The gastrointestinal microbiota was reported as an important factor for the response to cancer immunotherapy. Probiotics associated with gastrointestinal dysbiosis and bacterial richness may affect the efficacy of cancer immunotherapy drugs. However, the clinical impact of probiotics on the efficacy of cancer immunotherapy in patients with nonsmall cell lung cancer (NSCLC) is poorly understood. The outcomes of 294 patients with advanced or recurrent NSCLC who received antiprogrammed cell death-1 (PD-1) therapy (nivolumab or pembrolizumab monotherapy) at three medical centers in Japan were analyzed in our study. We used inverse probability of treatment weighting (IPTW) to minimize the bias arising from the patients' backgrounds.The IPTW-adjusted Kaplan-Meier curves showed that progression-free survival (nonuse vs use: hazard ratio [HR] [95% confidence interval {CI}] = 1.73 [1.42-2.11], log-rank test P = .0229), but not overall survival (nonuse vs use: HR [95%CI] = 1.40 [1.13-1.74], log-rank test P = .1835), was significantly longer in patients who received probiotics. Moreover, the IPTW-adjusted univariate analyses showed that nonuse or use of probiotics was significantly associated with disease control (nonuse vs use: odds ratio [OR] [95%CI] = 0.51 [0.35-0.74], P = .0004) and overall response (nonuse vs use: OR [95%CI] = 0.43 [0.29-0.63], P < .0001). In this multicenter and retrospective study, probiotics use was associated with favorable clinical outcomes in patients with advanced or recurrent NSCLC who received anti-PD-1 monotherapy. The findings should be validated in a future prospective study.
We retrospectively investigated 186 non-small cell lung cancer cases with N2 disease in order to clarify the significance of skip metastasis. Of the 186 patients with N2 disease, negative N1 nodes recognized to be skip metastasis were seen in 62 patients (33%). The incidence of skip metastasis was not statistically different regarding histology, T status, or M status. The incidence of the skip metastatic site consisted of 35 cases (56%) at sites 1, 2 and 3, while 8 cases (13%) were found at sites 8 and 9. Among the patients with right lung cancer, the skip metastatic incidence for site 7 (subcarinal) was higher in patients with either middle lobe or lower lobe cancer than in those with upper lobe cancer (P < 0.05). The 5-year survival rates of all N2 patients in comparison to those with skip metastasis were 22% and 24%, respectively. When the sites of mediastinal lymph nodes were classified as superior, aortic, and inferior, the 5-year survival rates of the patients with superior skip metastasis, aortic metastasis, and inferior metastasis were 23%, 36%, and 15%, respectively. No statistical difference was observed. The 5-year survival rate of the skip N2 patients with only aortic region involvement was 50% (n = 7). However, no statistically significant difference was found between the two groups (P = 0.08). Our results thus suggested that mediastinal involvement for the aortic region alone might have a better prognosis than the others. We thus conclude that a dissection of the complete hilar and mediastinal lymph nodes should be the procedure of choice in standard operations for non-small cell lung cancer because of the high frequency of skip metastasis.
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