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Hong Lu,1,2 Jongphil Kim,3 Jin Qi,1,2 Qian Li,1 Ying Liu,1 Matthew B Schabath,4 Zhaoxiang Ye,1 Robert J Gillies,2 Yoganand Balagurunathan2,5 1Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 2Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 3Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 4Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 5Department of Machine Language, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USACorrespondence: Yoganand Balagurunathan; Robert J GilliesH. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USAEmail Yoganand.Balagurunathan@moffitt.org; Robert.Gillies@moffitt.orgRationale and Objectives: Evaluate ability of radiological semantic traits assessed on multi-window computed tomography (CT) to predict lung cancer risk.Materials and Methods: A total of 199 participants were investigated, including 60 incident lung cancers and 139 benign positive controls. Twenty lung window features and 2 mediastinal window features were extracted and scored on a point scale in three screening rounds. Multivariate logistic regression analysis was used to explore the association of these radiological traits with the risk of developing lung cancer. The areas under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and positive predictive value (PPV) were computed to evaluate the best predictive model.Results: Combining mediastinal window-specific features with the lung window features-based model significantly improves performance compared to individual window features. Model performance is consistent both at baseline and the first follow-up scan, with an AUROC increased from 0.822 to 0.871 (p = 0.009) and from 0.877 to 0.917 (p = 0.008), respectively, for single to multi-window feature models. We also find that the multi-window CT based model showed better specificity and PPV, with PPV at the second follow-up scan improved to 0.953.Conclusion: We find combining window semantic features improves model performance in identifying cancerous nodules. We also find that lung window features are more informative compared to mediastinal features in predicting malignancy.Keywords: multi-window, radiological, CT, lung cancer, screening

Matthew B Schabath,1,2 Tapashi B Dalvi,3 Hongyue A Dai,4 Alan L Crim,4 Anita Midha,5 Norah Shire,3 Nicholas T Gimbrone,1 Jill Walker,6 Danielle M Greenawalt,7 David Lawrence,8 James R Rigas,9 Robert Brody,9 Danielle Potter,9 Naveen S Kumar,4 Shane A Huntsman,4 Jhanelle E Gray2 1Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 3Oncology R&D, AstraZeneca, Gaithersburg, MD, USA; 4M2Gen, Tampa, FL, USA; 5Department of Personalised Healthcare and Biomarkers, AstraZeneca, Cambridge, UK; 6Department of Precision Medicine Oncology, AstraZeneca, Cambridge, UK; 7Department of iMED Oncology Informatics, AstraZeneca, Waltham, MA, USA; 8Department of Global Medicines Development, AstraZeneca, Cambridge, UK; 9Department of Global Medical Affairs Oncology, AstraZeneca, Gaithersburg, MD, USACorrespondence: Matthew B SchabathH. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USATel +1 813 745 4150Fax +1 813 745 6525Email matthew.schabath@moffitt.orgPurpose: To characterize programmed cell death ligand-1 (PD-L1) expression in relation to survival and gene mutation status in patients with advanced NSCLC. The study also explored the influence of tumor mutational burden (TMB) on PD-L1 expression and patient characteristics.Patients and methods: Adult patients with histologically or cytologically documented Stage IIIB/Stage IV/recurrent/progressive NSCLC, Eastern Cooperative Oncology Group performance status 0 to 3, and >2 lines of prior systemic treatment regimens were included in this retrospective analysis. Patients were treated from 1997 to 2015 at H. Lee Moffitt Cancer Center and Research Institute, Tampa, or at 7 community centers across the United States. PD-L1 expression level was determined using the VENTANA PD-L1 (SP263) Assay. EGFR and KRAS mutation status and ALK rearrangements were determined by targeted DNA sequencing; these were obtained from clinical records where targeted DNA sequencing was not performed. TMB was calculated as the total number of somatic mutations per sample.Results: From a total of 136 patients included in the study, 23.5% had tumors with high PD-L1 expression (≥25%). There were no significant differences in patient characteristics, overall survival (OS), and progression-free survival (PFS) between patients with high PD-L1 expression (median OS: 39.5 months; median PFS: 15.8 months) vs low PD-L1 expression (

