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Treatment Patterns and Clinical and Economic Burden in Patients with Merkel Cell Carcinoma: Statistical and Machine Learning Approaches
Get PDFAlthough considered a rare form of nonmelanoma skin cancer, Merkel Cell Carcinoma incidence rate has increased to 0.74 per 100,000 and projections expect this number to steadily rise over the next decades and to reach an average of 3,285 cases per year in 2025. MCC incidence increases significantly with age. Among those aged 40-44, it is 0.44, it rises to 1.0/100,000 in the 60-64 age group and soars to 9.8/100,000 among those ≥85 years and above. Due to the small number of cases, MCC is often managed using institutional practices or provider preferences. Formal clinical trials that enroll early stage MCC are ongoing and therefore, robust estimates of overall survival by stage and clinical management are not yet available. However, case series and retrospective studies and single-site studies suggest better overall survival with early stages. Thus, the real benefit of current standard of care needs to be assessed in early-stages to obtain a comprehensive overview of MCC treatment. Further, chronic conditions are highly prevalent in older adults with MCC. Although, evidence speaks of their prevalence, less is known about their temporal origin and their influence on cancer treatment choice. As older adults with cancer have on average three or more chronic conditions, these comorbidities typically precede a cancer diagnosis. Patients with comorbidities have poor prognosis and survival, are less likely to receive curative treatment choices and also are more likely to be offered less aggressive care. Thus, the presence and type of chronic conditions in MCC requires serious investigation as well as their impact on the choice of MCC treatment type. Cancer comorbidities not only influence treatment but can also affect economic burden among older adults with MCC. A diagnosis of cancer often leads to the neglect of any underlying chronic condition. an acute cancer diagnosis with an underlying chronic condition. However, the impact of chronic conditions among MCC patients over time remains unknown. To fill this knowledge gap, the three related aims of this dissertation were: 1) To conduct a systematic review with meta-analysis, wherever possible, of the effectiveness and safety of SRx, RTx, CTx or combination therapies in MCC patients; 2) To investigate the association of presence and type of pre-existing chronic conditions with treatment patterns among patients with incident primary MCC using interpretable machine learning methods; 3) To build predictive and interpretable machine learning of economic burden (total healthcare and out-of-pocket expenditures) and their association with chronic conditions among patients with incident primary MCC. In the first aim, among early-stages MCC patients, a statistically significant improvement in overall survival (HR=0.78, 95% CI, 0.62 to 0.99), and disease-free survival (HR=0.35, 95% CI, 0.13 to 0.93) was observed for adjuvant RTx compared to SRx. Although not statistically significant, adjuvant RTx also improved control of regional recurrence (HR=0.41, 95% CI, 0.09 to 1.78), as well as disease specific survival (HR=0.58, 95% CI, 0.24 to 1.40). However, it decreased control of local recurrence LR (HR=1.52, 95% CI, 0.37 to 6.19) compared to SRx. Subgroup analyses revealed that adjuvant RTx was more effective among local compared to regional stages. The E-value informed on the likelihood of total radiotherapy dose as a confounder, but also suggested that chemotherapy provided to those that had already received adjuvant radiotherapy did not impact the strength of evidence of the aforementioned outcomes. In the second aim, among older (\u3e 65 years) adults with primary incident MCC (N=1,668), high cholesterol (75.5%), HIV (71.5%), hypertension (67.7%), arthritis (54.9%), coronary artery disease (47.1%), diabetes (43.5%), and hepatitis (37.1%) were some of the highly prevalent pre-existing chronic conditions. MCC treatment varied by type of chronic conditions and treatment modality. For example, a lower percentage of those with hypertension received ITx compared to those without hypertension (5.7% vs. 17.1%). XGBoost predictions revealed high predictive accuracy (area under the curve ranged from 0.72 (CTx) to 0.99 (ITx)). Hypertension (ITx), diabetes and thyroid disorders (HTx), thyroid diseases (RTx), and high cholesterol (CTx) were among the top ten predictors of specific MCC treatment. In the third aim, among older Medicare beneficiaries with incident MCC, congestive