Effectiveness and Safety of Anlotinib Combined with PD-1 Blockades in Patients with Previously Immunotherapy Treated Advanced Non-Small Cell Lung Cancer: A Retrospective Exploratory Study.

Objective: This study aimed to investigate the effectiveness and tolerability of anlotinib plus PD-1 blockades in patients with previously immunotherapy treated advanced non-small-cell lung cancer (NSCLC). Methods: A total of 67 patients with previously immunotherapy treated advanced NSCLC who received anlotinib plus PD-1 blockades in clinical practice were screened retrospectively. All the PD-1 blockades used in this study were approved in China and consisted of sintilimab, camrelizumab, tislelizumab and pembrolizumab. Effectiveness and safety of anlotinib plus PD-1 blockades were assessed, and all patients were followed up regularly. Clinical significance between response status to previous immune-related treatment regimens and therapeutic outcomes of anlotinib plus PD-1 blockades was further explored. Results: The best overall response among the 67 patients suggested that a partial response was observed in 16 patients, stable disease was noted in 41 patients and progressive disease was found in 10 patients, which yielded an objective response rate of 23.9% (95% CI: 14.3-35.9%) and a disease control rate of 85.1% (95% CI: 74.3-92.6%). Prognostic outcomes indicated that the median progression-free survival (PFS) was 6.1 months (95% CI: 2.37-9.83) and the median overall survival (OS) was 16.5 months (95% CI: 10.73-22.27). Exploratory analysis highlighted that patients who were intolerant to previous immune-related regimens (17 patients) might have a superior prognosis (median OS: 22.3 months vs 12.5 months, P=0.024). Additionally, adverse reactions with any grades during anlotinib plus PD-1 blockades administration were observed in 62 patients (92.5%), of which 31 patients (46.3%) had ≥grade 3 adverse reactions. Most common adverse reactions were fatigue, hypertension, diarrhea and hepatotoxicity. Conclusion: Anlotinib plus PD-1 blockades demonstrated promising effectiveness and tolerable safety in patients with previously immunotherapy treated advanced NSCLC. Those who were intolerant to previous immune-related regimens might benefit significantly from treatment with anlotinib plus PD-1 blockades. This conclusion should be confirmed in future studies.

METTL3 promotes non-small cell lung cancer (NSCLC) cell proliferation and colony formation in a m6A-YTHDF1 dependent way.

BACKGROUND: N6-methyladenosine (m6A) is the most common RNA modification, which plays a pivotal role in tumor development and progression. In this study, we assessed the role of m6A methyltransferase METTL3 in FRAS1-involved cell proliferation and colony formation of non-small cell lung cancer (NSCLC) cell lines. METHODS: Cell viability was analyzed by Cell Counting Kit (CCK-8) and colony formation. M6A RNA immunoprecipitation (IP), Ribosomal immunoprecipitation, RNA immunoprecipitation (RIP) were performed to verify the relationship between METTL3, FRAS1 and YTHDF1. Rescue experiments to confirm the regulatory mechanism of METTL3-FRAS1 promoted NSCLC cell proliferation through CDON by cooperating YTHDF1. RESULTS: We found that FRAS1 was correlated with poor prognosis in NSCLC patients, of which the transcript undergoes m6A modification regulated by METTL3. METTL3 silence reduced cell viability of NSCLC cells HCC827 and NCI-H1975, which could be restored by FRAS1 overexpression. The m6A modification of FRAS1 could be recognized by YTHDF1. FRAS1 silence or YTHDF1 silence could rescue the elevated NSCLC cell proliferation, colony formation, and tumor growth induced by METTL3 overexpression in vitro and in vivo. CONCLUSIONS: Our study reveals that METTL3-FRAS1 plays a crucial role in NSCLC cell proliferation, colony formation, and tumor growth through the regulation of CDON by cooperating YTHDF1.

Tumor size and lymph node metastasis are prognostic markers of small cell lung cancer in a Chinese population.

