Defining and Addressing Research Priorities in Cancer Cachexia through Transdisciplinary Collaboration.

For many patients, the cancer continuum includes a syndrome known as cancer-associated cachexia (CAC), which encompasses the unintended loss of body weight and muscle mass, and is often associated with fat loss, decreased appetite, lower tolerance and poorer response to treatment, poor quality of life, and reduced survival. Unfortunately, there are no effective therapeutic interventions to completely reverse cancer cachexia and no FDA-approved pharmacologic agents; hence, new approaches are urgently needed. In May of 2022, researchers and clinicians from Moffitt Cancer Center held an inaugural retreat on CAC that aimed to review the state of the science, identify knowledge gaps and research priorities, and foster transdisciplinary collaborative research projects. This review summarizes research priorities that emerged from the retreat, examples of ongoing collaborations, and opportunities to move science forward. The highest priorities identified include the need to (1) evaluate patient-reported outcome (PRO) measures obtained in clinical practice and assess their use in improving CAC-related outcomes; (2) identify biomarkers (imaging, molecular, and/or behavioral) and novel analytic approaches to accurately predict the early onset of CAC and its progression; and (3) develop and test interventions (pharmacologic, nutritional, exercise-based, and through mathematical modeling) to prevent CAC progression and improve associated symptoms and outcomes.

Clinical characteristics and treatment patterns of patients with NTRK fusion-positive solid tumors: A multisite cohort study at US academic cancer centers.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare oncogenic drivers prevalent in 0.3% of solid tumors. They are most common in salivary gland cancer (2.6%), thyroid cancer (1.6%), and soft-tissue sarcoma (1.5%). Currently, there are 2 US Food and Drug Administration-approved targeted therapies for NTRK gene fusions: larotrectinib, approved in 2018, and entrectinib, approved in 2019. To date, the real-world uptake of tyrosine receptor kinase inhibitor (TRKi) use for NTRK-positive solid tumors in academic cancer centers remains largely unknown. OBJECTIVE: To describe the demographics, clinical and genomic characteristics, and testing and treatment patterns of patients with NTRK-positive solid tumors treated at US academic cancer centers. METHODS: This was a retrospective chart review study conducted in academic cancer centers in the United States. All patients diagnosed with an NTRK fusion-positive (NTRK1, NTRK2, NTRK3) solid tumor (any stage) and who received cancer treatment at participating sites between January 1, 2012, and July 1, 2023, were included in this study. Patient demographics, clinical characteristics, genomic characteristics, NTRK testing data, and treatment patterns were collected from electronic medical records and analyzed using descriptive statistics as appropriate. RESULTS: In total, 6 centers contributed data for 55 patients with NTRK-positive tumors. The mean age was 49.3 (SD = 20.5) years, 51% patients were female, and the majority were White (78%). The median duration of time from cancer diagnosis to NTRK testing was 85 days (IQR = 44-978). At the time of NTRK testing, 64% of patients had stage IV disease, compared with 33% at cancer diagnosis. Prevalent cancer types in the overall cohort included head and neck (15%), thyroid (15%), brain (13%), lung (13%), and colorectal (11%). NTRK1 fusions were most common (45%), followed by NTRK3 (40%) and NTRK2 (15%). Across all lines of therapy, 51% of patients (n = 28) received a TRKi. Among TRKi-treated patients, 71% had stage IV disease at TRKi initiation. The median time from positive NTRK test to initiation of TRKi was 48 days (IQR = 9-207). TRKis were commonly given as first-line (30%) or second-line (48%) therapies. Median duration of therapy was 610 (IQR = 182-764) days for TRKi use and 207.5 (IQR = 42-539) days for all other first-line therapies. CONCLUSIONS: This study reports on contemporary real-world NTRK testing patterns and use of TRKis in solid tumors, including time between NTRK testing and initiation of TRKi therapy and duration of TRKi therapy.

