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The potential complications related to unplanned conversion to thoracotomy remains a major concern in thoracoscopic lobectomy and may limit the wide adoption of this strategy. We reviewed the literature from 1990 until February 2022, analyzing all papers comparing successful thoracoscopic lobectomy versus converted thoracoscopic lobectomy and/or upfront thoracotomy lobectomy to establish whether unplanned conversion negatively affected outcomes. Thirteen studies provided the most applicable evidence to evaluate this issue. Conversion to thoracotomy was reported to occur in up to 23% of cases (range, 5%–16%). Vascular injury, calcified lymph nodes, and dense adhesions were the most common reasons for conversion. Converted thoracoscopic lobectomy compared to successful thoracoscopic lobectomy was associated with longer operative time and hospital stay in all studies, with higher postoperative complication rates in seven studies, and with higher perioperative mortality rates in four studies. No significant differences were found between converted thoracoscopic lobectomy and upfront thoracotomy lobectomy. Five studies evaluated long‐term survival, and in all papers conversion did not prejudice survival. Surgeons should not fear unplanned conversion during thoracoscopic lobectomy, but to avoid unexpected conversion that may negatively impact surgical outcome, a careful selection of patients is recommended–especially for frail patients. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the leading cause of cancer‐related deaths. Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) are effective for advanced non‐small cell lung cancer (NSCLC) harboring EGFR mutations, some patients experience little or no response. The Glasgow prognostic score (GPS) is an inflammation‐related score based on C‐reactive protein (CRP) and albumin concentrations, and has prognostic value in various cancer settings. This study aimed to evaluate whether GPS could predict response of NSCLC to EGFR‐TKIs. Methods: This retrospective multicenter study evaluated patients with NSCLC harboring EGFR mutations who received EGFR‐TKI monotherapy from October 2006 to December 2016. GPS values were determined using CRP and albumin concentrations from before initiation of EGFR‐TKIs. The Kaplan‐Meier method and Cox proportional hazard models were used to evaluate progression‐free survival (PFS) and overall survival (OS). Results: In 214 patients, 141, 43, and two patients had GPS values of 0, 1, and 2, respectively. The GPS independently predicted the efficacy of EGFR‐TKIs; good GPS (0–1) conferred significantly better PFS (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.38–0.96, P = 0.03) and OS (HR: 0.56, 95% CI: 0.33–0.96, P = 0.03). Multivariate analysis confirmed that a good GPS (0–1) independently predicted good PFS and OS among patients who had PS of 0–1. Good GPS (0–1) independently predicted good OS among patients receiving treatment in first‐line settings. Conclusions: The GPS independently predicted the efficacy of EGFR‐TKIs for EGFR‐mutated NSCLC; however, further studies are needed to validate our findings. Key points: Significant findings of the study: Glasgow prognostic score (GPS) independently predicted the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) treatment for EGFR‐mutated NSCLC. What this study adds: The findings presented in this paper will help to identify patients who will be expected to experience limited or no response to EGFR‐TKI treatment by using GPS. [ABSTRACT FROM AUTHOR]

Background: The objective of our study was to analyze the prognostic value of the combination of serum ALP and pleural effusion LDH (AL score) for malignant pleural effusion (MPE) patients. Methods: This study includes retrospective, descriptive and observational research from 1 June 2006 to 1 December 2017, which aimed to identify prognostic factors related to MPE patients. We analyzed the association of various clinical features, routinely tested markers from peripheral blood and MPE at diagnosis and overall survival (OS). All MPE patients were assigned to three groups according to their AL score. The impact of the AL score and other prognostic factors were evaluated with multivariable regression. Results: According to their AL score, 193 patients were assigned to three groups with 25 in group 0 (sALP < 65 U/L and pLDH < 155 U/L), 121 in group 1 (sALP > 65 U/L or pLDH > 155 U/L) and 47 (sALP > 65 U/L and pLDH > 155 U/L) in group 2. For groups 0, 1 and 2, median survival times (MST) were 23, 15 and 7 months, respectively. Among the three groups, MST, serum albumin level, C reactive protein, erythrocyte sedimentation rate, the ratios of platelet‐to‐lymphocyte, neutrophil‐to‐lymphocyte showed significant differences. The counts of neutrophils, monocytes, platelets and AL score (0 vs. 1, P = 0.038, hazard ratio [HR]: 1.858, 95% confidence interval [CI]: [1.034, 3.339]; 0 vs. 2, P = 0.001, HR: 2.993, 95% CI: [1.556, 5.531]) were independent prognostic indicators for OS of MPE patients. Conclusion: AL score is a promising indicator which can be used to predict the prognosis of MPE patients. It can assist physicians in the selection of patients for appropriate palliative treatment. Key points: To our knowledge, this paper is the first study that combined two enzymes (sALP and pLDH) from serum and pleural effusion and studied the prognostic value for MPE patients. It has been proved to be a promising indicator to assist physicians select patients for appropriate palliative treatment. [ABSTRACT FROM AUTHOR]

Background: Tumor with adjacent lobe invasion (T‐ALI) is an uncommon condition. Controversy still exists regarding the optimal resection of adjacent lobe invasion, and the prognostic value in relation to fissure integrity at the tumor invasion point. The aims of this paper were to evaluate the prognosis of T‐ALI with regard to fissure integrity, and type of resection. Methods: This was a retrospective multicenter study which included all consecutive patients with T‐ALI undergoing surgical treatment. Based on radiological, intraoperative and histological findings, T‐ALI patients were differentiated into two groups based on whether the fissure was complete (T‐ALI‐A group) or incomplete (T‐ALI‐D Group) at the level of tumor invasion point. Clinico‐pathological features and survival of two study groups were analyzed and compared. Results: Study population included 135 patients, of these 98 (72%) were included into T‐ALI‐A group, and 37 (38%) into T‐ALI‐D Group. T‐ALI‐D patients had better overall survival than T‐ALI‐A patients (63.9 ± 7.0 vs. 48.9 ± 3.9; respectively, P = 0.01) who presented with a higher incidence of lymph node involvement (35% vs. 4%; P = 0.004), and recurrence rate (43% vs. 16%; P = 0.01). At multivariable analysis, T‐ALI‐D (P = 0.01), pN0 stage (P = 0.0002), and pT≤5 cm (P = 0.0001) were favorable survival prognostic factors. Conclusions: T‐ALI‐D presented a better prognosis than T‐ALI‐A while extent of resection had no effect on survival. Thus, in patients with small T‐ALI‐D and without lymph node involvement, sublobar resection of adjacent lobe rather than lobectomy could be indicated. Key points: The extent of resection of adjacent lobe had no effect on survival while T‐ALI‐D, pN0 stage, and pT≤5 cm were significant prognostic factors.In patients with small T‐ALI‐D and without lymph node involvement, sublobar resection of adjacent lobe could be indicated as an alternative to lobectomy. [ABSTRACT FROM AUTHOR]

