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Purpose: Health-related behaviors among underweight women have received less attention than overweight and obese women in the United States. Our purposes were to estimate the rate and modifiers of breast, cervical, and colorectal cancer screening adherence among underweight women and compare it to other body mass index (BMI) categories. Materials and Methods: We used sampling weighted data from 2016 Behavioral Risk Factor Surveillance System (BRFSS) of age-eligible women (breast cancer screening, n = 163,164; cervical, n = 113,883 and colorectal, n = 128,287). We defined breast, cervical, and colorectal cancer screening using the US Preventive Services Task Force (USPSTF) guidelines. We calculated the prevalence of screening among four BMI categories (underweight <18.5, normal weight ≥18.5 to <25, overweight ≥25 to <30, and obese ≥30). Logistic regression models assessed the independent effect of BMI on screening adherence. Results: Underweight women had significantly lower breast (62.9%), cervical (67.5%), and colorectal (62.6%) cancer screening rates compared to other BMI categories. In logistic regression models, being underweight was associated with decreased odds of breast (odds ratio [OR] = 0.66; 95% confidence interval [CI] = 0.49–0.88) and cervical (OR = 0.54, 95% CI = 0.34–0.84), but not colorectal (OR = 0.88; 95% CI = 0.66–1.18) cancer screening adherence. We did not demonstrate a significant association between obesity and screening rates for any of the three cancers. Underweight women reported higher rates of smoking and lower levels of educational attainment, income, and insurance coverage compared to all other groups. Higher rates of chronic illness and health access hardship were observed among underweight women. Conclusion: BMI variably affects cancer screening. Compared to normal-weight women, being underweight is associated with breast and cervical cancer screening nonadherence. Promoting breast and cervical cancer screening among this currently underserved population may reduce future disparities. [ABSTRACT FROM AUTHOR]

The article discusses the health disparities experienced by the lesbian, gay, bisexual, transgender, queer/questioning community (LGBTQ), often referred to as sexual and gender minorities (SGM). Topics include reason for the underrepresentation of SGMs in cancer databases and research, institutional efforts done to focus on the health disparities experienced by SGM populations, and the importance of the systemic collection and analysis of sexual orientation and gender identity (SOGI) data.

Purpose: To determine if clinical and CT characteristics of surgically resected lung adenocarcinomas can distinguish those harboring ALK rearrangements from EGFR mutations.Materials and Methods: Patients who had surgical resection and histologically confirmed lung adenocarcinoma were enrolled, including 41 patients with ALK rearrangements and 66 patients with EGFR mutations. Eighteen categorical and six quantitative CT characteristics were used to evaluate the tumors. Differences in clinical and CT characteristics between the two groups were investigated.Results: Age (P=0.003), histological subtypes (P<0.001), pathological stage (P=0.007), and five CT characteristics, including size (P<0.001), GGO (P=0.001), bubble-like lucency (P=0.048), lymphadenopathy (P=0.001), and tumor shadow disappearance rate (P=0.005) were significantly different between patients harboring ALK rearrangements compared to patients with EGFR mutations. When we compared histologic components, a solid pattern was more common (P=0.009) in tumors with ALK rearrangements, and lepidic and acinar patterns were more common (P<0.001 and P=0.040, respectively) in those with EGFR mutations. Backward elimination analyses revealed that age (OR=0.93; 95% CI 0.89-0.98), GGO (OR=0.14; 95% CI 0.03-0.67), and lymphadenopathy (OR=4.15; 95% CI 1.49-11.60) were significantly associated with ALK rearrangement status.Conclusion: Our analyses revealed that clinical and CT characteristics of lung adenocarcinomas harboring ALK rearrangements were significantly different, compared with those with EGFR mutations. These differences may be related to the molecular pathology of these diseases. [ABSTRACT FROM AUTHOR]

Lung cancer screening identifies cancers with heterogeneous behaviors. Some lung cancers will be identified among patients who had prior negative CT screens and upon follow-up scans develop a de novo nodule that was determined to be cancerous. Other lung cancers will be identified among patients who had one or more prior stable positive scans that were not determined to be lung cancer (indeterminate pulmonary nodules), but in follow-up scans was diagnosed with an incidence lung cancer. Using data from the CT arm of the National Lung Screening Trial, this analysis investigated differences in patient characteristics and survival endpoints between prevalence-, interval-, and screen-detected lung cancers, characterized based on sequence of screening results. Lung cancers immediately following a positive baseline (T0), and prior to the T1 screen, formed the prevalence cohort. Interval cancers were diagnosed following a negative screen at any time point prior to the next screening round. Two cohorts of screen-detected lung cancers (SDLC) were identified that had a baseline positive screen that was that was not determined to be lung cancer (i.e., an indeterminate pulmonary nodule), but in follow-up scans was diagnosed with an incidence lung cancer 12 (SDLC1) or 24 (SDLC2) months later. Two other incidence cohorts had screen-detected lung cancers that had baseline negative screen and upon follow-up scans developed a de novo nodule determined to be cancerous at 12 (SDLC3) or 24 (SDLC4) months later. Differences in patient characteristics, progression-free survival (PFS), and overall survival (OS) were assessed. The lung cancer-specific death rate was higher for SDLC3/SDLC4 compared to SDLC1/SDLC2 lung cancers (136.6/1,000 person-years vs. 71.3/1,000 person-years, P < 0.001). Moreover, PFS and OS were significantly lower for SDLC3/SDLC4 compared to SDLC1/SDLC2 (P < 0.004; P < 0.002, respectively). The findings were consistent when stratified by stage and histology. Multivariable Cox proportional models revealed that the SDLC3/SDLC4 case groups were associated with significantly poorer PFS (HR = 1.89; 95% CI 1.31–2.74) and OS (HR = 1.80; 95% CI 1.21–2.67) compared to SDLC1/SDLC2 lung cancers (HR = 1.00). Lung cancer patients who develop a de novo nodule that determined to be cancerous (i.e., at least one negative CT screen prior to cancer diagnosis) had poorer survival outcomes compared to patients who had at least one positive screen prior to cancer diagnosis. As such, the observation that de novo screen-detected are associated with poorer survival could be attributed to faster growing, more aggressive cancers that arose from a lung environment previously lacking focal abnormalities. [ABSTRACT FROM AUTHOR]

The lesbian, gay, bisexual, transgender/transsexual, queer/questioning, and intersex population experiences cancer health disparities due to a lack of disclosure and knowledge regarding increased cancer risk. Oncology health care providers and institutions should create environments that encourage the disclosure of sexual orientation and identity. [ABSTRACT FROM AUTHOR]

Objectives Moderate alcohol consumption can impair host defence against viral infections. The objective of this cross-sectional analysis was to assess the association between alcohol intake and prevalent human papillomavirus (HPV) infection among US men enrolled in the HPV in Men (HIM) study using quantitative alcohol intake measured from a Food Frequency Questionnaire. Methods The HIM study is a prospective, multinational study of the natural history of HPV infection. For this report, we restricted our analyses to men from the US cohort (N =1313). Samples from the corona of glans penis, penile shaft and scrotum were combined for HPV DNA testing. Self-reported alcohol intake was quantified by grams of alcohol intake per day. Multivariable prevalence ratios (mPRs) were used to assess the association between alcohol intake and HPV infections. Results Prevalent infections were significantly higher among men in the highest quartile of alcohol intake and multivariable models revealed that the highest quartile of alcohol intake was associated with significantly increased risks for any (mPR=1.13; 95% CI 1.00 to 1.27) HPV types and oncogenic (mPR=1.35; 95% CI 1.08 to 1.68) HPV types. The fourth quartile of alcohol intake was associated with elevated risks for prevalent HPV infection across all strata of number of sexual partners and among never-smokers and current smokers, but not among former smokers. Conclusions These results demonstrate that high intake of alcohol is associated with an increased risk for prevalent HPV infections among men. The biological role that alcohol plays in genital HPV infection remains understudied and limited epidemiological data exist, especially among men. [ABSTRACT FROM AUTHOR]