Evaluating clinical and radiomic features for predicting lung cancer recurrence pre- and post-tumor resection.

Among patients with early-stage non-small cell lung cancer (NSCLC) undergoing surgical resection, identifying who is at high-risk of recurrence can inform clinical guidelines with respect to more aggressive follow-up and/or adjuvant therapy. While predicting recurrence based on pre-surgical resection data is ideal, clinically important pathological features are only evaluated postoperatively. Therefore, we developed two supervised classification models to assess the importance of pre- and post-surgical features for predicting 5-year recurrence. An integrated dataset was generated by combining clinical covariates and radiomic features calculated from pre-surgical computed tomography images. After removing correlated radiomic features, the SHapley Additive exPlanations (SHAP) method was used to measure feature importance and select relevant features. Binary classification was performed using a Support Vector Machine, followed by a feature ablation study assessing the impact of radiomic and clinical features. We demonstrate that the post-surgical model significantly outperforms the pre-surgical model in predicting lung cancer recurrence, with tumor pathological features and peritumoral radiomic features contributing significantly to the model's performance.

The association of body composition phenotypes before chemotherapy with epithelial ovarian cancer mortality.

BACKGROUND: The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests high adiposity associates with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality. METHODS: Body composition from 500 women in The Body Composition and Epithelial Ovarian Cancer Survival Study was dichotomized as normal/low skeletal muscle index (SMI), a proxy for sarcopenia and high/low adiposity. Four phenotypes were classified as fit/reference (normal SMI/low adiposity; 16.2%), overweight/obese (normal SMI/high adiposity; 51.2%), sarcopenia/overweight-obese (low SMI/high adiposity; 15.6%), and sarcopenia/cachexia (low SMI/low adiposity; 17%). We used multivariable Cox models to estimate associations of each phenotype with mortality for EOC overall and high-grade serous ovarian carcinoma (HGSOC). RESULTS: Overweight/obesity was associated with up to 51% and 104% increased mortality in EOC and HGSOC (HR = 1.51, 95% CI: 1.05-2.19 and HR = 2.04, 95% CI: 1.29-3.21). Sarcopenia/overweight-obesity was associated with up to 66% and 67% increased mortality in EOC and HGSOC (HR = 1.66, 95% CI: 1.13-2.45 and HR = 1.67, 95% CI: 1.05-2.68). Sarcopenia/cachexia was associated with up to 73% and 109% increased mortality in EOC and HGSOC (HR = 1.73, 95% CI: 1.14-2.63 and HR = 2.09, 95% CI: 1.25-3.50). CONCLUSIONS: Overweight/obesity, sarcopenia/overweight-obesity and sarcopenia/cachexia phenotypes were each associated with increased mortality in EOC and HGSOC. Exercise and dietary interventions could be leveraged as ancillary treatment strategies for improving outcomes in the most fatal gynecological malignancy with no previously established modifiable prognostic factors.

Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification.

BACKGROUND: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored. METHODS: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold. RESULTS: Considerable variances in PRS point estimates at the individual level were observed for both methods, with an average standard deviation (s.d.) of 0.12 for PRS-16-CV and a much larger s.d. of 0.88 for PRS-Bayes. Using PRS-16-CV, only 25.0% of individuals with PRS point estimates in the lowest decile of PRS and 16.8% in the highest decile have their entire 95% CI fully contained in the lowest and highest decile, respectively, while PRS-Bayes was unable to find any eligible individuals. Only 19% of the individuals were concordantly identified as having high genetic risk (> 90th percentile) using the two PRS estimators. An increased relative risk of lung cancer comparing the highest PRS percentile to the lowest was observed when taking the CI into account (OR = 2.73, 95% CI: 2.12-3.50, P-value = 4.13 × 10-15) compared to using PRS-16-CV mean (OR = 2.23, 95% CI: 1.99-2.49, P-value = 5.70 × 10-46). Improved risk prediction performance with higher AUC was consistently observed in individuals identified by PRS-16-CV CI, and the best performance was achieved by incorporating age, gender, and detailed smoking pack-years (AUC: 0.73, 95% CI = 0.72-0.74). CONCLUSIONS: Lung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS.

Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies.

BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. RESULTS: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior. CONCLUSIONS: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. IMPACT: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.

A clinical overview of people living with HIV and genitourinary cancer care.

The number of people living with HIV infection has been increasing globally. Administration of antiretroviral therapy is effective in controlling the infection for most patients and, as a consequence, people living with HIV (PLWH) now often have a long life expectancy. However, their risk of developing cancer - most notably virus-related cancers - has been increasing. To date, few studies have assessed the risk of genitourinary cancers in PLWH, and robust scientific data on their treatment-related outcomes are lacking. Previous studies have noted that PLWH are at a reduced risk of prostate cancer; however, low adoption and/or availability of prostate cancer screening among these patients might be confounding the validity of this finding. In genitourinary cancers, advanced stage at diagnosis and reduced cancer-specific mortality have been reported in PLWH. These data likely reflect, at least in part, the inequity of health care access for PLWH. Notably, systemic chemotherapy and/or radiotherapy could decrease total CD4+ cell counts, which could, therefore, increase the risk of morbidity and mortality from cancer treatments in PLWH. Immune checkpoint inhibitors have become the therapeutic backbone for many advanced malignancies in the general population; however, most studies validating their efficacy have excluded PLWH owing to concerns of severe adverse effects from immune checkpoint inhibitors themselves and/or related to their immunosuppressed status. To our knowledge, no genitourinary cancer survivorship programme exists that specifically caters to the needs of PLWH. By including PLWH in ongoing cancer trials, we can gain invaluable insights that will help to improve cancer care specifically for PLWH.

Identification of genetically predicted DNA methylation markers associated with non-small cell lung cancer risk among 34,964 cases and 448,579 controls.

BACKGROUND: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non-small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated. METHODS: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established. The prediction models were applied to a fixed-effect meta-analysis of screening data sets with 27,120 NSCLC cases and 27,355 controls to identify the methylation markers, which were then replicated in independent data sets with 7844 lung cancer cases and 421,224 controls. Also performed was a multi-omics functional annotation for the identified CpGs by integrating genomics, epigenomics, and transcriptomics and investigation of the potential regulation pathways. RESULTS: Of the 29,894 CpG sites passing the quality control, 39 CpGs associated with NSCLC risk (Bonferroni-corrected p ≤ 1.67 × 10-6 ) were originally identified. Of these, 16 CpGs remained significant in the validation stage (Bonferroni-corrected p ≤ 1.28 × 10-3 ), including four novel CpGs. Multi-omics functional annotation showed nine of 16 CpGs were potentially functional biomarkers for NSCLC risk. Thirty-five genes within a 1-Mb window of 12 CpGs that might be involved in regulatory pathways of NSCLC risk were identified. CONCLUSIONS: Sixteen promising DNA methylation markers associated with NSCLC were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby. PLAIN LANGUAGE SUMMARY: The epigenetic consequences of DNA methylation in lung cancer development are still largely unknown. This study used summary data of large-scale genome-wide association studies to investigate the associations between genetically predicted levels of methylation biomarkers and non-small cell lung cancer risk at the first time. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. These findings will provide a unique insight into the epigenetic susceptibility mechanisms of lung cancer.

CYP2A6 Activity and Cigarette Consumption Interact in Smoking-Related Lung Cancer Susceptibility.

Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen-metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke-exposed cell models were used to detect gene expression patterns in relation to specific alleles. Data from the International Lung Cancer Consortium (29,266 cases and 56,450 controls) and UK Biobank (2,155 cases and 376,329 controls) indicated that the genetic variant rs56113850 C>T located in intron 4 of CYP2A6 was significantly associated with decreased lung cancer risk among smokers (OR = 0.88, 95% confidence interval = 0.85-0.91, P = 2.18 × 10-16), which might interact (Pinteraction = 0.028) with and partially be mediated (ORindirect = 0.987) by smoking status. Smoking intensity accounted for 82.3% of the effect of CYP2A6 activity on lung cancer risk but entirely mediated the genetic effect of rs56113850. Mechanistically, the rs56113850 T allele rescued the downregulation of CYP2A6 caused by cigarette smoke exposure, potentially through preferential recruitment of transcription factor helicase-like transcription factor. Together, this study provides additional insights into the interplay between host susceptibility and carcinogen exposure in smoking-related lung tumorigenesis. SIGNIFICANCE: The causal pathway connecting CYP2A6 genetic variability and activity, cigarette consumption, and lung cancer susceptibility in smokers highlights the need for behavior modification interventions based on host susceptibility for cancer prevention.

Overview of approaches to estimate real-world disease progression in lung cancer.

BACKGROUND: Randomized clinical trials of novel treatments for solid tumors normally measure disease progression using the Response Evaluation Criteria in Solid Tumors. However, novel, scalable approaches to estimate disease progression using real-world data are needed to advance cancer outcomes research. The purpose of this narrative review is to summarize examples from the existing literature on approaches to estimate real-world disease progression and their relative strengths and limitations, using lung cancer as a case study. METHODS: A narrative literature review was conducted in PubMed to identify articles that used approaches to estimate real-world disease progression in lung cancer patients. Data abstracted included data source, approach used to estimate real-world progression, and comparison to a selected gold standard (if applicable). RESULTS: A total of 40 articles were identified from 2008 to 2022. Five approaches to estimate real-world disease progression were identified including manual abstraction of medical records, natural language processing of clinical notes and/or radiology reports, treatment-based algorithms, changes in tumor volume, and delta radiomics-based approaches. The accuracy of these progression approaches were assessed using different methods, including correlations between real-world endpoints and overall survival for manual abstraction (Spearman rank ρ = 0.61-0.84) and area under the curve for natural language processing approaches (area under the curve = 0.86-0.96). CONCLUSIONS: Real-world disease progression has been measured in several observational studies of lung cancer. However, comparing the accuracy of methods across studies is challenging, in part, because of the lack of a gold standard and the different methods used to evaluate accuracy. Concerted efforts are needed to define a gold standard and quality metrics for real-world data.

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.

Protocol optimization of a targeted sequencing panel for genomic profiling of bronchoalveolar lavage fluid in lung cancer.

INTRODUCTION: We investigated a commercially available sequencing panel to study the effect of sequencing depth, variant calling strategy, and targeted sequencing region on identifying tumor-derived variants in cell-free bronchoalveolar lavage (cfBAL) DNA compared with plasma cfDNA. METHODS: Sequencing was performed at low or high coverage using two filtering algorithms to identify tumor variants on two panels targeting 77 and 197 genes respectively. RESULTS: One hundred and four sequencing files from 40 matched DNA samples of cfBAL, plasma, germline leukocytes, and archival tumor specimens in 10 patients with early-stage lung cancer were analyzed. By low-coverage sequencing, tumor-derived cfBAL variants were detected in 5/10 patients (50%) compared with 2/10 (20%) for plasma. High-coverage sequencing did not affect the number of tumor-derived variants detected in either biospecimen type. Accounting for germline mutations eliminated false-positive plasma calls regardless of coverage (0/10 patients with tumor-derived variants identified) and increased the number of cfBAL calls (5/10 patients with tumor-derived variants identified). These results were not affected by the number of targeted genes.

Examining disparities in large-scale patient-reported data capture using digital tools among cancer patients at clinical intake.

