Multiple Cancer Sites Research Articles

National Cancer Institute-funded grants focused on synchronous telehealth cancer care delivery: a portfolio analysis.

Telehealth use increased during the COVID-19 pandemic and remains a complementary source of cancer care delivery. Understanding research funding trends in cancer-related telehealth can highlight developments in this area of science and identify future opportunities. Applications funded by the US National Cancer Institute (NCI) between fiscal years 2016 and 2022 and focused on synchronous patient-provider telehealth were analyzed for grant characteristics (eg, funding mechanism), cancer focus (eg, cancer type), and study features (eg, type of telehealth service). Of 106 grants identified initially, 60 were retained for coding after applying exclusion criteria. Almost three-quarters (73%) of telehealth grants were funded during fiscal years 2020-2022. Approximately 67% were funded through R01 or R37 mechanism and implemented as randomized controlled trials (63%). Overall, telehealth grants commonly focused on treatment (30%) and survivorship (43%); breast cancer (12%), hematologic malignancies (10%), and multiple cancer sites (27%); and health disparity populations (ie, minorities, rural residents) (73%). Both audio and video telehealth were common (65%), as well as accompanying mHealth apps (20%). Telehealth services centered on psychosocial care, self-management, and supportive care (88%); interventions were commonly delivered by mental health professionals (30%). NCI has observed an increase in funded synchronous patient-provider telehealth grants. Trends indicate an evolution of awards that have expanded across the cancer control continuum, applied rigorous study designs, incorporated additional digital technologies, and focused on populations recognized for disparate cancer outcomes. As telehealth is integrated into routine cancer care delivery, additional research evidence will be needed to inform clinical practice.

Abstract 6464: Real-world evidence (RWE) presented at AACR annual meetings: A 10-year trend analysis

Abstract Introduction: RWE is increasingly used in the oncology community, particularly following the 2016 21st Century Cures Act. A recent analysis of RWE presented at ASCO reported a significant increase in relative frequency of RWE abstracts from 2011-2021[1]. We conducted a similar trend analysis of RWE presented at AACR and predictive factors associated with publication. Methods: EMBASE was queried for abstracts presented at AACR 2013-2022, using terms related to study designs and methodologies that employ use of RWE. Details on study design, location, data source, patient number, cancer site, analytical approach, endpoints, and presentation type (oral vs. poster) were extracted and analyzed. Searches in Google Scholar identified published manuscripts associated with each abstract. The Cochran-Armitage trend test and Monte-Carlo estimation of the exact test were used to detect trends over time; p-values are provided for descriptive purposes. Relative risk ratios were calculated to determine statistically significant predictors of publication. Results: Of 56,920 total abstracts presented at AACR from 2013-2022, 611 (1.1%) RWE abstracts were identified. The proportion of presented abstracts with RWE increased from 0.6% in 2013 to 2.0% in 2022 (p<0.001). Among the RWE abstracts, use of electronic medical record (2013: 0% vs. 2022: 9.3%; p=0.002) and genomics databases (i.e., GENIE) (2013: 0% vs. 2022: 8.3%; p=0.006) increased over time. While majority of RWE abstracts were presented as posters (95.9%), the proportion of oral presentations increased in the last decade (2013: 0.0% vs. 2022: 3.7%; p=0.005). Abstracts with sample sizes <500 decreased significantly over time (p=0.002); those with sample sizes 5,000-<50,000 increased significantly over time (p=0.001). The proportion of abstracts including multiple cancer sites (vs. single-site) increased from 5.1% in 2013 to 20.4% in 2022 (p<0.001). The most common cancer sites were lung, breast, and colorectal. Statistically significant factors associated with publishing an abstract into a manuscript included study sample size 500-<5,000 or ≥100,000, inferential statistics (vs. descriptive), propensity score matching, and effectiveness or disease burden endpoints.Conclusion: RWE studies presented at AACR increased in the recent decade, with more robust study designs, incorporation of novel clinico-genomic databases such as GENIE, and advanced analytical approaches. These findings suggest the value of RWE has been increasingly recognized by the oncology research community and that RWE is being used to provide critical insights and inform patient care. Given FDA’s recent guidance on RWE to support regulatory decision-making, this trend will likely continue. [1] Azad Fet al. Longitudinal trends of real-world evidence (RWE) reporting in oncology conferences: An 11-year ASCO Annual Meeting analysis. Citation Format: Jihong Zong, Lauren C. Bylsma, Orsolya Lunacsek, Jon Fryzek. Real-world evidence (RWE) presented at AACR annual meetings: A 10-year trend analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6464.

Increase in the Life Expectancy of Patients with Cancer in the United States.

