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The eighth edition of lung cancer nodal staging assignment includes the location of lymph node metastasis, but does not include single-nodal and multiple-nodal descriptors. Do the single-nodal and multiple-nodal statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? Using the National Cancer Database, we analyzed patients with pathologically staged N1 and N2 NSCLC. Nodal descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pathological single N2 (pSingle-N2), and pathological multiple N2 (pMulti-N2). Survival analysis was performed using the Kaplan-Meier method and multivariable Cox regression models. In the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 patients with NSCLC demonstrated pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2 disease, respectively. Patients with pMulti-N1 and pMulti-N2 disease showed a shorter survival than those with pSingle-N1 and pSingle-N2 disease, respectively (hazard ratio, 1.22 [ P <. 0001] for N1 and 1.39 [ P <. 0001] for N2). After adjusting age, sex, and histologic findings, the hazard ratio for pSingle-N2 compared with pMulti-N1 disease was 1.05 (P =. 0031). Patients with pN1 disease were categorized by metastatic lymph node count (1, 2, 3, ≥ 4), showing significant prognostic differences among groups (P <. 0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy, or more; survival ≥ 30 days; ≥ 10 examined lymph nodes; and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708), analyses supported these results. Patients with NSCLC with one metastatic lymph node, whether in N1 or N2 stations, showed better survival than those with more than one lymph node involved. Patients with NSCLC with a single-skip N2 lymph node metastasis showed survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to four or more was sequentially prognostic. [ABSTRACT FROM AUTHOR]

Purpose: Because patients younger than 40 years are rarely enrolled in clinical trials in non-small cell lung cancer (NSCLC), their survival benefit of immune checkpoint inhibitors (ICIs) needs to be clarified. Methods: The National Cancer Database was queried for patients who were diagnosed with stage IV NSCLC between 2016 and 2018. ICIs were administered in the first-line setting. The overall survival (OS) of patients with stage IV NSCLC according to the receipt of ICIs was compared in different age groups (< 40, 40–49, 50–59, 60–69, 70–79, and ≥ 80 years). Multivariate analyses identified the clinical characteristics predictive of OS. Propensity score matching (PSM) was conducted to reduce the biases arising from clinical characteristics. Results: This study included 126,476 patients with stage IV NSCLC. In univariate analysis, ICI treatment was not associated with a survival benefit in patients younger than 40 years with stage IV NSCLC relative to their ICI-naïve counterparts after PSM (median OS: 24.2 months vs. 24.0 months, hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 0.81–1.27, P = 0.9031). Multivariate analysis revealed that ICI use was not an independent predictor of OS in patients with stage IV NSCLC < 40 years old (HR = 0.96, 95% CI = 0.76–1.21, P = 0.7230). Sequential improvement of the HR was observed with increasing age. Conclusion: Our study suggested a poor survival benefit of ICIs in stage IV NSCLC patients younger than 40 years old, which should be validated in prospective studies. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has become a standard‐of‐care for patients with non‐small‐cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death‐1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first‐line ICI combined with or without chemotherapy. Materials and Methods: Two‐hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first‐line therapy. Cutoff value of the pretreatment PNI was set as 42.17. Results: Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression‐free survival (PFS; hazard ratio [HR] = 0.67, 95% confidence interval [CI]: 0.51–0.88, p = 0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32–0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p = 0.0011) and OS (p < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively). Conclusion: The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first‐line ICI therapy. [ABSTRACT FROM AUTHOR]

