Introduction: The main treatment regimen for small cell lung cancer (SCLC) involves platinum-based chemotherapy (cisplatin or carboplatin) and etoposide. Single nucleotide polymorphisms (SNPs) in TOP2A and ERCC1 genes were tested as prognostic and predictive factors in non-small cell lung cancer (NSCLC). There are limited data about the clinical relevance of these genetic alterations in SCLC. We undertook this retrospective study to determine the influence of SNPs in TOP2A (rs34300454; rs13695; rs11540720) and ERCC1 (rs11615; rs3212986) genes on the efficiency and toxicity of chemotherapy with platinum and etoposide in SCLC Caucasian patients. Material and methods: The studied group included 103 Caucasian SCLC patients (65 male, 38 female, median age 65 ±7.5 years). Detailed clinicaldemographical data were collected and response to treatment was monitored. DNA was isolated from peripheral blood leukocytes using QIAamp DNA Mini Kit. Single nucleotide polymorphisms were analyzed using TaqMan hydrolyzing probes in real-time PCR technique on an Eco Illumina device. Results: Patients with C/C genotype in rs13695 of the TOP2A gene had significantly lower risk of neutropenia during chemotherapy than C/T heterozygous patients (p = 0.02, χ² = 5.51, OR = 2.676, 95% CI = 1.165-6.143). Patients harbouring homozygous C/C genotype in rs3212986 of the ERCC1 gene had significantly higher risk of anaemia during chemotherapy, than heterozygous C/A patients (p = 0.045, χ² = 4.01, OR = 0.417, 95% CI = 0.175-0.991). Furthermore, heterozygous G/A genotype in rs11615 of the ERCC1 gene was associated with significant shortening of OS (9 vs. 12 months) compared to homozygous A/A genotype (p = 0.01, χ² = 6.31, HR = 1.657, 95% CI = 1.0710-2.5633). Conclusions: SNPs in ERCC1 and TOP2 genes may be associated with the toxicities and survival of SCLC patients treated with cisplatin and etoposide.

Introduction: Factors other than PD-L1 (Programmed Death Ligand 1) are being sought as predictors for cancer immuno- or chemoimmunotherapy in ongoing studies and long-term observations. Despite high PD-L1 expression on tumor cells, some patients do not benefit from immunotherapy, while others, without the expression of this molecule, respond to immunotherapy. Attention has been paid to the composition of the gut microbiome as a potential predictive factor for immunotherapy effectiveness. Materials and Methods: Our study enrolled 47 Caucasian patients with stage IIIB or IV non-small cell lung cancer (NSCLC). They were eligible for treatment with first- or second-line immunotherapy or chemoimmunotherapy. We collected stool samples before the administration of immunotherapy. We performed next-generation sequencing (NGS) on DNA isolated from the stool sample and analyzed bacterial V3 and V4 of the 16S rRNA gene. Results: We found that bacteria from the families Barnesiellaceae, Ruminococcaceae, Tannerellaceae, and Clostridiaceae could modulate immunotherapy effectiveness. A high abundance of Bacteroidaaceae, Barnesiellaceae, and Tannerellaceae could extend progression-free survival (PFS). Moreover, the risk of death was significantly higher in patients with a high content of Ruminococcaceae family (HR = 6.3, 95% CI: 2.6 to 15.3, p < 0.0001) and in patients with a low abundance of Clostridia UCG-014 (HR = 3.8, 95% CI: 1.5 to 9.8, p = 0.005) regardless of the immunotherapy line. Conclusions: The Clostridia class in gut microbiota could affect the effectiveness of immunotherapy, as well as the length of survival of NSCLC patients who received this method of treatment.

Background: CT lung screening (CTLS) detects two overlapping but potentially distinct groups of tumors. Prevalent tumors, found at baseline screening, are thought to be enriched with slow-growing, potentially indolent cancers while incident tumors, found on annual repeat scans, are thought to be more uniformly fast-growing and aggressive. Pathologically, squamous cell carcinomas, small cell carcinomas (SCC) and large cell neuroendocrine carcinomas (LCNEC) are uniformly fast-growing and aggressive while adenocarcinomas are more heterogenous in their growth-rates, behavior and histology. By comparing pathologic subtypes, I-ELCAP investigators reported a higher frequency of adenocarcinomas compared to squamous cell carcinomas in prevalent compared to incident tumors (ratio 8:1 vs. 3.4:1) and conversely a 4-fold lower frequency of SCC/LCNEC (7% vs. 30%, respectively). Based partly on these data, some worry about the risk of over diagnosis in CTLS subjects undergoing baseline screening in which the proportion of slow-growing potentially indolent adenocarcinomas may be enriched. Current guidelines recommend screening specific high-risk subjects for which pathologic comparisons of prevalent and incident cancers have not been thus far described. Method: The pathology of 134 CTLS cancers detected at Lahey Hospital and Medical Center was reviewed, including 93 detected at baseline and 41 at annual repeat screening. All individuals met the NCCN Guidelines Lung Cancer Screening v1.2012 high-risk criteria, were asymptomatic, had no known metastatic disease and were free of lung cancer for at least 5-years. Detailed pathologic analysis was performed for 65 stage I resected adenocarcinomas whereas lineage alone was determined for the cytologically diagnosed tumors. Result: The proportion of adenocarcinomas to squamous cell carcinomas was similar in prevalent compared to incident tumors (ratio 2.6:1 vs. 3.1:1). Small cell carcinomas were only half as frequent among prevalent vs. incident cancers (5% vs. 12%). Among stage I adenocarcinomas, a similar proportion of prevalent vs. incident cancers exhibited a 5% solid pattern (32% vs. 30%), 5% micropapillary pattern (23% vs. 22%), 10% cribriform pattern (30% vs. 26%), intermediate/high mitotic grade (57% vs. 57%), angiolymphatic invasion (43% vs. 48%), and STAS (36% vs. 39%). Visceral pleural invasion was actually higher in the prevalent cancers (27% vs. 17%) however no statistically significant differences were observed. Conclusion: Pathologic comparison of prevalent vs. incident CTLS cancers among NCCN defined high-risk subjects reveals less variability than previously described by I-ELCAP. In particular, histologically indolent adenocarcinomas are not enriched in prevalent compared to incident tumors and thus the risk of over diagnosis in baseline detected cancers may be less than once thought.

Conclusion: Using scRNA-seq with VDJ sequencing, the functional capacity of effector cells can be ascertained within the tumour microenvironment and immune cell responses to immunotherapy can be measured. Single cell sequencing has the potential to be used as a functional, predictive assay for treatment with IO.