Objective: To determine the burden of chronic obstructive pulmonary disease (COPD) on all-cause mortality in Blacks and Whites from four US communities.Methods: We determined prospectively the risk of death through December 2004 in relation to baseline (1987-1989) COPD status in 10,333 Black and White participants of the Atherosclerosis Risk in Communities (ARIC) study.Results: Over a mean follow-up of 15 years (maximum 18 years), 462 deaths occurred in Blacks and 1221 deaths occurred in Whites. Hazard ratios for all-cause mortality among Blacks and Whites were similar (hazard ratio [HR] = 1.74 in Blacks and HR = 1.59 in Whites), indicating a 59%-74% greater risk of mortality for those with COPD. However, for both those with and without COPD, crude death rates were approximately double in Blacks compared to Whites.Conclusions: Our findings suggest that given COPD, Blacks and Whites have the same proportionate increase in mortality and that the difference in death rates between Blacks and Whites cannot be explained by COPD status. The public health burden of COPD is enormous, and strategies to reduce COPD and smoking could have a large impact on total mortality rates of both Blacks and Whites. [ABSTRACT FROM AUTHOR]

Dietary folate, a water-soluble B vitamin found in a variety of fruits and vegetables, is of particular interest as a chemopreventive agent due to its role in DNA methylation and DNA synthesis and repair. We hypothesized that individuals with low folate intake would be at an increased risk for bladder cancer. Using an ongoing case-control study we assessed dietary folate in 409 incident bladder cancer patients and 451 healthy control subjects. A food-frequency questionnaire was used to estimate naturally occurring food folate (microg/kcal/day), dietary folate equivalents (DFE) from food sources (microg DFE/kcal/day), and DFE from all sources (microg DFE/kcal/day). Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Bladder cancer patients reported a statistically significant lower intake of folate than control subjects for food folate and DFE from food sources (P < 0.001) but not for DFE from all sources (P = 0.061). In the highest quartile of food folate intake there was a 54% reduced risk for bladder cancer (OR = 0.46; 95% CI = 0.29-0.73) after adjusting for age, gender, ethnicity, smoking, and total energy intake. Similarly, the highest quartile of intake was associated with a 59% reduced risk for DFE from food sources (OR = 0.41; 95% CI = 0.26-0.65) and a 35% reduced risk for DFE from all sources (OR = 0.65; 95% CI = 0.42-1.00). In the joint-effects analyses using never smokers with high folate intake as the reference group (OR = 1.0), heavy smokers with low food folate intake had a 2.31-fold (95% CI = 1.11-4.82) increased risk, whereas heavy smokers with high folate intake had a reduced OR of 1.31 (95% CI = 0.53-3.26). Although the ORs were not statistically significant, light smokers and high folate intake exhibited a protective effect (OR = 0.62; 95% CI = 0.20-1.94), whereas an increased risk was observed for light smoking and low folate intake (OR = 1.41; 95% CI = 0.57-3.45). These patterns were consistent for the joint effects of smoking and DFE from food sources and DFE from all sources. In summary, high intake of dietary folate was associated with an overall decrease in bladder cancer risk. These data may have important implications for cancer prevention; however, large, hypothesis-driven, population-based clinical trials will be required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests that high adiposity is associated 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 or low skeletal muscle index (SMI), a proxy for sarcopenia, and high or low adiposity. Four phenotypes were classified as fit (normal SMI and low adiposity; reference; 16.2%), overweight or obese (normal SMI and high adiposity; 51.2%), sarcopenia and overweight or obese (low SMI and high adiposity; 15.6%), and sarcopenia or cachexia (low SMI and 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 or obesity was associated with up to 51% and 104% increased mortality in EOC and HGSOC [Hazard Ratio (HR)] = 1.51, 95% CI = 1.05 to 2.19 and HR = 2.04, 95% CI = 1.29 to 3.21). Sarcopenia and overweight or obesity was associated with up to 66% and 67% increased mortality in EOC and HGSOC (HR = 1.66, 95% CI = 1.13 to 2.45 and HR = 1.67, 95% CI = 1.05 to 2.68). Sarcopenia or cachexia was associated with up to 73% and 109% increased mortality in EOC and HGSOC (HR = 1.73, 95% CI = 1.14 to 2.63 and HR = 2.09, 95% CI = 1.25 to 3.50)., Conclusions: Overweight or obesity, sarcopenia and overweight or obesity, and sarcopenia or 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., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Radon is a radioactive gas and a major risk factor for lung cancer (LC)., Methods: We investigated the dose-response relationship between radon and LC risk in the International Lung Cancer Consortium with 8927 cases and 5562 controls from Europe, North America, and Israel, conducted between 1992 and 2016. Spatial indoor radon exposure in the residential area (sIR) obtained from national surveys was linked to the participants' residential geolocation. Parametric linear and spline functions were fitted within a logistic regression framework., Results: We observed a non-linear spatial-dose response relationship for sIR < 200 Bq/m 3 . The lowest risk was observed for areas of mean exposure of 58 Bq/m 3 (95% CI: 56.1-59.2 Bq/m 3 ). The relative risk of lung cancer increased to the same degree in areas averaging 25 Bq/m 3 (OR = 1.31, 95% CI: 1.01-1.59) as in areas with a mean of 100 Bq/m 3 (OR = 1.34, 95% CI: 1.20-1.45). The strongest association was observed for small cell lung cancer and the weakest for squamous cell carcinoma. A stronger association was also observed in men, but only at higher exposure levels. The non-linear association is primarily observed among the younger population (age < 69 years), but not in the older population, which can potentially represent different biological radiation responses., Conclusions: The sIR is useful as proxy of individual radon exposure in epidemiological studies on lung cancer. The usual assumption of a linear, no-threshold dose-response relationship, as can be made for individual radon exposures, may not be optimal for sIR values of less than 200 Bq/m 3 ., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Health disparities in lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+), or sexual and gender minority (SGM) people are known. SGM people have higher cancer risk, but lower rates of screenings, resulting in a higher likelihood of late-stage disease. This study evaluates medical students' clinical cultural awareness in cancer care of SGM patients to identify gaps in education., Methods: This was a cross-sectional survey distributed to medical students at a academic center. There were 38 questions on demographics, attitudes, and knowledge of SGM topics. Descriptive statistics were used for demographic information and stratified analyses assessed responses by demographic subgroups., Results: There were 238 responses from 1145 students (response rate = 20.7 %). Of the responders, 91.2 % and 79 % were comfortable treating lesbian, gay, bisexual (LGB) and transgender patients respectively. Only 28.6 % and 21.8 % were confident treating LGB and transgender patients respectively after taking the survey. 91.2 % of students were interested receiving education regarding SGM health needs., Conclusion: While most medical students are comfortable treating LGBTQ+ patients, most are not confident in their knowledge. This difference is most profound in knowledge of transgender patients., Practice Implications: Schools must provide more education in SGM topics to improve student knowledge to produce competent providers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

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 ( NTRK 1, NTRK 2, NTRK 3) 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%). NTRK 1 fusions were most common (45%), followed by NTRK 3 (40%) and NTRK 2 (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.

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.

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., (© 2024. Springer Nature Limited.)

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., (© 2023 American Cancer Society.)

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., (©2024 The Authors; Published by the American Association for Cancer Research.)

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., (©2023 American Association for Cancer Research.)

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., (© 2024. The Author(s).)

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.

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., (© The Author(s) 2023. Published by Oxford University Press.)

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., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press.)

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., (©2023 The Authors; Published by the American Association for Cancer Research.)