BACKGROUND: Patient-reported data can improve quality of healthcare delivery and patient outcomes. Moffitt Cancer Center ("Moffitt") administers the Electronic Patient Questionnaire (EPQ) to collect data on demographics, including sexual orientation and gender identity (SOGI), medical history, cancer risk factors, and quality of life. Here we investigated differences in EPQ completion by demographic and cancer characteristics. METHODS: An analysis including 146,142 new adult patients at Moffitt in 2009-2020 was conducted using scheduling, EPQ and cancer registry data. EPQ completion was described by calendar year and demographics. Logistic regression was used to estimate associations between demographic/cancer characteristics and EPQ completion. More recently collected information on SOGI were described. RESULTS: Patient portal usage (81%) and EPQ completion rates (79%) were consistently high since 2014. Among patients in the cancer registry, females were more likely to complete the EPQ than males (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.14-1.20). Patients ages 18-64 years were more likely to complete the EPQ than patients aged ≥65. Lower EPQ completion rates were observed among Black or African American patients (OR = 0.59, 95% CI = 0.56-0.63) as compared to Whites and among patients whose preferred language was Spanish (OR = 0.40, 95% CI = 0.36-0.44) or another language as compared to English. Furthermore, patients with localized (OR = 1.16, 95% CI = 1.12-1.19) or regional (OR = 1.16, 95% CI = 1.12-1.20) cancer were more likely to complete the EPQ compared to those with metastatic disease. Less than 3% of patients self-identified as being lesbian, gay, or bisexual and <0.1% self-identified as transgender, genderqueer, or other. CONCLUSIONS: EPQ completion rates differed across demographics highlighting opportunities for targeted process improvement. Healthcare organizations should evaluate data acquisition methods to identify potential disparities in data completeness that can impact quality of clinical care and generalizability of self-reported data.

Psychosocial characteristics and quality of life among sexual and gender minority patients with cancer.

BACKGROUND: Underserved and minoritized patients with cancer often experience more psychosocial concerns and inferior quality of life (QOL) compared with majority populations. This study compared patient-reported psychosocial characteristics and QOL among self-identified sexual and gender minority patients with cancer vs cisgender-heterosexual patients with cancer treated at a National Cancer Institute-designated comprehensive cancer center in the United States. METHODS: Self-report data from 51 503 patients were obtained from an institutional standard-of-care electronic patient questionnaire that was completed prior to, or on the day of, the patient's initial visit. The electronic patient questionnaire collects demographic information, including sexual orientation and gender identity, psychosocial variables, and QOL using the validated Short Form Health Survey-12. Sexual orientation and gender identity information was used to identify self-identified sexual and gender minority and cisgender-heterosexual persons (ie, non-self-identified sexual and gender minority). Using parametric analyses, psychosocial variables and QOL measures were compared for self-identified sexual and gender minority vs non-self-identified sexual and gender minority patients with cancer. RESULTS: Compared with non-self-identified sexual and gender minority patients (n = 50 116), self-identified sexual and gender minority patients (n = 1387, 2.7%) reported statistically significantly greater concerns regarding getting help during treatment (2.6% vs 4.3%, respectively; P = .001) and concerns with ability to seek care (16.7% vs 21.6%, respectively, P < .001). Self-identified sexual and gender minority patients reported statistically significantly elevated mental health concerns and daily emotional and pain interference (all P < .001), whereas there was no statistically significant difference in daily interference due to physical functioning. CONCLUSION: These data reveal real-world disparities among self-identified sexual and gender minority patients with cancer, which can be used to develop psychosocial interventions tailored to address the unique psychosocial and QOL needs of this underserved and minoritized population and to ultimately improve cancer care.

Lung cancer screening adherence among people living with and without HIV: An analysis of an integrated health system in Florida, United States (2012-2021).

