol use and receiving information on moderating alcohol reduced alcohol consumption in adult cancer survivors. A total of 509 cancer survivors were cross-sectionally surveyed at follow-up for their alcohol use before and after cancer diagnosis and perceptions of continued drinking. Multivariable logistic regression models evaluated factors associated with changes in alcohol consumption after diagnosis. Among 299 patients who were drinking alcohol at diagnosis (13% exceeding gender-specific guidelines), 52% reduced/ceased alcohol consumption 1 year after diagnosis. Patients perceiving that alcohol worsened their own (a) quality of life, (b) cancer-related fatigue or (c) overall survival were more likely (aORs = 2.43-3.35, p < 0.002) to reduce (moderating or quitting) their alcohol use 1 year after diagnosis. Only 14% of individuals currently drinking regularly recalled receiving information/counselling from healthcare providers on alcohol consumption (7% from oncologists). However, there was a significant fourfold to sixfold increase in cessation with such information/counselling (p < 0.01). Similar trends were observed in patients exceeding gender-specific guidelines. Perception of negative effects of alcohol use on their health by cancer survivors was associated with reducing harmful alcohol consumption. Counselling, especially from the oncologist, may play a significant role for reducing consumption., (© 2018 John Wiley & Sons Ltd.)

Background: The INTEGRATE phase II multinational randomized controlled trial demonstrated the activity of regorafenib on progression-free survival (PFS) in patients with refractory advanced gastric adenocarcinoma. We sought to evaluate whether these PFS gains had the potential to be offset by quality of life (QoL) impacts from treatment side effects and to thereby determine the appropriateness of continuing development to phase III., Methods: QoL was assessed in INTEGRATE at baseline and at each 4 weeks thereafter, until discontinuation of study treatment, using the QLQ-C30, STO22, and EQ-5D questionnaires. The patient disease and treatment assessment (PTDATA) form was also provided to English-speaking participants. Randomized groups were compared on the QLQ-C30, STO22, and EQ-5D scales using a repeated-measures model; the frequency of troublesome symptoms and side effects measured by the PTDATA form; and deterioration-free survival (DFS). The prognostic value of baseline QoL information was also evaluated., Results: Of the 147 eligible randomized patients, 142 consented to participate in the QoL substudy, 136 completed a baseline QoL assessment, and 95 completed at least one post-baseline QoL assessment. The DFS rate was significantly improved with regorafenib, and there was no compelling statistical evidence that regorafenib had a broad negative effect across the spectrum of QoL indices evaluated. Fatigue, anxiety, appetite loss, and pain were among the issues most commonly reported for both randomized groups. Baseline levels of pain, appetite, constipation, and physical functioning were prognostic factors for survival., Conclusions: Regorafenib improved DFS without an excessively negative effect on QoL. Progressing development to the phase III setting is warranted.

Background: To improve the precision of health economics analyses in oncology, reference datasets of health utility (HU) scores are needed from cancer survivors across different disease sites. These data are particularly sparse amongst Canadian survivors., Methods: A survey was completed by 1759 ambulatory cancer survivors at the Princess Margaret Cancer Centre which contained demographic questions and the EuroQol-5D (EQ-5D) instrument. Clinical information was abstracted from electronic records and HU scores were calculated using Canadian health state valuations. Construct validity was assessed through correlation of HU and visual analog scale (VAS) scores (Spearman) and by comparing HU scores between performance status groups (effect size). The influence of socio-demographic clinical variables on HU was analyzed by non-parametric between-group comparisons and multiple linear regression., Results: Mean EQ-5D HU scores were derived for 26 cancers. Among all survivors, the mean ± standard error of the mean EQ-5D utility score was 0.81 ± 0.004. Scores varied significantly by performance status (p < 0.0001) and correlated with VAS (Spearman r = 0.61). The cancer sites with the lowest mean HU scores were acute lymphoblastic leukemia (0.70 ± 0.03) and pancreatic cancer (0.76 ± 0.03); testicular cancer (0.89 ± 0.02) and chronic lymphocytic leukemia (0.90 ± 0.05) had the highest mean scores. A multiple regression model showed that scores were influenced by disease site (p < 0.001), education level (p < 0.001), partner status (p < 0.001), disease extent (p = 0.0029), and type of most recent treatment (p = 0.0061)., Conclusions: This work represents the first set of HU scores for numerous cancer sites derived using Canadian preference weights. The dataset demonstrated construct validity and HU scores varied by general socio-demographic and clinical parameters.