heart failure (CHF), chronic kidney disease (CKD) and depression had the highest average incremental total expenditures during pre-diagnosis, treatment, and post-treatment phases respectively (24,221, and 22,524, 20,556 (CKD); and 22,055, 3703, 2,442 (CHF); 2,518, 3,278, 2,783 (depression). Except for hypertension, and HIV all chronic conditions had higher expenditures compared to those without the chronic conditions. Predictive models in each of the three phases indicated that CHF, CKD, and heart diseases were among the top 10 leading predictors. The root mean square error (RMSE) ranged from as low as 0.63 (during treatment) to as high as 1.05 (pre-diagnosis) for total expenditures, and from 0.52 (during treatment ) to 0.8 (pre-diagnosis) for out-of-pocket suggesting modest predictive performance. Although CHF, CKD, heart diseases was among the top common 10 leading predictors of total and out-of-pocket expenditures, their feature importance ranking declined over time. The findings from these three aims have implications for programs and policies, treatment, and practice. Our systematic review suggested that research with robust study designs are needed to compare the effectiveness of cancer therapies for early-stages MCC. Findings from our retrospective studies with real world data, comprehensive list of biological, clinical, lifestyle factors and social determinants of health applications of novel predictive and interpretable machine learning methods suggest the heterogeneous associations of chronic conditions with treatment and economic burden among older adults with MCC. These findings call for a personalized approach to treatment and cost containment efforts
Water Security and Justice: Community PFAS Exposure in Monongalia County
Get PDFWater security and justice is the right of all people to have reasonable access to clean and safe water. Pollution in the form of toxic discharge from various industries poses a significant risk to public and environmental health. Among these toxic pollutants are per- and poly-fluoroalkyl substances (PFAS), also known as forever chemicals” that compromise water quality in our communities. Despite the Safe Drinking Water Act (SDWA) in 1974 aimed at ensuring clean drinking water for WV, there is still an alarming pattern of neglect and injustice to communities related to race, ethnicity, socio-economic status, and language barriers . Non-compliance with the SDWA can lead to severe health consequences, including mass distribution of cancers, developmental issues and other diseases. In 2020, the Annual Compliance Report for the SDWA in WV revealed 3,142 violations regarding failure to monitor and report water quality issues. Our project addresses these challenges through community engagement, political advocacy, and scientific data collection on the causes of water pollution in West Virginia to promote environmental justice for all residents
Exploring the Intersection between West Virginia Farmland Protection Boards, Landowners, and the West Virginia Agrarian Commons
Get PDFNew Roots Community Farm (NRCF) came to life through the purchase of a piece of land by the Fayette County Farmland Protection Board in a buy-protect-sell model. NRCF then partnered with The Agrarian Land Trust, a New England based organization experimenting with land commons models across the United States, to purchase the property and create the West Virginia Agrarian Commons (WVAC), an entity that could advance land access for the next generation farmers in WV. The experience of NRCF and the WVAC and the vision for its operation and extension of the buy-protect-sell model in partnership with county farmland protection boards (FPB’s) remains an interesting model to support land commoning in a region that has a long history of dispossession. In Fall 2023, NRCF requested the support from the Center for Resilient Communities (CRC) in a process of action research and data collection on the state of farmland protection, conservation, and land trusts in West Virginia. An interview process following a snowball sampling method ensued to discover the organization and governance of farmland protection; the goals of farmland protection board members; the benefits and drawbacks of a landowner conserving their property; the relationship between land conservation, economic development, and community-based food systems; and the potential for farmland protection to contribute to the West Virginia Agrarian Commons. This process of collective inquiry will lay the groundwork for a longer-term action research process on farmland protection and land access for the next generation of farmers