This meta‐analysis aimed to evaluate the feasibility and oncological outcomes between video‐assisted thoracic surgery (VATS) and thoracotomy for non–small cell lung cancer (NSCLC) patients with pathologic N2 (pN2) disease. Data for analysis included short‐term outcomes and long‐term outcomes. We calculated the weighted mean differences (WMDs) for continuous data and the results of overall survival (OS) and disease free survival (DFS) were pooled using the hazard ratios (HRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the Q‐test and I2‐test. Sensitivity analysis was performed to further examine the stability of pooled HRs and WMDs. In the pooled analyses of 10 eligible studies, results showed that VATS for NSCLC patients with pN2 disease yielded significantly less blood loss (WMD = −61.43; 95% confidence intervals [CI], [−87.69, −35.18]; p < 0.001), less post‐operation hospital stay (WMD, −1.62; 95% CI, [−2.96, −0.28]; p = 0.02), and comparable operation time (WMD, −8.32; 95% CI, [−23.88, 7.23]; p = 0.29), post‐operation complication rate (risk ratio [RR], 0.95; 95% CI, [0.78, 1.15]; p = 0.59), chest tube duration to thoracotomy (WMD, −0.64; 95% CI, [−1.45, 0.17]; p = 0.12), extent of lymph node dissection (WMD, −1.46; 95% CI, [−3.87, 0.95]; p = 0.23) and 1‐year OS (HR, 1.30; 95% CI, [0.96, 1.76]; p = 0.09) than thoracotomy. However, VATS may improve 3‐year OS (HR, 1.26; 95% CI, [1.12, 1.42]; p = 0.0002) and yield comparable 1‐year DFS (HR, 1.14; 95% CI, [0.89, 1.46]; p = 0.32) and 3‐year DFS (HR, 1.03; 95% CI, [0.88, 1.22]; p = 0.70) for NSCLC patients with pN2 disease than thoracotomy. VATS could yield less surgical trauma and improve post‐operative recovery than thoracotomy. Moreover, VATS may improve the oncological outcomes of those patients. [ABSTRACT FROM AUTHOR]

Objectives: Pretreatment biomarkers are needed to identify patients with non‐small‐cell lung cancer (NSCLC) likely to have worse survival. This ensures that only patients with a real chance of benefit receive immune checkpoint inhibitor (ICI) treatment. In this study, we examined the associations of baseline nutritional and inflammatory biomarkers with overall survival in a real‐world cohort of NSCLC patients who received ICIs. Materials and Methods: We used prospectively collected data from the OncoLifeS data biobank. The cohort included 500 advanced‐stage NSCLC patients treated with ICIs from May 2015 to June 2021. Biomarkers were evaluated within 2 weeks before ICI treatment: neutrophil‐to‐lymphocyte ratio, C‐reactive protein (CRP), Glasgow prognostic score, CRP/albumin ratio (CAR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index. For each biomarker, low‐ and high‐risk groups were defined using literature‐based cut‐offs. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were estimated using adjusted survival analysis. Results: Most patients were male (60.8%), the mean baseline age was 65 ± 9 years, and 88% had stage IV disease. For each biomarker, low‐risk patients had better overall survival (all, p < 0.001), with CAR and PNI showing the strongest associations. In multivariable analyses a combined CAR/PNI risk score had a stronger association with overall survival (aHR 3.09, 95% CI 2.36–4.06) than CAR alone (aHR 2.22, 95% CI 1.79–2.76) or PNI alone (aHR 2.09, 95% CI 1.66–2.61). Conclusion: These results highlight the potential value of nutritional and inflammatory biomarkers, in particular CAR and PNI, in identifying NSCLC patients with highest mortality risk before starting ICI treatment. [ABSTRACT FROM AUTHOR]

Background: To elucidate the treatment and surgery outcomes with or without perioperative therapies in Japanese patients with clinical stage III non‐small cell lung cancer (NSCLC) in real‐world settings. Methods: We performed subset analyses of the SOLUTION study, a multicenter, noninterventional, observational study of Japanese patients diagnosed with clinical stage III NSCLC, for those who started first‐line treatment (surgery±perioperative therapy) between January 2013 and December 2014 (study registration: UMIN000031385). Follow‐up data were obtained using medical records from diagnosis to March 1, 2018. Results: Of 149 eligible patients, 67 underwent surgery alone (median age 71 years) and 82 underwent surgery+perioperative therapy (median age 63 years). Lung resection was performed in 137 patients and the others underwent exploratory thoracotomy or other procedures. Perioperative therapies included adjuvant therapy only (n = 41), neoadjuvant therapy only (n = 24), and neoadjuvant+adjuvant therapy (n = 17). The median overall survival (OS) and 3‐year OS rate were 29.3 months and 44.0%, respectively, in patients who underwent surgery alone, and not reached and 61.1%, respectively, in patients who underwent surgery+perioperative therapy. The 3‐year progression‐free survival (PFS) and disease‐free survival (DFS) rates were 42.4% and 47.1%, respectively, in patients who underwent surgery+perioperative therapy and 28.5% and 28.9%, respectively, in patients who underwent surgery alone. In multivariable Cox regression, perioperative therapy was associated with improved OS (hazard ratio [95% confidence interval] 0.49 [0.29–0.81]), PFS (0.62 [0.39–0.96]), and DFS (0.62 [0.39–0.97]) versus surgery alone. Conclusions: Our study suggested that perioperative therapy may be associated with better survival among patients undergoing surgical treatment of clinical stage III NSCLC. [ABSTRACT FROM AUTHOR]

Background: In patients with non‐small cell lung cancer (NSCLC), interstitial lung abnormalities (ILA) have been linked to mortality and can be identified on computed tomography (CT) scans. In the present study we aimed to evaluate the predictive value of automatically quantified ILA based on the Fleischner Society definition in patients with stage I NSCLC. Methods: We retrospectively reviewed 948 patients with pathological stage I NSCLC who underwent pulmonary resection between April 2009 and October 2022. A commercially available deep learning‐based automated quantification program for ILA was used to evaluate the preoperative CT data. The Fleischner Society definition, quantitative results, and interdisciplinary discussion led to the division of patients into normal and ILA groups. The sum of the fibrotic and nonfibrotic ILA components constituted the total ILA component and more than 5%. Results: Of the 948 patients with stage I NSCLC, 99 (10.4%) patients had ILA. Shorter overall survival and recurrence‐free survival was associated with the presence of ILA. After controlling for confounding variables, the presence of ILA remained significant for increased risk of death (hazard ratio [HR] = 3.09; 95% confidence interval [CI]: 1.91–5.00; p < 0.001) and the presence of ILA remained significant for increased recurrence (HR = 1.96; 95% CI: 1.16–3.30; p = 0.012). Conclusions: The automated CT quantification of ILA, based on the Fleischner Society definition, was significantly linked to poorer survival and recurrence in patients with stage I NSCLC. [ABSTRACT FROM AUTHOR]