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., (Copyright © 2023. Published by Elsevier Inc.)

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purposeof Review: The prevalence of problematic substance use is disproportionately higher among sexual and gender minority (SGM) adults compared to adults in the general population. mHealth as a treatment modality could reduce barriers to accessing substance use treatments among SGM populations. Through a qualitative literature search, the current narrative review aimed to understand the lived experiences of SGM individuals who use substances and to synthesize recommendations made in the literature to inform future mHealth interventions., Recent Findings: Positive and negative reinforcement motives were prominent reasons for substance use, which included SGM identity expression and conformity motives. Individual- and system-level treatment barriers included a lack of safe and nonjudgmental environment, shame and stigma, and limited knowledge about treatment options. Barriers were directly linked to the reported substance use treatment needs in this population., Summary: On-demand app features, real-time intervention and assessment, and anonymity should be considered in future mHealth trials., Supplementary Information: The online version contains supplementary material available at 10.1007/s40429-023-00497-0., Competing Interests: Conflicts of InterestMatthew B. Schabath, Ph.D. is a consultant for Bristol Myers Squibb., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

To alleviate health disparities experienced by sexual and gender minority (SGM) patients, cancer care professionals need further education on the needs of SGM cancer patients and their loved ones and caregivers. The Together-Equitable-Accessible-Meaningful (TEAM) Training to Improve Cancer Care for SGM Patients (TEAM SGM) was developed and piloted to address this need. This study reports healthcare professional learner outcomes from the TEAM SGM pilot intervention. The TEAM SGM Training pilot consisted of 2.5 h of content from the original online self-paced TEAM Training plus 12 1-h Zoom sessions on specialized topics in addition to readings and activities. Participants (n = 28), representing seven cancer service organizations from six states in the USA, were recruited through newsletter listservs and social media. All participants (n = 28) completed the pre-test and twenty-two participants completed the post-test. Using five factors confirmed in a separate Confirmatory Factor Analysis, paired t-tests of TEAM SGM participant pre- and post-test data were conducted. Statistically significant improvements were found in four of five factors: Environmental Cues (t(21) = 2.56, p = .018), Knowledge (t(21) = 2.15, p = .043), Clinical Preparedness (t(7) = 3.89, p = .006), Clinical Behaviors (t(21) = 2.48, p = .022). The Attitudes factor was not significantly improved from pre-intervention to post-intervention likely due to strong affirming attitudes toward SGM patients at baseline. TEAM SGM is a feasible, effective training to build capacity in SGM-affirming care for cancer care providers., (© 2022. The Author(s) under exclusive licence to American Association for Cancer Education.)

Background: The purpose of this systematic review was to examine the timing and patterns of recurrence for patients with regionally metastatic melanoma on the basis of nodal management and receipt of adjuvant therapy., Methods: We identified randomized controlled trials and non-randomized studies published between 2010 and 2020 that reported timing and/or patterns of recurrence. We evaluated recurrence-free survival (RFS), location of recurrence, and surveillance strategy on the basis of receipt of adjuvant systemic therapy and nodal management with observation versus completion dissection. We compared differences in patterns of recurrence across studies using RevMan. RFS was evaluated graphically using point estimates and confidence intervals., Results: Among the 19 publications, there was wide variation in study populations, imaging surveillance regimens, and format of recurrence reporting. Patterns of disease recurrence did not differ between adjuvant and placebo/observation groups. A total of 11 studies reported RFS at variable time intervals, which ranged in adjuvant therapy groups (38-88% at 1 year, 29-67% at 2 years, 33-58% at 3 years, and 34-53% at 5 years) and placebo/observation groups (47-63% at 1 year, 39-47% at 2 years, 33-68% at 3 years, and 57% at 5 years). Anti-PD-1 immune therapy and BRAF/MEK inhibitor therapy were superior to placebo at year 1., Discussion: We found that adjuvant treatment improved RFS but did not alter the patterns of disease recurrence compared with patients managed without adjuvant systemic treatment. Future studies should separately report sites of disease recurrence on the basis of specific adjuvant systemic treatment and surveillance practices to better advise patients about their patterns and risk of recurrence., (© 2022. Society of Surgical Oncology.)

