Search

Background: Appalachia is a region with significant cancer disparities in incidence and mortality compared to Kentucky and the United States. However, the contribution of these cancer health disparities to subsequent primary cancers (SPCs) among survivors of adult-onset cancers is limited. This study aimed to quantify the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types, residence and sex. Methods: This retrospective cohort study from the Kentucky Cancer Registry included 148,509 individuals aged 20-84 years diagnosed with FPCs from 2000- 2014 (followed until December 31, 2019) and survived at least 5 years. Expected numbers of SPC were derived from incidence rates in the Kentucky population; standardized incidence ratio (SIR) compared with those expected in the general Kentucky population. Results: Among 148,509 survivors (50.2% women, 27.9% Appalachian), 17,970 SPC cases occurred during 829,530 person-years of follow-up (mean, 5.6 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 20 of the 30 FPC types, as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 20 of the 31 FPC types, as compared to the general population. The highest overall SIR were estimated among oral cancer survivors (SIR, 2.14 [95% CI, 1.97-2.33] among men, and among laryngeal cancer survivors (SIR, 3.62 [95% CI, 2.93-4.42], among women. Appalachian survivors had significantly increased risk of overall SPC and different site specific SPC when compared to non-Appalachian survivors. The highest overall SIR were estimated among laryngeal cancer survivors for both Appalachian and non-Appalachian residents (SIR, 2.50: 95%CI, 2.10-2.95; SIR, 2.02: 95% CI, 1.77-2.03, respectively). Conclusion: Among adult-onset cancer survivors in Kentucky, several FPC types were significantly associated with greater risk of developing an SPC, compared with the general population. Risk for Appalachian survivors was even higher when compared to non-Appalachian residents, but was not explained by higher risk of smoking related cancers. Cancers associated with smoking comprised substantial proportions of overall SPC incidence among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors. [ABSTRACT FROM AUTHOR]

An editorial is presented on the confusion and anxiety that immediate release of critical cancer results can create, the stress on clinician teams, and "a lack of data showing that immediate conveyance of potentially complex and sensitive clinical information, before clinician discussion, improves outcomes or satisfaction.

Purpose: To determine differences in exceptional survival (ES)—survival of 5 years or more past diagnosis—between stage IV non‐small cell lung cancer (NSCLC) patients residing in the Appalachian versus non‐Appalachian regions of Kentucky. Methods: This was a population‐based, retrospective case‐control study of Kentucky patients, diagnosed with stage IV NSCLC between January 1, 2000, and December 31, 2011. The data were drawn from the Kentucky Cancer Registry. Findings: Findings from the multivariable logistic regression revealed no significant differences in the odds of ES between patients who resided in Appalachian versus non‐Appalachian Kentucky. Being female and undergoing surgery only as the first course of treatment were associated with higher odds of ES. Increasing age, unspecified histology, having poorly differentiated or undifferentiated carcinomas, and receiving radiation therapy only as the first course of treatment were associated with decreased odds of ES. Conclusion: Differences in the odds of ES among stage IV NSCLC patients were not related to residence in Appalachian versus non‐Appalachian Kentucky. ES was associated with other nongenetic and treatment factors that warrant further investigations. [ABSTRACT FROM AUTHOR]

Purpose: Large‐scale genomic sequencing studies are driving oncology drug development. However, rural populations, like those residing in Appalachian Kentucky, are underrepresented in these efforts. In this study, we determined the frequency of participation, reasons for nonparticipation, and factors predicting the decision to participate in the Total Cancer Care (TCC) prospective genomic cohort study. Methods: A total of 1,188 patients were invited to enroll in the TCC prospective cohort from December 2018 to May 2019. Declining patients were queried for their rationale for nonparticipation and their patient data were obtained from the Kentucky Cancer Registry (KCR). Logistic regression was used to assess the association between characteristics and study participation. The association of study participation with survival was modeled with Cox proportional‐hazards regression. Results: 90.9% (1,081) patients consented to participate. In multivariate analysis, factors significantly associated with participation were age, gender, treatment status, and race. Though overall more women participated in the study, men were more likely to participate than women when invited (OR 1.57). Younger, Caucasian individuals who had received chemotherapy, but not surgery, were also more likely to participate. Patients in the Kentucky Appalachian cohort were primarily rural, had less educational attainment, and lower socioeconomic status. Kentucky Appalachian patients were no less likely to enroll in TCC than non‐Appalachian patients. Consented individuals had higher overall survival compared to those who declined. Conclusion: Though minorities, those with low socioeconomic status, and rural populations are underrepresented in genomic studies, they were no less likely to participate when given the opportunity, and participation was associated with better clinical outcomes. [ABSTRACT FROM AUTHOR]