Objectives An assessment of temporal trends in patient survival is important to determine the progress toward patient outcomes and to reveal where advancements must be made. This study assessed temporal changes spanning 22 years in demographics, clinical characteristics, and overall survival of small cell lung cancer (SCLC) patients. Materials and methods This analysis included 1032 SCLC patients spanning two time-periods from the H. Lee Moffitt Cancer Center and Research Institute: 1986–1999 ( N = 410) and 2000–2008 ( N = 622). Kaplan–Meier survival curves and log-rank statistics were used to assess survival rates across the two time-periods and multivariable Cox proportional hazards models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs). Results The overall 5-year survival rate significantly increased from 8.3% for the 1986–1999 time-period to 11.0% ( P < 0.001) for the 2000–2008 time-period, and the median survival time increased from 11.3 months (95% CI 10.5–12.7) to 15.2 months (95% CI 13.6–16.6). We also observed significant increases in stage-specific median survival times and survival rates across the two time-periods. A multivariable Cox proportional hazards model for the entire cohort revealed significant increased risk of death for patients diagnosed in 1986–1999 (HR = 1.29; 95% CI 1.11–1.49), patients diagnosed between 60 and 69 years of age (HR = 1.33; 95% CI 1.04–1.49) and over 70 years of age (HR = 1.63; 95% CI 1.26–2.11), men (HR = 1.33; 95% CI 1.16–1.53), patients with no first course treatment (HR = 2.17; 95% CI 1.57–3.00) and extensive stage SCLC (HR = 2.79; 95% CI 2.35–3.30). Conclusion This analysis demonstrated significant improvements in overall and stage-specific median survival times and survival rates of SCLC patients treated at the Moffitt Cancer Center from 1986 to 2008. [ABSTRACT FROM AUTHOR]

In preparation for the development of a rapid tissue donation (RTD) programme, we surveyed healthcare providers (HCPs) in our institution about knowledge and attitudes related to RTD with lung cancer patients. A 31 -item web based survey was developed collecting data on demographics, knowledge and attitudes about RTD. The survey contained three items measuring participants' knowledge about RTD, five items assessing attitudes towards RTD recruitment and six items assessing HCPs' level of agreement with factors influencing decisions to discuss RTD. Response options were presented on a 5-point Likert scale. Ninety-one HCPs participated in the study. 66% indicated they had never heard of RTD prior to the survey, 78% rated knowledge of RTD as none or limited and 95.6% reported not having ethical or religious concerns about discussing RTD with patients. The majority were either not comfortable (17.8%) or not sure if they felt comfortable discussing RTD with cancer patients (42.2%). 56.1% indicated their knowledge of RTD would play an integral role in their decision to discuss RTD with patients. 71.4% reported concerns with RTD discussion and the emotional state of the patient. Physicians and nurses play an important role in initiating conversations about recruitment and donation to research that can ultimately influence uptake. Increasing HCP knowledge about RTD is a necessary step towards building an RTD programme. Our study provides important information about characteristics associated with low levels of knowledge and practice related to RTD where additional education and training may be warranted. [ABSTRACT FROM AUTHOR]

Presently, there are few validated biomarkers that can predict survival or treatment response for non-small cell lung cancer (NSCLC) and most are based on tumor markers. Biomarkers based on germ line DNA variations represent a valuable complementary strategy, which could have translational implications by subclassifying patients to tailored, patient-specific treatment. We analyzed single nucleotide polymorphisms (SNPs) in 53 inflammation-related genes among 651 NSCLC patients. Multivariable Cox proportional hazard models, adjusted for lung cancer prognostic factors, were used to assess the association of genotypes and haplotypes with overall survival. Four of the top 15 SNPs associated with survival were located in the TNF-receptor superfamily member 10b (TNFRSF10B) gene. The T-allele of the top ranked SNP (rs11785599) was associated with a 41% increased risk of death (95% confidence interval [CI] = 1.16–1.70) and the other three TNFRSF10B SNPs (rs1047275, rs4460370 and rs883429) exhibited a 35% (95% CI = 1.11–1.65), 29% (95% CI = 1.06–1.57) and 24% (95% CI = 0.99–1.54) increased risk of death, respectively. Haplotype analyses revealed that the most common risk haplotype (TCTT) was associated with a 78% (95% CI = 1.25–2.54) increased risk of death compared with the low-risk haplotype (CGCC). When the data were stratified by treatment, the risk haplotypes exhibited statistically significantly increased risk of death among patients who had surgery only and no statistically significant effects among patients who had surgery and adjuvant chemotherapy. These data suggest that possessing one or more risk alleles in TNFRSF10B is associated with an increased risk of death. Validated germ line biomarkers may have potential important clinical implications by optimizing patient-specific treatment. [ABSTRACT FROM PUBLISHER]

Abstract: 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 (μg/kcal/day), dietary folate equivalents (DFE) from food sources (μg DFE/kcal/day), and DFE from all sources (μg 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]

Context Despite lung-specific in vitro and in vivo studies that support a chemopreventive role for phytoestrogens, there has been little epidemiologic research focused on dietary intake of phytoestrogens and risk of lung cancer. Objective To examine the relationship between dietary intake of phytoestrogens and risk of lung cancer. Design, Setting, and Participants Ongoing US case-control study of 1674 patients with lung cancer (cases) and 1735 matched healthy controls. From July 1995 through October 2003, participants were personally interviewed with epidemiologic and food frequency questionnaires to collect demographic information and to quantify dietary intake of 12 individual phytoestrogens. Main Outcome Measure Risk of lung cancer, estimated using unconditional multivariable logistic regression analyses stratified by sex and smoking status and adjusted for established and putative lung cancer risk factors. Results Reductions in risk of lung cancer tended to increase with each increasing quartile of phytoestrogen intake. The highest quartiles of total phytosterols, isoflavones, lignans, and phytoestrogens were each associated with reductions in risk of lung cancer ranging from 21% for phytosterols (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.64-0.97; P = .03 for trend) to 46% for total phytoestrogens from food sources only (OR, 0.54; 95% CI, 0.42-0.70; P<.001 for trend). Sex-specific effects were also apparent. For men, statistically significant trends for decreasing risk with increasing intake were noted for each phytoestrogen group, with protective effects for the highest quartile of intake ranging from 24% for phytosterols (OR, 0.76; 95% CI, 0.56-1.02; P = .04 for trend) to 44% for isoflavones (OR, 0.56; 95% CI, 0.41-0.76; P<.001 for trend), while in women, significant trends were only present for intake of total phytoestrogens from food sources only, with a 34% (OR, 0.66; 95% CI, 0.46-0.96; P = .01 for trend) protective effect for the highest quartile of intake. The apparent benefits of high phytoestrogen intake were evident in both never and current smokers but less apparent in former smokers. In women, statistically significant joint effects were evident between hormone therapy use and phytoestrogen intake. Specifically, high intake of the lignans enterolactone and enterodiol and use of hormone therapy were associated with a 50% (OR, 0.50; 95% CI, 0.31-0.68; P = .04 for interaction) reduction in risk of lung cancer. Conclusions While there are limitations and concerns regarding case-control studies of diet and cancer, these data provide further support for the limited but growing epidemiologic evidence that phytoestrogens are associated with a decrease in risk of lung cancer. Confirmation of these findings is still required in large-scale, hypothesis-driven, prospective studies. [ABSTRACT FROM AUTHOR]