Importance: Transgender and gender-diverse individuals face unique challenges, including barriers to health care access and inequities in treatment, that may influence cancer risk and outcomes., Observations: In this narrative review, a scoping review was conducted focusing on primary and secondary prevention and epidemiology of cancer, barriers to health care services, and health care practitioners' knowledge about specific issues pertaining to transgender and gender-diverse individuals. PubMed, the Cochrane Library, and Embase, were reviewed for citations from their inception to December 31, 2021. This review revealed that transgender and gender-diverse people had a high prevalence of tobacco consumption and alcohol use and high rates of infection with human papillomavirus (HPV) and HIV. Transgender and gender-diverse individuals were less likely to adhere to cancer screening programs and had a higher incidence of HIV- and HPV-associated cancers. Social and economic determinants seemed to drive these disparities in risk factors and outcomes. A lack of knowledge about gender minorities' health needs among health care practitioners was evidenced, and it represented a major hurdle to cancer prevention, care, and survivorship for transgender and gender-diverse individuals. Discrimination, discomfort caused by gender-labeled oncological services, stigma, and lack of cultural sensitivity of health care practitioners were other barriers met by transgender and gender-diverse persons in the oncology setting., Conclusions and Relevance: The findings suggest that transgender and gender-diverse peoples' needs in the cancer care continuum are not optimally addressed. Effective solutions are needed to offer the best care to every patient in a person-centric and gender diversity-sensitive environment.

Objectives: To assess training needs for providers who care for adolescent and young adult (AYA) lesbian, gay, bisexual, transgender/queer questioning (LGBTQ) cancer patients, we conducted a mixed-method survey. During their cancer care experience, AYA cancer patients experience physical, psychosocial, and reproductive health challenges. In addition to these challenges, AYA LGBTQ individuals are a diverse and medically underserved population who experience unique challenges and disparities in medical care. Methods: Health care providers ( n  = 351) who participated in our reproductive health in cancer training program completed a survey with 28 quantitative items and 4 open-ended items assessing knowledge, confidence discussing reproductive health, and confidence in knowledge specific to reproductive needs and general health needs among AYA LGBTQ patients. Results: Confidence discussing and confidence in knowledge of reproductive and general health needs are lower regarding transgender and nonbinary patients. Nearly half of providers (45%) demonstrated low knowledge, while 38% and 17% demonstrated moderate and high knowledge, respectively. Open comments indicated providers desired more training around the needs of Trans and nonbinary patients, and creating welcoming environments. Conclusions: The majority of our participants demonstrate low or moderate knowledge regarding factors that can influence AYA LGBTQ patient care, suggesting that this is a key area for improvement. Furthermore, improving provider knowledge may subsequently improve confidence in general and reproductive needs of LGBTQ patients, resulting in improved patient-centered care. Improving provider knowledge and confidence may then ultimately help reduce disparities in cancer care among this patient population.

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., (Copyright © 2022. Published by Elsevier Inc.)