Cancer is becoming more of a chronic disease due to improvements in treatment and early detection for multiple cancer sites. To gain insight on increased life expectancy due to these improvements, we quantified trends in the loss in expectation of life (LEL) due to a cancer diagnosis for six cancer sites from 1975 through 2018. We focused on patients diagnosed with female breast cancer, chronic myeloid leukemia (CML), colon and rectum cancer, diffuse large B-cell lymphoma (DLBCL), lung cancer, or melanoma between 1975 and 2018 from nine Surveillance, Epidemiology, and End Results cancer registries. Life expectancies for patients with cancer ages 50+ were modeled using flexible parametric survival models. LEL was calculated as the difference between general population life expectancy and life expectancy for patients with cancer. Over 2 million patients were diagnosed with one of the six cancers between 1975 and 2018. Large increases in life expectancy were observed between 1990 and 2010 for female breast, DLBCL, and CML. Patients with colon and rectum cancer and melanoma had more gradual improvements in life expectancy. Lung cancer LEL only began decreasing after 2005. Increases in life expectancy corresponded with decreases in LEL for patients with cancer. The reported gains in life expectancy largely correspond to progress in the screening, management, and treatment of these six cancers since 1975. LEL provides an important public health perspective on how improvements in treatment and early detection and their impacts on survival translate into changes in cancer patients' life expectancy.

Enabling real-world cancer care quality surveillance and analytics through a novel population-based statewide linked database.

545 Background: Population-based linked datasets are vital tools to generate real-world evidence (RWE) that can inform interventions and policies to improve cancer care quality and outcomes. The novel University of North Cancer Information & Population Health Resource (CIPHR) links statewide cancer registry data, public and private health insurance claims, and provider- and area-level data since 2003, representing more than 80% of North Carolina’s large, diverse cancer patient population. This scoping review included all articles that have used CIPHR data (N=44) to characterize the breadth of RWE generated and to identify further opportunities for population-based care quality surveillance. Methods: Articles published between 2012-2022 were categorized by cancer site(s) of focus, exposure variables, and outcomes examined across the cancer care continuum. For each article, notable results and conclusions were extracted and summarized, including statistically significant associations between patient-level factors (e.g., demographics, clinical variables, insurance type, distance to providers), provider-level factors (e.g., specialties, facility type, networks), system/policy-level factors and outcomes. Results: Of the 44 articles included, findings were reported across 23 unique cancer sites; 9 articles reported results aggregated across multiple cancer sites. Across the cancer care continuum, the majority of articles’ outcomes were categorized as focused on treatment and survivorship (n=25), with most examining treatment initiation and/or adherence (n=13). Other common outcomes included costs of care (n=8) and mortality/survival (n=8). Fewer articles focused on cancer screening (n=2), recurrence (n=1), long-term care use (n=1), or incidence (n=1). The cancer site most frequently examined was breast cancer (n=19), followed by colorectal (n=6), cervical (n=5), and uterine cancers (n=5). The majority of articles focused on racial/ethnic, rural/geographic, and socioeconomic inequities in care and outcomes, as well as multilevel predictors of observed trends. Conclusions: These findings demonstrate the value of creating and sustaining robust, longitudinal, population-based databases to facilitate the generation of RWE that can be used to monitor cancer care delivery trends, including cancer inequities that warrant intervention and policy attention. Lessons learned from more than a decade of analytics utilizing this unique data resource highlight opportunities to explore less frequently studied cancers and outcomes; motivate targeted implementation of equity-focused interventions and policies responding to trends; and inform development of similar resources in other states.

TransQA: deep hybrid transformer network for measurement-guided volumetric dose prediction of pre-treatment patient-specific quality assurance

Objective. Performing pre-treatment patient-specific quality assurance (prePSQA) is considered an essential, time-consuming, and resource-intensive task for volumetric modulated arc radiotherapy (VMAT) which confirms the dose accuracy and ensure patient safety. Most current machine learning and deep learning approaches stack excessive convolutional/pooling operations (CPs) to predict prePSQA with two-dimensional or one-dimensional information input. However, these models generally present limitations in explicitly modeling long-range dependency for volumetric dose prediction due to the loss of spatial dose features and the inherent locality of CPs. The purpose of this work is to construct a deep hybrid network by combining the self-attention mechanism-based Transformer with modified U-Net for predicting measurement-guided volumetric dose (MDose) of prePSQA. Approach. The enrolled 307 cancer patients underwent VMAT were randomly divided into 246 and 61 cases for training and testing the model. The input data included computed tomography images, radiotherapy dose images exported from the treatment planning system, as well as the MDose distribution from the verification system. The output was the predicted high-quality voxel-wise prePSQA dose distribution. Main results: qualitative and quantitative experimental results show that the proposed prediction method could achieve comparable or better performance on MDose prediction over other approaches in terms of spatial dose distribution, dose–volume histogram metrics, gamma passing rates, mean absolute error, root mean square error, and structural similarity. Significance. The preliminary results on multiple cancer sites show that our approach can be taken as a clinical guidance tool and help medical physicists to reduce the measurement work of prePSQA.