PURPOSE: With the introduction of precision medicine, treatment options for non–small-cell lung cancer have improved dramatically; however, underutilization, especially in disadvantaged patients, like those living in rural Appalachian regions, is associated with poorer survival. Molecular tumor boards (MTBs) represent a strategy to increase precision medicine use. UK HealthCare at the University of Kentucky (UK) implemented a statewide MTB in January 2017. We wanted to test the impact of UK MTB review on overall survival in Appalachian and other regions in Kentucky. METHODS: We performed a case-control study of Kentucky patients newly diagnosed with non–small-cell lung cancer between 2017 and 2019. Cases were reviewed by the UK MTB and were compared with controls without UK MTB review. Controls were identified from the Kentucky Cancer Registry and propensity-matched to cases. The primary end point was the association between MTB review and overall patient survival. RESULTS: Overall, 956 patients were included, with 343 (39%) residing in an Appalachian region. Seventy-seven (8.1%) were reviewed by the MTB and classified as cases. Cox regression analysis showed that poorer survival outcome was associated with lack of MTB review (hazard ratio [HR] = 8.61; 95% CI, 3.83 to 19.31; P <.0001) and living in an Appalachian region (hazard ratio = 1.43; 95% CI, 1.17 to 1.75; P =.004). Among individuals with MTB review, survival outcomes were similar regardless of whether they lived in Appalachia or other parts of Kentucky. CONCLUSION: MTB review is an independent positive predictor of overall survival regardless of residence location. MTBs may help overcome some health disparities for disadvantaged populations. [ABSTRACT FROM AUTHOR]

This study determined the frequency and factors associated with EGFR testing rates and erlotinib treatment as well as associated survival outcomes in patients with non small cell lung cancer in Kentucky. Data from the Kentucky Cancer Registry (KCR) linked with health claims from Medicaid, Medicare and private insurance groups were evaluated. EGFR testing and erlotinib prescribing were identified using ICD-9 procedure codes and national drug codes in claims, respectively. Logistic regression analysis was performed to determine factors associated with EGFR testing and erlotinib prescribing. Cox-regression analysis was performed to determine factors associated with survival. EGFR mutation testing rates rose from 0.1% to 10.6% over the evaluated period while erlotinib use ranged from 3.4% to 5.4%. Factors associated with no EGFR testing were older age, male gender, enrollment in Medicaid or Medicare, smoking, and geographic region. Factors associated with not receiving erlotinib included older age, male gender, enrollment in Medicare or Medicaid, and living in moderate to high poverty. Survival analysis demonstrated EGFR testing or erlotinib use was associated with a higher likelihood of survival. EGFR testing and erlotinib prescribing were slow to be implemented in our predominantly rural state. While population-level factors likely contributed, patient factors, including geographic location (areas with high poverty rates and rural regions) and insurance type, were associated with lack of use, highlighting rural disparities in the implementation of cancer precision medicine. [ABSTRACT FROM AUTHOR]

