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Tumor profiling of 431 pancreatic tumors from elderly patients.
Background: Pancreatic cancer (PC) is frequently a disease of the elderly and controversy exists as to whether these patients benefit from aggressive treatments. We aimed to investigate biomarker features from tumors taken from elderly PC patients to identify therapeutic implications. We also compared the results to those from younger patients to assess differences. Methods: PC tumors were tested at Caris Life Sciences between 2009 and 2015 by immunohistochemistry, fluorescent/chromogenic in-situ hybridization and sequencing. De-identified biomarker data were analyzed. Results: A total of 431 tumors from PC patients aged > = 75 were analyzed: 50% were samples from pancreas, 50% were from metastatic sites. 26 of 47 genes sequenced carried mutations with frequencies ranging from 0.6% to 84%. The highest mutation rates were seen in KRAS (84%), TP53 (55%), BRCA2 (21%), SMAD4 (12%), ATM (4.4%), BRCA1 (4.2%) and PIK3CA (3.8%). Overexpression of TOPO1 and low expression of ERCC1, RRM1 and TS were seen in 45%, 73%, 86% and 79%, respectively, indicating potential benefit from irinotecan, platinums, gemcitabine and fluoropyrimidine, respectively. Tumor expression of PD-L1 was seen in 14% and tumor-infiltrating lymphocyte expression of PD-1 was seen in 45%. Overexpression of EGFR and cMET were seen in 91% and in 62%, respectively. When compared to 470 tumors from PC patients aged < = 50, KRAS mutations were significantly more common in the elderly than in younger patients (84% vs. 74%, p = 0.0018), while MLH1 mutations were seen exclusively in younger patients (0% vs. 4%, p = 0.0241). Moreover, expression of TOP2A (53%vs. 45%), ERCC1 (36% vs. 27%), RRM1 (20% vs. 14%), SPARC (20% vs. 14%) and PR (5% vs. 1%) were significantly more prevalent in the younger group (all p < 0.05). Conclusions: Tumor profiling of 431 tumors from elderly PC patients suggests therapeutic opportunities including cytotoxic, biological as well as targeted agents for this patient group. A comparison with younger patients indicated that irinotecan, fluoropyrimidine and taxanes may provide equal benefit to elderly and younger patients, while platinums and gemcitabine may be more likely to benefit elderly patients.