Effectiveness of neoadjuvant immunochemotherapy compared to neoadjuvant chemotherapy in non-small cell lung cancer patients: Real-world data of a retrospective, dual-center study.

Background: Studying the application of neoadjuvant immunochemotherapy (NICT) in the real world and evaluating its effectiveness and safety in comparison with neoadjuvant chemotherapy (NCT) are critically important. Methods: This study included the II-IIIB stage non-small cell lung cancer (NSCLC) patients receiving NCT with or without PD-1 inhibitors and undergoing surgery after neoadjuvant treatments between January 2019 to August 2022. The clinical characteristics and treatment outcomes were retrospectively reviewed and analyzed. Results: A total of 66 patients receiving NICT and 101 patients receiving NCT were included in this study. As compared to NCT, NICT showed similar safety while not increasing the surgical difficulty. The ORR in the NICT and NCT groups was 74.2% and 53.5%, respectively, P = 0.009. A total of 44 patients (66.7%) in the NICT group and 21 patients (20.8%) in the NCT group showed major pathology response (MPR) (P <0.001). The pathology complete response (pCR) rate was also significantly higher in NICT group than that in NCT group (45.5% vs. 10.9%, P <0.001). After Propensity Score Matching (PSM), 42 pairs of patients were included in the analysis. The results showed no significant difference in the ORR between the two groups (52.3% vs. 43.2%, P = 0.118), and the proportions of MPR (76.2%) and pCR (50.0%) in NICT group were significantly higher than those of MPR (11.9%) and pCR (4.7%) in the NCT group (P <0.001). The patients with driver mutations might also benefit from NICT. Conclusions: As compared to NCT, the NICT could significantly increase the proportions of patients with pCR and MPR without increasing the operation-related bleeding and operation time.

Identifying Genomic Alterations in Small Cell Lung Cancer Using the Liquid Biopsy of Bronchial Washing Fluid.

Objective: With the rapid development of cancer genomics and immunomics, some new treatments of small cell lung cancer (SCLC) are emerging. However, there are limitations to the clinical use of tumor tissue. Our study aimed to evaluate the potential use of bronchial washing fluid (BWF) in the liquid biopsy of SCLC. Methods: Twenty-one extensive SCLC (ES-SCLC) patients were enrolled in this study. For all patients, four sample types, BWF supernatant (BWFs), BWF precipitate (BWFp), plasma and tumor tissue, were collected before receiving chemotherapy, and one type, plasma, was collected after chemotherapy. All samples were conducted to NGS using the 1021-gene panel. The concordance rates of genomic profiling using NGS in the four types of samples were evaluated. Multiple clinical information was analyzed for correlation. Results: We successfully tested 20 BWFs samples, 21 BWFp samples, 21 tumor tissue samples, 20 pre-treatment plasma, and 13 post-treatment plasma of these 21 patients. The detectability of somatic mutations was 100% for BWFs, BWFp, tumor tissues, and post-treatment plasma, and only one pre-treatment plasma was absent with any mutation. Matched tumor tissue, BWFs, BWFp, and pre-treatment plasma samples were subsistent for 19 patients. For these patients, 204 genomic alterations were identified in tissue samples, while 189 (92.6%), 175 (85.5%), and 163 (79.9%) alterations were detected in the matched BWFs, BWFp, and pre-treatment plasma, respectively. Moreover, we found that the three tumor markers associated with SCLC have a lower sensitivity than genomic alterations. The endocrine resistance pathway was found enriched in hyponatremia patients which may be related to the hyponatremia. The TMBs of BWF, BWFp, and pre-treatment plasma samples all had a strong correlation with that of tissue samples. Both the VAF and the MVAF of mutations in post-treatment plasma were less than those in pre-treatment plasma, which was in accordance with the evaluation of curative effect. Conclusions: For ES-SCLC patients, the liquid biopsy of BWF showed a highly potential advantage to identify DNA alterations, which suggested that genomic analysis of BWF liquid biopsy may have clinical value as a supplement for tissue and blood detection. Through the restricted validation, it can be widely used in routine clinical practice.

Programmed cell death-ligand 1 (PD-L1) expression and fibroblast growth factor receptor 1 (FGFR1) amplification in stage III/IV lung squamous cell carcinoma (SQC).

