Maternal and childhood medical history and the risk of childhood brain tumours: a case-control study in Ontario, Canada.

BACKGROUND: Studies to date have yielded inconclusive results as to whether maternal medical history during pregnancy, and a child's early-life medical history contribute to the development of childhood brain tumours (CBTs). This study examined associations between maternal and childhood medical history and the risk of CBTs. METHODS: The Childhood Brain Tumour Epidemiology Study of Ontario (CBREO) examined children 0-15 years of age with newly diagnosed CBTs from 1997 to 2003. Multivariable logistic regression analysis determined associations for prenatal medications and childhood medical history, adjusted for child's demographics, and maternal education. Analyses were stratified by histology. A latency period analysis was conducted using 12- and 24-month lead times. RESULTS: Maternal intake of immunosuppressants during the prenatal period was significantly associated with glial tumours (OR 2.73, 95% CI 1.17-6.39). Childhood intake of anti-epileptics was significantly associated with CBTs overall, after accounting for 12-month (OR 8.51, 95% CI 3.35-21.63) and 24-month (OR 6.04, 95% CI 2.06-17.70) lead time before diagnosis. No associations for other medications were found. CONCLUSIONS: This study underscores the need to examine potential carcinogenic effects of the medication classes highlighted and of the indication of medication use. Despite possible reverse causality, increased CBT surveillance for children with epilepsy might be warranted.

Differential prognostic significance of sarcopenia in metastatic esophageal squamous and adenocarcinoma.

BACKGROUND: Sarcopenia indicates poor prognosis in various malignancies. We evaluated the association of sarcopenia with overall (OS) and progression-free survival (PFS) in metastatic esophageal cancer (MEC) patients, a population often presenting with poor nutritional status. METHODS: In newly diagnosed MEC patients managed at the Princess Margaret (PM) Cancer Centre (diagnosed 2006-2015), total muscle area, visceral adiposity (VA), and subcutaneous adiposity (SA) were quantified on abdominal computed tomography at L3. Sarcopenia was determined using published cutoffs, based on sex and height. RESULTS: Of 202 MEC patients, most were male (166/82%), < 65 years (116/57%), and had adenocarcinoma histology (141/70%); 110/54% had recurrent MEC after initial curative-intent treatment; 92/46% presented with de novo MEC. At stage IV diagnosis, 20/10% were underweight, 97/48% were normal-weight and 84/42% were overweight/obese; 103/51% were sarcopenic. Sarcopenia was associated with worse median OS (4.6 vs. 7.9 months; log-rank p = 0.03) and 1-year survival, even after adjusting for other body composition variables (e.g., BMI, VA, and SA): adjusted-HR 1.51 [95% CI 1.1-2.2, p = 0.02]. In post hoc analysis, sarcopenia was highly prognostic in adenocarcinomas (p = 0.003), but not squamous cell carcinomas (SCC). In patients receiving palliative systemic treatment (104/51%), sarcopenia was associated with shorter PFS (p = 0.004) in adenocarcinoma patients (75/72%). CONCLUSIONS: In metastatic esophageal adenocarcinomas, sarcopenia is associated with worse PFS and OS. In metastatic esophageal SCC, there was a non-significant trend for worse PFS but no association with OS. In order to offset the poor prognosis associated with sarcopenia particularly in metastatic esophageal adenocarcinoma patients, future research should focus on possible countermeasures.

Childhood head trauma and the risk of childhood brain tumours: A case-control study in Ontario, Canada.