Background: The accuracy of artificial intelligence (AI) and experts in diagnosing early esophageal cancer (EC) and its infiltration depth was summarized and analyzed, thus identifying the advantages of AI over traditional manual diagnosis, with a view to more accurately assisting doctors in evaluating the patients' conditions and improving their cure and survival rates. Methods: The PubMed, EMBASE, Cochrane, Google, and CNKI databases were searched for relevant literature related to AI diagnosis of early EC and its invasion depth published before August 2023. Summary analysis of pooled sensitivity, specificity, summary receiver operating characteristics (SROC) and area under the curve (AUC) of AI in diagnosing early EC were performed, and Review Manager and Stata were adopted for data analysis. Results: A total of 19 studies were enrolled with a low to moderate total risk of bias. The pooled sensitivity of AI for diagnosing early EC was markedly higher than that of novices and comparable to that of endoscopists. Moreover, AI predicted early EC with markedly higher AUCs than novices and experts (0.93 vs. 0.74 vs. 0.89). In addition, pooled sensitivity and specificity in the diagnosis of invasion depth in early EC were higher than that of experts, with AUCs of 0.97 and 0.92, respectively. Conclusion: AI‐assistance can diagnose early EC and its infiltration depth more accurately, which can help in its early intervention and the customization of personalized treatment plans. Therefore, AI systems have great potential in the early diagnosis of EC. [ABSTRACT FROM AUTHOR]

Background: In China, real‐world data on surgical challenges and postoperative complications after neoadjuvant immunotherapy of lung cancer are limited. Methods: Patients were retrospectively enrolled from January 2018 to January 2023, and their clinical and pathological characters were subsequently analyzed. Surgical difficulty was categorized into a binary classification according to surgical duration: challenging or routine. Postoperative complications were graded using Clavien–Dindo grades. Logistic regression was used to identify risk factors affecting the duration of surgery and postoperative complications greater than Clavien–Dindo grade 2. Results: In total, 261 patients were included. Of these, stage III patients accounted for 62.5% (163/261) at initial diagnosis, with 25.3% (66/261) at stage IIIB. Central‐type non‐small‐cell lung cancer accounted for 61.7% (161/261). One hundred and forty patients underwent video‐assisted thoracoscopic surgery and lobectomy accounted for 53.3% (139/261) of patients. Surgical time over average duration was defined as challenging surgeries, accounting for 43.7%. The postoperative complications rate of 261 patients was only 22.2%. Smoking history (odds ratio [OR] = 9.96, 95% [CI] 1.15–86.01, p = 0.03), chemoimmunotherapy (OR = 2.89, 95% CI 1.22–6.86, p = 0.02), and conversion to open surgery (OR = 11.3, 95% CI 1.38–92.9, p = 0.02) were identified as independent risk factors for challenging surgeries, while pneumonectomy (OR = 0.36, 95% CI 0.15–0.86, p= 0.02) was a protective factor. Meanwhile, pneumonectomy (OR = 7.51, 95% CI 2.40–23.51, p < 0.01) and challenging surgeries (OR = 5.53, 95% CI 1.50–20.62, p = 0.01) were found to be risk factors for postoperative complications greater than Clavien–Dindo grade 2. Conclusions: Compared to immunotherapy alone or in combination with apatinib, neoadjuvant chemoimmunotherapy could increase the difficulty of surgery while the incidence of postoperative complications remained acceptable. The conversion to open surgery and pneumonectomy after neoadjuvant immunotherapy should be reduced. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoimmunotherapy (NCIT) for locally advanced esophageal squamous cell carcinoma (ESCC) is supported by increasing data, but the sample size is limited, and the findings are not completely consistent. We conducted a real‐world study and a meta‐analysis to evaluate the efficacy and safety of NCIT in locally advanced ESCC. Methods: We retrospectively assessed the outcomes of patients with locally advanced ESCC who completed NICT and subsequent esophagectomy at our hospital between January 2019 and December 2022, including pathological complete response (pCR) rate, major pathological response (MPR) rate, 1‐, 2‐, and 3‐year overall survival (OS) rates, disease control rate (DCR), objective response rate (ORR), 1‐year recurrence rate, R0 resection rate and adverse events. Moreover, a meta‐analysis of 27 published literatures was also conducted for comparison. Results: In the analysis, 128 patients were studied, with 25% achieving pCR, 46.1% MPR, and 99.2% R0 resection. The 1‐, 2‐, and 3‐year OS rates were 91.41% (95% CI: 85.15%–95.63%), 75.00% (95% CI: 66.58%–82.23%) and 64.84% (95% CI: 55.91%–73.07%).ORR and DCR were 31.2% (95% CI: 23.31–39.99) and 64.1% (95% CI: 55.15%–72.38%), and the 1‐year recurrence rate was 26.7% (95% CI: 22.5%–38.1%). Treatment‐related events occurred in 96.1% but were acceptable. In a meta‐analysis of 27 studies with 1734 patients, pooled rates for pCR, MPR, ORR, DCR, and R0 resection were 29%, 52%, 71%, 97%, and 98%, respectively, with a 1‐year recurrence rate of 12%. Conclusion: NCIT is safe and provides potential survival benefits for patients with locally advanced ESCC. However, randomized phase 3 trial data is still needed. [ABSTRACT FROM AUTHOR]