Sarcomas are relatively rare malignancies accounting for about 1% of all cancer diagnoses. Studies on sarcomas comprising large cohorts covering extended time periods are lacking. Therefore, this study aimed to evaluate the impact of demographic, behavioral, and clinical characteristics on overall survival (OS) among individuals diagnosed with soft tissue sarcoma (STS) or bone sarcoma at the Moffitt Cancer Center between 1986 and 2014. Unadjusted and multivariable Cox proportional hazard regression (CPHR) models were constructed to generate hazard ratios (HRs) and 95% confidence intervals (CIs) to evaluate associations between a range of demographic, behavioral, and clinical characteristics, and OS. Additionally, Kaplan-Meier survival curves, associated log-rank statistics, and adjusted CPHR models were generated by time periods based on the year of first contact (1986-1994, 1995-1999, 2000-2005, 2006-2010, 2011-2014) to evaluate for temporal differences in OS. Of the 2570 patients, 2037 were diagnosed with STS, whereas 533 were diagnosed with bone sarcoma. At the time of analysis, 50% of the population were alive. In multivariable analyses, we observed poorer survival for patients ≥ 40 years of age (HR = 1.54, 95% CI = 1.34-1.78), current smokers (HR = 1.18, 95% CI = 1.01-1.37), patients with metastasis (HR = 2.19, 95% CI = 1.95-2.47), and patients not receiving first-line surgery treatment (HR = 2.11, 95% CI = 1.82-2.45). We discovered limited improvements in OS over time among individuals diagnosed with STS or bone sarcomas with the exception of gastrointestinal stromal tumors (GIST), which showed a significant improvement in OS across time periods ( p = 0.0034). Overall, we identified well-established characteristics associated with OS (e.g., metastasis) in addition to factors (e.g., smoking status) not previously reported to impact OS. Improvements in survival over time have been relatively modest, suggesting the need for improved therapeutic options, especially for those diagnosed with less frequent sarcomas.

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.

Background: The lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) community experiences health disparities. It is thus imperative that medical trainees receive training in the care of LGBTQ community. The objective of this study was to identify gaps in knowledge and comfort among medical school students in providing care for the LGBTQ community., Methods: An online survey was administered to medical students at 3 institutions in the United States from December 2020 to March 2021. Using a Likert scale, the survey assessed attitudes, comfort, and knowledge in providing care for the LGBTQ community. The survey included questions for each specific LGBTQ population. Results were quantified using descriptive and stratified analyses, and an exploratory factor analysis was used to calculate attitude summary measure (ASM) scores. A total knowledge score was calculated, with higher values indicating greater knowledge., Results: Among the 300 medical students who completed the survey, the majority were female (55.7%), White (54.7%), and heterosexual (64.3%). The majority of medical students felt comfortable (strongly agree/agree) participating in the care of lesbian (94.3%), gay (96.0%), and bisexual (96.3%) patients; this percentage dropped to 82.3% for non-binary and 71.3% for transgender patients. Only 27.0% of medical students reported confidence in their knowledge of health needs of transgender patients. LGBTQ self-identification, percent of core rotations completed in school, region of country, and friends and/or family who are part of the LGBTQ community were significantly associated with various ASM scores. Knowledge questions yielded high percentages of "neutral" responses, and medical students who identified as LGBTQ had significantly higher total knowledge scores., Conclusions: Overall, the surveyed medical students feel comfortable and willing to provide care for LGBTQ persons. But, there is limited knowledge about specific LGBTQ health needs. More education and training in the needs of transgender and non-binary patients, in particular, is indicated.

Purpose: This article describes the development of the LGBTQ Oncofertility Education (LOvE-ECHO). The Enriching Communication skills for Health professionals in Oncofertility (ECHO) team created this new education module in response to the needs of oncology allied health professionals to provide inclusive and affirming care to lesbian, gay, bisexual, transgender, and queer (LGBTQ) AYA patients with cancer. The new module is part of the ECHO, a web-based educational training program for oncology allied health professionals to improve communication with AYA about reproductive health. Methods: The development of LOvE-ECHO includes five phases-learner needs assessment, content development and revision, piloting, and finalizing. Results from a survey of past ECHO learners and a comprehensive literature review provided the basis of need for this module and identified the most prominent gaps in knowledge and training. Content development and revision were iterative, including input, feedback, and voices from LQBTA youth and survivors, researchers, reproductive health experts, oncology clinicians, and web developer. Results: The complete LOvE-ECHO module consists of both didactic and interactive lessons. A glossary of terms and narrated PowerPoint establishes a knowledge base and shared vocabulary. Three interactive cases and a plan for action provide learners opportunities to test their new knowledge and transfer it to their practice. Conclusion: The module has received positive feedback to date. It is currently being piloted with new learners who complete a pre-test and post-test, as well as a feedback survey. Analysis of these results will inform revisions to the module.