Head trauma in early childhood has been hypothesized as a potential risk factor for childhood brain tumours (CBTs). However, head trauma has not been extensively studied in the context of CBTs and existing studies have yielded conflicting results. A population-based and hospital-based case-control study of children 0 to 15 years with newly diagnosed CBTs from 1997 to 2003 recruited across Ontario through paediatric oncology centres was conducted. Controls were frequency-matched with cases by age, sex and geographical region. The association was assessed based on multivariable logistic regressions, accounting for child's age, sex, ethnicity, highest level of maternal education and maternal pack-years of smoking during the pregnancy. Analyses were conducted separately based on age of first head trauma, sex and histology. A latency period analysis was conducted. Overall, based on 280 cases and 919 controls, CBTs were not significantly associated with previous history of head trauma (OR 1.34, 95% CI 0.96, 1.86), head trauma severity, number of head injuries, or head or neck X-rays or computed tomography (CT) examinations. Results were consistent across sexes and histological subtypes. However, head trauma within the first year of life was significantly associated with CBTs (OR 2.00, 95% CI 1.01, 3.98), but the association diminished when adjusted for X-ray or CT occurring during the same time period (OR 1.62, 95% CI 0.75, 3.49), albeit limited sample size. Overall, no association was observed between head trauma and CBTs among all children, while head trauma occurring within first year of life may warrant further investigation in future research.

Internet and social media use in cancer patients: association with distress and perceived benefits and limitations.

OBJECTIVE: Cancer patients may turn to social media (SM) to cope with distress. We investigated associations between distress and internet/SM use for cancer information/support. METHODS: Adult patients at a Canadian cancer centre completed a cross-sectional survey on sociodemographics, health status, use of cancer online resources and distress (EQ5D-5L). Statistical models adjusted for relevant variables. RESULTS: Of 376 participants, median age was 52 years, time since diagnosis was 1.63 years, 272 (74%) had post-secondary education and 192 (51%) were female. For cancer information/support, 276 (73%) used internet and 147 (39%) SM. Dose response relationships were observed between distress and cancer-related internet (p = 0.02), and SM use (p < 0.001). Respondents using internet/SM for cancer information/support reported greater internet confidence (internet OR = 4.0, 95% CI: 1.9-8.3; SM OR = 4.18, 95%, CI: 1.9-11.3), higher education (internet OR = 3.0, 95% CI: 1.7-5.2; SM OR = 2.21, 95% CI: 1.2-4.1) and were more likely female (internet OR = 2.6, 95% CI 1.5-4.6; SM OR = 2.1, 95% CI: 1.3-3.4). For SM for cancer information/support, more used SM > 30 min daily (OR = 3.4; 95% CI: 2.1-5.7), and were distressed (OR = 1.67, 95% CI: 1.0-2.7). SM benefits were to learn about cancer (93; 25%), distract from cancer (85; 23%) and connect with survivors (81; 22%). SM limitations were privacy (161; 43%), quality (90; 24%) and personal applicability (85; 23%). Females used SM more to connect with survivors than males (p = 0.001). CONCLUSIONS: Greater internet confidence, higher education and being female were associated with cancer-related internet/SM use. Distressed cancer patients were also more likely to turn to SM. Privacy concerns may limit SM use for coping. Future research should determine how to optimize SM in caring for and connecting with patients and reduce cancer-related distress.

The impact of symptoms and comorbidity on health utility scores and health-related quality of life in small cell lung cancer using real world data.

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.

Health-related social media use and preferences of adolescent and young adult cancer patients for virtual programming.

PURPOSE: Adolescents and young adults (AYA) with cancer are increasingly using the internet and social media (SM) for cancer-related information. AYA face specific challenges and thus require tailored resources that meet their needs. We describe the internet and SM preferences of AYA related to their cancer information seeking behaviors and their preferences for a future resource compared to middle-aged adults (MAA). METHODS: Cancer patients completed a cross-sectional survey related to their internet and SM usage, cancer information, and preferences for future resources. Chi-square tests were used to compare AYA and MAA. RESULTS: The mean (±SD) age in the AYA group was 30±6.1 years (n = 129); in MAA 55±6.7 years (n = 157). In general, AYA preferred internet sites over SM platforms for cancer-related information and prefer a website platform over a SM platform for a new resource. Few AYA were aware of hospital-based AYA-specific resources. MAA were less likely to use SM compared with AYA (13% vs 4%, p = 0.01); however, websites and SM platforms that were used were similar between the 2 groups. Participants endorsed having already researched certain topics - yet, these were also those desired in a new resource. Compared to MAA, AYA sought more information on diet/nutrition, physical activity, exercise/fitness, fertility, sexual health, and body image (all p values < 0.05). CONCLUSION: AYA and MAA use similar resources on the internet and SM, but AYA sought information related to specific needs. Development of future resources should focus on an internet-based platform rather than a SM platform, coupled with promoting awareness of the resource.