Introduction: Kentucky is recognized as the state with the highest lung cancer burden for more than 2 decades, but how lung cancer differs in Kentucky relative to other US populations is not fully understood., Patients and Methods: We examined lung cancer reported to the Surveillance, Epidemiology, and End Results (SEER) Program by Kentucky and the other SEER regions for patients diagnosed between 2012 and 2016. Our analyses included histologic types, incidence rates, stage at diagnosis, and survival in Kentucky and Appalachian Kentucky relative to other SEER regions., Results: We found that both squamous cell carcinomas and small-cell lung cancers represent larger proportions of lung cancer diagnoses in Kentucky and Appalachian Kentucky than they do in the SEER registries. Furthermore, age-adjusted cancer incidence rates were higher in Kentucky for every subtype of lung cancer examined. Most notably, for Appalachian women the rate of small-cell carcinomas was 3.5-fold higher, and for Appalachian men the rate of squamous cell carcinoma was 3.1-fold higher, than the SEER rates. In Kentucky, lung cancers were diagnosed at later stages and lung cancer survival was lower for adenocarcinoma and neuroendocrine carcinomas than in SEER registries. Squamous cell carcinomas and small-cell carcinomas were most lethal in Appalachian Kentucky., Conclusion: Together, these data highlight the considerable disparities among lung cancer cases in the United States and demonstrate the continuing high burden and poor survival of lung cancer in Kentucky and Appalachian Kentucky. Strategies to identify and rectify causes of these disparities are discussed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: SEER registries do not report results of epidermal growth factor receptor ( EGFR ) and anaplastic lymphoma kinase ( ALK ) mutation tests. To facilitate population-based research in molecularly defined subgroups of non-small-cell lung cancer (NSCLC), we assessed the validity of natural language processing (NLP) for the ascertainment of EGFR and ALK testing from electronic pathology (e-path) reports of NSCLC cases included in two SEER registries: the Cancer Surveillance System (CSS) and the Kentucky Cancer Registry (KCR)., Methods: We obtained 4,278 e-path reports from 1,634 patients who were diagnosed with stage IV nonsquamous NSCLC from September 1, 2011, to December 31, 2013, included in CSS. We used 855 CSS reports to train NLP systems for the ascertainment of EGFR and ALK test status (reported v not reported) and test results (positive v negative). We assessed sensitivity, specificity, and positive and negative predictive values in an internal validation sample of 3,423 CSS e-path reports and repeated the analysis in an external sample of 1,041 e-path reports from 565 KCR patients. Two oncologists manually reviewed all e-path reports to generate gold-standard data sets., Results: NLP systems yielded internal validity metrics that ranged from 0.95 to 1.00 for EGFR and ALK test status and results in CSS e-path reports. NLP showed high internal accuracy for the ascertainment of EGFR and ALK in CSS patients-F scores of 0.95 and 0.96, respectively. In the external validation analysis, NLP yielded metrics that ranged from 0.02 to 0.96 in KCR reports and F scores of 0.70 and 0.72, respectively, in KCR patients., Conclusion: NLP is an internally valid method for the ascertainment of EGFR and ALK test information from e-path reports available in SEER registries, but future work is necessary to increase NLP external validity.

Appalachian Kentucky (App KY) leads the nation in lung cancer incidence and mortality. Trace elements, such as As, have been associated with lung cancers in other regions of the country and we hypothesized that a population-based study would reveal higher trace element concentrations in App KY individuals with cancer compared to controls. Using toenail and drinking water trace element concentrations, this study investigated a possible association between lung cancer incidence and trace-element exposure in residents of this region. This population-based case-control study had 520 subjects, and 367 subjects provided toenail samples. Additionally, we explored the relationship between toenail and fingernail trace-element concentrations to determine if fingernails could be used as a surrogate for toenails when patients are unable to provide toenail samples. We found that, contrary to our initial hypothesis, trace element concentrations (Al, As, Cr, Mn, Co, Fe, Ni, Cu, Se, and Pb) were not higher in cancer cases than controls with the exception of Zn where concentrations were slightly higher in cases. In fact, univariate logistic regression models showed that individuals with lower concentrations of several elements (Al, Mn, Cr, and Se) were more likely to have lung cancer, although only Mn was significant in multivariate models which controlled for confounding factors. While drinking water concentrations of Al, Cr and Co were positively related to cancer incidence in univariate models, only Co remained significant in multivariate models. However, since the drinking water concentrations were extremely low and not reflected in the toenail concentrations, the significance of this finding is unclear. We also found that fingernail concentrations were not consistently predictive of toenail concentrations, indicating that fingernails should not be used as surrogates for toenails in future studies., Competing Interests: The authors have declared that no competing interests exist.