• Role of postoperative radiation therapy in persistent N2 is unclear. • Our analysis suggests that it improved survival in those patients. • Individuals with persistent N2 may benefit from postoperative radiation. Role of adjuvant radiation therapy in stage III (N2) non-small cell lung cancer has been controversial over the decades. Recent large, randomized trials have demonstrated that adjuvant radiation did not improve overall survival or disease-free survival; however, the trials either excluded or enrolled very few cases that have undergone neoadjuvant chemotherapy. Role of adjuvant radiation after neoadjuvant chemotherapy remains unclear. Whether the use of adjuvant radiation is associated with improved overall survival in those who have received neoadjuvant chemotherapy, especially in a subgroup of patients with persistent N2, is unknown. Patients with clinical stage III (N2) non-small cell lung cancer diagnosed from 2004 through 2017 were queried to National Cancer Database. Eligibility criteria included completely resected (R0), pathological diagnosis, neoadjuvant multi-agent chemotherapy, information regarding post-surgical N2 status (persistent versus downstaged to pN0-1), adjuvant radiation (45 Gy+ versus none), and American Joint Commission on Cancer staging version (6th versus 7th). Those who have received neoadjuvant radiation with any dose or adjuvant radiation with less than 45 Gy total dose were excluded. Kaplan-Meier and log-rank tests were used for survival analyses. Propensity-score matching analysis was used for validation. All statistical analyses were two-sided, and p < 0.05 was required for statistical significance. A total of 1,855 patients met the eligibility criteria for analysis. In the overall cohort, there was a significant difference in overall survival between persistent N2 (Cohort P: N = 854, median survival 50.7 months) and downstaged N (Cohort D: N = 1,001, median survival 82.7 months). The use of adjuvant radiation showed a non-significant detrimental effect in overall survival in the overall and Cohort D (univariate p-values 0.27 and 0.077, respectively); however, both univariate and multivariate analyses demonstrated a significant improvement in overall survival in Cohort P (p = 0.004 and 0.028, respectively). These findings are also verified by propensity-score matching analysis (p = 0.0347). This large-scale retrospective analysis suggests that adjuvant radiation may still have a role in persistent N2 disease after neoadjuvant chemotherapy. Further investigations are warranted. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of delayed chemotherapy-induced nausea and vomiting (CINV) in patients with non-small cell lung cancer (NSCLC) receiving carboplatin (CBDCA)-based chemotherapy (CBDCA + pemetrexed or paclitaxel) has not been clearly described. Therefore, we attempted to evaluate whether delayed CINV could be controlled using a combination of three antiemetics and identify individual risk factors. Methods: We pooled data from two prospective observational studies, namely a nationwide survey of CINV and a prospective, observational study in Japan, to assess whether delayed CINV could be controlled using a combination of three antiemetics and identified individual risk factors via inverse probability treatment-weighted analysis. Results: In total, 240 patients were evaluable in this study (median age, 66 years; male, 173; female, 67). The three-antiemetic regimen controlled delayed nausea (31.6% vs 47.3%) and vomiting (5.1% vs 23.1%) better than two antiemetics. Younger age (< 70 years; odds ratio [OR] = 2.233), motion sickness (OR = 3.472), drinking habits (OR = 1.972), receipt of the CBDCA + pemetrexed regimen (OR = 2.041), and the use of two antiemetics (OR = 1.926) were risk factors for delayed nausea. Female sex (OR = 3.372), drinking habits (OR = 2.272), receipt of the CBDCA+ pemetrexed regimen (OR = 2.314), and the use of two antiemetics (OR = 6.830) were risk factors for delayed vomiting. Conclusion: Female sex, younger age, and receipt of the CBDCA + pemetrexed regimen increased the risk of CINV. Therefore, we recommend additional supportive antiemetics treatment for these patients. [ABSTRACT FROM AUTHOR]

Introduction: Recently, several meta-analyses have investigated the association between sex and the efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC). However, this issue remains controversial, because the results have been inconsistent. Moreover, the effect of sex on outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy is poorly understood. The aim of this study was to examine the association between sex and outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy. Methods: We searched PubMed and Scopus from database inception to Feb 18, 2022 and performed a systematic review and meta-analysis of randomized and controlled clinical trials investigating ICI+non-ICI vs non-ICI as a first-line therapy in NSCLC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) in male and female patients were calculated using common and random-effects models. Results: We analyzed 5,830 patients, comprising 4,137 (71.0%) males and 1,693 (29.0%) females, from nine randomized clinical trials. The pooled HR (95%CI) for OS comparing ICI+non-ICI vs non-ICI was 0.80 (0.72–0.87) for males and 0.69 (0.54–0.89) for females. The pooled HR (95%CI) for PFS comparing ICI+non-ICI vs non-ICI was 0.60 (0.55–0.66) for males and 0.56 (0.44–0.70) for females. Conclusions: In patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy, a greater improvement in OS and PFS was observed in female patients than in male patients. [ABSTRACT FROM AUTHOR]