Awareness of the Harms of Continued Smoking Among Cancer Survivors.

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.

Acceptability of Routine Evaluations Using Patient-Reported Outcomes of Common Terminology Criteria for Adverse Events and Other Patient-Reported Symptom Outcome Tools in Cancer Outpatients: Princess Margaret Cancer Centre Experience.

BACKGROUND: Recent studies have demonstrated improved outcomes with real-time patient-reported outcome questionnaires (PRO questionnaires) using questions adapted for patient use from the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). Outside of the clinical trial setting, limited information exists on factors affecting the completion of PRO questionnaires in routine practice. The primary aim of this prospective cross-sectional study was to evaluate patient willingness to complete PRO questionnaires on a regular basis and to better understand responder biases to improve patient feedback. MATERIALS AND METHODS: Patients performing PRO-CTCAE toxicity and symptom PRO questionnaires in oncology clinics at Princess Margaret Cancer Centre from 2013 to 2016 were assessed for their willingness to complete PRO questionnaires using a nine-item, tablet-based acceptability survey. Patient-reported characteristics (i.e., age, sex, language, marital status, education, occupation, etc.), cancer type, treatment modalities, and health metrics (i.e., Eastern Cooperative Oncology Group) were also collected. Characteristics were evaluated by logistic regression (odds ratios [OR]) using the primary outcome with prespecified levels of significance for univariate (p ≤ .10), and additional multivariate (p ≤ .05) testing. RESULTS: A total of 1,792 patients (median age 60 years; range 18-97) with various cancer diagnoses were assessed. A greater proportion of female (56%) and white (74%) respondents with an annual household income of <$100,000 (69%) participated. More than half (58%) of respondents were willing to complete PRO questionnaires at every clinic visit, and a high proportion (77%) found utility in reporting physical and emotional feelings to clinicians using PRO questionnaires. In general, patients did not find that PRO questionnaires made clinic visits more difficult (93%). In uni- and multivariable testing, patients were more willing to complete sleep- and fatigue-related PRO questionnaires relative to chemotoxicity-based PRO questionnaires (OR 1.52; p = .012). Patients aged 40-65 versus 18-40 years were also more likely to report high PRO questionnaire acceptability (OR 1.49; p = .025). Additional patient characteristics such as white ethnicity (OR 1.76), Canada as country of birth (OR 1.66), and English language (OR 2.15) relative to other had higher acceptability on uni- (p < .001) and multivariable (p < .001) analyses. Patients reporting treatment intent as palliative (OR 0.69; p = .0013) or hematological (OR 0.73; p = .027) were less likely to report high PRO questionnaire acceptability on univariable analysis; however, only palliative patients (OR 0.72) maintained this effect on multivariable testing (p = .012). Patients reporting higher health utility scores (per change in .05) also had significantly increased PRO questionnaire acceptability in uni- (OR 1.06; p < .001) and multivariable (OR 1.05; p = .008) analyses. No significant differences in PRO questionnaire acceptability were seen between cancer types, education level, household income, employment status, or treatment modality. CONCLUSION: Routine assessment using PRO questionnaires is associated with moderate acceptability by patients with cancer. Specific patient characteristics are associated with higher completion willingness. Additional research is necessary to identify factors associated with low acceptability of PRO questionnaires and to develop site-, ethnicity-, and treatment-specific instruments to assess the value of PRO questionnaires for symptom monitoring in clinical practice. IMPLICATIONS FOR PRACTICE: This study will help to identify the clinical, demographic, and survey characteristics associated with willingness to complete patient-reported outcome questionnaires regularly in the cancer outpatient setting.