Although lung cancer is a leading cause of death among people living with HIV (PLWH), limited research exists characterizing real-world lung cancer screening adherence among PLWH. Our objective was to compare low-dose computed tomography (LDCT) adherence among PLWH to those without HIV treated at one integrated health system. Using the University of Florida's Health Integrated Data Repository (01/01/2012-10/31/2021), we identified PLWH with at least one LDCT procedure, using Current Procedural Terminology codes(S8032/G0297/71271). Lung cancer screening adherence was defined as a second LDCT based on the Lung Imaging Reporting and Data System (Lung-RADS®). Lung-RADS categories were extracted from radiology reports using a natural language processing system. PLWH were matched with 4 randomly selected HIV-negative patients based on (+/- 1 year) age, Lung-RADS category, and calendar year. Seventy-three PLWH and 292 matched HIV-negative adults with at least one LDCT were identified. PLWH were more likely to be male (66% vs.52%,p < 0.04), non-Hispanic Black (53% vs.23%,p < 0.001), and live in an area of high poverty (45% vs.31%,p < 0.001). PLWH were more likely to be diagnosed with lung cancer after first LDCT (8% vs.0%,p < 0.001). Seventeen percent of HIV-negative and 12% of PLWH were adherent to LDCT screenings. Only 25% of PLWH diagnosed with category 4A were adherent compared to 44% of HIV-negative. On multivariable analyses, those with older age (66-80 vs.50-64 years) and with either Medicaid, charity-based, or other government insurance (vs. Medicare) were less likely to be adherent to LDCT screenings. PLWH may have poorer adherence to LDCT compared to their HIV-negative counterparts.

Cancer survivors' health behaviors and outcomes: a population-based study of sexual and gender minorities.

BACKGROUND: Most case-control studies compare cancer survivors with general population controls without considering sexual orientation or gender identity. This case-control analysis compared health risk behaviors and health outcomes among sexual and gender minority cancer survivors to those of matched sexual and gender minority participants without cancer (controls). METHODS: Using data from the 2014-2021 Behavioral Risk Factor Surveillance System, a population-based sample of 4507 cancer survivors who self-identified as transgender, gay men, bisexual men, lesbian women, or bisexual women were 1:1 propensity score matched, using age at survey, race and ethnicity, marital status, education, access to health care, and US census region. Within each sexual and gender minority group, behaviors and outcomes were compared between survivors and participants without cancer, and survivors' odds ratios and 95% confidence intervals calculated. RESULTS: Gay male survivors had higher odds of depression, poor mental health, limited usual activities, difficulty concentrating, and fair or poor health. Few differences were observed between bisexual male survivors and participants without cancer. Compared with controls, lesbian female survivors had greater odds of overweight-obese status, depression, poor physical health, and fair or poor health. Bisexual female survivors had the highest rates of current smoking, depression, poor mental health, and difficulty concentrating across all sexual and gender minority groups. Statistically significantly different from transgender controls, transgender survivors had greater odds of heavy alcohol use, physical inactivity, and fair or poor health. CONCLUSIONS: This analysis revealed an urgent need to address the high prevalence of engaging in multiple health risk behaviors and not following guidelines to avoid second cancers, additional adverse outcomes, and cancer recurrences among sexual and gender minority cancer survivors.

Lung Cancer Screening Adherence Among People with HIV Treated at an Integrated Health System in Florida.

We evaluated low-dose computed tomography (LDCT) adherence among people with HIV (PWH) treated at University of Florida (UF). From the UF Health Integrated Data Repository, we identified PWH who underwent at least one LDCT procedure (January 1, 2012-October 31, 2021). Lung cancer screening adherence was defined as having a second LDCT within recommended observation window, based on the Lung Imaging Reporting and Data System (Lung-RADS®). We identified 73 PWH with a history of at least one LDCT. PWH were mostly male (66%), non-Hispanic Black (53%), and living in urban (86%), high poverty (45%) areas. Almost 1 in 10 of PWH were diagnosed with lung cancer after their first LDCT. Overall, 48% and 41% of PWH were diagnosed with Lung-RADS categories 1 and 2, respectively. We observed that 12% of PWH were adherent to LDCT. Only 25% of PWH diagnosed with category 4A were adherent. PWH may have poor adherence to lung cancer screening.