BACKGROUND: This study was conducted to explore programmed cell death-ligand-1 (PD-L1) expression and fibroblast growth factor receptor 1 (FGFR1) amplification in stage IIIB/IV lung squamous cell carcinoma (SQC). Correlations between PD-L1 and FGFR1, and with clinicopathological characteristics, efficacy of platinum-based chemotherapy, and prognosis were analyzed. METHODS: One hundred and twenty-eight consecutive stage III/IV SQC patients were enrolled in this study from 2009 to 2014. Seventy-eight patients received platinum-based chemotherapy. Immunohistochemistry was used to assess PD-L1 expression and fluorescence in situ hybridization was applied to detect FGFR1 amplification. RESULTS: PD-L1 expression was detected in 61.7% (79/128) of lung SQC patients. Smokers had significantly higher PD-L1 expression rates than non-smokers (66.1% vs. 44.0%, P = 0.042, respectively). The objective response and disease control rates for platinum-based chemotherapy were not significantly different between PD-L1 negative and positive patients (43.3% vs. 36.2%, P = 0.434; 80.0% vs. 78.7% P = 0.840, respectively); however, overall survival in PD-L1-negative patients was significantly longer than in PD-L1-positive patients (41.5 vs. 19.3 months, P = 0.001). Twenty-five percent (32/128) of patients displayed FGFR1 amplification, with a lower rate in stage III patients compared to stage IV (17.1% vs. 36.5%, P = 0.013, respectively). There was no significant difference in FGFR1 amplification levels between overall response, disease control or overall survival rates. No correlation was observed between PD-L1 expression and FGFR1 amplification ( P = 0.916). CONCLUSION: PD-L1 expression may function as a prognostic factor in Chinese stage III/IV SQC patients. FGFR1 amplification is more prevalent in late stage SQC patients but does not predict chemotherapy response. There is no apparent correlation between PD-L1 expression and FGFR1 amplification.

XRCC1 codon 280 polymorphism and susceptibility to lung cancer: a meta-analysis of the literatures.

The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair, and the genetic polymorphisms in the XRCC1 gene influence its function. XRCC1 codon 280 polymorphism is an Arg-His change in the XRCC1 gene. Many studies were published to investigate the association between XRCC1 codon 280 polymorphism and risk of lung cancer, but the results were inconsistent. We performed a meta-analysis of 16 studies with a total of 18,660 subjects (8,736 cases and 9,924 controls). The pooled odds ratios (OR) and corresponding 95 % confidence intervals (95 % CI) for the gene-disease association were calculated. Overall, there was a significant association between XRCC1 codon 280 polymorphism and increased risk of lung cancer (HisHis vs. ArgArg: OR = 1.53, 95 % CI 1.08-2.16, P = 0.016; HisHis vs. ArgArg/ArgHis: OR = 1.55, 95 % CI 1.10-2.19, P = 0.012). However, subgroup analysis by race failed to confirm the obvious association in Europeans and Asians. Therefore, there is a significant association between XRCC1 codon 280 polymorphism and increased risk of lung cancer. More studies with a large sample are needed to further evaluate the possible race-specific effect in the association above.

[Clinical study of ifosfamide and cisplatin in the treatment of advanced non-small cell lung cancer].

BACKGROUND: To evaluate the efficacy and toxicity of ifosfamide and cisplatin in the treatment of advanced non-small cell lung cancer. METHODS: Fifty-six patients with advanced non-small cell lung cancer were treated by combination chemotherapy of ifosfamide and cisplatin for two cycles: ifosfamide 1.5-2.0g/m² iv drip on day 1-4, mesna 400mg iv at 0,4,8 hours after using ifosfamide; DDP 25-30mg/m² iv drip on day 5-7. The response, toxicity, relievable period and survival period were evaluated. RESULTS: The total response rate was 50.0%. The response rate of patients in primary treatment was 52.8% and that of return cases was 45.0% (P > 0.05). The median relievable period was five months. The median duration of survival (MDS) was nine months. The major toxicity was inhibition of bone marrow, especially of leukocyte and platelet. CONCLUSIONS: Combination chemotherapy of ifosfamide and cisplatin is effective in the treatment of advanced non-small cell lung cancer including the return cases, and the toxicity is tolerable. If G-CSF is used as a complementary therapy, this regimen could be quite clinically valuable.