In vitro and in vivo studies have shown that carotenoid supplementation is associated with decreased DNA damage, but the role of dietary carotenoids in cancer risk remains controversial because epidemiologic studies have yielded conflicting results. Limited data exist regarding the role of dietary carotenoids in the context of constitutional genetic instability in cancer risk. This case-control study estimated dietary carotenoid intake [microg/(kJ . d)] from a FFQ for 423 patients with bladder cancer and 467 healthy controls, and quantified baseline and benzo[a]pyrene diol epoxide (BPDE)- and gamma-radiation-induced DNA damage in the peripheral blood lymphocytes using the comet assay. Overall, intake of total carotenoids was lower (P < 0.01) for bladder cancer cases (mean +/- SD: 1273.4 +/- 688.9) compared with healthy controls (1501.3 +/- 791.5). When categorized into quartiles, there was an inverse association between increasing levels of carotenoid intake and bladder cancer risk with greatest protective effect [odds ratio (OR) = 0.56, 95% CI, 0.37-0.85] in the quartile with the highest level of intake. Baseline and mutagen-induced DNA damage was significantly higher in cases than in controls; when analyzed jointly with carotenoid intake, high DNA damage and low carotenoid intake were associated with the highest risk. For example, with high baseline DNA damage and low total carotenoid intake, the OR was 3.08 (95% CI, 1.64-5.77); with high baseline DNA damage and high total carotenoid intake, the risk was somewhat attenuated (OR = 2.49, 95% CI, 1.28-4.84). The risk was decreased further for low baseline DNA damage and low total carotenoid intake (OR = 2.18; 95% CI, 1.13-4.22). This study provides evidence of a preventive role for carotenoids in bladder cancer, and these data may have important implications for cancer prevention, especially for individuals susceptible to DNA damage. [ABSTRACT FROM AUTHOR]

Background: Latent genetic instability has been associated with an increased risk for several cancers. We used the comet assay (single-cell gel electrophoresis) to assess whether genetic instability, as reflected by susceptibility to DNA damage, was associated with the risk of bladder cancer in a case-control study.Methods: We used the comet assay to measure baseline and benzo[a]pyrene diol epoxide (BPDE)- and gamma-radiation-induced DNA damage in individual peripheral blood lymphocytes from 114 incident case patients with bladder cancer and 145 matched healthy control subjects. All subjects provided personal information, including smoking history. DNA damage was visualized with the comet assay and quantified by the Olive tail moment parameter, a relative measure. Multivariable analysis was used to assess relative risks for bladder cancer associated with DNA damage. All statistical tests were two-sided.Results: Baseline levels of DNA damage were statistically significantly higher in case patients (tail moment = 1.40) than in control subjects (tail moment = 1.21) (difference = 0.19, 95% confidence interval [CI] = 0.04 to 0.32; P =.015), as were gamma-radiation-induced (tail moment = 4.76 versus 4.22; difference = 0.54, 95% CI = 0.11 to 0.96; P =.013) and BPDE-induced (tail moment = 4.06 versus 3.45; difference = 0.61, 95% CI = 0.23 to 0.99; P =.002) DNA damage. When data were dichotomized at the median value for DNA damage in control subjects and adjusted for age, sex, ethnicity, and smoking status, an increased estimated relative risk of bladder cancer was statistically significantly associated with DNA damage at baseline (odds ratio [OR] = 1.84, 95% CI = 1.07 to 3.15) and after gamma-radiation (OR = 1.81, 95% CI = 1.04 to 3.14) but not after BPDE treatment (OR = 1.69, 95% CI = 0.98 to 2.93).Conclusion: Latent genetic instability as measured by the comet assay is associated with an increased estimated relative risk of bladder cancer. [ABSTRACT FROM AUTHOR]

Myeloperoxidase (MPO) is a metabolic/oxidative enzyme found in neutrophils and monocytes that contributes to pulmonary carcinogenesis through activation of specific procarcinogens including benzo[a]pyrene intermediates, 4-aminobiphenyl and the arylamines. There is a G→A polymorphism located in the 5′ untranslated region of the MPO gene that may be responsible for reduced transcriptional activity due to the decreased binding affinity for the SP1 transcription factor. Individuals with one or two copies of the A-allele may be afforded protection due to decreased transcriptional activity of MPO and subsequent decreased metabolic activation of procarcinogens. Previous studies have reported a range of protective effects in different ethnic populations. We employed a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) assay to identify the MPO genotypes in 375 lung cancer cases and 378 healthy controls, all of whom were Caucasian. Our results demonstrate a reduced risk of lung cancer when the A-allele genotypes (G/A+A/A) were combined (odds ratio (OR)=0.66; 95% confidence interval (CI) 0.49–0.90). We also noted a protective effect (OR=0.63; 95% CI 0.45–0.87) in ever smokers with the A-allele genotypes which was not evident in never smokers (OR=1.14; 95% CI 0.42–3.11). We observed an incremental decrease in the protective effects as cigarette pack-years increased. Thus, lightest smokers were provided the greatest protection. When the data were stratified by gender, there was a statistically significant reduced risk of lung cancer among men (OR=0.55; 95% CI 0.36–0.84), but not among women (OR=0.81; 95% CI 0.55–1.26) for the A-allele genotypes. Lastly, an age effect was evident only in men but not women. The protective effects of the A-allele genotypes decreased with increasing age. This report provides further support for the hypothesis that a single nucleotide polymorphism in the MPO gene is a protective factor in lung cancer carcinogenesis. [Copyright &y& Elsevier]

Simple Summary: Sarcomas are comparatively rare cancers; thus, large sarcoma studies covering extended time periods are lacking. Therefore, our study analyzed data from 2570 adolescents (15–39 years) and adults (≥40 years) treated at the Moffitt Cancer Center between 1986 and 2014. We aimed to evaluate the impact of characteristics such as sex, age, ethnicity, race, tobacco use, diagnosis, cancer metastasis, treatment, and family history on overall survival among individuals diagnosed with soft tissue or bone sarcomas. The collected data gave us the advantage of including a large patient number and made possible the evaluation of several sarcoma subtypes. Lastly, data collected over 28 years allowed us to look for changes over time, often not possible in small studies and capture improvements in treatment. Our study showed poorer overall survival rates in older adults (≥40 years), current smokers, patients with metastatic cancer, and patients not receiving first-line surgery treatment. There was a moderate improvement in overall survival rates over time, with gastrointestinal stromal tumors experiencing better overall survival in more recent years. We believe that our study provides important findings for the field of sarcoma research and highlights the need for future research to better understand barriers to survivorship. 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. [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. [ABSTRACT FROM AUTHOR]

Lesbian, gay, bisexual, transgender, queer/questioning, or other sexual and/or gender expansive identities (LGBTQ+) in the United States are facing an insurmountable reintroduction of discriminatory and stigmatizing policies and legislation (i.e., Zombie Laws) particularly those pertaining to sexual practices, minoritized sexual orientations and gender identities, and access to equitable healthcare. This has a particularly devastating effect on cancer-related care and outcomes. Therefore, a call to action among researchers, policymakers, and activists is needed to protect LGBTQ + rights and ensure gains continue to ameliorate cancer-related health disparities. [ABSTRACT FROM AUTHOR]