Background: Health utility (HU) scores play an essential role in pharmacoeconomic analyses. Routine clinical administration of the EuroQol-5 Dimensions (EQ-5D) can allow for HU and health related quality of life (HRQOL) assessments in the real-world setting., Objectives: The primary goals of this study were to evaluate whether patients were willing to complete the EQ-5D instrument on a routine basis and which clinical or demographic factors influence this willingness., Methods: 618 adult cancer survivors across multiple cancer disease sites at the Princess Margaret Cancer Centre completed an acceptability survey after completing the EQ-5D instrument., Results: The mean (SD) EQ-5D score was 0.81 (0.15). Among those surveyed, 88% reported that the EQ-5D was easy to complete. 91% took under 5 minutes and 88% were satisfied with its length. 85% were satisfied with the types of questions asked on the EQ-5D. Importantly, 92% reported that they would complete the EQ-5D, even if it were used solely for research purposes; 73% agreed with the notion of completing it regularly at their clinic visits. Patients with lower EQ-5D scores (p=0.0006), and non-Caucasians (p=0.0024; 60% willing) were less willing to complete the instrument on a regular basis. Curability of tumour, disease site, age, and gender did not influence willingness., Conclusions: The majority of cancer patients across disease sites are willing to complete the EQ-5D instrument regularly, even if it were solely for research purposes, but up to 39% declined participation in the first place.

407 Background: Patients undergoing cancer treatment often need to visit the emergency department (ED), straining the healthcare system. We aim to use long-term electronic health record (EHR) data to deploy and evaluate a previously built warning system designed to accurately identify those at risk of ED visits. This system, once validated, will enable clinicians to take early, personalized actions to prevent these ED visits, saving resources and enhancing the quality of life for cancer patients. Methods: Machine learning models were trained usinglongitudinal retrospective EHR data from patients receiving intravenous systemic therapies for gastrointestinal cancers at the Princess Margaret Cancer Centre, aiming to predict ED visits within 30 days of each treatment. Treatments followed by ED visits within one day were excluded to ensure the system focuses on detecting early warning signs rather than imminent ED visits. The models, including tree-based methods and neural networks, were tuned with Bayesian hyperparameter optimization and calibrated using isotonic regression. A temporal split was applied to establish a held-out retrospective test cohort. The best model was silently deployed for prospective validation in patients with gastrointestinal cancer through our internally developed 'MIRA' platform that supports clinical integration. Within MIRA, the patients' EHR data with treatments scheduled the next day are extracted from the EHR system and forwarded to the model for analysis. Results: In the retrospective cohort from January 1, 2014, to December 31, 2019, 1,997 patients underwent 24,350 treatments, with 2,219 (9.11%) leading to ED visits within 30 days. The top-performing model, an extreme gradient boosting tree, achieved an area under the receiver operating characteristic curve (AUROC) of 0.68 and an area under the precision-recall curve (AUPRC) of 0.19 in the held-out test set. Although the evaluation of the system through prospective silent deployment is ongoing, here we report on patients with treatments during March 2024, with adequate 30-day follow up by April 30th, 2024. During this period, 357 patients received 676 treatments, with ED visits within 30-days following 60 (8.88%) treatments. The deployed system achieved an AUROC of 0.66 (confidence interval: 0.60-0.72) and an AUPRC of 0.22 (confidence interval: 0.15-0.32), which closely aligns with those observed during its retrospective testing. At a 10% alarm rate, model has a positive predictive value of 0.33 and sensitivity of 0.22. Conclusions: During a silent prospective deployment, our system predicted ED visits in cancer patients undergoing medical treatment. These findings indicate that the system should be integrated into the clinical workflow and combined with interventions to prevent ED visits. [ABSTRACT FROM AUTHOR]