Background: Lung cancer is the leading cause of cancer mortality in the United States (U.S.). Squamous cell carcinoma (SQCC) represents 22.6% of all lung cancers nationally, and 26.4% in Appalachian Kentucky (AppKY), where death from lung cancer is exceptionally high. The Cancer Genome Atlas (TCGA) characterized genetic alterations in lung SQCC, but this cohort did not focus on AppKY residents., Methods: Whole-exome sequencing was performed on tumor and normal DNA samples from 51 lung SQCC subjects from AppKY. Somatic genomic alterations were compared between the AppKY and TCGA SQCC cohorts., Results: From this AppKY cohort, we identified an average of 237 nonsilent mutations per patient and, in comparison with TCGA, we found that PCMTD1 (18%) and IDH1 (12%) were more commonly altered in AppKY versus TCGA. Using IDH1 as a starting point, we identified a mutually exclusive mutational pattern ( IDH1, KDM6A, KDM4E, JMJD1C ) involving functionally related genes. We also found actionable mutations (10%) and/or intermediate or high-tumor mutation burden (65%), indicating potential therapeutic targets in 65% of subjects., Conclusions: This study has identified an increased percentage of IDH1 and PCMTD1 mutations in SQCC arising in the AppKY residents versus TCGA, with population-specific implications for the personalized treatment of this disease., Impact: Our study is the first report to characterize genomic alterations in lung SQCC from AppKY. These findings suggest population differences in the genetics of lung SQCC between AppKY and U.S. populations, highlighting the importance of the relevant population when developing personalized treatment approaches for this disease., (©2018 American Association for Cancer Research.)

Recent metabolic and genetic research has demonstrated that risk for specific histological types of lung cancer varies in relation to cigarette smoking and obesity. This study investigated the spatial and temporal distribution of lung cancer histological types in Kentucky, a largely rural state with high rates of smoking and obesity, to discern population-level trends that might reflect variation in these and other risk factors. The Kentucky Cancer Registry provided residential geographic coordinates for lung cancer cases diagnosed from 1995 through 2014. We used multinomial and discrete Poisson spatiotemporal scan statistics, adjusted for age, gender, and race, to characterize risk for specific histological types-small cell, adenocarcinoma, squamous cell, and other types-throughout Kentucky and compared to maps of risk factors. Toward the end of the study period, adenocarcinoma was more common among all population subgroups in north-central Kentucky, where smoking and obesity are less prevalent. During the same time frame, squamous cell, small cell, and other types were more common in rural Appalachia, where smoking and obesity are more prevalent, and in some high poverty urban areas. Spatial and temporal patterns in the distribution of histological types of lung cancer are likely related to regional variation in multiple risk factors. High smoking and obesity rates in the Appalachian region, and likely in high poverty urban areas, appeared to coincide with high rates of squamous cell and small cell lung cancer. In north-central Kentucky, environmental exposures might have resulted in higher risk for adenocarcinoma specifically.

Screening for distress in cancer patients is recommended by the National Comprehensive Cancer Network, and a Distress Thermometer has previously been developed and empirically validated for this purpose. The present study sought to determine the rates and predictors of distress in a sample of patients being seen in a multidisciplinary lung cancer clinic. Consecutive patients (N=333) were recruited from an outpatient multidisciplinary lung cancer clinic to complete the Distress Thermometer, an associated Problem Symptom List, and two questions about interest in receiving help for symptoms. Over half (61.6%) of patients reported distress at a clinically significant level, and 22.5% of patients indicated interest in receiving help with their distress and/or symptoms. Problems in the areas of family relationships, emotional functioning, lack of information about diagnosis/treatment, physical functioning, and cognitive functioning were associated with higher reports of distress. Specific symptoms of depression, anxiety, pain and fatigue were most predictive of distress. Younger age was also associated with higher levels of distress. Distress was not associated with other clinical variables, including stage of illness or medical treatment approach. Similar results were obtained when individuals who had not yet received a definitive diagnosis of lung cancer (n=134) were excluded from analyses; however, family problems and anxiety were no longer predictive of distress. Screening for distress in a multidisciplinary lung cancer clinic is feasible and a significant number of patients can be expected to meet clinical criteria for distress. Results also highlight younger age and specific physical and psychosocial symptoms as predictive of clinically significant distress. Identification of the presence and predictors of distress are the first steps toward appropriate referral and treatment of symptoms and problems that contribute to cancer patients' distress.

Oral/pharyngeal squamous carcinoma is a largely preventable problem. Most patients have significant tobacco and alcohol histories. Treatment reflects the locally and regionally aggressive nature of these tumors. In advanced disease neither surgery nor radiation therapy can be used as a primary modality, and often combined treatment is necessary. Chemotherapy has a less well-defined role, but is increasing control rates in advanced tumors.