Background: Many studies have recently reported the association of concomitant medications with the response and survival in patients with non-small-cell lung cancer (NSCLC) treated with cancer immunotherapy. However, the clinical impact of statin therapy on the outcome of cancer immunotherapy in patients with NSCLC is poorly understood. Methods: In our database, we retrospectively identified and enrolled 390 patients with advanced or recurrent NSCLC who were treated with anti-programmed cell death-1 (PD-1) monotherapy in clinical practice between January 2016 and December 2019 at 3 medical centers in Japan to examine the clinical impact of statin therapy on the survival of patients with NSCLC receiving anti-PD-1 monotherapy. A propensity score-matched analysis was conducted to minimize the bias arising from the patients' backgrounds. Results: The Kaplan–Meier curves of the propensity score-matched cohort showed that the overall survival (OS), but not the progression-free survival (PFS), was significantly longer in patients receiving statin therapy. However, a Cox regression analysis in the propensity score-matched cohort revealed that statin therapy was not an independent favorable prognostic factor, although it tended to be correlated with a favorable outcome. Conclusions: Statin therapy may be a combination tool for cancer immunotherapy in patients with NSCLC. These findings should be validated in further prospective studies with larger sample sizes. [ABSTRACT FROM AUTHOR]

A recent study suggested that proton pump inhibitor (PPI) use in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs) was associated with poor clinical outcomes. However, the clinical impact of PPI use on the outcome of patients receiving ICIs for postoperative recurrent NSCLC is unknown. The outcomes of 95 patients with postoperative recurrence of NSCLC receiving ICIs at 3 medical centers in Japan were analyzed. We conducted adjusted Kaplan–Meier survival analyses with the log-rank test, a Cox proportional hazards regression analysis, and a logistic regression analysis using inverse probability of treatment weighting (IPTW) to minimize the bias arising from the patients' backgrounds. The IPTW-adjusted Kaplan–Meier curves revealed that the progression-free survival (PFS), but not the overall survival (OS), was significantly longer in patients who did not receive PPIs than in those who did receive them. The IPTW-adjusted Cox regression analysis revealed that PPI use was an independent poor prognostic factor for the PFS and OS. Furthermore, in the IPTW-adjusted logistic regression analysis, PPI non-use was an independent predictor of disease control. In this multicenter and retrospective study, PPI use was associated with poor clinical outcomes in patients with postoperative recurrence of NSCLC who were receiving ICIs. PPIs should not be prescribed indiscriminately to patients with postoperative recurrence of NSCLC who intend to receive ICIs. These findings should be validated in a future prospective study. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have markedly improved the prognosis of many patients with advanced non-small cell lung cancer (NSCLC). However, the relationship between the patient's nutritional/immunologic status and the outcomes of ICI treatment remains unclear. In previous retrospective studies, we reported that the controlling nutritional status (CONUT) score, skeletal muscle area, and neutrophil-to-lymphocyte ratio were independent predictors of the response of NSCLC patients to anti-PD-1 drugs. The aim of this prospective multi-center study is to investigate the clinical impact of pre-treatment nutritional/immunologic indices and early post-treatment changes in the indices on treatment outcomes in advanced NSCLC. The main inclusion criteria are: (1) stage IV NSCLC, or stage III NSCLC not applicable for definitive chemoradiotherapy; (2) treatment with ICIs (monotherapy or combined with chemotherapy) as first-line therapy; and (3) available data on PD-L1 expression on tumor cells. A total of 300 patients will be enrolled prospectively. Enrollment will begin in 2020 and the final analyses will be completed by 2025. [ABSTRACT FROM AUTHOR]