Background: To identify independent factors of cognitive frailty (CF) and construct a nomogram to predict cognitive frailty risk in patients with lung cancer receiving drug therapy. Methods: In this cross‐sectional study, patients with lung cancer undergoing drug therapy from October 2022 to July 2023 were enrolled. The data collected includes general demographic characteristics, clinical data characteristics and assessment of tools for cognitive frailty and other factors. Logistic regression was harnessed to determine the influencing factors, R software was used to establish a nomogram model to predict the risk of cognitive frailty. The enhanced bootstrap method was employed for internal verification of the model. The performance of the nomogram was evaluated by using calibration curves, the area under the receiver operating characteristic curve, and decision curve analysis. Results: A total of 372 patients were recruited, with a cognitive frailty prevalence of 56.2%. Age, education background, diabetes mellitus, insomnia, sarcopenia, and nutrition status were identified as independent factors. Then, a nomogram model was constructed and patients were classified into high‐ and low‐risk groups with a cutoff value of 0.552. The internal validation results revealed good concordance, calibration and discrimination. The decision curve analysis presented prominent clinical utility. Conclusions: The prevalence of cognitive frailty was higher in lung cancer patients receiving drug therapy. The nomogram could identify the risk of cognitive frailty intuitively and simply in patients with lung cancer, so as to provide references for early screening and intervention for cognitive frailty at the early phases of drug treatment. [ABSTRACT FROM AUTHOR]

Background: The effective therapeutic approach is still an unmet need for patients diagnosed with both lung cancer and interstitial lung disease (ILD). This is primarily due to the possible risk of ILD exacerbation caused by surgery or radiotherapy. The current study aimed to investigate the efficacy and safety of local ablative therapy (LAT) for this specific population. Methods: Consecutive patients with non-small cell lung cancer (NSCLC) and ILD who received LAT between January 2018 and August 2022 were enrolled, and propensity score matching (PSM) was utilized to match the non-ILD group. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints included overall survival (OS), adverse events (AEs) and hospital length of stay (HLOS). Results: The PSM algorithm yielded matched pairs in the ILD group (n = 25) and non-ILD group (n = 72) at a ratio of 1:3. There were no statistically significant differences in RFS (median 16.4 vs. 18 months; HR = 1.452, p = 0.259) and OS (median: not reached vs. 47.9 months; HR = 1.096, p = 0.884) between the two groups. Meanwhile, no acute exacerbation of ILD was observed in the ILD group. However, the incidence of pneumothorax, especially pneumothorax requiring chest tube drainage, was significantly higher (36.0% vs. 11.2%, p = 0.005) among patients with NSCLC and co-existing ILD, which resulted in longer HLOS (p = 0.045). Conclusion: Although ILD was associated with a higher incidence of pneumothorax, the efficacy of LAT for NSCLC patients with ILD was comparable to those without ILD, suggesting that LAT might be a reliable and effective treatment option for this population, particularly in the early stage. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have characterized the gut microbiome (GM) in lung cancer (LC). Yet, the causality between GM and LC and its subtypes remain uncharacterized. Methods: Two‐sample Mendelian randomization (MR) was designed to investigate the causal relationship between the GM and LC and its subtypes, using publicly available summary data of genome‐wide association studies. The researchers ran two groups of MR analyses, including the genome‐wide statistical significance threshold (5 × 10−8) and the locus‐wide significance level (1 × 10−5). Results: Using MR analysis, we ascertained 42 groups of GM that are intimately linked to LC and its subtypes at the locus‐wide significance level. Of the 42 groups, 12 were in LC, nine in non‐small cell lung cancer (NSCLC), six in small cell lung cancer (SCLC), two in lung adenocarcinomas, and 13 in lung squamous carcinomas. After false discovery rate correction, we still found a remarkable causal interaction between the Eubacterium ruminantium group and SCLC. Moreover, five groups of GM closely linked to LC and its subtypes were recognised at the genome‐wide statistical significance threshold. This finding included one group each in LC, NSCLC and SCLC, two groups in lung adenocarcinoma and none in lung squamous carcinoma. None of the foregoing findings were heterogeneous or horizontal pleiotropy. Reverse MR revealed that genetic susceptibility to LC and its subtypes caused significant changes in three groups of GM. Conclusion: Our findings substantiate the causality between GM and LC and its subtypes. This study offers fresh insights into the function of GM in mediating the progression of LC. [ABSTRACT FROM AUTHOR]

Background: Non‐small cell lung cancer (NSCLC) is often diagnosed at an advanced stage. Clinical trials have demonstrated that first‐line immunotherapy alone or in combination with chemotherapy improves overall survival. However, reports of survival outcomes in real‐world settings are limited. We assessed survival in advanced NSCLC patients treated with immunotherapy alone or in combination with chemotherapy in first‐ or second‐line at the Windsor Regional Cancer Program (WRCP) and compared it to existing literature. Methods: We included patients diagnosed with stage IV NSCLC from January 2015 to December 2020 and treated with first‐line chemoimmunotherapy (ChemoImmuno1), chemotherapy followed by immunotherapy (Chemo1), or immunotherapy followed by chemotherapy (Immno1) in our survival analysis. Patients with oncogene‐addicted mutations were excluded. Results: There were 160 patients of which 41.5% were female. Mean age was 68 years. Median overall survival from time of diagnosis was 474 days (95% CI: 249, 949) with an estimated 5‐year survival of 11.1% (95% CI: 4.5, 21.3). Median OS in ChemoImmuno1 was 9.6 months, in Chemo1 was 19.2 months from time of diagnosis and 10.5 months from time of initiation of immunotherapy, and in Immuno1 was 18.4 months, respectively. Estimated survival at three years from time of diagnosis for ChemoImmuno1 was 17.6% and for Immuno1 was 17.9%. For Chemo1, from diagnosis it was 20.1% and from second‐line therapy it was 15.4%. Survival outcomes were comparable to clinical trials and other studies. Conclusion: Real‐world survival outcomes of immunotherapy for advanced NSCLC are comparable to the existing literature in this single center study. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) increases the risk of death or adverse outcomes in patients with lung cancer. Therefore, early identification and treatment of high‐risk groups of VTE have been the research focus. In this systematic review, the risk assessment tools of VTE in patients with lung cancer were systematically analyzed and evaluated to provide a reference for VTE management. Methods: Relevant studies were retrieved from major English databases (The Cochrane Library, Embase, Web of Science, PubMed, Scopus, Medline) and Chinese databases (China National Knowledge Infrastructure [CNKI] and WanFang Data) until July 2023 and extracted by two researchers. This systematic review was registered at PROSPERO (no. CRD42023409748). Results: Finally, two prospective cohort studies and four retrospective cohort studies were included from 2019. There was a high risk of bias in all included studies according to the Prediction Model Risk of Bias Assessment tool (PROBAST). In the included studies, Cox and logistic regression were used to construct models. The area under the receiver operating characteristic curve (AUC) of the model ranged from 0.670 to 0.904, and the number of predictors ranged from 4 to 11. The D‐dimer index was included in five studies, but significant differences existed in optimal cutoff values from 0.0005 mg/L to 2.06 mg/L. Then, three studies validated the model externally, two studies only validated the model internally, and only one study validated the model using a combination of internal and external validation. Conclusion: VTE risk prediction models for patients with lung cancer have received attention for no more than 5 years. The included model shows a good predictive effect and may help identify the risk population of VTE at an early stage. In the future, it is necessary to improve data modeling and statistical analysis methods, develop predictive models with good performance and low risk of bias, and focus on external validation and recalibration of models. [ABSTRACT FROM AUTHOR]