Automatic Segmentation with Deep Learning in Radiotherapy.

This review provides a formal overview of current automatic segmentation studies that use deep learning in radiotherapy. It covers 807 published papers and includes multiple cancer sites, image types (CT/MRI/PET), and segmentation methods. We collect key statistics about the papers to uncover commonalities, trends, and methods, and identify areas where more research might be needed. Moreover, we analyzed the corpus by posing explicit questions aimed at providing high-quality and actionable insights, including: "What should researchers think about when starting a segmentation study?", "How can research practices in medical image segmentation be improved?", "What is missing from the current corpus?", and more. This allowed us to provide practical guidelines on how to conduct a good segmentation study in today's competitive environment that will be useful for future research within the field, regardless of the specific radiotherapeutic subfield. To aid in our analysis, we used the large language model ChatGPT to condense information.

Cannabis use among recently treated cancer patients: perceptions and experiences.

To characterize cannabis use among cancer patients, we aimed to describe 1) patterns of cannabis use across multiple cancer sites; 2) perceived goals, benefits, harms of cannabis; and 3) communication about cannabis. Patients with 9 different cancers treated at Memorial Sloan Kettering Cancer Center between March and August 2021 completed an online or phone survey eliciting cannabis use, attitudes, and communication about cannabis. Multivariable logistic regression estimated the association of cancer type and cannabis use, adjusting for sociodemographic characteristics and prior cannabis use. Among 1258 respondents, 31% used cannabis after diagnosis, ranging from 25% for lung cancer to 59% for testicular cancer. Characteristics associated with cannabis use included younger age, lower education level, and cancer type. In multivariable analysis, compared to lung cancer patients, gastrointestinal cancer patients were more likely to use cannabis (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.25-5.43). Cannabis use in the year prior to diagnosis was strongly associated with cannabis use after diagnosis (OR 19.13, 95% CI 11.92-30.72). Among users, reasons for use included difficulty sleeping (48%); stress, anxiety, or depression (46%); and pain (42%). Among respondents who used cannabis to improve symptoms, 70-90% reported improvement; < 5% reported that any symptom worsened. Only 25% discussed cannabis with healthcare providers. Almost a third of cancer patients use cannabis, largely for symptom management. Oncologists may not know about their patients' cannabis use. To improve decision making about cannabis use during cancer care, research is needed to determine benefits and harms of cannabis use.

Pan-Cancer Analysis of Postdiagnosis Exercise and Mortality.

The impact of postdiagnosis exercise on cause-specific mortality in cancer survivors and whether this differs on the basis of cancer site is unclear. We performed an analysis of 11,480 patients with cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. Patients with a confirmed diagnosis of cancer completing a standardized survey quantifying exercise after diagnosis were included. The primary outcome was all-cause mortality (ACM); secondary end points were cancer mortality and mortality from other causes. Cox models were used to estimate the cause-specific hazard ratios (HRs) for ACM, cancer, and noncancer mortality as a function of meeting exercise guidelines versus not meeting guidelines with adjustment for important clinical covariates. After a median follow-up of 16 years from diagnosis, 4,665 deaths were documented (1,940 due to cancer and 2,725 due to other causes). In multivariable analyses, exercise consistent with guidelines was associated with a 25% reduced risk of ACM compared with nonexercise (HR, 0.75; 95% CI, 0.70 to 0.80). Compared with nonexercise, exercise consistent with guidelines was associated with a significant reduction in cancer mortality (HR, 0.79; 95% CI, 0.72 to 0.88) and mortality from other causes (HR, 0.72; 95% CI, 0.66 to 0.78). The inverse relationship between exercise and cause-specific mortality varied by exercise dose. Exercise consistent with guidelines was associated with a reduced hazard of ACM for multiple cancer sites. Reduction in cancer mortality for exercisers was only observed in head and neck and renal cancer. In this pan-cancer sample of long-term cancer survivors, exercise consistent with guidelines was associated with substantial ACM benefit driven by both reductions in cancer and noncancer mortality. The cause-specific impact of exercise differed as a function of cancer site.

Long-term Cancer Survival Trends by Updated Summary Stage.