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/m3. The lowest risk was observed for areas of mean exposure of 58 Bq/m3 (95% CI: 56.1–59.2 Bq/m3). The relative risk of lung cancer increased to the same degree in areas averaging 25 Bq/m3 (OR = 1.31, 95% CI: 1.01–1.59) as in areas with a mean of 100 Bq/m3 (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/m3. [ABSTRACT FROM AUTHOR]

Simple Summary: Cachexia occurs in up to 80% of patients with cancer. Although cancer-associated cachexia dramatically decreases overall survival and quality of life, it is often overlooked. To make meaningful progress in identifying cancer cachexia earlier and finding treatments for this condition, Moffitt Cancer Center held its first Cachexia Working Group Retreat in 2022. This manuscript describes the priorities discussed at the retreat and highlights collaborations that arose afterward. 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. [ABSTRACT FROM AUTHOR]

Background: For the advancement of cancer research, the collection of tissue specimens from drug‐resistant tumors after targeted therapy is crucial. Although patients with lung cancer are often provided targeted therapy, post‐therapy specimens are not routinely collected due to the risks of collection, limiting the study of targeted therapy resistance mechanisms. Posthumous rapid tissue donation (RTD) is an expedient collection process that provides an opportunity to understand treatment‐resistant lung cancers. Methods: Consent to participate in the thoracic RTD protocol was obtained during patient care. When death occurred, tumor and paired non‐tumor, cytology, and blood specimens were collected within 48 hours and preserved as formalin‐fixed and frozen specimens. Tissue sections were evaluated with hematoxylin and eosin staining and immunohistochemistry (IHC) against multiple biomarkers, including various programmed death ligand 1 (PD‐L1) clones. Next‐generation sequencing was performed on 13 specimens from 5 patients. Results: Postmortem specimens (N = 180) were well preserved from 9 patients with lung cancer. PD‐L1 IHC revealed heterogeneity within and between tumors. An AGK‐BRAF fusion was newly identified in tumor from a donor with a known echinoderm microtubule‐associated protein‐like 4 to anaplastic lymphoma kinase (EML4‐ALK) fusion and history of anaplastic lymphoma kinase (ALK) inhibitor therapy. RNA expression analysis revealed a clonal genetic origin of metastatic cancer cells. Conclusions: Post‐therapy specimens demonstrated PD‐L1 heterogeneity and an acyl glycerol kinase to B‐rapidly accelerated fibrosarcoma (AGK‐BRAF) fusion in a patient with an EML4‐ALK–positive lung adenocarcinoma as a potential resistance mechanism to ALK inhibitor therapy. Rapid tissue donation collection of postmortem tissue from lung cancer patients is a novel approach to cancer research that enables studies of molecular evolution and drug resistance. [ABSTRACT FROM AUTHOR]

A response to a letter to the editor is presented regarding an article by Dr. Schabath and colleagues' study of phytoestrogens and the risk of lung cancer presented in a previous issue.

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. [ABSTRACT FROM AUTHOR]

The article "Prevalence of cancer survivors in the United States" highlights the increasing number of long-term and very long-term cancer survivors with diverse healthcare needs. It emphasizes the importance of understanding social determinants of health, including sexual orientation and gender identity, to provide holistic care. The lack of data on sexual orientation and gender identity in cancer registries hinders efforts to address health disparities in sexual and gender minority communities. The authors stress the need for collecting this data and training oncology professionals to provide tailored care to all cancer survivors. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Introduction Until recently, there has not been a valid and reliable screening test for lung cancer. As compared to chest X-ray, low-dose computed tomography (LDCT) lung cancer screening has demonstrated greater sensitivity resulting in lung cancer diagnosis at an earlier stage, thereby reducing lung cancer mortality among high-risk individuals by 20%. In the current study, we sought to examine knowledge and attitudes about LDCT screening for lung cancer among an ethnically and racially diverse sample of high risk (HR) community members and primary care providers (PCP). Methods Eligible individuals participated in a focus group using semi-structured interview guides. Focus groups were conducted with PCPs (by telephone) and HRs (in-person). Sessions were audio-taped and transcribed verbatim. The constant comparison method and content analysis were used to analyze results. Results The majority of PCPs had limited knowledge of lung cancer CT screening. PCPs cited barriers to recommendation including, cost/insurance barriers and the potential for false positives. PCPs perceived the main benefit to be early detection of lung cancer. The majority of HRs had never heard of lung LDCT screening and had never had a healthcare provider recommend it to them. Perceived barriers included fear of results (bad news) and financial costs. The main perceived benefit was early detection. Conclusion Lack of knowledge about LDCT was a key a barrier across both the PCP and HR. respondents. Understanding the barriers to lung screening across diverse community populations is necessary to improve screening rates and shared decision-making. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. Schools must provide more education in SGM topics to improve student knowledge to produce competent providers. • Medical students are willing to care for sexual gender minority (SGM) patients. • There are gaps in student knowledge of SGM patient cancer risk and screening. • Medical students are less confident in their knowledge of transgender patient care. • There is a need for student education in SGM patient cancer care. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Two CT features were developed to quantitatively describe lung adenocarcinomas by scoring tumor shape complexity (feature 1: convexity) and intratumor density variation (feature 2: entropy ratio) in routinely obtained diagnostic CT scans. The developed quantitative features were analyzed in two independent cohorts (cohort 1: n = 61; cohort 2: n = 47) of patients diagnosed with primary lung adenocarcinoma, retrospectively curated to include imaging and clinical data. Preoperative chest CTs were segmented semi-automatically. Segmented tumor regions were further subdivided into core and boundary sub-regions, to quantify intensity variations across the tumor. Reproducibility of the features was evaluated in an independent test-retest dataset of 32 patients. The proposed metrics showed high degree of reproducibility in a repeated experiment (concordance, CCC≥0.897; dynamic range, DR≥0.92). Association with overall survival was evaluated by Cox proportional hazard regression, Kaplan-Meier survival curves, and the log-rank test. Both features were associated with overall survival (convexity: p = 0.008; entropy ratio: p = 0.04) in Cohort 1 but not in Cohort 2 (convexity: p = 0.7; entropy ratio: p = 0.8). In both cohorts, these features were found to be descriptive and demonstrated the link between imaging characteristics and patient survival in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: LGBT patients may have unique psychosocial cancer care needs, and healthcare providers should have knowledge and understanding of these unique needs to effectively address disparities through the delivery of personalized healthcare. As such, our group developed and piloted a web-based LGBT cultural competency training designed specifically for oncologists called the Curriculum for Oncologists on LGBT populations to Optimize Relevance and Skills (COLORS). We designed a randomized pragmatic trial for oncologists to compare the effectiveness of the COLORS training versus a general online LGBT cultural competency training in improving LGBT-related knowledge, attitudes, and clinical practices. Methods/design: Study procedures include an 8-step approach for recruitment, randomization, retention, and completion of the interventions. Oncologists of any subspecialty who are currently practicing physicians will be identified from the American Medical Association Masterfile. Approximately 5000 oncologists will be sent a FedEx envelope with an invitation letter and study timeline. Electronic consent is obtained using a secure REDCap (Research Electronic Data Capture) portal hosted at the Moffitt Cancer Center (Tampa, FL) where the oncologists will complete the eligibility questionnaire, pre-training assessments, and then will be randomized to complete the COLORS training or an online general healthcare training offered by the National LGBT Health Education Center. Effectiveness of both trainings will be assessed utilizing self-reported measures of LGBT-related knowledge, attitudes, and affirming clinical practices. The measures will be collected before and directly after training completion, as well as 3-month post-training completion. The primary outcomes are changes in knowledge, attitudes, and practice behaviors regarding LGBT cancer patients from pre-test to post-test training in the COLORS training vs. the comparison training. Discussion: The overarching premise of this trial is to assess the effectiveness of the COLORS cultural competency training program. If successful, among oncologists who completed the COLORS training should yield statistically significantly improvements in knowledge, attitudes, and affirming practice. [ABSTRACT FROM AUTHOR]