Background: Thymic epithelial tumors (TET) are rare malignancies and lack well‐defined biomarkers for neoadjuvant therapy. This study aimed to evaluate the clinical utility of artificial intelligence (AI)‐powered tumor‐infiltrating lymphocyte (TIL) analysis in TET. Methods: Patients initially diagnosed with unresectable thymoma or thymic carcinoma who underwent neoadjuvant therapy between January 2004 and December 2021 formed our study population. Hematoxylin and eosin‐stained sections from the initial biopsy and surgery were analyzed using an AI‐powered spatial TIL analyzer. Intratumoral TIL (iTIL) and stromal TIL (sTIL) were quantified and their immune phenotype (IP) was identified. Results: Thirty‐five patients were included in this study. The proportion of patients with partial response to neoadjuvant therapy was higher in the group with nondesert IP in preneoadjuvant biopsy (63.6% vs. 17.6%, p = 0.038). A significant increase in both iTIL (median 22.18/mm2 vs. 340.69/mm2, p < 0.001) and sTIL (median 175.19/mm2 vs. 531.02/mm2, p = 0.004) was observed after neoadjuvant therapy. Patients with higher iTIL (>147/mm2) exhibited longer disease‐free survival (median, 29 months vs. 12 months, p = 0.009) and overall survival (OS) (median, 62 months vs. 45 months, p = 0.002). Patients with higher sTIL (>232.1/mm2) exhibited longer OS (median 62 months vs. 30 months, p = 0.021). Conclusions: Nondesert IP in initial biopsy was associated with a better response to neoadjuvant therapy. Increased infiltration of both iTIL and sTIL in surgical specimens were associated with longer OS in patients with TET who underwent resection followed by neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: To develop a radiomics model based on chest computed tomography (CT) for the prediction of a pathological complete response (pCR) after neoadjuvant or conversion chemoimmunotherapy (CIT) in patients with non‐small cell lung cancer (NSCLC). Methods: Patients with stage IB–III NSCLC who received neoadjuvant or conversion CIT between September 2019 and July 2021 at Hunan Cancer Hospital, Xiangya Hospital, and Union Hospital were retrospectively collected. The least absolute shrinkage and selection operator (LASSO) were used to screen features. Then, model 1 (five radiomics features before CIT), model 2 (four radiomics features after CIT and before surgery) and model 3 were constructed for the prediction of pCR. Model 3 included all nine features of model 1 and 2 and was later named the neoadjuvant chemoimmunotherapy‐related pathological response prediction model (NACIP). Results: This study included 110 patients: 77 in the training set and 33 in the validation set. Thirty‐nine (35.5%) patients achieved a pCR. Model 1 showed area under the curve (AUC) = 0.65, 64% accuracy, 71% specificity, and 50% sensitivity, while model 2 displayed AUC = 0.81, 73% accuracy, 62% specificity, and 92% sensitivity. In comparison, NACIP yielded a good predictive value, with an AUC of 0.85, 81% accuracy, 81% specificity, and 83% sensitivity in the validation set. Conclusion: NACIP may be a potential model for the early prediction of pCR in patients with NSCLC treated with neoadjuvant/conversion CIT. [ABSTRACT FROM AUTHOR]

More and more patients with small cell lung cancer (SCLC) have received surgical treatment in the last 20 years. This meta‐analysis compared whether surgical treatment can bring greater survival benefits to patients with stage I–III SCLC compared with chemotherapy, radiotherapy and chemoradiotherapy. Pubmed, Embase, Web of Science, Cochrane library database, and ClinicalTrials were searched for relevant articles. The main outcomes were overall survival (OS), reported as hazard ratios (HRs), and 95% confidence intervals (CIs). A total of 19 articles containing 30 185 patients (3940 patients receiving surgical treatment and 26 245 patients receiving nonsurgical treatment) were included in this study. Surgical resection significantly improved OS when compared to nonsurgical treatment in retrospective studies (HR: 0.55, 95% CI: 0.47–0.64, p < 0.01). In the subgroup analysis for retrospective studies, surgical resection was associated with superior OS in stage I (HR: 0.42, 95% CI: 0.24–0.71, p < 0.01), stage II (HR: 0.61, 95% CI: 0.52–0.73, p < 0.01), and stage III diseases (HR: 0.66, 95% CI: 0.51–0.86, p < 0.01). Sublobar resection resulted in worse OS than a lobectomy (HR: 0.78,95% CI: 0.60–1.00, p < 0.01) for patients undergoing surgical resection. Compared with nonsurgical treatment, surgical treatment can indeed bring more significant survival benefits to patients with stage I–III SCLC, and lobectomy can bring longer survival compared with sublobectomy. More prospective studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Systemic therapy is the primary treatment for advanced thymic malignancies. However, there is an urgent need to improve clinical outcome. Personalized treatment based on predictive biomarkers is a potential approach to address this requirement. In this study, we aimed to show the correlation between drug sensitivity tests on CTCs‐derived organoids and clinical response in patients with thymic malignancies. This approach carries the potential to create personalized cancer avatars and improve treatment outcome for patients. Methods: We previously reported potential treatment outcome prediction with patient‐derived organoids (cancer avatars) in patients with pancreatic ductal adenocarcinoma. To further investigate the feasibility of this approach in advanced thymic malignancies, we conducted a study in which 12 patients were enrolled and 21 liquid biopsies were performed. Results: Cancer avatars were successfully derived in 16 out of 21 samples (success rate 76.2%). We found a sensitivity of 1.0 and specificity of 0.6 for drug sensitivity tests on the cancer avatars, and a two‐tailed Fisher's exact test revealed a significant correlation between drug sensitivity tests and clinical responses (p = 0.0275). Conclusion: This study supports the potential of circulating tumor cell‐derived organoids to inform personalized treatment for advanced thymic malignancies. Further validation of this proof of concept finding is ongoing. [ABSTRACT FROM AUTHOR]