Stage is the most important prognostic factor for understanding cancer survival trends. Summary stage (SS) classifies cancer based on the extent of spread: In situ, Localized, Regional, or Distant. Continual updating of staging systems poses challenges to stage comparisons over time. We use a consistent summary stage classification and present survival trends for 25 cancer sites using the joinpoint survival (JPSurv) model. We developed a modified summary stage variable, Long-Term Site-Specific Summary Stage, based on as consistent a definition as possible and applied it to a maximum number of diagnosis years, 1975-2019. We estimated trends by stage by applying JPSurv to relative survival data for 25 cancer sites in SEER-8, 1975-2018, followed through December 31, 2019. To help interpret survival trends, we report incidence and mortality trends using the joinpoint model. Five-year relative survival improved for nearly all sites and stages. Large improvements were observed for localized pancreatic cancer [4.25 percentage points annually, 2007-2012 (95% confidence interval, 3.40-5.10)], distant skin melanoma [2.15 percentage points annually, 2008-2018 (1.73-2.57)], and localized esophagus cancer [1.18 percentage points annually, 1975-2018 (1.11-1.26)]. This is the first analysis of survival trends by summary stage for multiple cancer sites. The largest survival increases were seen for cancers with a traditionally poor prognosis and no organized screening, which likely reflects clinical management advances. Our study will be particularly useful for understanding the population-level impact of new treatments and identifying emerging trends in health disparities research.

Incidence of 'Low-Risk but Not No-Risk' Features of Cancer Prior to High-Risk Feature Occurrence: An Observational Cohort Study in Primary Care.

Diagnosing cancer may be expedited by decreasing referral risk threshold. Clinical Practice Research Datalink participants (≥40 years) had a positive predictive value (PPV) ≥3% feature for breast, lung, colorectal, oesophagogastric, pancreatic, renal, bladder, prostatic, ovarian, endometrial or laryngeal cancer in 2016. The numbers of participants with features representing a 1-1.99% or 2-2.99% PPV for same cancer in the previous year were reported, alongside the time difference between meeting the ≥3% criteria and the lower threshold criteria. A total of 8616 participants had a PPV ≥3% feature, of whom 365 (4.2%) and 1147 (13.3%), respectively, met 2-2.99% and 1-1.99% criteria in the preceding year. The median time difference was 131 days (Interquartile Range (IQR) 27 to 256) for the 2-2.99% band and 179 days (IQR 58 to 289) for the 1-1.99% band. Results were heterogeneous across cancer sites. For some cancers, participants may progress from presenting lower- to higher-risk features before meeting urgent referral criteria; however, this was not usually the case. The details of specific features across multiple cancer sites will allow for a tailored approach to future reductions in referral thresholds, potentially improving the efficiency of urgent cancer referrals for the benefit both of individuals and the National Health Service (NHS).

Associations between an obesity-related dietary pattern and incidence of overall and site-specific cancers: a prospective cohort study

BackgroundA dietary pattern (DP) may impact on cancer incidence more strongly than individual foods, but this association remains uncertain. Here, we aimed to broadly explore the associations of an obesity-related DP with overall and 19 site-specific cancers.MethodsThis study included 114,289 cancer-free participants with at least two dietary assessments. A total of 210 food items were classified into 47 food groups, and the mean amount of each food group was used in reduced-rank regression to derive the obesity-related DP. Cox regressions were conducted to explore the associations of the obesity-related DP with overall and 19 site-specific cancers. The parallel mediation model was constructed to quantify the mediating roles of potential mediators.ResultsDuring a median follow-up period of 9.4 years, 10,145 (8.9%) incident cancer cases were documented. The derived-DP was characterized by a higher intake of beer and cider, processed meat, high sugar beverages, red meat, and artificial sweetener, and a lower intake of fresh vegetables, olive oil, tea, and high fiber breakfast cereals. Observational analysis showed that a higher obesity-related DP Z-score was linearly associated with an increased risk of overall cancer (adjusted hazard ratio (HR) = 1.02, 95% CI: 1.01, 1.04 per 1-SD increase, corrected P < 0.001). For site-specific cancer, positive linear associations for six cancer sites (oral, colorectal, liver, lung, endometrium, and thyroid) and nonlinear associations for six cancer sites (esophagus, malignant melanoma, prostate, kidney, bladder, and multiple myeloma) were observed. The paralleled mediation analysis suggested that the association between the obesity-related DP and overall cancer is mediated by the body mass index (BMI), the waist-to-hip ratio (WHR), C-reactive protein, high-density lipoproteins (HDLs), and triglycerides.ConclusionsThe developed obesity-related DP is strongly associated with overall and multiple cancer sites. Our findings highlight the complicated and diverse associations between an obesity-related DP and cancers and provide clues for future research directions.

