BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Objective:To discuss the effect of Compound Rehmannia Granules on intestinal flora of the pneumonia model rats induced by Streptococcus pneumoniae(Spn)through 16s rRNA sequencing technology,and to clarify its potential mechanism.Methods:A total of 30 rats were randomly divided into control group(normal rats),model group(Spn-induced pneumonia rat models),low dose of Compound Rehmannia Granules group(pneumonia rat models administered 1.75 g·kg-1 Compound Rehmannia Granules by gavage),medium dose of Compound Rehmannia Granules group(pneumonia rat models administered 3.50 g·kg-1 Compound Rehmannia Granules by gavage),and high dose of Compound Rehmannia Granules group(pneumonia rat model administered 7.00 g·kg-1 Compound Rehmannia Granules by gavage),with 6 rats in each group.The wet/dry weight(W/D)ratio of lung tissue and blood gas indexes were measured;HE staining was used to observe the pathomorphology and the degree of lung injury in lung tissue of the rats in various groups were assessed;kit assay was used to detect the bacterial load level and the levels of interleukin(IL)-6,IL-8,and IL-10 in bronchoalveolar lavage fluid(BALF)of the rats in various groups;16s rRNA intestinal flora sequencing analysis was performed.Results:Compared with control group,the arterial partial pressure of carbon dioxide(PaCO2)of the rats in model group was significantly increased(P<0.05),and the arterial partial pressure of oxygen(PaO2)and oxygen saturation(SaO2)were significantly decreased(P<0.05);compared with model group,the PaCO2 of the rats in low,medium,and high doses of Compound Rehmannia Granules groups was significantly decreased(P<0.05),and the PaO? and SaO?were significantly increased(P<0.05),showing a dose-dependent manner.The HE staining results showed no significant injury in lung tissue of the rats in control group;the cells in lung tissue of the rats in model group were arranged disorderly with massive inflammatory cell infiltration,and the alveolar wall capillaries were significantly dilated;compared with model group,the morphological damage of lung tissue of the rats in low,medium,and high doses of Compound Rehmannia Granules groups was improved.Compared with control group,the W/D value and pathological score of lung tissue of the rats in model group were significantly increased(P<0.05);compared with model group,the W/D value and pathological scores of lung tissue of the rats in low,medium,and high doses of Compound Rehmannia Granules groups were significantly decreased(P<0.05),showing a dose-dependent manner.Compared with control group,the bacterial load level in BALF of the rats in model group was significantly increased(P<0.05);compared with model group,the bacterial load level in BALF of the rats in low,medium,and high doses of Compound Rehmannia Granules groups was significantly decreased(P<0.05),showing a dose-dependent manner.Compared with control group,the levels of IL-6 and IL-8 in BALF of the rats in model group were significantly increased(P<0.05),and the IL-10 level was significantly decreased(P<0.05);compared with model group,the levels of IL-6 and IL-8 in BALF of the rats in low,medium,and high doses of Compound Rehmannia Granules groups were significantly decreased(P<0.05),and the IL-10 level was significantly increased(P<0.05),showing a dose-dependent manner.Compared with control group,the microbial abundance indicator(Chao1),microbial diversity and evenness indicator(Shannon),microbial dominance indicator(Simpson),and observed species indicator(observed_species)of the rats in model group were significantly decreased(P<0.05);compared with model group,the Chao1,Shannon,Simpson,and(observed_species)indices of the rats in low,medium,and high doses of Compound Rehmannia Granules groups were significantly increased(P<0.05),showing a dose-dependent manner.Compared with control group,the relative abundance of Bacteroidetes in model group was decreased,the relative abundance of Firmicutes was increased,and the Firmicutes/Bacteroidetes ratio was significantly increased(P<0.05);compared with model group,the relative abundances of Bacteroidetes in low,medium,and high doses of Compound Rehmannia Granules groups were increased,the relative abundance of Firmicutes was decreased,and the Firmicutes/Bacteroidetes ratio was significantly decreased(P<0.05),showing a dose-dependent manner.At the family level,compared with control group,the relative abundances of Corynebacteriaceae,Staphylococcaceae,and Moraxellaceae in model group were significantly increased,while the relative abundances of Lactobacillaceae,Lachnospiraceae,and Akkermansiaceae were significantly decreased;compared with model group,the relative abundances of Corynebacteriaceae,Staphylococcaceae,and Moraxellaceae in low,medium,and high doses of Compound Rehmannia Granules groups were significantly decreased,and the relative abundances of Lactobacillaceae,Lachnospiraceae,and Akkermansiaceae were significantly increased.At the genus level,compared with control group,the relative abundances of Desulfovibrio and Facklamia in model group were significantly increased,and the relative abundances of Bifidobacterium and Ruminococcaceae were significantly decreased;compared with model group,the relative abundances of Desulfovibrio and Facklamia in low,medium,and high doses of Compound Rehmannia Granules groups were significantly decreased,and the relative abundances of Bifidobacterium and Ruminococcaceae were significantly increased.Conclusion:Compound Rehmannia Granules can alleviate inflammation and lung injury in Spn-induced pneumonia rats,which may be related to the increase in the abundance and diversity of intestinal flora.