Background: LGBT patients may have unique psychosocial cancer care needs, and healthcare providers should have knowledge and understanding of these unique needs to effectively address disparities through the delivery of personalized healthcare. As such, our group developed and piloted a web-based LGBT cultural competency training designed specifically for oncologists called the Curriculum for Oncologists on LGBT populations to Optimize Relevance and Skills (COLORS). We designed a randomized pragmatic trial for oncologists to compare the effectiveness of the COLORS training versus a general online LGBT cultural competency training in improving LGBT-related knowledge, attitudes, and clinical practices.Methods/design: Study procedures include an 8-step approach for recruitment, randomization, retention, and completion of the interventions. Oncologists of any subspecialty who are currently practicing physicians will be identified from the American Medical Association Masterfile. Approximately 5000 oncologists will be sent a FedEx envelope with an invitation letter and study timeline. Electronic consent is obtained using a secure REDCap (Research Electronic Data Capture) portal hosted at the Moffitt Cancer Center (Tampa, FL) where the oncologists will complete the eligibility questionnaire, pre-training assessments, and then will be randomized to complete the COLORS training or an online general healthcare training offered by the National LGBT Health Education Center. Effectiveness of both trainings will be assessed utilizing self-reported measures of LGBT-related knowledge, attitudes, and affirming clinical practices. The measures will be collected before and directly after training completion, as well as 3-month post-training completion. The primary outcomes are changes in knowledge, attitudes, and practice behaviors regarding LGBT cancer patients from pre-test to post-test training in the COLORS training vs. the comparison training.Discussion: The overarching premise of this trial is to assess the effectiveness of the COLORS cultural competency training program. If successful, among oncologists who completed the COLORS training should yield statistically significantly improvements in knowledge, attitudes, and affirming practice. [ABSTRACT FROM AUTHOR]

Coffee contains polyphenolic antioxidants and caffeine, which may favorably affect pulmonary function. Therefore, the authors studied cross-sectional associations (1987–1989) between coffee intake and pulmonary function in the Atherosclerosis Risk in Communities Study, a population-based cohort study (analytic sample = 10,658). They also conducted analyses stratified by smoking status, since smoking is a strong risk factor for respiratory disease and could influence the effects of caffeine and antioxidants. Self-reported coffee intake was categorized as rare/never, <7 cups/week, 1 cup/day, 2–3 cups/day, and ≥4 cups/day. Pulmonary function was characterized by the spirometric measures forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). After adjustment for demographic factors, lifestyle characteristics, and dietary factors, pulmonary function values increased across increasing categories of coffee consumption in never and former smokers but not in current smokers. In never or former smokers who consumed ≥4 cups of coffee daily, FVC and FEV1 were 2%–3% greater than in never or former smokers who rarely/never consumed coffee (Ptrend values: in never smokers, 0.04 for FVC and 0.07 for FEV1; in former smokers, <0.001 for FVC and <0.001 for FEV1). These data show a possible beneficial effect of coffee (or a coffee ingredient) on pulmonary function, but it appears to be limited to nonsmokers. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Image-based biomarkers could have translational implications by characterizing tumor behavior of lung cancers diagnosed during lung cancer screening. In this study, peritumoral and intratumoral radiomics and volume doubling time (VDT) were used to identify high-risk subsets of lung patients diagnosed in lung cancer screening that are associated with poor survival outcomes. METHODS: Data and images were acquired from the National Lung Screening Trial. VDT was calculated between two consequent screening intervals approximately 1 year apart; peritumoral and intratumoral radiomics were extracted from the baseline screen. Overall survival (OS) was the main endpoint. Classification and Regression Tree analyses identified the most predictive covariates to classify patient outcomes. RESULTS: Decision tree analysis stratified patients into three risk-groups (low, intermediate, and high) based on VDT and one radiomic feature (compactness). High-risk patients had extremely poor survival outcomes (hazard ratio [HR] = 8.15; 25% 5-year OS) versus low-risk patients (HR = 1.00; 83.3% 5-year OS). Among early-stage lung cancers, high-risk patients had poor survival outcomes (HR = 9.07; 44.4% 5-year OS) versus the low-risk group (HR = 1.00; 90.9% 5-year OS). For VDT, the decision tree analysis identified a novel cut-point of 279 days and using this cut-point VDT alone discriminated between aggressive (HR = 4.18; 45% 5-year OS) versus indolent/low-risk cancers (HR = 1.00; 82.8% 5-year OS). CONCLUSION: We utilized peritumoral and intratumoral radiomic features and VDT to generate a model that identify a high-risk group of screen-detected lung cancers associated with poor survival outcomes. These vulnerable subset of screen-detected lung cancers may be candidates for more aggressive surveillance/follow-up and treatment, such as adjuvant therapy. [ABSTRACT FROM AUTHOR]

Sulfotransferases (SULT) catalyze both the bioactivation and detoxification of a wide range of promutagens and procarcinogens. SULT1A1 appears to be an important phenol SULT because of its abundance and distribution in many tissues and wide substrate specificity. The SULT1A1 gene possesses a G→A polymorphism that results in an Arg to His amino acid substitution, and the His213 allele has been shown to have low activity and low thermal stability. Because of its functional role and published data showing the influence of Arg213His polymorphism on the risk of some cancers, we hypothesized that the His213 allele of the SULT1A1 gene may modify bladder cancer risk. To test this hypothesis, we determined the SULT1A1 Arg213His genotypes in 384 incident bladder cancer patients and 386 healthy frequency-matched controls. A comprehensive epidemiologic interview was conducted on all participants to collect personal information, such as demographics and smoking status. The Arg/His and His/His genotypes were more common in the controls than the cases (P=0.035), resulting in a His213 allele frequency of 35.0% in controls and 28.8% in cases. When individuals with the His213 allele genotypes (Arg/His+His/His) were combined and compared to individuals with the Arg/Arg genotype, we observed a statistically significant reduced risk of bladder cancer (OR=0.72; 95% CI 0.54–0.97). When we examined the data by gender, there was a statistically significant reduced risk of bladder cancer only in women (OR=0.42; 95% CI 0.23–0.78) and not in men (OR=0.84; 95% CI 0.60–1.19) with the His213 genotypes. In addition, there was a reduced bladder cancer risk in never smokers (OR=0.59; 95% CI 0.36–0.98) with the His213 allele genotypes, but not in former (OR=0.82; 95% CI 0.54–1.25) or current smokers (OR=0.68; 95% CI 0.29–1.58). The His213 allele genotypes also appeared to provide some protective benefit for current and former smokers, as compared to those with the Arg/Arg genotype. In conclusion, this study provides epidemiologic evidence of a reduced bladder cancer risk associated with the SULT1A1 His213 polymorphism. Further studies are warranted to elucidate the function of this SULT1A1 polymorphism with regard to organ specificity, gene-environment interactions, and the gender-related difference we observed. [Copyright &y& Elsevier]