Cannabis use among recently treated cancer patients: Perceptions and experiences.

e24163 Background: To characterize cannabis use among cancer patients, we aimed to describe 1) patterns of cannabis use across multiple cancer sites; 2) perceived goals, benefits, harms of cannabis; and 3) communication about cannabis. Methods: Patients with 9 different cancers treated at Memorial Sloan Kettering Cancer Center between March and August 2021 completed an anonymous online survey eliciting cannabis use, attitudes toward cannabis, and communication about cannabis. Multivariable logistic regression estimated the association of cancer type and cannabis use, adjusting for sociodemographic characteristics and prior cannabis use. Results: Among 1258 respondents, 83% believed there were benefits to cannabis use for cancer patients (N = 1032), and 55% (N = 666) believed there were potential harms. Thirty-one percent (N = 385) used cannabis after diagnosis (range: 25% among lung cancer to 59% among testicular cancer patients). Fifty-two percent of those using cannabis after diagnosis (N = 197) reported use in the past month. Characteristics associated with cannabis use after cancer diagnosis included younger age, lower education level, cancer type, and cannabis use in the year prior to diagnosis. In multivariable analysis, compared to lung cancer patients, gastrointestinal cancer patients were more likely to use cannabis (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.25-5.43). Cannabis use in the year prior to diagnosis was strongly associated with cannabis use after diagnosis (OR 19.13, 95% CI 11.92-30.72). Among users, the most common modes of ingestion were eating (30%, N = 115), smoking (26%, N = 99), and pills/tincture (23%, N = 87). The most commonly endorsed reasons for use included difficulty sleeping (48%, N = 182); stress, anxiety, or depression (46%, N = 175); and pain (42%, N = 160); 29% (N = 123) reported using cannabis for recreation, and 5% (N = 17) used for treatment or cure of their cancer. Among respondents who used cannabis to improve symptoms, 70-90% reported improvement; &lt; 5% reported that any symptom worsened. Among cannabis users, 48% (N = 185) discussed cannabis with an oncology provider, and cannabis products were most commonly acquired through friends, family members, or members of the community (47%, N = 176). Conclusions: In a large sample of recently or currently treated patients with a range of cancers, almost a third of patients used cannabis after their cancer diagnosis, most commonly edibles. Patients who used cannabis largely did so for symptom relief rather than with the goal of treating or curing their cancer. Limited communication about cannabis and acquisition of cannabis outside the medical setting suggests that oncology providers may not know about their patients’ cannabis use. To improve informed decision making about cannabis use during cancer care, research to determine benefits and harms of cannabis use is needed alongside enhanced clinical communication.

Preclinical circulating tumor DNA (ctDNA) shedding duration and prognostic implications of modeling 3669 participants from American Cancer Society Cancer Prevention Study-3 (CPS-3) and Circulating Cell-free Genome Atlas substudy 3 (CCGA3).

3060 Background: Early detection of cancer occurs in the preclinical phase, when development of cancers is unobservable. Shedding of ctDNA has previously been associated with aggressive cancers, suggesting these tumors may develop rapidly before diagnosis. Assays of ctDNA in blood samples from prospective cohort studies at various lead times (interval between blood draw and diagnosis) may provide insight into the timescales of preclinical cancer development, as well as prognosis. Methods: We used a targeted methylation assay and the associated locked classifier for cancer signal detection (CSD) on samples from two large prospective biobank studies: 1) CPS-3, where blood draw at enrollment (2006-13) occurred ≤3 years (Ys) before clinical diagnosis (n=1065); 2) CCGA3 (NCT02889978), where blood draw (2016-19) was concurrent with clinical diagnosis (n=2604). We constructed a model for detectability including study, inherent shedding of ctDNA at clinical diagnosis, and effect of lead time by cancer type and stage. We additionally evaluated prognosis stratified by ctDNA status (CSD positivity), compared to expected cancer-specific survival (CSS) matched by age, cancer type, and stage for ≤9 Ys of follow-up, noting that ctDNA status may change during lead time. Results: Estimated inherent ctDNA detectability did not differ between CCGA3 and CPS-3 studies (95% confidence interval [CI] for difference is [-8.2%, 4.6%] and spans zero). Median [CI] detection timescales for exponential decay of detection by time were 0.75 [0.47, 1.3] Ys for localized stage, 0.89 [0.61, 1.33] Ys for regional, and 1.2 [0.84, 1.67] Ys for distant, consistent with a published model, and ranged by type from 0.49 [0.26, 0.88] Ys for pancreas to 2.45 [1.14, 4.87] for lymphoma. For CPS-3, estimated CSS at 9 Ys from blood draw was 54% for ctDNA+ and 79.5% for ctDNA- participants. Hazard ratios (HR) [CI] for ctDNA+ vs ctDNA- alone predicting CSS were 7 [4.2, 12.2], 4.2 [2.9, 6], and 3.5 [2.5, 4.7] for those diagnosed up to 1, 2, and 3 Ys after blood draw, respectively. Compared to synthetic controls for age, cancer type, stage, and lead time in Surveillance, Epidemiology, and End Results (SEER) data, CSS was better in each group: ctDNA+ HR 0.63 (CI: 0.54, 0.74); ctDNA- HR 0.45 (CI: 0.22, 0.74). Conclusions: These results provide estimates for the average detection window in tumors shedding ctDNA across multiple cancer sites and stages, including cancer types with no current screening paradigm. Taking lead time into account, preclinical ctDNA status selected clinically significant cancers, limiting potential for overdiagnosis. Additionally, long-term survival remained better than in SEER data, suggesting that ctDNA+ cancers can be survivable. Results require confirmation in future prospective analyses.