The Impact of Brain Metastases and Associated Neurocognitive Aspects on Health Utility Scores in EGFR Mutated and ALK Rearranged NSCLC: A Real World Evidence Analysis.

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 (EGFRm) and ALK-rearrangements (ALKr). There were no HUS differences by BM status overall and in subsets by demographics. In multivariable analyses, superior HUS was associated with having EGFRm/ALKr (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 EGFRm and ALKr. 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.

Association of two BRM promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis.

Brahma (BRM), of the SWI/SNF complex, has two 6 to 7 bp insertion promoter polymorphisms (BRM-741/BRM-1321) that cause epigenetic BRM suppression, and are associated with risk of multiple cancers. BRM polymorphisms were genotyped in malignant pleural mesothelioma (MPM) cases and asbestos-exposed controls. Multivariable logistic regression (risk) and Cox regression (prognosis) were performed, including stratified analyses by smoking status to investigate the effect of polymorphisms on MPM risk and prognosis. Although there was no significant association overall between BRM-741/BRM-1321 and risk in patients with MPM, a differential effect by smoking status was observed (P-interaction < .001), where homozygous variants were protective (aOR of 0.18-0.28) in ever smokers, while never smokers had increased risk when carrying homozygous variants (aOR of 2.7-4.4). While there was no association between BRM polymorphisms and OS in ever-smokers, the aHR of carrying homozygous-variants of BRM-741, BRM-1321 or both were 4.0 to 8.6 in never-smokers when compared to wild-type carriers. Mechanistically, lower mRNA expression of BRM was associated with poorer general cancer prognosis. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments (ChIP) revealed high BRM insertion variant homology to MEF2 regulatory binding sites. ChIP experimentation confirmed MEF2 binding only occurs in the presence of insertion variants. DNA-affinity purification assays revealed YWHA scaffold proteins as vital to BRM mRNA expression. Never-smokers who carry BRM homozygous variants have an increased chance of developing MPM, which results in worse prognosis. In contrast, in ever-smokers, there may be a protective effect, with no difference in overall survival. Mechanisms for the interaction between BRM and smoking require further study.

Development and prospective evaluation of CAPLET, a cancer ambulatory patient physical function longitudinal evaluation tool for routine clinical practice.

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.

Patterns, perceptions and their association with changes in alcohol consumption in cancer survivors.

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.

Patterns, perceptions, and perceived barriers to physical activity in adult cancer survivors.

PURPOSE: Physical activity (PA) during and after cancer treatment is associated with improved cancer- and non-cancer-related outcomes. We assessed for predictors of change in PA levels among cancer survivors. METHODS: Adult cancer survivors from a comprehensive cancer center completed a one-time questionnaire retrospectively assessing PA levels before, during, and after cancer treatment along with their perceptions of PA. Multivariable logistic regression models evaluated the association of clinico-demographics variables and perceptions of PA with changes in whether patients were meeting PA guidelines after cancer diagnosis. RESULTS: Among the 1003 patients, 319 (32%) met moderate to vigorous PA (MVPA) guidelines before diagnosis. Among those meeting guidelines before diagnosis, 50% still met guidelines after treatment; 12% not meeting MVPA guidelines initially met them after treatment/at follow-up. Among patients meeting guidelines before diagnosis, better ECOG performance status at follow-up, receiving curative therapy, and spending a longer time on PA initially were each associated with meeting guidelines at follow-up. After controlling for other variables, perceiving that PA improves quality of life (adjusted odds ratio, aOR = 11.09, 95%CI [1.42-86.64], P = 0.02) and overall survival (aOR = 8.52, 95%CI [1.12-64.71], P = 0.04) was each associated with meeting MVPA guidelines during/after treatment, in patients who did not meet guidelines initially. Only 13% reported receiving counseling, which was not associated with PA levels. Common reported barriers to PA included fatigue, lacking motivation, and being too busy. CONCLUSIONS: Patient perceptions of PA benefits are strongly associated with improving PA levels after a cancer diagnosis. Clinician counseling should focus on patient education and changing patient perceptions.