Glutathione transferases (GSTs), a multiple gene family of phase II enzymes, catalyze detoxifying endogenous reactions with glutathione and protect cellular macromolecules from damage caused by cytotoxic and carcinogenic agents. Glutathione S-transferase p1 (GSTP1), the most abundant GST isoform in the lung, metabolizes numerous carcinogenic compounds including benzo[a]pyrene, a tobacco carcinogen. Previous studies suggest that genetic polymorphisms of GSTP1 exon 5 (Ile105Val) and exon 6 (Ala114Val) have functional effects on the GST gene product resulting in reduced enzyme activity. Individuals with reduced GST enzymatic activity may be at a greater risk for cancer due to decreased detoxification of carcinogenic and mutagenic compounds. Utilizing a hospital-based case-control study, we investigated the association between GSTP1 polymorphisms at exons 5 and 6 with lung cancer risk. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to successfully genotype the GSTP1 exons 5 and 6 polymorphism in 582 Caucasian lung cancer cases and 600 frequency matched Caucasian controls. There was no association between the exon 5 variant genotypes (A/G+G/G) and overall lung cancer risk (OR=1.09; 95% CI 0.82–1.45) nor when stratified by age, gender, and smoking status. However, the exon 6 variant genotypes (C/T+T/T) were associated with a statistically significant elevated lung cancer risk (OR=1.40; 95% CI 1.06–1.92). Additionally, there was an increase in lung cancer risk for the exon 6 variant genotypes in younger individuals (<62 years) (OR=1.63; 95% C.I. 1.07–2.49) but no effect in older individuals (OR=1.14; 95% CI 0.72–1.81). A statistically significant increased risk of lung cancer was also observed for the exon 6 variant genotypes among men (OR=2.17; 95% CI 1.41–3.33), but not among women (OR=0.80; 95% CI 0.51–1.28). Among ever smokers, the exon 6 variant genotypes were associated with an elevated lung cancer risk (OR=1.58; 95% CI 1.14–2.19), which was not evident for never smokers (OR=0.53; 95% CI 0.21–1.33). These data demonstrate that the GSTP1 exon 6 polymorphism, but not the exon 5 polymorphism, is associated with lung cancer risk that is especially evident in men, younger individuals, and ever smokers. [Copyright &y& Elsevier]

Background: Approximately 50% of cancer patients eventually develop a syndrome of prolonged weight loss (cachexia), which may contribute to primary resistance to immune checkpoint inhibitors (ICI). This study utilised radiomics analysis of 18F-FDG-PET/CT images to predict risk of cachexia that can be subsequently associated with clinical outcomes among advanced non-small cell lung cancer (NSCLC) patients treated with ICI.Methods: Baseline (pre-therapy) PET/CT images and clinical data were retrospectively curated from 210 ICI-treated NSCLC patients from two institutions. A radiomics signature was developed to predict the cachexia with PET/CT images, which was further used to predict durable clinical benefit (DCB), progression-free survival (PFS) and overall survival (OS) following ICI.Results: The radiomics signature predicted risk of cachexia with areas under receiver operating characteristics curves (AUCs) ≥ 0.74 in the training, test, and external test cohorts. Further, the radiomics signature could identify patients with DCB from ICI with AUCs≥0.66 in these three cohorts. PFS and OS were significantly shorter among patients with higher radiomics-based cachexia probability in all three cohorts, especially among those potentially immunotherapy sensitive patients with PD-L1-positive status (p < 0.05).Conclusions: PET/CT radiomics analysis has the potential to predict the probability of developing cachexia before the start of ICI, triggering aggressive monitoring to improve potential to achieve more clinical benefit. [ABSTRACT FROM AUTHOR]

Objectives: Sexual and gender minority (SGM) individuals experience cancer-related health disparities and reduced quality of cancer care compared to the general population in part due to a lack of knowledgeable providers. This study explored oncologists' experiences and perspectives in providing patient-centered care for SGM individuals with cancer.Methods: We conducted a qualitative analysis of oncologists' responses to four open-ended items on a national survey eliciting their experiences, reservations, and suggestions in treating SGM patients.Results: Over 50 % of the 149 respondents of the national survey responded to at least one open-ended item. Many oncologists reported positive experiences reflecting personal growth and affirmative care practices, such as open, non-judgmental communication, compassion, competence, and supporting patients' identity. There was a notable lack of experience with transgender patients in particular. Lack of knowledge, interpersonal communication concerns (e.g., fear of offending patients), and microaggressions ("don't ask, don't tell") were identified as barriers to providing affirming care.Conclusions: Oncologists recognize their knowledge deficits and need strategies to overcome communication barriers and microaggressions among the cancer care team to provide SGM-affirming care.Practice Implications: Curricula are needed to train oncologists in SGM healthcare needs and affirming communication skills to facilitate patient-centered care for SGM individuals with cancer. [ABSTRACT FROM AUTHOR]

The Data Availability statement is being updated with a new data location. Reference 1 Grove O, Berglund AE, Schabath MB, Aerts HJWL, Dekker A, Wang H, et al. (2015) Quantitative Computed Tomographic Descriptors Associate Tumor Shape Complexity and Intratumor Heterogeneity with Prognosis in Lung Adenocarcinoma. [Extracted from the article]

• Sex, smoking status and race interact with the BMI-survival relationship in Non-Small-Cell-Lung-Cancer patients in various ways. • Black patients had more favourable outcomes in the BMI-extremes when compared to White patients. • Female ever-smokers had worse outcomes when compared to male ever-smokers. • Asian patients and never smokers were not significantly associated with OS in general. • These distinct associations reflect sex and racial differences in body composition and etiological differences in NSCLC carcinogenesis. The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC). Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses. Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; p interaction = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (p interaction = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (p interaction <0.001) and obese categories (p interaction = 0.004) relative to the normal-BMI category, when compared to male ever-smokers. Underweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of disease-onset. Methods: To demonstrate efficacy, we evaluated this method on two simulation data sets to estimate the type I error rate and power. Simulations showed that ES-MDR identified interactions using less computational workload and allowed for adjustment of covariates. We applied ES-MDR on the OncoArray-TRICL Consortium data with 14,935 cases and 12,787 controls for lung cancer (SNPs = 108,254) to search over all two-way interactions to identify genetic interactions associated with lung cancer age-of-onset. We tested the best model in an independent data set from the OncoArray-TRICL data. Results: Our experiment on the OncoArray-TRICL data identified many one-way and two-way models with a single-base deletion in the noncoding region of BRCA1 (HR 1.24, P = 3.15 × 10–15), as the top marker to predict age of lung cancer onset. Conclusions: From the results of our extensive simulations and analysis of a large GWAS study, we demonstrated that our method is an efficient algorithm that identified genetic interactions to include in our models to predict survival outcomes. [ABSTRACT FROM AUTHOR]