The effect of exercise on physical function and medication adherence in women receiving endocrine therapy for breast cancer: The breast cancer endocrine therapy fitness (BE-FIT) randomized controlled trial.

12069 Background: Approximately 20% of women receiving endocrine therapy (ET) for early-stage breast cancer (BrCa) discontinue their regimen due to side effects, including vasomotor symptoms and arthralgias, subjecting them to higher rates of disease recurrence. Exercise is one approach to mitigate ET-related toxicity and potentially improve medication adherence by mitigating ET-related symptoms. However, only 11% of women with BrCa adhere to recommended exercise guidelines. Purpose: To examine the effect of a virtual supervised exercise program for women receiving ET for early-stage BrCa on physical function (PF) (primary outcome) and adherence to ET (secondary outcome). Methods: Participants were recruited through referral by oncology care providers from multiple BC Cancer sites and self-referral. Eligible participants were: females with stage I-III BrCa being treated with curative intent, 19-75 years, taking ET for at least 3 months up to 3 years. Using a partial cross-over design (NCT04824339), participants were randomized to the immediate exercise group (INT) or the delayed exercise group (CON), which crossed over at 8 weeks. The 8-week intervention was comprised of a 50-minute resistance exercise circuit, delivered virtually by an exercise physiologist twice per week via Zoom, and self-directed aerobic exercise (progressing to 90 minutes or more per week of at least moderate intensity). PF was assessed using the 30-second chair stand test. ET adherence was measured by the Voils self-reported medication non-adherence questionnaire. Values reported as means and standard deviations. The difference at 8 weeks by intervention arm was examined using two sample t-test (continuous) or kappa measure of agreement (categorical). Results: A total of 132 women were randomized. On average, women were 54 years, White (European) (47%), married (64%), had at least a bachelor’s degree or higher (51%), and had a body mass index of 27.7 kg/m2. The most common type of ET women received was Letrozole (43%), followed by Tamoxifen (36%). At 8 weeks, there was a significant improvement in PF for INT versus CON (mean change +2.5±2.9 vs. +0.7±2.2 stands, p&lt; 0.001). There was no difference between groups in change in medication adherence status (k = 0.35). Conclusions: An 8-week virtual supervised exercise program for women receiving ET for early-stage BrCa significantly improved PF but did not change medication adherence at 8 weeks. The potential impact of the intervention on long-term medication adherence will be explored up to one year and with covariates. Based on improvement in PF, future trials to establish effectiveness and inform implementation are warranted. Clinical trial information: NCT04824339 .

Abstract A015: Examination of the role of area deprivation indices on head and neck cancer survival adjusting for clinical and behavioral factors

Abstract Background: This study aims to evaluate the association between area deprivation and survival of head and neck squamous cell carcinoma (HNSCC) in the context of social and behavioral factors. Previously, area deprivation indices (ADIs) corresponding to decreasing neighborhood affluence have been associated with poorer survival of ovarian and lung cancer (Hufnagel et. al., 2021; Fairfield et. al., 2020). Further, neighborhood deprivation indices have been shown to be related to the survival of oropharynx cancer (Reitzel et. al., 2012). However, the relationship between area deprivation and the survival of multiple head and neck cancer sites has yet to be examined while considering the full extent of possible mediating or interacting factors, including the following: smoking, alcohol, human papillomavirus (HPV), urbanicity, and other dietary factors. Methods: We used 759 patients collected as a part of the University of Michigan Head and Neck Specialized Program of Research Excellence (UM HN-SPORE) prospective cohort study for whom we were able to assign an Area Deprivation Index (ADI) score. We calculated the ADI based on 17 census variables to describe neighborhood socioeconomics. Census block group level data was downloaded from the American Community Survey. The neighborhoods were categorized into ADI tertiles, least (Q1) to most deprived (Q3) neighborhoods. The role of ADI on disease-specific and overall survival was evaluated using Cox proportional hazards models adjusting for factors such as gender, age, body mass index (BMI), stage, site, smoking status, and, HPV status. Effect modification by comorbidity indices was also evaluated. Analyses used R studio (r-project.org).Results: Initial findings show that the hazard of head and neck cancer mortality is 1.74 (95% CI = 1.27, 2.39) times higher among the highest tertile of ADI scores relative to the lowest tertile, indicating that those in more highly disadvantaged areas had a lower survival proportion. However, after adjusting for age, stage at diagnosis, site, HPV status, BMI, and smoking status, and comorbidities the hazard ratio for was reduced to 1.12 (95% CI = 0.80, 1.58). Conclusion: Higher ADI indicative of increased area deprivation is associated with poorer survival of HNSCC. However, much of this association is accounted for by the presence of comorbidities, smoking and BMI in our cohort. Citation Format: Sarah Soppe, Mackenzie Gilson, A. A. Chamila Perera, Madhav KC, Edward S. Peters, Emily Belile, Steven Chinn, Gregory T. Wolf, Jeremy M.G. Taylor, Laura Rozek. Examination of the role of area deprivation indices on head and neck cancer survival adjusting for clinical and behavioral factors [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A015.