Molecular drugs targeting mutated or rearranged oncogene drivers have become one of the standard recognized treatments in patients with advanced and recurrent non-small cell lung cancer. RET is located in the long arm of human chromosome 10 and encodes a receptor tyrosine kinase protein, and RET fusion-positive lung adenocarcinoma occurs in 1%–2% of cases. Clinical trials of multikinase inhibitors, including cabozantinib, vandetanib, sorafenib, and lenvatinib, that inhibit RET oncogene activity have shown their antitumor efficacy. Recently, RET inhibitors such as pralsetinib and selpercatinib that are specialized for RET kinase have also been developed, and their efficacy was investigated in previous clinical trials (BLU-667 and LOXO-292). In this review, we summarized the effects and adverse events of multikinase and selective RET inhibitors and the various diagnostic techniques for RET gene fusion. In the perspective part, we focused on the unsolved issues on treatment for RET fusion-positive lung cancer and future developments. [ABSTRACT FROM AUTHOR]

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. What's new? 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. 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. Probiotics are a widely‐used drug in the clinical setting with few side effects. The results suggest that prescription of probiotics could be considered in patients with NSCLC who expect to receive immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have become a standard therapy in non-small cell lung cancer (NSCLC). Although lung cancer adjoining emphysematous bullae (Ca-ADJ) were reported to express higher programmed cell death-ligand 1 (PD-L1), the predictive impact of Ca-ADJ on the response to ICIs is unknown. Methods: Two hundred and fifty-seven advanced or recurrent NSCLC patients treated with ICI monotherapy at Kyushu University Hospital and National Hospital Organization Kyushu Cancer Center were analyzed. To minimize the bias arising from the patients' background, adjusted Kaplan–Meier survival curves and Cox proportional hazards regression analyses using inverse probability of treatment weights (IPTW) were performed. Results: Of the 257 patients, 55 had Ca-ADJ. Patients with Ca-ADJ were significantly associated with younger age (P = 0.0343), male sex (P = 0.0070), and smoking (P = 0.0080). The objective response rate of cases with Ca-ADJ was significantly higher than that of those without Ca-ADJ (36.4% vs. 20.8%, respectively; P = 0.0167). The disease control rate of cases with Ca-ADJ was also significantly higher than tumors without Ca-ADJ (63.6% vs. 47.5%, respectively; P = 0.0341). The IPTW-adjusted Kaplan–Meier curves showed that patients with Ca-ADJ had significantly longer progression-free survival (PFS) and overall survival (OS) than those without Ca-ADJ (P = 0.0407 and P = 0.0126, respectively). On IPTW-adjusted Cox analysis, Ca-ADJ was an independent predictor of PFS and OS (P < 0.0001 and P < 0.0001, respectively). Conclusions: Patients with Ca-ADJ may be good candidates for ICIs. These findings should be validated prospectively. [ABSTRACT FROM AUTHOR]

Purpose: Anti-programmed death 1 (PD-1) antibodies have emerged as frontline treatments for patients with advanced non-small cell lung cancer (NSCLC) on the basis of global Phase III trials. However, current data regarding responses to anti–PD-1 therapy in older patients with NSCLC or those with poor performance status (PS) are limited. Therefore, we examined the therapeutic effect of anti PD-1 antibody in these patients. Patients: We retrospectively examined consecutive patients treated with anti–PD-1 monotherapy (pembrolizumab or nivolumab) from January 2016 to September 2018. Results: We enrolled 125 patients (median age, 60 years), 80.8% of whom were men. Patients aged ≥ 75 years were considered older patients (n = 15), and those with PS 2– 3 were regarded as having poor PS (n = 11). The objective response and disease control rates were 15.4% and 46.2%, respectively, in older patients and 9.1% and 27.3%, respectively, in those with poor PS. Progression-free survival (PFS) and overall survival (OS) did not significantly differ between older and younger patients. However, poor PS was significantly associated with poor survival. High programmed death ligand 1 (PD-L1) expression in tumor specimens (≥ 50%) was associated with favorable survival in the entire cohort as well as patients with poor PS. Safety analyses demonstrated no significant difference in the occurrence of any adverse event, including grade ≥ 3 adverse events, between patients with poor PS or older age and the remaining patients. Conclusion: Anti–PD-1 therapy had similar efficacy in older and younger patients with NSCLC, whereas survival was significantly worse in patients with poor PS. However, immune checkpoint inhibitors may be considered for patients with poor PS harboring positive PD-L1 expression. [ABSTRACT FROM AUTHOR]

