Figure 4. Tumor mutation burden.
(a) Grade 3 neuroendocrine neoplasms (NEN) rank 4th in order of highest tumor mutation burden (TMB) when compared to 33 tumor types in The Cancer Genome Atlas project. Red line indicates median TMB. N = 40.
(b) Mean TMB of grade 3 NENs (7.08, SD = 8.5, n = 40) compared to lower grade tumors previously reported (pancreas 0.82, small intestine 0.77, lung 0.4). (Fernandez-Cuesta, et al. 2014; Mafficini and Scarpa 2019; Yao, et al. 2019)
(c) TMB among grade 3 NENs separated by tissue origin. Dotted line marks 10 mutations/MB, a known predictor of response to immunotherapy as validated in other cancers. The miscellaneous group has the highest TMB (vs GEP: p = 0.04), with head and neck primaries in this group showing the highest TMB (21.5 mutations/MB). Mean ± SD: GEP (4.28 ± 8.17, n = 15), Lung (6.01 ± 3.82, n = 14), Misc (12.28 ± 11.24, n = 11). One-way ANOVA/Tukey’s multiple comparison test.
(d) Patients with high TMB had better overall survival than patients with lower TMB. Multivariate analysis accounted for age, stage, primary site, resected tumor and number of treatment lines, p = 0.03.
Abbreviations: GEP, gastroenteropancreatic. NEN, neuroendocrine neoplasm. TMB, tumor mutation burden. SD, standard deviation.