The Impact of Body Mass Index and Residence in Food Priority Areas on Patterns-of-Care and Cancer Outcomes in Patients with Stage III Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Nutritional deficiencies have been linked to poor prognosis in multiple cancer sites. Patients living in food priority areas (FPAs) where access to healthy meals is scarce may be at higher risk of nutritional deficits, leading to poor cancer outcomes. Currently, there is no published data analyzing how FPA residence impacts treatments rendered or outcomes for patients with locally advanced non-small cell lung cancer (LA-NSCLC). We aim to characterize socioeconomic and cancer demographics of LA- NSCLC patients living in zip code-designated FPAs treated with curative intent at a single institution. We hypothesize that living in a FPA will impact treatments rendered, patterns of failure, and cancer outcomes. <h3>Materials/Methods</h3> This is an IRB-approved retrospective study of 573 LA-NSCLC patients curatively treated January 2000-January 2020. Chi-square tests were done to compare variables stratified by residence in FPAs. Mann-Whitney U-test was used to compare differences between continuous variables. Kaplan-Meier analysis and cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence (FFR) for whole cohort and stratified by BMI. Cox regression with forward model selection was used for multivariate analysis (MVA). <h3>Results</h3> Of the 32% of patients living in FPAs (N=183), more were black (80%, p<0.0001), single (p<0.001), <60yo (p=0.001), uninsured (p< 0.0001), and had a lower median income (p< 0.001). Patients in FPAs had lower mean pre-chemoradiation (CRT) albumin (p=.002) and pre-CRT BMI (p= 0.026) and were less likely to receive trimodality therapy (p=<0.001) or consolidative immunotherapy (p=0.012). There was no difference in OS (21.8m vs. 26.2m, p=0.207) or FFR (11.2m vs 11.3m, p=0.739) between FPA vs No FPA groups. In the subset with pre- and post-CRT normal BMI, there was a significant difference in OS for patients living in an FPA (Median OS 18.4m vs 25.0m, p=0.005 and 15.1m vs. 28.1m, p=0.002; respectively) but no difference in FFR (11.0m in pre (p=0.463) and post-CRT (p=0.526)) There was no significant difference in OS or FFR for obese, underweight, or overweight patients. In all patients, nutritional aspects predictive of OS on MVA were pre-CRT albumin (HR 0.753, p=0.010) and post-CRT BMI (Obese as REF; Underweight: HR 1.737, p=0.043). In patients with post-CRT normal BMI (N=152), living in a FPA (HR 1.888, p=0.008) and pre-CRT albumin (HR 0.645, p=0.004) were predictors of OS on MVA. <h3>Conclusion</h3> In this institutional analysis examining impact of FPAs in patients with LA- NSCLC, we demonstrate a socioeconomic divide in this population, where residing in FPAs reflects distinct patient demographics and receipt of less aggressive therapy. Patients with normal BMI before therapy and particularly after CRT had worse OS if living in a FPA but there was no difference in FFR in this group. To overcome limitations of a retrospective analysis, we are currently characterizing nutritional needs of our patients in a prospective study.

Data Set for the Reporting of Carcinomas of the Vagina: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

Primary carcinomas of the vagina are uncommon and currently detailed recommendations for the reporting of resection specimens of these neoplasms are not widely available. The International Collaboration on Cancer Reporting (ICCR) is developing standardized, evidence-based reporting data sets for multiple cancer sites. We describe the development of a cancer data set by the ICCR expert panel for the reporting of primary vaginal carcinomas and present the core and noncore data elements with explanatory commentaries. This data set has incorporated the updates in the 2020 World Health Organization Classification of Female Genital Tumours, 5th edition. The data set addresses controversial issues such as tumor grading, margin assessment, and the role of ancillary studies. The adoption of this data set into clinical practice will help ensure standardized data collection across different countries, facilitate future research on vaginal carcinomas, and ultimately lead to improvements in patient care.

Self-reported symptoms among cancer survivors in the Women's Health Initiative (WHI) Life and Longevity after Cancer (LILAC) cohort.

