Adverse Events Following Limited Resection versus Stereotactic Body Radiation Therapy for Early Stage Lung Cancer.

Rationale: Approximately a quarter of patients with early stage lung cancer are not medically fit for lobectomy. Limited resection and stereotactic body radiation therapy (SBRT) have emerged as alternatives for these patients. Given the equipoise on the effectiveness of the two treatments, treatment-related adverse events (AEs) could have a significant impact on patients' decision-making and treatment outcomes. Objectives: To compare the AE profile between SBRT versus limited resection. Methods: Data were derived from a prospective cohort of patients with stage I-IIA non-small cell lung cancer who were deemed as high-risk for lobectomy recruited from five centers across the United States. Propensity scores and inverse probability weighting were used to compare the rates of 30- and 90-day AEs among patients treated with limited resection versus SBRT. Results: Overall, 65% of 252 patients underwent SBRT. After adjusting for propensity scores, there was no significant difference in developing at least one AE comparing SBRT to limited resection (odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.65-1.55 and OR: 1.27; 95% CI: 0.84-1.91 at 30 and 90 days, respectively). SBRT was associated with lower risk of infectious AEs than limited resection at 30 days (OR: 0.05; 95% CI: 0.01-0.39) and 90 days posttreatment (OR: 0.41; 95% CI: 0.17-0.98). Additionally, SBRT was associated with persistently elevated risk of fatigue (OR: 2.47; 95% CI: 1.34-4.54 at 30 days and OR: 2.69; 95% CI: 1.52-4.77 at 90 days, respectively), but significantly lower risks of respiratory AEs (OR: 0.36; 95% CI: 0.20-0.65 and OR: 0.51; 95% CI: 0.31-0.86 at 30 and 90 days, respectively). Conclusions: Though equivalent in developing at least one AE, we found that SBRT is associated with less toxicity than limited resection in terms of infectious and respiratory AEs but higher rates of fatigue that persisted up to 3 months posttreatment. This information, combined with data about oncologic effectiveness, can help patients' decision-making regarding these alternative therapies.

Mutational Landscapes of Smoking-Related Cancers in Caucasians and African Americans: Precision Oncology Perspectives at Wake Forest Baptist Comprehensive Cancer Center.

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high mutational load. These tumors are characterized by high-frequency mutations in TP53, DNA damage repair genes (BRCA2 and ATM), and chromatin remodeling genes (the lysine methyltransferases KMT2D or MLL2, and KMT2C or MLL3). These tobacco-related cancers also exhibit augmented tumor heterogeneities. Smoking related genetic mutations were validated by The Cancer Genome Atlas dataset that includes 2,821 cases with known smoking status. The Wake Forest and The Cancer Genome Atlas cohorts (431 and 7,991 cases, respectively) revealed a significantly increased mutation rate in the TP53 gene in the African-American subgroup studied. Both cohorts also revealed 5 genes (e.g. CDK8) significantly amplified in the African-American population. Conclusions: These results provide strong evidence that tobacco is a major cause of genomic instability and heterogeneity in cancer. TP53 mutations and key oncogene amplifications emerge as key factors contributing to cancer outcome disparities among different racial/ethnic groups.