• GPS is calculated based on serum albumin and C-reactive protein values. • GPS was associated with DCR in NSCLC patients treated with ICI. • GPS was an independent prognostic factor in NSCLC patients receiving ICI. • GPS was the most powerful prognostic factor of the GPS, mGPS, and CAR. Immune checkpoint inhibitors (ICIs) have become one of the standard therapies in non-small-cell lung cancer (NSCLC). Although inflammatory indices, including Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and C-reactive protein/albumin ratio (CAR) were reported to be reliable predictors for survival in cancer patients, their clinical utility in NSCLC patients treated with ICIs is unknown. Advanced or recurrent NSCLC patients (n = 304) treated with ICI monotherapy at the National Hospital Organization Kyushu Cancer Center and Kyushu University Hospital between January 2016 and December 2019 were analyzed. Information on patient demographics, GPS, mGPS, and CAR at diagnosis were collected. The time-dependent area under curves (AUCs) of receiver operating characteristic curves for the prediction of overall survival (OS) for each factor were compared. Of the three indices, GPS was the most significantly correlated with the degree of disease control rate (DCR) (DCR of GPS of 0, 1, and 2: 63.6 %, 49.4 %, and 41.4 %, respectively). The time-dependent AUC values of GPS for the prediction of OS were superior to those of mGPS and CAR (time-dependent AUC values of GPS, mGPS, and CAR for the prediction of 1-year OS: 0.7005, 0.6736, and 0.6565, respectively). GPS was significantly correlated with performance status (PS) (P < 0.0001) and clinical stage (P = 0.0139). GPS in combination with PS effectively predicted survival at 1 year ranging from 83.5 % (GPS = 0, PS = 0) to 25.0 % (GPS = 2, PS = 2, 3). A multivariable analysis revealed that GPS was an independent predictor of PFS and OS (P = 0.0009 and P = 0.0100, respectively). We report for the first time that GPS represents a simple and useful prognostic factor in NSCLC patients treated with ICIs and should be validated prospectively. [ABSTRACT FROM AUTHOR]

Immunocheckpoint inhibitors (ICIs) have become a standard pharmacological therapy in non‐small cell lung cancer (NSCLC). Because brain metastases (BMs) have historically been listed as exclusion criteria in previous clinical trials involving ICIs in advanced NSCLC, the survival benefit from ICI in NSCLC patients with BMs remains unclear. The National Cancer Database was queried for stage IV NSCLC patients with or without BMs between 2014 and 2015. Overall survival (OS) of stage IV NSCLC patients who received immunotherapy and that of stage IV NSCLC patients who did not receive immunotherapy were compared according to the presence or absence of BMs. Multivariable logistic analyses identified the clinical characteristics predictive of overall survival. A propensity score analysis was conducted with the aim of adjusting the potential biases arising from the clinical characteristics. This study included 42,512 patients with stage IV NSCLC; 11,810 patients with BMs and 30,702 patients without BMs. In univariate analysis, stage IV NSCLC patients with BMs treated with immunotherapy had a significantly longer OS than those without immunotherapy after propensity score matching (median OS: 12.8 vs 10.1 months, hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.72–0.89, p < 0.0001). Multivariable Cox modeling after propensity score matching confirmed the survival benefit from ICI for stage IV NSCLC patients with BMs (HR: 0.75, 95% CI: 0.67–0.83, p < 0.0001). The HR in NSCLC patients without BMs treated with ICI compared with those without ICI was 0.77 (95% CI: 0.73–0.82, p < 0.0001). Survival in stage IV NSCLC patients with BMs was significantly improved by ICI treatment at levels comparable to those without BMs using a retrospective database. ICI may be one of the promising treatment options for stage IV NSCLC patients with BMs. These findings should be validated in future prospective studies. [ABSTRACT FROM AUTHOR]

