The presence of comutations (co-mut+) in DNA damage response and repair (DDR) pathways was associated with improved survival for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC). However, it remains unknown whether co-mut+ status could be a predictive biomarker for immunotherapy. We aimed to explore the predictive role of co-mut+ status in the efficacy of ICIs. A total of 853 NSCLC patients from OAK and POPLAR trials were included in the analyses for the relationship between co-mut status and clinical outcomes with atezolizumab treatment. In co-mut+ NSCLC patients, significantly prolonged progression-free survival (PFS) (p = 0.004) and overall survival (OS) (p < 0.001) were observed in atezolizumab over docetaxel. The interaction between co-mut status and treatment was significant for PFS (p for interaction = 0.010) and OS (p for interaction = 0.017). In patients with negative or low programmed death receptor-ligand 1 expression, co-mut+ status still predicted improved clinical outcomes from atezolizumab therapy. These findings suggested that co-mut status may be a promising predictor of ICI therapy in NSCLC.

Background This study was designed to investigate the difference between brain metastases (BM) and non-brain metastases (non-BM) treated by osimertinib in advanced patients with an acquired EGFR T790M mutation after obtaining first-generation EGFR-TKI resistance. Methods A total number of 135 first-generation EGFR-TKI-resistant patients with an acquired EGFR T790M mutation were retrospectively analyzed. The patients were divided into BM and non-BM groups. According to the type of treatment (whether brain radiotherapy), the BM patients were divided into an osimertinib combined with brain radiotherapy group and an osimertinib without brain radiotherapy group. In addition, according to the type of BM (the sequence between BM and osimertinib), the BM patients were subdivided into an osimertinib after BM group (initial BM developed after obtaining first-generation EGFR-TKI resistance) and an osimertinib before BM group (first-generation EGFR-TKI resistance then osimertinib administration performed; initial BM was not developed until osimertinib resistance). The progression-free survival (PFS) and overall survival (OS) were evaluated. The primary endpoint was OS between BM and no-BM patients. The secondary endpoints were PFS of osimertinib, and OS between brain radiotherapy and non-brain radiotherapy patients. Results A total of 135 patients were eligible and the median follow-up time of all patients was 50 months. The patients with BM (n = 54) had inferior OS than those without BM (n = 81) (45 months vs. 55 months, P = 0.004). And in BM group, the OS was longer in patients that received osimertinib combined with brain radiotherapy than in those without brain radiotherapy (53 months vs. 40 months, P = 0.014). In addition, the PFS was analysed according to whether developed BM after osimertinib resistance. The PFS of the patients that developed BM after acquiring osimertinib resistance was shorter than that without BM development, whether patients developed initial BM after first-generation EGFR-TKI resistance (7 months vs. 13 months, P = 0.003), or developed non-BM after first-generation EGFR-TKI resistance (13 months vs. 17 months, P < 0.001). Conclusions In advanced patients with an acquired EGFR T790M mutation after obtaining first-generation EGFR-TKI resistance, osimertinib may be more limited in its control in BM than in non-BM. Also, osimertinib combined with brain radiotherapy may improve the survival time of BM patients.

ObjectivesImmune-checkpoint inhibitors (ICIs) combined with chemotherapy are more widely used than monotherapy and have shown better survival in patients with advanced non-small cell lung cancer (NSCLC) without oncogenic driver alterations. The monocyte-to-lymphocyte ratio (MLR) might predict the treatment outcomes of ICI therapy in advanced NSCLC patients but has not yet been investigated. In addition, the cutoff of MLR is controversial. Therefore, the present study aimed to explore the associations between changes in MLR at the initial stage of treatment and clinical outcomes in stage IIIB-IV NSCLC patients receiving first-line PD-1 inhibitor combined with chemotherapy.MethodsThe present study included 139 stage IIIB-IV NSCLC patients treated with first-line PD-1 inhibitor combined with chemotherapy. The blood results were assessed 10 days before initiation of PD-1 inhibitor-based combination therapy (time point 1, baseline) and before the third cycle of combined therapy (time point 2). Compared to altered MLR, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in baseline and in time point 2, patients were divided into decreased MLR/NLR/PLR and increased MLR/NLR/PLR groups. The objective response rate (ORR), progression-free survival (PFS), and the association with the changes in blood indicators were analyzed.ResultsA total of 48 patients were categorized in the decreased MLR group and 91 in the increased MLR group. Patients with decreased MLR had a significantly higher ORR in the univariate (P&lt;0.001) and multivariate (P&lt;0.001) Cox proportional hazards models. On the other hand, decreased MLR was significantly associated with prolonged PFS in the univariate (P=0.007) and multivariate (P=0.016) analyses. Next, 91 patients comprised the decreased NLR group and 48 as the increased NLR group. Patients with decreased NLR exhibited high ORR (P=0.001) and prolonged PFS in univariate analysis (P=0.033). Then, 64 patients comprised the decreased PLR group and 75 the increased PLR group. Decreased PLR was significantly associated with high ORR in univariate (P&lt;0.001) and multivariate (P=0.017) analyses. The subgroup analyses showed that decreased MLR was significantly associated with satisfactory outcomes in patients with all PD-L1 expressions.ConclusionDecreased MLR was associated with high ORR and long PFS and might have a potential predictive value in patients with stage IIIB-IV NSCLC treated with first-line PD-1 inhibitor combined with chemotherapy. In addition, changes in MLR might have predictive value in all PD-L1-expressing populations. Decreased NLR and PLR also showed improved survival, suggesting that changes in NLR and PLR may be complementary to predicting prognosis.

