PD-L1 expression and Tumor mutation burden as Pathological response biomarkers of Neoadjuvant immunotherapy for Early-stage Non-small cell lung cancer: A systematic review and meta-analysis

Author(s):  
Hongsheng Deng ◽  
Yi Zhao ◽  
Xiuyu Cai ◽  
Hualin Chen ◽  
Bo Cheng ◽  
...  
2020 ◽  
Author(s):  
kun zou(Former Corresponding Author) ◽  
Li Li ◽  
Shuailong Yang ◽  
Zhang Lei(New Corresponding Author)

Abstract Background: We performed this meta-analysis to assess the prognostic value of tumor mutation burden (TMB) for patients with non-small cell lung cancer (NSCLC). Methods: Tow authors independently searched the studies in PubMed, web of science, Google Scholar, Cochrane library (from inception to November 2019), according to the key words “non-small cell lung cancer”, “tumor mutation burden”, “prognosis”. The studies were set up according to the inclusion/exclusion criteria. The estimate hazard ratio (HR), odds ratio (OR), risk ratio (RR) and their 95% confidence intervals (95% CIs) were set as effect measures. All analyses were performed by STATA 12.0. Results:28 studies were involved in this meta-analysis, high TMB was associated with good overall survival (OS) (HR=0.53; 95% CI: 0.42-0.67, p<0.001), progression-free survival (PFS) (HR = 0.53; 95% CI: 0.46-0.62, p<0.001), durable clinical benefits (RR = 2.27; 95% CI: 1.79-2.89, P<0.001), and object response rate (RR = 2.27; 95% CI: 1.80-2.85; p<0.001) in patients treated with immune checkpoint inhibits (ICIs). For treated with non-ICIs, poor PFS (HR = 1.62; 95% CI: 1.27-2.07, p<0.001) and OS (HR = 1.56; 95% CI: 1.30-1.87, p=0.001) was found in high TMB. Compared with chemotherapy, ICIs treatment alone had better OS (HR = 0.68; 95% CI: 0.56 to 0.82, p<0.001) and PFS (HR = 0.64; 95% CI: 0.55 to 0.76, p<0.001) for patients with high TMB, however, for low TMB patients, no benefit was found in ICIs treatment. TMB was correlated with EGFR status (OR = 0.28; 95% CI: 0.08- 0.95; p= 0.040), ECOG score (OR = 1.79; 95% CI: 1.09-2.92; p=0.021) and smoking history (OR = 6.01; 95% CI: 1.28 - 28.13; p=0.023). Conclusions: TMB was associated with better survival in cancer patients receiving immunotherapy, and worse survival in cancer patients receiving non-ICIs. Compared with chemotherapy, ICIs was more effective in high TMB patients, but not in low TMB patients.


2021 ◽  
Vol 28 (6) ◽  
pp. 4686-4701
Author(s):  
Christopher Cao ◽  
Anthony Le ◽  
Matthew Bott ◽  
Jeffrey Yang ◽  
Dominique Gossot ◽  
...  

Purpose: Immunotherapy has created a paradigm shift in the treatment of metastatic non-small cell lung cancer (NSCLC), overcoming the therapeutic plateau previously achieved by systemic chemotherapy. There is growing interest in the utility of immunotherapy for patients with resectable NSCLC in the neoadjuvant setting. The present systematic review and meta-analysis aim to provide an overview of the existing evidence, with a focus on pathological and radiological response, perioperative clinical outcomes, and long-term survival. Methods: A systematic review was conducted using electronic databases from their dates of inception to August 2021. Pooled data on pathological response, radiological response, and perioperative outcomes were meta-analyzed where possible. Results: Eighteen publications from sixteen studies were identified, involving 548 enrolled patients who underwent neoadjuvant immunotherapy, of whom 507 underwent surgery. Pathologically, 52% achieved a major pathological response, 24% a complete pathological response, and 20% reported a complete pathological response of both the primary lesion as well as the sampled lymph nodes. Radiologically, 84% of patients had stable disease or partial response. Mortality within 30 days was 0.6%, and morbidities were reported according to grade and frequency. Conclusion: The present meta-analysis demonstrated that neoadjuvant immunotherapy was feasible and safe based on perioperative clinical data and completion rates of surgery within their intended timeframe. The pathological response after neoadjuvant immunotherapy was superior to historical data for patients who were treated with neoadjuvant chemotherapy alone, whilst surgical and treatment-related adverse events were comparable. The limitations of the study included the heterogenous treatment regimens, lack of long-term follow-up, variations in the reporting of potential prognostic factors, and potential publication bias.


2021 ◽  
Author(s):  
Yueling Zhou ◽  
Ping Wen ◽  
Yue Yu ◽  
Zhenyi Yang ◽  
Yixuan Luo ◽  
...  

Abstract Background: Stereotactic body radiation therapy (SBRT) is considered as the preferred treatment method for inoperable early-stage non-small cell lung cancer (NSCLC). However, there is still a debate on the efficacy of SBRT and surgery. This meta-analysis aimed to compare survival outcomes of SBRT and surgery for early-stage NSCLC (≤5cm).Methods: A systematic review and meta-analysis were performed to compare survival outcomes of surgery and SBRT. And the pooled analysis was conducted with STATA 14.0 software. Results: Thirty-nine comparative studies were included for systematic review and twenty-eight of which for quantitative analysis. Compared with SBRT, overall survival (OS) was superior after surgical resection, included lobectomy, sublobar resection, video-assisted thoracoscopic surgery, and thoracotomy, for patients with early-stage NSCLC (≤5cm). And the results of subgroup analysis remained the support of surgery except for the OS of operable matched cohorts and the one matched cohort of age ≥75. However, the HR of OS showed a reduction from patients with unspecific age, ≥65 to ≥75 years old and histopathologically confirmed NSCLC to clinical NSCLC. Although cancer-specific survival and local control was superior after surgery, the recurrence rate of tumors, locoregional control, distant control, and regional control of matched patients demonstrated no significantly different outcomes between SBRT and surgery for early-stage NSCLC.Conclusions: Results show that surgery has superior OS, CSS and local control compared to SBRT for early-stage NSCLC. There is still necessary to explore the survival difference between SBRT and surgery for patients with different characteristics by large-sample, long-term follow-up randomized clinical studies.


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