Background: Evidence on the influence of programmed death‐ligand 1 (PD‐L1) expression on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in EGFR‐mutant non‐small cell lung cancer (NSCLC) patients is at variance. Methods: A single‐center retrospective study was conducted to evaluate the influence of PD‐L1 expression on the efficacy of EGFR‐TKIs for NSCLC patients with EGFR mutation. Clinical information was retrieved from electronic medical records. The patients were divided into three subgroups according to PD‐L1 expression level: PD‐L1 < 1% (negative), PD‐L1 1%–49% and PD‐L1 ≥ 50%. The clinicopathological features, overall response rate (ORR), progression‐free survival (PFS) and comutation information were collected and compared between the three subgroups. Results: A total of 117 patients were included. For PD‐L1 < 1%, PD‐L1 1%–49% and PD‐L1 ≥ 50% group, there were 39 (33.3%), 51 (43.5%) and 27 (23.0%) patients respectively, and the ORR was 43.2%, 64.0%, and 51.9%, respectively (p = 0.162), and the median progression‐free survival (mPFS) was 22.0 months (95% CI: 14.0–29.9 months), 15.4 months (95% CI: 8.9–21.8 months) and 13.0 months (95% CI: 10.6–15.3 months), respectively (log‐rank, p = 0.01). The mPFS was negatively correlated with PD‐L1 expression level (r = −0.264, p = 0.041) and PD‐L1 expression was an independent risk factor for worse PFS of EGFR‐TKIs in multivariate Cox regression. Patients with concurrent TP53 mutation had shorter PFS (p = 0.039) and the patients harboring both mutant TP53 and positive PD‐L1 had the shortest PFS (p = 0.006). Conclusions: The efficacy of EGFR‐TKIs was influenced by the baseline PD‐L1 expression. Higher PD‐L1 expression was associated with shorter PFS. The combined indicators of TP53 and PD‐L1 identified subgroups showing divergent benefits from EGFR‐TKIs. [ABSTRACT FROM AUTHOR]

Background: Lung cancer has significantly higher incidence and mortality rates worldwide. In this study, we analyzed the metabolic profiles of non‐small cell lung cancer (NSCLC) patients and constructed prediction models for smokers and nonsmokers with internal validation. Methods: Plasma was collected from all patients enrolled for metabolic profiling by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The total population was divided into two groups according to smoking or not. Statistical analysis of metabolites was performed separately for each group and prediction models were constructed. Results: A total of 1723 patients (1109 NSCLC patients and 614 healthy controls) were enrolled from the affiliated hospital during 2018 to 2021. After grouping by smoking history, each group was statistically analyzed and prediction models were constructed, which resulted in eight indicators (propionylcarnitine, arginine, citrulline, etc.) significantly associated with lung cancer risk for smokers and eight indicators (dodecanoylcarnitine, hydroxybutyrylcarnitine, asparagine, etc.) for nonsmokers (p < 0.05). The smoker model indicated an AUC of 0.860 in the training set and 0.850 in the validation set. The nonsmoker model showed an AUC of 0.783 in the training set and 0.762 in the validation set. Further calibration tests for both models indicated excellent goodness‐of‐fit results. Conclusions: In this study, we found a series of metabolites significantly associated with lung cancer incidence and constructed respectively prediction models for NSCLC risk in smokers and nonsmokers, with internal validation to confirm the efficiency to discriminate lung cancer risk in both smoking and nonsmoking states. [ABSTRACT FROM AUTHOR]

Background: The benefits of breast conserving surgery for breast cancer patients are well established. To achieve adequate margins of excision, intraoperative management of breast margins is a critical factor through reducing reoperation for inadequate positive margin excision and associated morbidity and cost. Radiofrequency spectroscopy is a technology that could significantly reduce positive margins when used intraoperatively as an adjunct to other margin management methods. Methods: A meta‐analysis was completed with 10 publications comparing use of radiofrequency spectroscopy technology (MarginProbe) with standard margin assessment procedures. Three randomized controlled studies and seven retrospective studies comparing MarginProbe to historical controls were included. The primary endpoint was reduction of re‐excision rates. Statistical significance level was set at the two‐sided 5% level corresponding to two‐sided 95% confidence intervals (CIs) of the pooled relative risk estimates. Results: A total of 2335 patients from 10 publications were included in this meta‐analysis. The overall relative reduction in re‐excision rate was 0.49 (95% CI: 0.38–0.64, p < 0.001). Statistical methods were used to examine publication bias. Conclusion: Despite the limited randomized controlled trials available comparing radiofrequency spectroscopy to standard operation procedures, the data from the 10 studies demonstrate a statistically significant reduction in re‐excision rate of 49% for MarginProbe usage, currently the only technology indicated for intraoperative identification of breast cancer tissue at the lumpectomy specimen margin. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the response prediction and prognostic values of different peripheral blood cell biomarkers for advanced lung adenocarcinoma (LUAD) patients receiving first‐line therapy. Methods: Patients diagnosed with advanced LUAD as well as healthy controls and patients with benign pulmonary diseases were collected in this retrospective study. Propensity score matching (PSM) was performed in a 1:1 ratio. Survival state was estimated by the Kaplan–Meier method and the Cox proportional hazard model was used to assess the prognostic factors. Results: Compared with the control groups, the level of peripheral blood leucocyte, neutrophil, monocyte, platelet, and neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, platelet to lymphocyte ratio, and systemic inflammation response index (SIRI) were higher in LUAD patients (all p < 0.001). Some inflammatory markers decreased at the time of optimal response and then increased again as the disease progressed. Multivariate analysis revealed that SIRI and lactate dehydrogenase (LDH) were independent prognostic factors no matter before or after PSM analysis. Area under the curve (AUC) of SIRI and LDH were 0.625 (p < 0.001) and 0.596 (p = 0.008), respectively. When SIRI and LDH were combined, the AUC reached 0.649 (p < 0.001). Conclusions: Pretreatment SIRI was an independent prognostic factor of progression free survival (PFS) in advanced LUAD patients. Dynamic monitoring of inflammatory index changes could help to predict therapeutic efficacy. The combination of SIRI and LDH is expected to be a promising clinically accessible biomarker in the future. [ABSTRACT FROM AUTHOR]