Background: This study examined long‐term health utility and symptom‐toxicity trajectories among patients with head and neck cancer (HNC). Methods: For patients diagnosed with HNC (2014‐2019), Health Utility Index 3 (HUI‐3), Edmonton Symptom Assessment Scale (ESAS), and MD Anderson Symptom Inventory (MDASI) surveys (including both the core and head and neck cancer modules) were prospectively collected at multiple time points (at the baseline, after surgery, during radiotherapy, and 3, 6, 12, and 24 months after treatment). Locally estimated scatterplot smoothing plots were generated to describe HUI‐3, ESAS, and MDASI trajectories over time by clinicodemographic factors, treatment modality, and tumor subsite. Contributions of clinical factors were assessed with univariable and multivariable analyses. Results: In 800 patients, the treatment modality and the tumor subsite produced unique HUI‐3, ESAS, and MDASI trajectories. Patients treated with surgery alone experienced rapid improvements in HUI‐3, ESAS, and MDASI scores postoperatively. Among patients treated with chemoradiotherapy, patients with nasopharyngeal carcinoma had greater declines in HUI‐3 during treatment in comparison with patients with oropharyngeal carcinoma, but they had similar ESAS/MDASI scores. Among patients treated with radiotherapy, patients with laryngeal carcinoma had better HUI‐3/ESAS/MDASI scores than those with oropharyngeal carcinoma during treatment, but they slowly converged after treatment. Female sex, an age > 75 years, a household income < $40,000, a Charlson comorbidity score > 1, an Eastern Cooperative Oncology Group performance status > 0 (at the baseline), and current smoking were independently associated with worse HUI‐3 trajectories. HUI‐3 had mild to moderate correlations (ρ = 0.2‐0.5) with individual symptom‐toxicity trajectories. Conclusions: Long‐term HUI‐3 trajectories are associated with tumor subsite, clinicodemographic, and treatment factors, and this may be partly explained by relationships with symptoms/toxicities. Separate evaluations by subsite and treatment should occur in health utility and symptom‐toxicity studies of HNC. Lay Summary: This study indicates that the long‐term health utility and symptoms/toxicities of patients with the most common head and neck cancers (ie, squamous cell carcinomas and nasopharyngeal carcinomas) differ over time with a variety of factors, including the tumor anatomic site, treatment volume, clinicodemographic characteristics (eg, age, human papillomavirus status, tumor stage, gender, smoking status, alcohol status, education, and comorbidities), and treatment modalities.Generalizations across all head and neck cancers should be strongly discouraged.Future studies should evaluate health utility, symptoms and toxicities, and patient need assessments separately for each anatomic site and treatment modality. Long‐term Health Utility Index 3 trajectories are associated with tumor subsite, clinicodemographic, and treatment factors, which are themselves partly explained by relationships with symptoms/toxicities. Separate evaluations by subsite and treatment should occur in health utility and symptom‐toxicity studies of head and neck cancer. [ABSTRACT FROM AUTHOR]

Background Knowledge regarding cognitive problems in metastatic non-small cell lung cancer (mNSCLC) is limited. Such problems may include both patient-reported cognitive concerns and demonstrable cognitive impairment. Greater understanding of these outcomes is needed to inform rehabilitation strategies for these difficulties. We aimed to identify the frequency of cognitive problems and associated factors in patients with mNSCLC. Methods In this cross-sectional study, adults with mNSCLC completed validated neuropsychological tests and self-report questionnaires measuring cognitive concerns, neurobehavioral concerns, depression, demoralization, illness intrusiveness, self-esteem, and physical symptoms. Cognitive impairment (performance based) was defined according to International Cancer and Cognition Task Force criteria. Clinically significant cognitive concerns were defined by a score ≥1.5 SD below the normative mean on the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI). Univariate and multivariate logistic regression analyses were performed to identify associated factors. Results Of 238 patients approached, 77 participated (median age: 62 years; range: 37-82). Brain metastases were present in 41 patients (53%), and 23 (29%) received cranial irradiation. Cognitive impairment and cognitive concerns were present in 31 (40%) and 20 patients (26%), respectively. Cognitive impairment and cognitive concerns co-occurred in 10 patients (13%), but their severity was unrelated. Cognitive impairment was associated with cranial irradiation (odds ratio [OR] = 2.89; P =.04), whereas cognitive concerns were associated with greater illness intrusiveness (OR = 1.04; P =.03) and lower self-esteem (OR = 0.86; P =.03). Conclusions Cognitive impairment and cognitive concerns are both common in patients with mNSCLC but are not necessarily related, and their risk factors differ. The association of illness intrusiveness and self-esteem with cognitive concerns can inform therapeutic interventions in this population. [ABSTRACT FROM AUTHOR]

