Background and Objectives Melanoma mutational burden is high and approximately 50% have oncogenic mutations in BRAF. We sought to evaluate age‐related mutational differences in melanoma. Methods We analyzed melanoma samples in the Genomics Evidence Neoplasia Information Exchange database. Targetable mutations were identified using the Precision Oncology Knowledge Base (OncoKB). Results We found 1194 patients with a common set of 30 genes. The top mutated genes in patients <40 years old (y/o) (n = 98) were BRAF (59%), TP53 (31%), NRAS (17%), and PTEN (14%); in 40–59 y/o (n = 354) were BRAF (51%), NRAS (30%), TP53 (26%), and APC (13%); and in ≥60 y/o (n = 742) were BRAF (38%), NRAS (33%), TP53 (26%), and KDR (19%). BRAF mutations were almost mutually exclusive from NRAS mutations in <40 y/o (58/59). Mutational burden increased with age, with means of 2.39, 2.92, and 3.67 mutations per sample in patients <40, 40–59, and ≥60 y/o, respectively (p < 0.0001). There were 10 targetable mutations meeting OncoKB criteria for melanoma: BRAF (level 1), RET (level 1), KIT (level 2), NRAS (level 3A), TP53 (level 3A), and FGFR2, MET, PTEN, PIK3CA, and KRAS (level 4). Conclusions Mutations in melanoma have age‐related differences and demonstrates potential targetable mutations for personalized therapies.
Background and Objectives: Selecting frail elderly patients with pancreatic cancer (PC) for pancreas resection using biologic age has not been elucidated. This study determined the feasibility of the deficit accumulation frailty index (DAFI) in identifying such patients and its association with surgical outcomes. Methods:The DAFI, which assesses frailty based on biologic age, was used to identify frail patients using clinical and health-related quality-of-life data. The characteristics of frail and nonfrail patients were compared.Results: Of 242 patients (median age, 75.5 years), 61.2% were frail and 32.6% had undergone pancreas resection (surgery group). Median overall survival (mOS) decreased in frail patients (7.13 months, 95% confidence interval [CI]: 5.65-10.1) compared with nonfrail patients (16.1 months, 95% CI: 11.47-34.40, p = 0.001). In the surgery group, mOS improved in the nonfrail patients (49.4%; 49.2 months, 95% CI: 29.3-79.9) compared with frail patients (50.6%, 22.1 months, 95% CI: 18.3-52.4, p = 0.10). In the no-surgery group, mOS was better in nonfrail patients (54%; 10.81 months, CI 7.85-16.03) compared with frail patients (66%; 5.45 months, 95% CI: 4.34-7.03, p = 0.02). Conclusions:The DAFI identified elderly patients with PC at risk of poor outcomes and can identify patients who can tolerate more aggressive treatments.
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