Aims and objectives: To evaluate the knowledge and attitudes towards sexual and gender minority (SGM) oncology patients' needs among advanced practice providers (APPs). Background: SGM individuals experience health disparities, in part due to lack of access to knowledgeable providers. Despite the important role of APPs in cancer care, less is known about their attitudes and knowledge towards SGM cancer patients. Design: Cross‐sectional study. Methods: A survey of APPs at a National Cancer Institute‐Designated Comprehensive Cancer Center assessed self‐reported demographics, attitudes, knowledge and postsurvey confidence in knowledge of SGM oncology patient needs. Reporting of this study adheres to STROBE guidelines. Results: Knowledge of health needs was low with an average of 2.56 (SD = 1.27) items answered correctly out of 6. The majority of APPs self‐reported being comfortable treating SGM patients (93.6% and 87.2%, respectively), but less confident in knowledge of their health needs (68.0% and 53.8%, respectively). Although less than half of APPs believed education should be mandatory (44.9%), 79.5% were interested in education about SGMs' unique health needs. Political affiliation, medical specialty, licensure, and having SGM friends or family were associated with various attitude items, but not knowledge. Moderation analyses indicated that APPs who had greater overall knowledge scores were more likely to agree, on average, that knowing sexual orientation, gender identity and sex assigned at birth are important to providing quality oncology care. Conclusion: APPs report being comfortable providing care for SGMs with cancer, but knowledge gaps remain that may inhibit the quality of care provided. Given the interest in education, results would support the development of SGM‐related healthcare training for oncology APPs. Relevance to clinical practice: Targeted education for providers during training and continuing education is likely to improve the provision of quality care for SGMs with cancer. [ABSTRACT FROM AUTHOR]

The National Lung Screening Trial (NLST) demonstrated that screening with low-dose computed tomography (LDCT) is associated with a 20% reduction in lung cancer mortality. One potential limitation of LDCT screening is overdiagnosis of slow growing and indolent cancers. In this study, peritumoral and intratumoral radiomics was used to identify a vulnerable subset of lung patients associated with poor survival outcomes. Incident lung cancer patients from the NLST were split into training and test cohorts and an external cohort of non-screen detected adenocarcinomas was used for further validation. After removing redundant and non-reproducible radiomics features, backward elimination analyses identified a single model which was subjected to Classification and Regression Tree to stratify patients into three risk-groups based on two radiomics features (NGTDM Busyness and Statistical Root Mean Square [RMS]). The final model was validated in the test cohort and the cohort of non-screen detected adenocarcinomas. Using a radio-genomics dataset, Statistical RMS was significantly associated with FOXF2 gene by both correlation and two-group analyses. Our rigorous approach generated a novel radiomics model that identified a vulnerable high-risk group of early stage patients associated with poor outcomes. These patients may require aggressive follow-up and/or adjuvant therapy to mitigate their poor outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Immunotherapy has improved outcomes for patients with non-small cell lung cancer (NSCLC), yet durable clinical benefit (DCB) is experienced in only a fraction of patients. Here, we test the hypothesis that radiomics features from baseline pretreatment 18F-FDG PET/CT scans can predict clinical outcomes of NSCLC patients treated with checkpoint blockade immunotherapy. Methods: This study included 194 patients with histologically confirmed stage IIIB-IV NSCLC with pretreatment PET/CT images. Radiomics features were extracted from PET, CT, and PET+CT fusion images based on minimum Kullback–Leibler divergence (KLD) criteria. The radiomics features from 99 retrospective patients were used to train a multiparametric radiomics signature (mpRS) to predict DCB using an improved least absolute shrinkage and selection operator (LASSO) method, which was subsequently validated in both retrospective (N = 47) and prospective test cohorts (N = 48). Using these cohorts, the mpRS was also used to predict progression-free survival (PFS) and overall survival (OS) by training nomogram models using multivariable Cox regression analyses with additional clinical characteristics incorporated. Results: The mpRS could predict patients who will receive DCB, with areas under receiver operating characteristic curves (AUCs) of 0.86 (95%CI 0.79–0.94), 0.83 (95%CI 0.71–0.94), and 0.81 (95%CI 0.68–0.92) in the training, retrospective test, and prospective test cohorts, respectively. In the same three cohorts, respectively, nomogram models achieved C-indices of 0.74 (95%CI 0.68–0.80), 0.74 (95%CI 0.66–0.82), and 0.77 (95%CI 0.69–0.84) to predict PFS and C-indices of 0.83 (95%CI 0.77–0.88), 0.83 (95%CI 0.71–0.94), and 0.80 (95%CI 0.69–0.91) to predict OS. Conclusion: PET/CT-based signature can be used prior to initiation of immunotherapy to identify NSCLC patients most likely to benefit from immunotherapy. As such, these data may be leveraged to improve more precise and individualized decision support in the treatment of patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: Lesbian, gay, bisexual, and transgender (LGBT) cancer patients experience substantial health disparities, including poorer overall health and lower satisfaction with their cancer care than their heterosexual and cisgender counterparts, which may be due in part to a lack of culturally competent providers. To address these disparities, a web-based LGBT cultural competency training tailored to oncologists was developed by an interdisciplinary team of scientists, LGBT cancer survivors, cultural competency experts, oncologists, a web designer, and an instructional designer.Methods: Oncologists (n = 44) were recruited from 3 academic cancer centers in Florida. Participants were administered the LGBT cultural competency training Curriculum for Oncologists on LGBT populations to Optimize Relevance and Skills (COLORS) and completed pre- and posttraining measures regarding LGBT-related knowledge, attitudes (including general negative attitudes and health care-related attitudes), and clinical practices. After the training, participants completed training acceptability measures.Results: Of the 44 participants, 33 (75%) completed the COLORS training. Participants were 55% non-Hispanic white, 63% male, and had a mean age of 47 years. Participants demonstrated significant improvements in LGBT-related knowledge (t = -4.9, P < .001), attitudes (Z = -3.0, P = .002; t = -2.5, P = .019), and clinical practices (Z = -3.5, P < .001) after completing the COLORS training (Wilcoxon signed rank tests were used for nonnormally distributed variables). Moreover, training acceptability was high, with 82% of participants rating the training as high quality, and 97% being willing to recommend the training to a colleague.Conclusion: The COLORS training is both feasible to administer and acceptable for use with oncologists, and may improve oncologists' LGBT-related knowledge, attitudes, and clinical practices. Larger trials are needed to examine the training's effectiveness in reducing LGBT cancer disparities, as well as its applicability to other types of care providers. [ABSTRACT FROM AUTHOR]

Purpose: Recent efforts have demonstrated that radiomic features extracted from the peritumoral region, the area surrounding the tumor parenchyma, have clinical utility in various cancer types. However, as like any radiomic features, peritumoral features could also be unstable and/or nonreproducible. Hence, the purpose of this study was to assess the stability and reproducibility of computed tomography (CT) radiomic features extracted from the peritumoral regions of lung lesions where stability was defined as the consistency of a feature by different segmentations, and reproducibility was defined as the consistency of a feature to different image acquisitions. Methods: Stability was measured utilizing the "moist run" dataset and reproducibility was measured utilizing the Reference Image Database to Evaluate Therapy Response test–retest dataset. Peritumoral radiomic features were extracted from incremental distances of 3–12 mm outside the tumor segmentation. A total of 264 statistical, histogram, and texture radiomic features were assessed from the selected peritumoral region‐of‐interests (ROIs). All features (except wavelet texture features) were extracted using standardized algorithms defined by the Image Biomarker Standardisation Initiative. Stability and reproducibility of features were assessed using the concordance correlation coefficient. The clinical utility of stable and reproducible peritumoral features was tested in three previously published lung cancer datasets using overall survival as the endpoint. Results: Features found to be stable and reproducible, regardless of the peritumoral distances, included statistical, histogram, and a subset of texture features suggesting that these features are less affected by changes (e.g., size or shape) of the peritumoral region due to different segmentations and image acquisitions. The stability and reproducibility of Laws and wavelet texture features were inconsistent across all peritumoral distances. The analyses also revealed that a subset of features were consistently stable irrespective of the initial parameters (e.g., seed point) for a given segmentation algorithm. No significant differences were found in stability for features that were extracted from ROIs bounded by a lung parenchyma mask versus ROIs that were not bounded by a lung parenchyma mask (i.e., peritumoral regions that extended outside of lung parenchyma). After testing the clinical utility of peritumoral features, stable and reproducible features were shown to be more likely to create repeatable models than unstable and nonreproducible features. Conclusions: This study identified a subset of stable and reproducible CT radiomic features extracted from the peritumoral region of lung lesions. The stable and reproducible features identified in this study could be applied to a feature selection pipeline for CT radiomic analyses. According to our findings, top performing features in survival models were more likely to be stable and reproducible hence, it may be best practice to utilize them to achieve repeatable studies and reduce the chance of overfitting. [ABSTRACT FROM AUTHOR]