Due to cancer survivors living longer and morbidity associated with cancer treatments, it is necessary to understand symptoms experienced by cancer survivors. This study will analyze the symptom burden among a large cohort of survivors across multiple cancer sites. Data from the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study were used to examine the symptom burden of older cancer survivors. Poisson regression with robust standard errors was utilized to determine differences in symptoms by cancer site, treatment, and other covariates. The most frequently reported symptoms among cancer survivors were fatigue (15.8%) and feeling sad or depressed (14.1%). Multivariable analyses indicated that more symptoms were reported among survivors who were younger (p = 0.002), divorced or separated (p = 0.03), and had a combination of public and private insurance (p = 0.01). Survivors who received chemotherapy (p < 0.001), radiation (p = 0.01), or hormone therapy (p = 0.02) reported more symptoms than survivors who did not receive these treatments. Survivors diagnosed with cancer < 5years ago reported fewer symptoms than longer-term survivors, particularly those diagnosed > 10years ago (p = 0.02). Results indicate that common physical and psychological symptoms are reported across cancer types. Cancer survivors diagnosed with cancer 10 or more years ago reported more symptoms than those recently diagnosed. This suggests that symptoms may remain a problem for some survivors decades after their diagnosis. Future research should focus on implementing active surveillance of cancer survivors. Healthcare providers and those who care for cancer survivors should understand that the symptom burden associated with cancer may persist even decades following diagnosis.

Abstract 43: Global Burden of Cancer in 2020 Attributable to Alcohol Consumption: A Population-Based Study

Abstract Purpose: Alcohol use is causally linked to multiple cancer sites. We present global, regional and national estimates of alcohol-attributable cancer burden in 2020 to inform alcohol policy and cancer control across different settings globally. Methods: In this population-based study, we calculated population attributable fractions (PAFs) using relative risk estimates and alcohol use prevalence by age, sex, and country. Assuming a 10-year latency period between alcohol consumption and cancer occurrence, we used alcohol consumption prevalence from 2010 and GLOBOCAN 2020 data to estimate new cancer cases attributable to alcohol consumption. We also calculated the contribution of moderate (&amp;lt;20 g alcohol per day), risky (20 to 60 g per day), and heavy (&amp;gt;60 g per day) drinking to the total alcohol-attributable cancer burden. Results: Globally, an estimated 702 900, or 3.9%, of all new cases of cancer in 2020 were attributable to alcohol consumption. Males represented 71.1% of the total alcohol-attributable cancer cases. The cancer sites which contributed the most alcohol-attributable cases were cancers of the esophagus (183 000 cases), liver (142 600 cases), and breast (114 300 cases). PAFs were lowest in Northern Africa and Western Asia (less than 1%) in both sexes, and highest in Eastern Asia (7.7%) and Central and Eastern Europe (6.9%) in men, and in Central and Eastern Europe (3.8%), Western Europe (3.5%) and Australia and New Zealand (3.55%) in women. Risky and heavy drinking contributed most to the burden of alcohol-attributable cancers (42.6% and 42.5%, respectively), and moderate drinking contributed 14.9%. Conclusion: Our findings highlight the need for effective policy and interventions to increase awareness of cancer risks associated with alcohol use and decrease overall alcohol consumption to avoid future rises in alcohol-attributable cancer burden in several regions of the world. Citation Format: Harriet Rumgay, Kevin Shield, Hadrien Charvat, Pietro Ferrari, Bundit Sornpaisarn, Isidore Obot, Farhad Islami, Valery Lemmens, Jürgen Rehm, Isabelle Soerjomataram. Global Burden of Cancer in 2020 Attributable to Alcohol Consumption: A Population-Based Study [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 43.

Discovering novel driver mutations from pan-cancer analysis of mutational and gene expression profiles.

As the genomic profile across cancers varies from person to person, patient prognosis and treatment may differ based on the mutational signature of each tumour. Thus, it is critical to understand genomic drivers of cancer and identify potential mutational commonalities across tumors originating at diverse anatomical sites. Large-scale cancer genomics initiatives, such as TCGA, ICGC and GENIE have enabled the analysis of thousands of tumour genomes. Our goal was to identify new cancer-causing mutations that may be common across tumour sites using mutational and gene expression profiles. Genomic and transcriptomic data from breast, ovarian, and prostate cancers were aggregated and analysed using differential gene expression methods to identify the effect of specific mutations on the expression of multiple genes. Mutated genes associated with the most differentially expressed genes were considered to be novel candidates for driver mutations, and were validated through literature mining, pathway analysis and clinical data investigation. Our driver selection method successfully identified 116 probable novel cancer-causing genes, with 4 discovered in patients having no alterations in any known driver genes: MXRA5, OBSCN, RYR1, and TG. The candidate genes previously not officially classified as cancer-causing showed enrichment in cancer pathways and in cancer diseases. They also matched expectations pertaining to properties of cancer genes, for instance, showing larger gene and protein lengths, and having mutation patterns suggesting oncogenic or tumor suppressor properties. Our approach allows for the identification of novel putative driver genes that are common across cancer sites using an unbiased approach without any a priori knowledge on pathways or gene interactions and is therefore an agnostic approach to the identification of putative common driver genes acting at multiple cancer sites.