BRM polymorphisms, pancreatic cancer risk and survival.

Variant alleles of two promoter polymorphisms in the BRM gene (BRM-741, BRM-1321), create MEF2D transcription binding sites that lead to epigenetic silencing of BRM, the key catalytic component of the SWI/SNF chromatin remodeling complex. BRM suppression can be reversed pharmacologically.(1) Our group and others have reported associations with lung, head and neck, hepatocellular cancer risk,(1-3) and with lung and esophageal cancer prognosis (ASCO 2013; abstract 11057 & 4077). Herein, we assessed risk and survival associations with pancreatic cancer. A provincial population-based case-control study was conducted with 623 histologically confirmed pancreatic adenocarcinoma cases and 1,192 age/gender distribution-matched controls.(4) Survival of cases was obtained through the Ontario Cancer Registry. Logistic and Cox proportional hazard regression models were fitted, adjusting for relevant covariates. Median age was 65 y; 52% were male; Stage I (8%), II (55%), III (14%), IV (23%); 53% after curative resection, 79% after chemotherapy; and 83% had died. In the risk analysis, adjusted odds ratios (aOR) were 1.01 (95% CI: 0.1-2.0) and 0.96 (95% CI: 0.7-1.3) for the homozygotes of BRM-741 and BRM-1321, respectively; aOR of double-homozygotes was 1.11 (95% CI: 0.80-1.53), compared to the double-wildtype. For the survival analysis, adjusted hazard ratios (aHR) were 2.19 (95% CI: 1.9-2.5) for BRM-741 and 1.94 (95% CI: 1.7-2.2) for BRM-1321, per unit increase in variant alleles. Compared with the double-wildtype, aHR for carrying no, one, and two double-homozygotes were 2.14 (95% CI: 1.6-2.8), 4.17 (95% CI: 3.0-5.7), 8.03 (95% CI: 5.7-11.4), respectively. In conclusion, two functional promoter BRM polymorphisms were not associated with pancreatic adenocarcinoma risk, but are strongly associated with survival.

The role of second-hand smoke exposure on smoking cessation in non-tobacco-related cancers.

BACKGROUND: Second-hand smoke (SHS) is a significant barrier to smoking cessation after a diagnosis of cancer in patients with lung as well as head and neck cancers. In the current study, the authors evaluated the effect of SHS on smoking cessation among patients with those cancers not traditionally perceived to be strongly associated with smoking. METHODS: Patients recruited from a single tertiary care center completed a self-administered questionnaire. Multivariate logistic regression and Cox proportional hazards models evaluated the association of sociodemographics, clinicopathological variables, and exposure to SHS with either smoking cessation or time to quitting. RESULTS: In all, 926 patients with diverse cancer subtypes completed the questionnaire. Of the 161 who were current smokers at the time of their cancer diagnosis, 48% quit after diagnosis. Lack of exposure to SHS at home was found to be associated with smoking cessation at any time after diagnosis (adjusted odd ratio, 4.28; 95% confidence interval, 1.56-11.78 [P =.005]), with similar trends noted 1 year after diagnosis (adjusted odds ratio, 2.56; 95% confidence interval, 0.91-7.22 [P =.08]). There was a significant inverse dose-response relationship between hours of SHS exposure at home and smoking cessation. Spousal and peer smoking were not found to be significantly associated with smoking cessation on multivariate analysis (P>.05). Kaplan-Meier analysis found that of patients who did quit smoking, 61% quit within 6 months of their cancer diagnosis. CONCLUSIONS: Exposure to SHS at home is a significant barrier to smoking cessation in patients whose cancers are not traditionally perceived as being related to tobacco. SHS should be a key consideration in the development of survivorship programs geared toward smoking cessation for all patients with cancer.

Real-World Treatment Sequencing, Toxicities, Health Utilities, and Survival Outcomes in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer.