Background: Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small‐cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. Methods: In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. Results: The SNP rs3806915C>A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (p = 0.04 and p = 0.04, respectively). The SNP rs11265375C>T in nescient helix–loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (p = 0.04 and p = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (p = 4 × 10−6). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (p = 0.001). Conclusion: These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer (EC) is a global health problem. Asia represents a huge burden of EC globally, and incidence and mortality vary considerably across different Asian regions. Methods: Data on incidence, mortality, and preference were extracted from GLOBOCAN 2020. Age‐standardized incidence and mortality rates were calculated overall by sex, age, country, region, and continent. The predicted burden of incidence and mortality in 2040 was calculated based on global demographic projections. Results: It was estimated there were 481 552 new cases of and 434 363 deaths from EC in Asia in 2020, accounting for 79.7% and 79.8% of world EC cases and deaths, respectively. EC incidence and mortality in Asia ranked the highest among all continents. Eastern Asia represents the highest age‐standardized world incidence rate (ASWIR) of 12.3 per 100 000 for all Asian regions. Western Asia represents the lowest ASWIR of 1.7 per 100 000, accounting for 0.7% of the globe. There exist obvious differences in epidemiological features in Asian countries, including incidence, mortality, prevalence, and mortality incidence ratio. There is forecast to be up to 781 000 new cases of EC in Asia by 2040, with increasing rates of 63% for incidence and 72% for mortality from 2020. Conclusions: Asia has an increasing number of EC cases and deaths. Strategies for targeting in high‐incidence areas, the elderly, and survival should be prioritized to reduce the global EC burden, especially in low‐ and middle‐income countries in Asia. [ABSTRACT FROM AUTHOR]

Background: The addition of immune checkpoint inhibitors (ICIs) to chemotherapy is the new standard of care in the first‐line treatment of small cell lung cancer (SCLC). However, although the concomitant use of immunotherapy and chemotherapy can increase the antitumor efficacy, it can also increase toxicity. The present study evaluated the tolerability of immune‐based combinations in the first‐line treatment of SCLC. Methods: Relevant trials were identified by searching electronic databases and conference meetings. Seven phase II and III randomized controlled trials and 3766 SCLC patients were included in the meta‐analysis (immune‐based combinations = 2133; chemotherapy = 1633). Outcomes of interest included treatment‐related adverse events (TRAEs) and the rate of discontinuation due to TRAEs. Results: Immune‐based combination treatment was associated with a higher risk of grade 3–5 TRAEs (odds ratio [OR], 1.16; 95% confidence interval [CI]: 1.01–1.35). Immune‐based combinations were associated with a higher risk of TRAEs leading to discontinuation (OR, 2.30; 95% CI: 1.17–4.54). No differences were observed in grade 5 TRAEs (OR, 1.56; 95% CI: 0.93–2.63). Conclusion: This meta‐analysis indicates that the addition of immunotherapy to chemotherapy in SCLC patients is associated with a higher risk of toxicity and probably of treatment discontinuation. Tools for identifying SCLC patients that would not benefit from immune‐based therapy are urgently needed. [ABSTRACT FROM AUTHOR]

Objectives: MYC family genes including MYC, MYCN, and MYCL are amplified and overexpressed as oncogenic drivers in high-grade neuroendocrine carcinoma of the lung (HGNEC), but little is known about their clinical significance. This study evaluated the prognostic impact of MYC family protein expression in patients with surgically resected HGNEC. Methods: Immunohistochemical analyses were performed on 83 resected specimens of HGNEC using antibodies against MYC family proteins (c-MYC, n-MYC, and l-MYC). When nuclear staining of any intensity in =10% of tumor cells showed immunoreactivity with any one or more of c-MYC, n-MYC, or l-MYC, the specimens were defined as MYC family-positive. Results: A total of 83 patients were analyzed. MYC family-positive status was observed in 33.7% (28 of 83 cases) and was not correlated with clinicopathological factors. The protein expression was mutually exclusive and no duplicate cases were observed. A log-rank test showed that MYC family-positive status was significantly associated with shorter overall survival (OS) (p = 0.003) and recurrence-free survival (RFS) (p = 0.039). According to Cox multivariate analysis, MYC family-positive status had a significant effect on shorter OS (hazard ratio [HR] = 2.217, 95% confidence interval [CI] 1.179-4.169, p = 0.014) and RFS (HR = 1.802, 95% CI 1.014-3.202, p = 0.045). In patients with pathological stage I, MYC family-positive status also showed significantly poor OS (HR = 2.847, 95% CI 1.236-6.557, p = 0.014) and RFS (HR = 2.088, 95% CI 1.006-4.332, p = 0.048) in the multivariate analysis. Conclusions: MYC family protein expression could be an independent unfavorable prognostic factor in patients with surgically resected HGNEC. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have become one important therapeutic strategy for advanced non-small-cell lung cancer (NSCLC). It remains imperative to identify reliable and convenient biomarkers to predict both the efficacy and toxicity of immunotherapy, and tumor-associated autoantibodies (TAAbs) are recognized as one of the promising candidates for this. Patients and Methods: This study enrolled 97 advanced NSCLC patients with ICIbased immunotherapy treatment, who were divided into a training cohort (n = 48) and a validation cohort (n = 49), and measured for the serum level of 35 TAAbs. According to the statistical association between the serum positivity and clinical outcome of each TAAb in the training cohort, a TAAb panel was developed to predict the progression-free survival (PFS), and further examined in the validation cohort and in different subgroups. Similarly, another TAAb panel was derived to predict the occurrence of immune-related adverse events (irAEs). Results: In the training cohort, a 7-TAAb panel composed of p53, CAGE, MAGEA4, GAGE7, UTP14A, IMP2, and PSMC1 TAAbs was derived to predict PFS (median PFS [mPFS] 9.9 vs. 4.3 months, p = 0.043). The statistical association between the panel positivity and longer PFS was confirmed in the validation cohort (mPFS 11.1 vs. 4.8 months, p = 0.015) and in different subgroups of patients. Moreover, another 4-TAAb panel of BRCA2, MAGEA4, ZNF768, and PARP TAAbs was developed to predict the occurrence of irAEs, showing higher risk in panel-positive patients (71.43% vs. 28.91%, p = 0.0046). Conclusions: Collectively, our study developed and validated two TAAb panels as valuable prognostic biomarkers for immunotherapy. [ABSTRACT FROM AUTHOR]

Background: With the widespread use of alectinib in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), its cardiotoxicity has gradually emerged, including new-onset sinus bradycardia (SB). However, the incidence, timing, severity, and risk factors of alectinib-induced bradycardia remain unknown. Methods: From January 2020 to June 2022, 93 patients with ALK-positive NSCLC treated with alectinib were enrolled in this retrospective analysis. These patients had heart rate (HR) recorded before and after alectinib administration. By reviewing electronic medical records and follow-up, the HR changes of patients during medication were recorded. The potential risk factors associated with alectinib-induced SB were explored. Results: According to an HR cut-off of 60 beats per minute (bpm), 47 patients (50.54%) experienced at least one recorded bradycardia. The mean HR of total participants before alectinib administration was 78.32 (standard deviation [SD], 9.48) and after was 64.88 (SD, 12.21). The median maximum change in HR (range) for all patients was 11 (-55, +4) bpm. For the bradycardia subgroup, the HR of most patients (76.60%) hovered around 50-60 bpm, and 61.70% of SB occurred within 3 months after alectinib administration. Multivariate analysis indicated that baseline HR (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.79-0.93, p < 0.001) and history of hypertension (OR 13.71, 95% CI 2.49-76.38, p = 0.003) were independent risk factors for alectinib-related bradycardia. Conclusions: Alectinib-induced bradycardia had a high incidence, appeared relatively early, and was reversible by dose reduction or withdrawal. [ABSTRACT FROM AUTHOR]