Differences by sex in lung cancer incidence and mortality have been reported which cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene-sex interaction analysis using genotypes from a lung cancer cohort including ~ 47 000 individuals with European ancestry. Three low-frequency variants (minor allele frequency < 0.05), rs17662871 [odds ratio (OR) = 0.71, P = 4.29×10-8); rs79942605 (OR = 2.17, P = 2.81×10-8) and rs208908 (OR = 0.70, P = 4.54×10-8) were identified with different risk effect of lung cancer between men and women. Further expression quantitative trait loci and functional annotation analysis suggested rs208908 affects lung cancer risk through differential regulation of Coxsackie virus and adenovirus receptor gene expression in lung tissues between men and women. Our study is one of the first studies to provide novel insights about the genetic and molecular basis for sex disparity in lung cancer development., (© The Author(s) 2022. Published by Oxford University Press.)

Background: While societal acceptance for sexual and gender minority (SGM) individuals is increasing, this group continues to face barriers to quality healthcare. Little is known about clinicians' experiences with SGM patients in the oncology setting. To address this, a mixed method survey was administered to members of the ECOG-ACRIN Cancer Research Group., Materials and Methods: We report results from the open-ended portion of the survey. Four questions asked clinicians to describe experiences with SGM patients, reservations in caring for them, suggestions for improvement in SGM cancer care, and additional comments. Data were analyzed using content analysis and the constant comparison method., Results: The majority of respondents noted they had no or little familiarity with SGM patients. A minority of respondents noted experience with gay and lesbian patients, but not transgender patients; many who reported experience with transgender patients also noted difficulty navigating the correct use of pronouns. Many respondents also highlighted positive experiences with SGM patients. Suggestions for improvement in SGM cancer care included providing widespread training, attending to unique end-of-life care issues among SGM patients, and engaging in efforts to build trust., Conclusion: Clinicians have minimal experiences with SGM patients with cancer but desire training. Training the entire workforce may improve trust with, outreach efforts to, and cancer care delivery to the SGM community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tamargo, Mitchell, Wagner, Simon, Carlos, Giantonio, Schabath and Quinn.)

Background: Previous studies show an association between smoking and anal cancer. The objective of this study was to assess the association between smoking and anal HPV (human papillomavirus) prevalence, incidence, and persistence in men., Methods: The HPV Infection in Men (HIM) Study is a multinational study that enrolled HIV-negative men. At baseline and follow-up visits, anal specimens were collected. HPV genotyping was assessed by linear array. Prevalence ratios (PR) were used to assess the association between smoking and anal HPV prevalence. Odds ratios (OR) were used to assess the association between smoking and anal HPV incidence and ≥12-months persistence., Results: Current smokers have a higher prevalence [adjusted PR (aPR), 1.36; 95% confidence interval (CI), 1.06-1.73) and incidence [adjusted OR (aOR), 1.74; 95% CI, 1.26-2.39] and ≥12-months persistence (aOR, 1.67; 95% CI, 1.19-2.33) of any anal HPV compared with never smokers. There were no differences in the prevalence, incidence, or persistence of anal HPV between former and never smokers. Smoking status was not associated with the prevalence or persistence of anal HPV among men who have sex with men but was associated with higher incidence of HR-HPV. Among men that have sex with women (MSW), current smokers had an increased prevalence and incidence of LR-HPV compared with never smokers., Conclusions: Current smokers had a higher prevalence, persistence, and incidence of HPV compared with never smokers. Further research is needed to assess the role smoking in anal HPV persistence and progression to disease., Impact: Prevention initiatives should raise awareness about smoking and the risk factor of anal HPV infection and anal cancer., (©2022 American Association for Cancer Research.)