Patient-Reported Outcomes as Interradiographic Predictors of Response in Non-Small Cell Lung Cancer.

PURPOSE: Minimally invasive biomarkers have been used as important indicators of treatment response and progression in cancers such as prostate and ovarian. Unfortunately, all biomarkers are not prognostic in all cancer types and are often not routinely collected. Patient-reported outcomes (PRO) provide a non-obtrusive, personalized measure of a patient's quality of life and symptomatology, reported directly from the patient, and are increasingly collected as part of routine care. Previous literature has shown correlations between specific PROs (i.e., insomnia, fatigue) and overall survival. Although promising, these studies often only consider single time points and ignore patient-specific dynamic changes in individual PROs, which might be early predictors of treatment response or progression. EXPERIMENTAL DESIGN: In this study, PRO dynamics were analyzed to determine if they could be used as interradiographic predictors of tumor volume changes among 85 patients with non-small cell lung cancer undergoing immunotherapy. PRO questionnaires and tumor volume scans were completed biweekly and monthly, respectively. Correlation and predictive analysis were conducted to identify specific PROs that could accurately predict patient response. RESULTS: Changes in tumor volume over time were significantly correlated with dizziness (P < 0.005), insomnia (P < 0.05), and fatigue (P < 0.05). In addition, cumulative changes in insomnia could predict progressive disease with a 77% accuracy, on average 45 days prior to the next imaging scan. CONCLUSIONS: This study presents the first time that patient-specific PRO dynamics have been considered to predict how individual patients will respond to treatment. This is an important first step in adapting treatment to improve response rates.

Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk: Insight From the INTEGRAL-ILCCO Cohort Analysis.

INTRODUCTION: Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer. METHODS: In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls. RESULTS: We identified a comprehensive list of autosomal mCAs, ChrX mCAs, and mosaic ChrY (mChrY) losses from these samples. Autosomal mCAs were detected in 4.3% of subjects, in addition to ChrX mCAs in 3.6% of females and mChrY losses in 9.6% of males. Multivariable logistic regression analysis indicated that the presence of autosomal mCAs in white blood cells was associated with an increased lung cancer risk after adjusting for key confounding factors, including age, sex, smoking status, and race. This association was mainly driven by a specific type of mCAs: copy-neutral loss of heterozygosity on autosomal chromosomes. The association between autosome copy-neutral loss of heterozygosity and increased risk of lung cancer was further confirmed in two major histologic subtypes, lung adenocarcinoma and squamous cell carcinoma. In addition, we observed a significant increase of ChrX mCAs and mChrY losses in smokers compared with nonsmokers and racial differences in certain types of mCA events. CONCLUSIONS: Our study established a link between mCAs in white blood cells and increased risk of lung cancer.

Qualitative Findings From a Survey on Patient Experiences and Satisfaction with Lung Cancer Screening.

BACKGROUND: To reveal successes and potential limitations of the lung cancer screening program, we conducted a survey that included both quantitative and open-ended questions to measure patient experiences and satisfaction with screening. METHODS: We report on the five open-ended items related to barriers to returning for screening, experience with other cancer prevention screenings, positive and negative experiences, and suggestions for improving future appointments. The open-ended responses were analyzed using constant comparison method and inductive content analysis. RESULTS: Respondents (182 patients, 86% response rate for open-ended questions) provided generally positive comments about their lung cancer screening experience. Negative comments were related to desire for more information about results, long wait times for results, and billing issues. Suggestions for improvements included: scheduling on-line appointments and text or email reminders, lower costs, and responding to uncertainty about eligibility criteria. CONCLUSION: Findings provide insights about patient experiences and satisfaction with lung cancer screening which is important given low uptake. Ongoing patient-centered feedback may improve the lung cancer screening experience and increase follow-up screening rates.