Inflammatory biomarkers have been associated with clinical outcomes in non-small cell lung cancer (NSCLC). However, the best prognostic marker(s) has not been identified, and the association between inflammatory markers and clinical characteristics is poorly understood. We selected 1,237 patients with resected NSCLC from Kyushu University (2003–2015) and Kyushu Cancer Center (2009–2015) in Japan. Pearson product-moment correlation coefficient among inflammatory markers and area under curve (AUC) of receiver operating characteristic (ROC) curve analyses for overall survival (OS) were calculated. We analyzed the associations between inflammatory markers and clinical factors using Student's t-test. Univariate and multivariate analyses with Cox proportional hazards regression analyses were performed to evaluate the relationship between survival and clinical factors. The cut-off values for neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio, and derived NLR (dNLR) were determined by ROC curve analyses for OS. We found a strong positive correlation between NLR and dNLR (r = 0.9629). The AUC of LMR was the highest amongst the measured metrics, and the AUC of NLR was higher than dNLR. Levels of some inflammatory markers were associated with sex, smoking, squamous cell carcinoma, and pathological stage. LMR ≥ 5.11 and lactate dehydrogenase (LDH) concentration ≥ 222 (U/L) were independent predictors of both disease-free survival (DFS) and OS (LMR; P = 0.0009 and 0.0008, LDH; P = 0.0195 and 0.0187, respectively). Certain inflammatory markers, potentially linked to smoking, were associated with an advanced pathological stage in NSCLC. LMR and LDH were independent predictors of both DFS and OS. [ABSTRACT FROM AUTHOR]

Immunotherapy targeting programmed cell death‐1 (PD‐1) has become a standard pharmacological therapy. Although tumor mutation burden level was reported to depend on the tumor location in nonsmall cell lung cancer (NSCLC), predictive impact of the tumor location on the response to anti‐PD‐1 therapy is unknown. Two hundred and seventeen advanced or recurrent NSCLC patients treated with anti‐PD‐1 therapy at Kyushu University Hospital and National Hospital Organization Kyushu Cancer Center were analyzed. To minimize the bias arising from the patients' background, adjusted Kaplan‐Meier survival curves and Cox proportional hazards regression analyses using inverse probability of treatment weights (IPTW) were performed. Of the 217 patients, 132, 27, and 58 had primary NSCLC in upper, middle, and lower lobes, respectively. Patients with NSCLC in upper lobe were significantly associated with younger age (P =.0070) and smoker (P =.0003). The epidermal growth factor receptor‐wild type and tumor location in upper lobe were independent predictors of disease control (P =.0175 and P =.0425, respectively). The IPTW‐adjusted Kaplan‐Meier curves showed that patients with NSCLC in the upper lobes had significantly longer progression‐free survival (PFS) and overall survival (OS) than those in middle/lower lobes (P =.0026 and P =.0015, respectively). On IPTW adjusted Cox analysis, NSCLC in the upper lobe was an independent predictor of PFS and OS (P =.0078 and P =.0034, respectively). Patients with primary NSCLC in the upper lobes may be good candidates for anti‐PD‐1 therapy. These findings should be validated prospectively. What's new? Tumor mutation burden (TMB) can predict clinical benefit of anti‐programmed death‐1 (anti‐PD‐1) immunotherapy in non‐small cell lung cancer (NSCLC) patients. Evidence suggests that TMB depends on tumor location, though whether tumor location influences anti‐PD‐1 drug efficacy is unclear. This study shows that tumor location in the upper lobe of the lung independently predicts disease control by anti‐PD‐1 therapy in NCSLC patients. Patients with tumors in the upper lobes exhibited improved progression‐free and overall survival compared to patients with tumors in the middle or lower lobes. The findings identify potential benefits of anti‐PD‐1 therapy based specifically on NSCLC location. [ABSTRACT FROM AUTHOR]