Purpose: Lack of collection of sexual orientation and gender identity (SOGI) data in oncology practices limits assessment of sexual and gender minority (SGM) cancer patients' experiences and restricts opportunities to improve health outcomes of SGM patients. Despite national calls for routine SOGI data collection, individual-level and institutional barriers hinder progress. This study aimed to identify these barriers in oncology., Methods: An online survey of ASCO members and others assessed SOGI data collection in oncology practices, institutional characteristics related to SOGI data collection, respondents' attitudes about SOGI data and SGM patients, and respondent demographics. Logistic regression calculated adjusted odds ratios (ORs) and 95% CIs for factors associated with sexual orientation (SO) and gender identity (GI) data collection., Results: Less than half of 257 respondents reported institutional SO and GI data collection (40% and 46%, respectively), whereas over a third reported no institutional data collection (34% and 32%, respectively) and the remainder were unsure (21% and 17%, respectively). Most respondents felt that knowing both SO and GI was important for quality care (77% and 85%, respectively). Collection of SO and GI was significantly associated in separate models with leadership support (ORs = 8.01 and 6.02, respectively), having resources for SOGI data collection (ORs = 10.6 and 18.7, respectively), and respondents' belief that knowing patient SO and GI is important (ORs = 4.28 and 2.76, respectively). Themes from qualitative comments mirrored the key factors identified in our quantitative analysis., Conclusion: Three self-reinforcing factors emerged as critical drivers for collecting SOGI data: leadership support, dedicated resources, and individual respondents' attitudes. Policy mandates, implementation science, and clinical reimbursement are strategies to advance meaningful data collection and use in clinical practice.

Introduction: Although genome-wide association studies have been conducted to investigate genetic variation of lung tumorigenesis, little is known about gene-gene (G × G) interactions that may influence the risk of non-small cell lung cancer (NSCLC)., Methods: Leveraging a total of 445,221 European-descent participants from the International Lung Cancer Consortium OncoArray project, Transdisciplinary Research in Cancer of the Lung and UK Biobank, we performed a large-scale genome-wide G × G interaction study on European NSCLC risk by a series of analyses. First, we used BiForce to evaluate and rank more than 58 billion G × G interactions from 340,958 single-nucleotide polymorphisms (SNPs). Then, the top interactions were further tested by demographically adjusted logistic regression models. Finally, we used the selected interactions to build lung cancer screening models of NSCLC, separately, for never and ever smokers., Results: With the Bonferroni correction, we identified eight statistically significant pairs of SNPs, which predominantly appeared in the 6p21.32 and 5p15.33 regions (e.g., rs521828 C6orf10 and rs204999 PRRT1 , OR interaction  = 1.17, p = 6.57 × 10 -13 ; rs3135369 BTNL2 and rs2858859 HLA-DQA1 , OR interaction  = 1.17, p = 2.43 × 10 -13 ; rs2858859 HLA-DQA1 and rs9275572 HLA-DQA2 , OR interaction  = 1.15, p = 2.84 × 10 -13 ; rs2853668 TERT and rs62329694 CLPTM1L , OR interaction  = 0.73, p = 2.70 × 10 -13 ). Notably, even with much genetic heterogeneity across ethnicities, three pairs of SNPs in the 6p21.32 region identified from the European-ancestry population remained significant among an Asian population from the Nanjing Medical University Global Screening Array project (rs521828 C6orf10 and rs204999 PRRT1 , OR interaction  = 1.13, p = 0.008; rs3135369 BTNL2 and rs2858859 HLA-DQA1 , OR interaction  = 1.11, p = 5.23 × 10 -4 ; rs3135369 BTNL2 and rs9271300 HLA-DQA1 , OR interaction  = 0.89, p = 0.006). The interaction-empowered polygenetic risk score that integrated classical polygenetic risk score and G × G information score was remarkable in lung cancer risk stratification., Conclusions: Important G × G interactions were identified and enriched in the 5p15.33 and 6p21.32 regions, which may enhance lung cancer screening models., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.