Background: Small cell lung cancer (SCLC) represents approximately 15% of lung cancers, and approximately 70% are diagnosed as extensive‐stage SCLC (ES‐SCLC). Although ES‐SCLC is highly responsive to chemotherapy, patients typically progress rapidly, and there is an urgent need for new therapies. Immune checkpoint inhibitors (ICIs) have recently been investigated in SCLC, and this review provides guidance on the use of these agents in ES‐SCLC based on phase III evidence. Methods: Published and presented literature on phase III data addressing use of ICIs in ES‐SCLC was identified using the key search terms "small cell lung cancer" AND "checkpoint inhibitors" (OR respective aliases). Directed searches of eligible studies were periodically performed to ensure capture of the most recent data. Results: Six phase III trials were identified, with four assessing the benefits of ICIs plus chemotherapy first‐line, one evaluating ICIs as first‐line therapy maintenance, and one assessing ICI monotherapy after progression on platinum‐based chemotherapy. The addition of ipilimumab or tremelimumab to first‐line treatment or as first‐line maintenance did not improve survival. Two out of three studies combining PD‐1/PD‐L1 inhibitors with first‐line platinum‐based chemotherapy demonstrated significant long‐lasting survival benefits and improved quality of life with no unexpected safety concerns. PD‐1/PD‐L1 inhibitors as first‐line maintenance or in later lines of therapy did not improve survival. Biomarker research is ongoing as well as research into the role of ICIs in combination with radiation therapy in limited‐stage SCLC. Conclusion: The addition of atezolizumab or durvalumab to first‐line platinum‐based chemotherapy for ES‐SCLC prolongs survival and improves quality of life. Implications for Practice: Platinum‐based chemotherapy has been standard of care for extensive‐stage small cell lung cancer (ES‐SCLC) for more than a decade. Six recent phase III trials investigating immune checkpoint inhibitors (ICIs) have clarified the role of these agents in this setting. Although ICIs were assessed first‐line, as first‐line maintenance, and in later lines of therapy, the additions of atezolizumab or durvalumab to first‐line platinum‐based chemotherapy were the only interventions that significantly improved overall survival and increased quality of life. These combinations should therefore be considered standard therapy for first‐line ES‐SCLC. Biomarker research and investigations into the role of ICIs for limited‐stage disease are ongoing. Immune checkpoint inhibitors have recently been investigated in small cell lung cancer. This review provides guidance on the use of these agents in extensive‐stage small cell lung cancer based on phase III evidence. [ABSTRACT FROM AUTHOR]

Background: The treatment of head and neck cancer (HNC) may cause significant financial toxicity to patients. Herein, the authors have presented the development and validation of the Financial Index of Toxicity (FIT) instrument.Methods: Items were generated using literature review and were based on expert opinion. In item reduction, items with factor loadings of a magnitude <0.3 in exploratory factor analysis and inverse correlations (r < 0) in test-retest analysis were eliminated. Retained items constituted the FIT. Reliability tests included internal consistency (Cronbach α) and test-retest reliability (intraclass correlation). Validity was tested using the Spearman rho by comparing FIT scores with baseline income, posttreatment lost income, and the Financial Concerns subscale of the Social Difficulties Inventory. Responsiveness analysis compared change in income and change in FIT between 12 and 24 months.Results: A total of 14 items were generated and subsequently reduced to 9 items comprising 3 domains identified on exploratory factor analysis: financial stress, financial strain, and lost productivity. The FIT was administered to 430 patients with HNC at 12 to 24 months after treatment. Internal consistency was good (α = .77). Test-retest reliability was satisfactory (intraclass correlation, 0.70). Concurrent validation demonstrated mild to strong correlations between the FIT and Social Difficulties Inventory Money Matters subscale (Spearman rho, 0.26-0.61; P < .05). FIT scores were found to be inversely correlated with baseline household income (Spearman rho, -0.34; P < .001) and positively correlated with lost income (Spearman rho, 0.24; P < .001). Change in income was negatively correlated with change in FIT over time (Spearman rho, -0.25; P = .04).Conclusions: The 9-item FIT demonstrated internal and test-retest reliability as well as concurrent and construct validity. Prospective testing in patients with HNC who were treated at other facilities is needed to further establish its responsiveness and generalizability. [ABSTRACT FROM AUTHOR]

Purpose: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy.Methods and Materials: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m2/day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m2) during weeks 1, 3, 5, and 7, and an additional week 9 dose in the final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2.Results: Among the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m2 cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks.Conclusion: Cisplatin can be safely delivered with 5-FU-based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen. [ABSTRACT FROM AUTHOR]

Summary Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function, including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a critical mechanism for loss of consciousness in focal temporal lobe seizures. [ABSTRACT FROM AUTHOR]