OBJECTIVES: This real-world analysis describes treatment patterns, sequencing and clinical effectiveness, toxicities, and health utility outcomes in advanced-stage, incurable ALK-positive NSCLC patients across five different ALK-TKIs. MATERIALS AND METHODS: Clinicodemographic, treatment, and toxicity data were collected retrospectively in patients with advanced-stage ALK-positive NSCLC at Princess Margaret Cancer Centre. Patient-reported symptoms, toxicities, and health utilities were collected prospectively. RESULTS: Of 148 ALK-positive NSCLC patients seen July 2009-May 2021, median age was 58.9 years; 84 (57%) were female; 112 (76%) never-smokers; 54 (47%) Asian and 40 (35%) white; 139 (94%) received at least one ALK-TKI: crizotinib (n = 74; 54%) and alectinib (n = 61; 44%) were administered mainly as first-line ALK-TKI, ceritinib, brigatinib and lorlatinib were administered primarily after previous ALK-TKI failure. Median overall survival (OS) was 54.0 months; 31 (21%) patients died within two years of advanced-stage diagnosis. Treatment modifications were observed in 35 (47%) patients with crizotinib, 19 (61%) with ceritinib, 41 (39%) with alectinib, 9 (41%) with brigatinib and 8 (30%) with lorlatinib. Prevalence of dose modifications and self-reported toxicities were higher with early versus later generation ALK-TKIs (P<.05). The presence of early treatment modification was not negatively associated with progression-free survival (PFS) and OS analyses. CONCLUSION: Serial ALK-TKI sequencing approaches are viable therapeutic options that can extend quality of life and quantity-of-life, though a fifth of patients died within two years. No best single sequencing approach could be determined. Clinically relevant toxicities occurred across all ALK-TKIs. Treatment modifications due to toxicity may not necessarily compromise outcomes, allowing multiple approaches to deal with ALK-TKI toxicities.

Presentation and outcomes of KRASG12C mutant non-small cell lung cancer patients with stage IV disease at diagnosis (de novo) versus at recurrence.

Close monitoring after diagnosis of patients with stage I-III non-small cell lung cancer (NSCLC) may result in fitter patients with lower disease burden at the time of metastatic recurrence or progression compared to patients diagnosed initially as stage IV (de novo). We compared the presentation, treatments, and outcomes of patients with KRASG12C-mutated NSCLC with de novo versus recurrent stage IV disease. Of 109 patients, 94% had a smoking history. When compared to patients with KRASG12C-mutated NSCLC who developed stage IV disease at recurrence (n = 38), de novo stage IV patients (n = 71) had worse ECOG performance status (p = 0.007), greater numbers of extra-thoracic metastatic sites (p = 0.001), and were less likely to receive 2nd/3rd line systemic therapy (p = 0.05, p = 0.002) or targeted therapy (p = 0.001). De novo metastatic patients had shorter overall survival than metastatic patients at recurrence (9.1 versus 24.2 months; adjusted-hazard-ratio=1.94 (95% CI: 1.14-3.28; p = 0.01)). There is a critical need for well-tolerated targeted therapies in the first-line setting for metastatic patients with de novo, high-burden, stage IV KRASG12C-mutated NSCLCs.

Respiratory and Cardiometabolic Comorbidities and Stages I to III NSCLC Survival: A Pooled Analysis From the International Lung Cancer Consortium.

