Background/Aim: KRAS mutation is the most frequent molecular alteration found in advanced non-small cell lung cancer (NSCLC). It is associated with a poor prognosis without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICIs), and data about their efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC. Patients and Methods: All stage IV NSCLC patients treated in our institution from January 2016 to December 2017 with immunotherapy were included in our analysis. We collected the status of KRAS and other mutations, as well as the type of ICI administered. We assessed four clinical outcomes: i) disease control rate (DCR), ii) partial response (PR), iii) progression-free survival (PFS) and iv) overall survival (OS). Results: A total of 45 patients were initially identified but 7 were excluded due to insufficient clinical data, so 38 were included in the end. In the KRAS wildtype cohort, the DCR was 59% with 49% PR, while the PFS was 8.4 months and OS 16.8 months. Among KRAS mutated patients, results were more favourable, the DCR was 81%, with 62% PR. PFS was 13.6 months and OS was 18.5 months. The median follow-up was 24 months (17 to 34 months) and 7 patients were still on treatment at the time of analysis. Conclusion: Our data suggest that KRAS mutation is predictive of a superior response to immunotherapy. Furthermore, the lack of response of STK11 and KRAS co-mutated NSCLC patients to ICIs, is indeed negated by an additional TP53 mutation.
statistically significant difference was observed in the NLR value for the time period up to the OS (p:0.026; p < 0.05). OS was observed in 44 (38%) of the patients under levels of 18.00 ALI, and 71 (62%) of patients over 18.00 ALI. The average time for OS under ALI 18.00 was 4.24 months versus 10.13 months for the others. A statistically significant difference was observed between the ALI value and the OS (p:0.000; p < 0.05). There was no significant difference between PFS and OS for PLR value (p > 0.05). Conclusions: We found that the NLR and ALI values at diagnosis were related to survival in patients with advanced lung cancer, and that the cutoff values indicated may be useful in predicting the survival and prognosis of the patient.
P value of <0.05 (Wilcoxon paired test) was considered statistically significant. Result: The median time between primary LC diagnosis and BM occurrence was 13 months range, 0 to 91 months), and synchronous BM were diagnosed in 12% of patients. Overall survival in the entire group was 22.5 months. The number of CNA was significantly higher in BM than in primary tumor, regardless of clinical/demographic data or type of aneuploidy (gains/losses). Primary tumors harbored significantly more gains and almost no losses. In both tumor sites, the most frequent gains affected 1q, 5p, 7p, 8q and 20q, whereas gains of 17q and 19q, and losses of 4p, 4q, 5q, 8p, 9p, 16q, 17p, 18q, 22q were identified only in BM. The fraction of the genome affected by mutational events in BM correlated positively with time to BM development. Three the top altered genes (IL7R, MLT11, SETDB1) were identical in both primary lesions and BM. Conclusion: Our results indicate that while primary LC lesions harbor frequent amplifications, the CNA landscape of BM is dominated by deletion events. Higher number of CNA harbored by late compared to synchronous BM suggests high levels of genomic instability.
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