Purpose: Low-dose radiotherapy (LDRT) may enhance the synergistic antitumor effect of combined immunotherapy and stereotactic body radiotherapy (SBRT). The safety and efficacy of this novel triple-combination therapy were evaluated for the first time as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC). Patients and Methods: This prospective phase I study enrolled 29 patients and included a dose-escalation and dose-expansion phase. Patients received SBRT [30 Gray (Gy)/3f] to small lesions and LDRT (2 Gy/1f, 4 Gy/2f, or 10 Gy/5f) to a large lesion concurrently, followed by sintilimab (a programmed death-1 inhibitor). The primary endpoint was safety and tolerability; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: No dose-limiting toxicities were observed during the dose-escalation phase; 4 Gy/2f was the recommended LDRT dose. Median follow-up was 15.6 months. Treatment-related adverse events (TRAE) occurred in 96.6% (28/29) of patients [grade ≥ 3; 20.7% (6/29)]; 2 patients (6.9%) discontinued due to TRAEs. Seven patients experienced pneumonitis (grade 2, n = 6; grade 3, n = 1). Immune-related adverse events were noted in 58.6% (17/29) of patients. In patients with tumor assessment (n = 28), ORR and confirmed ORR were 60.7% and 57.1%, respectively. Median PFS was 8.6 months (95% confidence interval, 3.7–16.5), and median OS was not reached. Exploratory analyses suggested both expanded and newly emerging T-cell receptor clonotypes were associated with better PFS. Conclusions: The findings indicate that the novel SBRT + LDRT + sintilimab therapy is safe and promising in patients with programmed death ligand-1–positive, driver gene–negative primary metastatic NSCLC.

Background: The NCCN (National Comprehensive Cancer Network) Clinical Practice Guidelines in Oncology (NCCN guidelines) recommend radical resection for T1-2N0M0 patients with limited-stage small cell lung cancer (LS-SCLC). However, only about 5% of patients with small cell cancer (SCLC) were initially diagnosed as T1-2N0M0. The purpose of our study was to analyze and compare the effects of the comprehensive treatment including radical surgery and concurrent chemoradiotherapy on the prognosis of patients with LS-SCLC. Methods: We comprehensively reviewed the medical data of patients with SCLC diagnosed by pathology in our hospital from January 2011 to April 2018. The Ethics Committee of West China Hospital of Sichuan University approved the study. Finally, 50 patients with good follow-up and complete medical data were selected as the surgical group (S group). According to the clinical characteristics of the patients in the S group, 102 LS-SCLC patients who received concurrent chemoradiotherapy in the same period were included in the CCRT group (concurrent chemoradiotherapy group) as the control group. Then according to the orders of the adjuvant treatments, the patients in the S group were divided into the SA group (radical surgery + adjuvant chemotherapy + adjuvant radiotherapy group, 30 cases in total) and the NS group (neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy group, 20 cases in total) for subgroup analysis. The SPSS 23.0 software was used for statistical analysis, and the t test was used for group comparison; Kaplan-Meier was used for survival analysis. P < 0.05 demonstrates a statistically significant difference. Results: The median progress-free survival (PFS) in the S group (73 months) was significantly better than that in the CCRT group (10.5 months, P < 0.0001), and the median overall survival (OS) in the S group (79 months) was also significantly better than that in the CCRT group (23 months, P < 0.0001). Subgroup analysis showed that there was no significant difference between the NS group and the SA group. Conclusions: For LS-SCLC patients, the comprehensive treatment including radical surgery (radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy/neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy)may be superior to concurrent chemoradiotherapy.

Background: Chemotherapy is an important approach for lung cancer patients. The study was designed to evaluate the feasibility of the compound probiotic supplements in improving the quality of life for lung cancer patients undergoing chemotherapy.Methods: This randomized, double‐blind, placebo‐controlled trial enrolled chemotherapy‐naive patients with lung cancer who were scheduled to receive platinum‐based doublet chemotherapy. All eligible patients were randomly administered (1:1) compound probiotic supplements (group BP‐1) or placebo (group C) for two chemotherapy cycles. The EORTC QLQ C30 questionnaire scores were evaluated before the first, second, and third cycles of chemotherapy. The primary endpoint was the difference in the EROTC QLQ C30 questionnaire score between the two groups after two cycles of chemotherapy.Results: A total of 110 patients were recruited from March 2021 to January 2022. After undergoing two cycles of chemotherapy, group BP‐1 were significantly better in various dimensions of the overall quality of life, role function, nausea and vomiting, appetite loss, constipation, and diarrhea relative to group C (76.90 ± 18.31 vs. 58.89 ± 17.17; 93.33 ± 11.58 vs. 85.93 ± 15.06; 0.00 ± 0.00 vs. 27.04 ± 29.15; 6.67 ± 13.53 vs. 22.22 ± 18.80; 0.95 ± 5.63 vs. 28.15 ± 22.42; 2.86 ± 9.47 vs. 15.56 ± 16.82; p < 0.05, respectively). The incidence of nausea and vomiting, appetite loss, constipation, and diarrhea in group BP‐1 was significantly lower than in group C (0% vs. 71.43%, 16.67% vs. 57.14%, 2.38% vs. 63.27%, and 7.14% vs. 42.86%, respectively, p < 0.001).Conclusions: Compound probiotic supplements can improve the quality of life and relieve chemotherapy‐related gastrointestinal side effects for lung cancer patients receiving platinum‐based doublet chemotherapy. (Chinese Clinical Trial Registry: ChiCTR1800019269).

Background: Cancer survivors perceive cancer‐related fatigue (CRF) as one of the most common symptoms. However, the potential relationship between CRF and gut microbiota has not been elucidated. Our study aimed to preliminary explore the diverse gut microbiota composition between mild and severe CRF in advanced lung cancer patients undergoing first‐line chemotherapy.Methods: A total of 20 advanced lung patients treated with first‐line chemotherapy were enrolled, 10 with mild CRF and 10 with severe CRF. The self‐reported Piper Fatigue Scale and stool samples were collected from all eligible patients. The 16 S ribosomal ribonucleic acid gene was performed to analyze the intestinal microbiome.Results: We identified the significantly diverse gut microbiota composition among patients with mild and severe CRF. The pattern was characterized by the increasing abundance in short‐chain fatty acid‐producing taxa for mild CRF patients (genus Lachnospiraceae‐UCG‐008 and family Lachnospiraceae, p < 0.05), whereas higher abundance in taxa related to inflammation (family Enterobacteriaceae and genus Escherichia‐Shigella, p < 0.05) for severe CRF patients. Significantly different Kyoto Encyclopedia of Genes and Genomes pathways between mild and severe CRF patients were evaluated concerning fatty acid metabolism, nucleotide metabolism, brain function, amino acid metabolism, and so on (p < 0.05).Conclusions: Our study observed a plausible association between different levels of CRF and the diverse gut microbiota composition, with increasing proinflammation taxa in severe CRF patients and anti‐inflammation taxa growing in mild CRF patients. Further studies are warranted to evaluate whether CRF can be improved by modulating the gut microbiota composition.