• dNLR is a novel serum inflammatory marker. • dNLR is calculated from white blood cell concentration and neutrophil count. • dNLR was associated with treatment response in NSCLC treated with anti-PD-1 drugs. • dNLR was an independent prognostic factor in NSCLC treated with anti-PD-1 drugs. • dNLR might be the most important factor for the efficacy of anti-PD-1 therapy. Several serum markers have been associated with treatment response and clinical outcome in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors. We performed univariate and multivariate analyses on 226 patients with advanced or recurrent NSCLC treated with anti-programmed cell death-1 (PD-1) therapy. The cut-off values for body mass index (BMI), albumin (Alb), and serum inflammatory markers were determined by receiver operating characteristic curve analyses. Tumor response was assessed by computed tomography according to the Response Evaluation Criteria in Solid Tumors, version 1.1. BMI ≥ 19.1 kg/m2 and derived neutrophil-lymphocyte ratio (dNLR) < 2.79 were independent predictors of overall response, and Alb ≥ 3.5 g/dL and dNLR < 2.79 were independent predictors of disease control. Analyses of survival revealed that Alb < 3.5 g/dL, dNLR ≥ 2.79, lymphocyte-monocyte ratio < 2.12, and red blood cell distribution width ≥ 15.9 % were independent predictors of both progression-free and overall survival. Moreover, these markers tended to have a strong impact on survival, especially among patients with programmed cell death-ligand 1 tumor proportion score ≥ 50 %. dNLR might be the most important factor for predicting the efficacy in NSCLC patients treated with anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to elucidate the clinical impact of skeletal muscle area (SMA) in patients with non-small cell lung cancer (NSCLC) treated with anti-programmed cell death-1 (PD-1) inhibitors. Methods: Univariate and multivariate analyses were performed on data of 103 patients with advanced or recurrent NSCLC treated with anti-PD-1 inhibitors. The SMA was measured at the level of the third lumbar vertebral (L3) on computed tomography images using OsiriX software (32-bit, version 5.8; OsiriX, Geneva, Switzerland). The L3 muscle index (cm2/m2) was defined as the SMA (cm2) at the L3 level divided by the height (m) squared. Results: L3 muscle index Low was an independent predictor of both progression-free (P = 0.0399) and overall survival (P = 0.0155). Moreover, the disease control rate was significantly lower in the L3 muscle index Low group (49.0% [25/51]) than in the L3 muscle index High group (73.1% [38/52]; P = 0.0117). However, there was no significant difference between the response rates of the L3 muscle index Low group (21.6% [11/51]) and L3 muscle index High group (32.7% [17/52]; P = 0.2031). Conclusions: L3 muscle index Low is an independent predictor of worse outcomes in NSCLC patients treated with anti-PD-1 inhibitors. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to elucidate the relationship between family‐associated factors and the postoperative prognosis in patients with nonsmall cell lung cancer (NSCLC). Additionally, we investigated whether having children was associated with the postoperative maintenance of the nutritional status. We selected 438 NSCLC patients who had undergone curative lung resection between 2004 and 2011 at Kyushu University (Fukuoka, Japan), whose family‐associated factors were available. Nutritional indices, including the prognostic nutritional index (PNI), were used to estimate the change in the nutritional status for 1 year after surgery. A propensity score analysis was conducted after adjusting the following variables: sex, age, smoking history, performance status, pathological stage, and histological type. Three hundred patients (68.5%) had both children and partners. Forty‐nine patients (11.2%) only had children, and 56 (12.8%) patients only had a partner. Thirty‐three patients (7.5%) did not have a partner or children. The overall survival (OS) and disease‐free survival (DFS) of the partner‐present and partner‐absent patients did not differ to a statistically significant extent (P = .862 and P = .712, respectively). However, childless patients showed significantly shorter OS and DFS in comparison with patients with children (P = .005 and P = .002, respectively). The postoperative exacerbation of PNI was significantly greater in childless patients than in patients with children (P = .003). These results remained after propensity score matching. Childless patients had a significantly poorer postoperative prognosis than those with children. Surgeons caring for childless NSCLC patients should be aware of the poorer postoperative outcomes in this population. [ABSTRACT FROM AUTHOR]