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Background: Anlotinib is a novel anti-angiogenesis drug. In non-small cell lung cancer (NSCLC), high body mass index (BMI) was not associated with worse survival in patients treated with bevacizumab compared with those with normal or low BMI. However, it remains unknown whether such an association still exists in NSCLC patients receiving anlotinib therapy. Hence, we conducted this study to investigate whether BMI is associated with clinical outcomes in patients treated with anlotinib for advanced NSCLC.Methods: Data of 554 patients from the ALTER-0302 and the ALTER-0303 trials were analyzed in this study. The patients were classified into non-obesity (BMI &lt;28 kg/m2) and obesity (BMI ≥28 kg/m2) subgroups. The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). OS was defined as the interval between the first drug administration and death. PFS was defined as the time span from the date of initiating the treatment to the first documented progression or death from any cause, whichever occurred first. ORR included complete response (CR) and partial response (PR).Results: There were 354 patients (63.9%) who received anlotinib in this study. Restricted cubic spline model showed a U-shaped relation between BMI and the risk of death in the anlotinib group. In a multivariable Cox regression model, a trend of worse overall survival was observed in obese patients who received anlotinib compared with placebo (HR, 2.33; 95% CI, 0.77–7.06; p = 0.136). The interaction between BMI stratification and treatment was significant for OS (P for interaction = 0.038).Conclusion: Our results revealed a U-shaped relationship between BMI and risk of death in patients receiving anlotinib for advanced NSCLC. More importantly, obesity (BMI ≥28 kg/m2) might be a potential predictor of use of anlotinib in advanced NSCLC.

The 92 patients had air leakage at the time of transferring to intensive care unit or recovery room (postoperative air leakage: POAL). The log data of these 89 patients were analyzed retrospectively and We examined their characteristics using univariate and multivariate manners in logistic regression analysis. Result: The median age at the time of pulmonary resection in these 89 patients (72 men and 17 women) was 72 years (range, 40 to 86 years). The 75 patients (84%) had smoking history. The 17 patients (19%) had diabetes mellitus. The 49 patients (55%) had emphysema. Surgical procedures were a lobectomy in 71 patients, a segmentectomy in 4 patients, and a wedge resection in 14 patients. Fibrin glue was used during surgery in 45 patients (51%). The mean flow of POAL was 70.4 ml/min (range, 20.2-1267.9). The mean duration of air leakage was 60 hours (range, 9-257). In univariate analysis, diabetes mellitus (DM, p¼0.0284, OR; 3.450), use of fibrin glue (p¼0.0452, OR; 0.411), and POAL (p¼0.0101) were statistically significant. In the final multivariate model, DM (p¼0.0441) and flow of POAL (p¼0.0228) were independently associated with PAL. In ROC curve, considering less than 20% false positive rate, the optimal cutoff in patients with DM was 100ml/min (sensitivity; 67%, specificity; 82%). The optimal cutoff in patients without DM was 150ml/min (sensitivity; 53%, specificity; 84%). Conclusion: The POAL flow of 150ml/min or more in patients without DM and that of 100 ml/min or more in patients with DM will be likely to develop PAL with high probability. Pleurodesis may be considered earlier for this population.

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