INTRODUCTION: We explored the association of respiratory and cardiometabolic comorbidities with NSCLC overall survival (OS) and lung cancer-specific survival (LCSS), by stage, in a large, multicontinent NSCLC pooled data set. METHODS: On the basis of patients pooled from 11 International Lung Cancer Consortium studies with available respiratory and cardiometabolic comorbidity data, adjusted hazard ratios (aHRs) were estimated using Cox models for OS. LCSS was evaluated using competing risk Grey and Fine models and cumulative incidence functions. Logistic regression (adjusted OR [aOR]) was applied to assess factors associated with surgical resection. RESULTS: OS analyses used patients with NSCLC with respiratory health or cardiometabolic health data (N = 16,354); a subset (n = 11,614) contributed to LCSS analyses. In stages I to IIIA NSCLC, patients with respiratory comorbidities had worse LCCS (stage IA aHR = 1.51, confidence interval [CI]: 1.17-1.95; stages IB-IIIA aHR = 1.20, CI: 1.06-1.036). In contrast, patients with stages I to IIIA NSCLC with cardiometabolic comorbidities had a higher risk of death from competing (non-NSCLC) causes (stage IA aHR = 1.34, CI: 1.12-1.69). The presence of respiratory comorbidities was inversely associated with having surgical resection (stage IA aOR = 0.54, CI: 0.35-0.83; stages IB-IIIA aOR = 0.57, CI: 0.46-0.70). CONCLUSIONS: The presence of either cardiometabolic or respiratory comorbidities is associated with worse OS in stages I to III NSCLC. Patients with respiratory comorbidities were less likely to undergo surgery and had worse LCSS, whereas patients with cardiometabolic comorbidities had a higher risk of death from competing causes. As more treatment options for stages I to III NSCLC are introduced into the practice, accounting for cardiometabolic and respiratory comorbidities becomes essential in trial interpretation and clinical management.

Association between duration of smoking abstinence before non-small-cell lung cancer diagnosis and survival: a retrospective, pooled analysis of cohort studies.

BACKGROUND: The association between duration of smoking abstinence before non-small-cell lung cancer (NSCLC) diagnosis and subsequent survival can influence public health messaging delivered in lung-cancer screening. We aimed to assess whether the duration of smoking abstinence before diagnosis of NSCLC is associated with improved survival. METHODS: In this retrospective, pooled analysis of cohort studies, we used 26 cohorts participating in Clinical Outcomes Studies of the International Lung Cancer Consortium (COS-ILCCO) at 23 hospitals. 16 (62%) were from North America, six (23%) were from Europe, three (12%) were from Asia, and one (4%) was from South America. Patients enrolled were diagnosed between June 1, 1983, and Dec 31, 2019. Eligible patients had smoking data before NSCLC diagnosis, epidemiological data at diagnosis (obtained largely from patient questionnaires), and clinical information (retrieved from medical records). Kaplan-Meier curves and multivariable Cox models (ie, adjusted hazard ratios [aHRs]) were generated with individual, harmonised patient data from the consortium database. We estimated overall survival for all causes, measured in years from diagnosis date until the date of the last follow-up or death due to any cause and NSCLC-specific survival. FINDINGS: Of 42 087 patients with NSCLC in the COS-ILCCO database, 21 893 (52·0%) of whom were male and 20 194 (48·0%) of whom were female, we excluded 4474 (10·6%) with missing data. Compared with current smokers (15 036 [40·0%] of 37 613), patients with 1-3 years of smoking abstinence before NSCLC diagnosis (2890 [7·7%]) had an overall survival aHR of 0·92 (95% CI 0·87-0·97), patients with 3-5 years of smoking abstinence (1114 [3·0%]) had an overall survival aHR of 0·90 (0·83-0·97), and patients with more than 5 years of smoking abstinence (10 841 [28·8%]) had an overall survival aHR of 0·90 (0·87-0·93). Improved NSCLC-specific survival was observed in 4301 (44%) of 9727 patients who had quit cigarette smoking and was significant at abstinence durations of more than 5 years (aHR 0·87, 95% CI 0·81-0·93). Results were consistent across age, sex, histology, and disease-stage distributions. INTERPRETATION: In this large, pooled analysis of cohort studies across Asia, Europe, North America, and South America, overall survival was improved in patients with NSCLC whose duration of smoking abstinence before diagnosis was as short as 1 year. These findings suggest that quitting smoking can improve overall survival, even if NSCLC is diagnosed at a later lung-cancer screening visit. These findings also support the implementation of public health smoking cessation strategies at any time. FUNDING: The Alan B Brown Chair, The Posluns Family Fund, The Lusi Wong Fund, and the Princess Margaret Cancer Foundation.