Objectives The oxidized purine nucleoside triphosphatase, mutT homolog 1 (MTH1), physiologically sanitizes 8-oxo-dGTP in the nucleotide pool. Previous studies indicated that MTH1 is associated with tumor proliferation and invasion in non-small cell lung cancer (NSCLC) cell lines; however, the role of MTH1 in patients with NSCLC remains unclear. Materials and Methods Two patient cohorts that underwent surgery for NSCLC in our institution were investigated retrospectively. In one cohort consisting of 197 patients, the associations between MTH1 expression and clinicopathological factors or prognosis were analyzed. In another cohort consisting of 41 patients, the relationship between MTH1 expression in the tumors and serum oxidative stress levels (evaluated by the diacron-reactive oxygen metabolites [d-ROMs] test) or antioxidant capacity in the patients (evaluated by the biological antioxidant potential (BAP) test) was analyzed. A total of 238 patients were assessed for MTH1 protein levels using immunohistochemistry. Results Among the 197 patients in the former cohort, 111 (56.3%) exhibited high MTH1 expression, while 86 (43.7%) exhibited low MTH1 expression. Male sex, smoking habit of ≥20 pack-years, squamous cell carcinoma, pathological stage ≥ II, tumor diameter ≥30 mm, lymph node metastases, pleural invasion, lymphatic permeation and vascular infiltration were significantly associated with high MTH1 expression ( p < 0.05). The high MTH1 expression group had a significantly worse prognosis than that of the low MTH1 expression group (5-year overall survival: 81.6% vs. 92.3%, p = 0.0011; 5-year disease-free survival: 55.0% vs. 83.7%, p = 0.0002). d-ROMs and BAP test values were significantly higher in the high than in the low MTH1 expression group ( p < 0.05). Conclusion This study showed that MTH1 protein expression was closely related to factors associated with a high malignant potential and poor patient survival. MTH1 may be a novel therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

Objectives Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength. We aimed to investigate sarcopenia in patients with stage I non-small cell lung cancer (NSCLC) who underwent complete resection, and the relationship of sarcopenia with clinicopathological factors. Methods All consecutive patients who underwent lung resection between January 2005 and December 2008 were enrolled in this retrospective study. Eligible patients were assigned to one of 2 groups according to the presence or absence of sarcopenia, as assessed by the sum of cross-sectional areas of skeletal muscles in the region of the third lumbar vertebra (L3) on preoperative computed tomography (CT). Results Sixteen of 52 male (30.8%) and 22 of 38 female (57.9%) patients were identified with sarcopenia ( p = 0.01). Patients with sarcopenia were more likely to have a low body mass index (BMI) ( p < 0.0001). Kaplan-Meier analysis showed that patients with sarcopenia had a significantly worse outcome than patients without sarcopenia (5-year-survival: 72.8% vs 85.8%, respectively, p = 0.028). Multivariate analysis found that sarcopenia was a significant independent prognostic factor (hazard ratio: 7.09, p = 0.0008). Conclusions Sarcopenia identified on a cross-sectional CT image of the L3 level was associated with poor outcome with completely resected early-stage NSCLC. [ABSTRACT FROM AUTHOR]

Background The most effective treatment for early-stage non-small cell lung cancer (NSCLC) is surgical resection. Nevertheless, up to 20% of patients, even those with stage I NSCLC, relapse after surgery and die. The prognostic nutritional index (PNI) is used to assess immunonutritional conditions or is a predictor of postoperative recurrence in patients with digestive malignancies. However, the usefulness of the PNI for lung cancer is still unknown. We retrospectively analyzed clinicopathological features of stage I NSCLC patients to identify predictors of recurrence and to investigate effects of preoperative PNI levels. Methods We selected 141 consecutive stage I NSCLC patients who were treated from August 2005 to August 2010. We measured their preoperative PNI levels in uni- and multivariate Cox regression analyses of recurrence-free survival. Results A low PNI was significantly associated with sex ( P = 0.0117), preoperative serum carcino embryonic antigen levels ( P = 0.0228), and postoperative recurrence ( P < 0.0001). In multivariate analysis, PNI (RR: 9.243; 95% CI: 3.662–25.823; P < 0.0001), pleural invasion (RR: 8.664; 95% CI: 2.510–38.056; P = 0.0005), and intratumoral blood vessel invasion (RR: 3.151; 95% CI: 1.259–7.681; P = 0.0152) were independent prognostic factors. The low-PNI group had a significantly shorter recurrence-free survival than the high-PNI group, regardless of pathological T factors (T1a, P = 0.0422; T1b, P < 0.0001; T2a, P = 0.0098). Conclusions The preoperative PNI level is a simple and novel predictor of recurrence in stage I NSCLC patients, and might help identify patients who will need multimodality therapy such as induction or adjuvant therapy. [ABSTRACT FROM AUTHOR]