Small cell lung cancer (SCLC) is a high-grade neuroendocrine tumor characterized by rapid growth, early metastatic spread, and poor prognosis. This study aimed to explore the prognosis factors of survival in Chinese SCLC patients.A total of 78 patients with stage IIIA SCLC (mean age: 53.9 years, 65 males and 13 females) were enrolled in this retrospective study. At least of 5 years follow-up was performed.The survival time of these patients ranged from 1 month to 66 months with a median survival time of 11 months. Kaplan-Meier method with log-rank test was performed and showed that survival time in patients with tumor size ≤4 cm (median: 16 months) was significantly longer (P < .001) than that in patients with tumor size > 4 cm (median: 8 months); the median survival time of the patients with single lymph node metastasis was significantly longer than that in patients with multiple lymph node metastasis (P = .043). Combined multiple lymph node metastasis and tumor size >4 cm presented the worst survival outcome than others. Multivariate analysis by Cox Hazard model shows that the lymph node metastasis and tumors size were prognostic factors independent of age, sex, smoke, surgery, and treatment regimen (P < .05).Results showed that larger tumor size and multiple lymph node metastasis were associated with the poor survival in SCLC.

[Analysis of Efficacy of Surgical Treatment for IIIa Small Cell Lung Cancer].

BACKGROUND: Small cell lung cancer (SCLC) accounts for nearly 15% of all cases of cancer. As a type of highly invasive tumors, SCLC has high degree of malignancy, early and extensive metastasis, and is sensitive to chemotherapy and radiotherapy. The early treatment response rate of SCLC is high but it can also relapse rapidly without any treatment. Its median survival time is merely four to six months. Although many studies on SCLC have been conducted in recent years, its clinical treatment strategies have remained unchanged. The treatment of SCLC is still confined to chemotherapy regimens of etoposide plus cisplatin (EP) and other classic treatments because the surgical treatment of SCLC, particularly for IIIa treatment, has yet to reach a consensus. This study investigated the prognostic factors and clinical therapy effect in the comprehensive treatment of IIIa SCLC after surgical treatment. METHODS: This study was conducted through the retrospective analysis of the clinical data of 78 patients with SCLC who underwent surgical treatment in Beijing Chest Hospital affiliated to Capital Medical University between January 1995 and December 1995. Through follow-up, we performed statistical analysis of each patient's gender, age, tumor size, lymph node metastasis, tumor-node-metastasis (TNM) staging, surgical methods, and adjuvant radiation and chemotherapy. RESULTS: The median survival in this clinical trial team was 13.93 months. Among the participants, 47 patients accepted neoadjuvant chemotherapy and their median survival were 14.25 months. By contrast, 31 patients accepted postoperative adjuvant chemotherapy and their median survival were 13.83 months. No statistical difference was observed between the two groups. Moreover, 28 patients were of single Lymph node metastasis and their median survival was 17.1 months. By contrast, 50 patients were of multiple lymph node metastasis and their median survival was 11.9 months. Significant statistical difference was observed between the two groups (P<0.01). CONCLUSIONS: In performing further evaluation of the status and value of surgical treatment in the comprehensive treatment of SCLC, several patients benefitted from IIIa SCLC surgery with comprehensive treatment.

[Preoperative chemotherapy for long-term results of small cell lung cancer].

OBJECTIVE: To reveal the pre-operative chemotherapy for long-term of small cell lung cancer. METHODS: From January 1994 to January 2005, 263 patients with small cell lung cancer underwent combined therapy. The comparison of long-term survival rates was made between pre-operative chemotherapy group (n = 111) (group A) and post-operative chemotherapy (n = 96) (group B). RESULTS: The analyses disclosed that the overall 5-year survival rate was 42.16%. The 5-year survival rate of group A was 38.25% while in group B it was 46.57%. 5-year survival rate of group A for N0-1 and N2 was 40.12% and 39.22%, that for stage I, II, IIIa, IIIb, IV was 60.15%, 35.70%, 40.16%, 14.29% and 0 respectively. 5-year survival rate of group B for N0-1 and N2 was 51.91% and 42.69%, that for stage I, II, IIIa, IIIb, IV was 61.1%, 50.23%, 42.32%, 26.47% and 0 respectively. CONCLUSION: The comparison of the survival rate between patients with the pre-operative chemotherapy and those with chemotherapy post-operatively revealed trend of variation. Operation plus post-operative chemotherapy mode is indispensable for better prognosis of small cell lung cancer.