Objective: Despite substantial LGBT cancer health disparities, there are no LGBT cultural competency trainings tailored for oncologists. Here we describe the systematic development of a web-based, oncology-focused LGBT cultural competency training.Methods: A literature review regarding LGBT cancer outcomes and competency training was conducted to identify potential training content. An expert panel meeting, including LGBT cancer survivors, cultural competency experts, oncologists, a web designer, and an instructional designer, was held to solidify the training content focus. Following the panel, the training was developed in collaboration with an instructional designer, a web designer, and LGBT community members.Results: The training modules include: 1) LGBT Basics; 2) Inclusive Environments; 3) Initiating Oncology Care with LGBT Patients; and 4) Issues in Cancer Survivorship among LGBT Patients. Module content is interactive, and models effective communication.Conclusion: The process of collaboration with a diverse group of stakeholders and three cancer centers in Florida has resulted in a practical and efficient web-based resource for LGBT cultural competency training for oncologists.Practice Implications: Feedback from stakeholders indicates that training in this area is needed and will be well-received by oncologists. We are currently conducting an evaluation of this training among oncologists and LGBT community members. [ABSTRACT FROM AUTHOR]

Highlights • Models that included radiomics and clinical data predicted patients that responded to checkpoint blockades. • Hyperprogressive disease was observed in a subset of patients were associated with extremely poor outcomes. • Radiomic features extracted from peritumoral regions of lung tumors were shown to be more informative. Abstract Objectives Immune-checkpoint blockades have exhibited durable responses and improved long-term survival in a subset of advanced non-small cell lung cancer (NSCLC) patients. However, highly predictive markers of positive and negative responses to immunotherapy are a significant unmet clinical need. The objective of this study was to identify clinical and computational image-based predictors of rapid disease progression phenotypes in NSCLC patients treated with immune-checkpoint blockades. Materials and methods Using time-to-progression (TTP) and/or tumor growth rates, rapid disease progression phenotypes were developed including hyperprogressive disease. The pre-treatment baseline predictors that were used to identify these phenotypes included patient demographics, clinical data, driver mutations, hematology data, and computational image-based features (radiomics) that were extracted from pre-treatment computed tomography scans. Synthetic Minority Oversampling Technique (SMOTE) was used to subsample minority groups to eliminate classification bias. Patient-level probabilities were calculated from the final clinical-radiomic models to subgroup patients by progression-free survival (PFS). Results Among 228 NSCLC patients treated with single agent or double agent immunotherapy, we identified parsimonious clinical-radiomic models with modest to high ability to predict rapid disease progression phenotypes with area under the receiver-operator characteristics ranging from 0.804 to 0.865. Patients who had TTP < 2 months or hyperprogressive disease were classified with 73.41% and 82.28% accuracy after SMOTE subsampling, respectively. When the patient subgroups based on patient-level probabilities were analyzed for survival outcomes, patients with higher probability scores had significantly worse PFS. Conclusions The models found in this study have potential important translational implications to identify highly vulnerable NSCLC patients treated with immunotherapy that experience rapid disease progression and poor survival outcomes. [ABSTRACT FROM AUTHOR]

DNase I hypersensitive sites (DHS) are abundant in regulatory elements, such as promoter, enhancer and transcription factor binding sites. Many studies have revealed that disease-associated variants were concentrated in DHS-related regions. However, limited studies are available on the roles of DHS-related variants in lung cancer. In this study, we performed a large-scale case–control study with 20 871 lung cancer cases and 15 971 controls to evaluate the associations between regulatory genetic variants in DHS and lung cancer susceptibility. The expression quantitative trait loci (eQTL) analysis and pathway-enrichment analysis were performed to identify the possible target genes and pathways. In addition, we performed motif-based analysis to explore the lung-cancer-related motifs using sequence kernel association test. Two novel variants, rs186332 in 20q13.3 (C>T, odds ratio [OR] = 1.17, 95% confidence interval [95% CI]: 1.10–1.24, P = 8.45 × 10−7) and rs4839323 in 1p13.2 (T>C, OR = 0.92, 95% CI: 0.89–0.95, P = 1.02 × 10−6) showed significant association with lung cancer risk. The eQTL analysis suggested that these two SNPs might regulate the expression of MRGBP and SLC16A1, respectively. What's more, the expression of both MRGBP and SLC16A1 was aberrantly elevated in lung tumor tissues. The motif-based analysis identified 10 motifs related to the risk of lung cancer (P < 1.71 × 10−4). Our findings suggested that variants in DHS might modify lung cancer susceptibility through regulating the expression of surrounding genes. This study provided us a deeper insight into the roles of DHS-related genetic variants for lung cancer. Associations between regulatory genetic variants in DNase I hypersensitive sites and lung cancer susceptibility were evaluated with a total of 20 871 lung cancer cases and 15 971 controls. Two novel variants, rs186332 in 20q13.3 and rs4839323 in 1p13.2 were identified. [ABSTRACT FROM AUTHOR]

Background: Current guidelines for lung cancer screening increased a positive scan threshold to a 6 mm longest diameter. We extracted radiomic features from baseline and follow‐up screens and performed size‐specific analyses to predict lung cancer incidence using three nodule size classes (<6 mm [small], 6‐16 mm [intermediate], and ≥16 mm [large]). Methods: We extracted 219 features from baseline (T0) nodules and 219 delta features which are the change from T0 to first follow‐up (T1). Nodules were identified for 160 incidence cases diagnosed with lung cancer at T1 or second follow‐up screen (T2) and for 307 nodule‐positive controls that had three consecutive positive screens not diagnosed as lung cancer. The cases and controls were split into training and test cohorts; classifier models were used to identify the most predictive features. Results: The final models revealed modest improvements for baseline and delta features when compared to only baseline features. The AUROCs for small‐ and intermediate‐sized nodules were 0.83 (95% CI 0.76‐0.90) and 0.76 (95% CI 0.71‐0.81) for baseline‐only radiomic features, respectively, and 0.84 (95% CI 0.77‐0.90) and 0.84 (95% CI 0.80‐0.88) for baseline and delta features, respectively. When intermediate and large nodules were combined, the AUROC for baseline‐only features was 0.80 (95% CI 0.76‐0.84) compared with 0.86 (95% CI 0.83‐0.89) for baseline and delta features. Conclusions: We found modest improvements in predicting lung cancer incidence by combining baseline and delta radiomics. Radiomics could be used to improve current size‐based screening guidelines. We demonstrated that combining delta radiomics with baseline radiomics generally improved the performance statistics to predict lung cancer incidence when compared to using only baseline radiomic features. We note inconsistent results in the performance statistics when we comparing overall models compared to models based on nodule size. As such, our findings suggest there is a trade‐off in terms of performance using nodule size‐specific models vs. an overall model. [ABSTRACT FROM AUTHOR]