Background: Oncolytic viral therapy is a promising method for tumor treatment. Currently, several oncolytic viruses (OVs) have been used as tumor therapy at different phases of research and clinical trials. OVs not only directly lyse tumor cells due to viral replication but also initiate host antitumor immune responses. Previous studies have primarily focused on how OVs activate adaptive immune responses in immune cells. However, the role of innate immune responses in tumors induced by OVs remains unclear. Methods: To determine the innate immune responses induced by vesicular stomatitis virus (VSV), the mutant VSVΔM51 strain was used for the infection and quantitative polymerase chain reaction (qPCR) was employed to measure the transcriptional levels of antiviral genes. The knockdown efficiency of RIG‐I was examined by qPCR. Viral titers were measured by plaque assays. Tumor models were established by intradermally implanting RIG‐I‐knockdown and control LLC cells into the flank of wild type C57BL/6J mice. When the tumors reached approximately 50mm3, they were infected with VSVΔM51 via intratumoral injections to examine its therapeutic effect. Results: Infection with VSVΔM51 triggered remarkable innate immune responses in several tumor cell lines through the cytoplasmic RIG‐I sensing pathway. Moreover, we found that intratumoral injection of VSVΔM51 effectively reduced tumor growth in murine LCC lung cancer model. Importantly, VSVΔM51‐induced antitumor therapy was more effective in murine LLC tumor model established using Rig‐I‐knockdown cells compared with the tumor model established using control cells. Conclusion: RIG‐I‐mediated innate immune signaling in tumor cells plays a negative role in regulating antitumor therapy with VSVΔM51 virus. [ABSTRACT FROM AUTHOR]

Purpose: Although radial probe endobronchial ultrasound (R‐EBUS) has been used to investigate peripheral pulmonary lesions (PPLs), its diagnostic performance without fluoroscopy remains unclear. We sought to determine the diagnostic yield of R‐EBUS‐guided transbronchial biopsy (TBB) without fluoroscopy. Methods: We performed a systematic literature review using Pubmed, Embase, and the Cochrane Central Register. Then, we performed a proportional meta‐analysis to determine the diagnostic yield of this modality. Subgroup and meta‐regression analyses were used to identify factors affecting the performance of R‐EBUS‐guided TBB without fluoroscopy. Results: We identified 31 studies consisting of a total of 6491 patients. Pooled overall diagnostic yield of R‐EBUS‐guided TBB without fluoroscopy was 0.70 (95% confidence interval [CI], 0.67–0.74). There was significant heterogeneity across studies (I2 = 89.45%, p < 0.001). In subgroup and meta‐regression analyses, air bronchus sign on chest computed tomography scans, larger size PPLs, probe location within lesions, and heterogeneous echogenicity were associated with significantly higher diagnostic yield. Diagnostic yield from the upper lobe was statistically lower than that from the middle and lower lobes. Pooled pneumothorax rate was 0.01 (95% CI, 0.01–0.01, I2 = 63.51%, p < 0.001). Conclusions: R‐EBUS‐guided TBB without fluoroscopy appears to be a relatively useful tool with a low pneumothorax rate for the diagnosis of PPLs. Factors mentioned above may affect the diagnostic yield of this tool. Because of substantial between‐study heterogeneity, our results should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: Although the utility of segmentectomy for early‐stage non‐small cell lung cancer (NSCLC) has been reported, the adaptation criterion for segmentectomy is unclear. Methods: In total, 171 NSCLC patients who underwent segmentectomy or lobectomy with a consolidation tumor diameter on computed tomography of ≤20 mm were analyzed. Results: Consolidation diameter (p = 0.01), consolidation to tumor ratio (CTR) (p < 0.01), maximum standardized uptake value (SUVmax) (p < 0.01), and segmentectomy (p = 0.01) were significantly different upon univariate analysis among patients stratified by recurrence. Positive correlations were observed between the consolidation diameter on CT and CEA (correlation coefficient; r = 0.19, p = 0.01), SUVmax (r = 0.48, p < 0.01), and CTR (r = 0.83, p < 0.01). Because there was a significant correlation among the consolidation diameter of tumors on CT, CTR, and SUVmax in this study, we integrated these factors into one. Consolidation, CTR, and SUVmax (hazard ratio [HR]: 3.77, 95% confidence interval [CI]: 1.35–11.29, p = 0.01) and segmentectomy (HR: 0.24, 95% CI: 0.03–0.90, p = 0.03) were risk factors for recurrence in a multivariate analysis. There was a significant difference between the segmentectomy and lobectomy groups (5‐year relapse‐free survival [RFS] 96.5% vs. 80.7%, p = 0.02). Conclusions: Consolidation tumor diameter on CT, CTR, and SUVmax is a risk factor for recurrence. These results suggest that for patients with small‐sized early stage NSCLC, this combined factor is important for determining the indication for segmentectomy. [ABSTRACT FROM AUTHOR]

Background: Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is used to evaluate hilar/interlobar/lobar lymph nodes. This study aimed to assess the clinical utility of EBUS‐TBNA for station 10/11/12 lymph nodes (LNs) in patients with primary lung cancer. Methods: This was a retrospective analysis of a prospectively collected database of patients with primary lung cancer who underwent EBUS‐TBNA for station 10/11/12 LNs from January 2015 to December 2019. Patients with benign results from EBUS‐TBNA who did not undergo surgical sampling/clinical follow‐up or who received radiotherapy/chemotherapy were excluded. Results: The analyses were conducted on 889 LNs from 797 patients. The overall diagnostic sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predictive value of EBUS‐TBNA were 95.7, 100, 97.3, 93.2, and 100%, respectively. Diagnostic sensitivity was significantly lower for LNs <10 mm than ≥10 mm in size (90.1% vs. 97.8%; p < 0.001). There was no significant difference in diagnostic performance according to the nodal station (10 vs. 11/12) and left‐ versus right‐sided LNs. The diagnostic sensitivity (100 vs. 95.5%; p = 0.221) and specificity (100 vs. 100%) of N3 LNs was not significantly different from those of N1 LNs. In this study, eight (8/91, 8.8%) patients with cN1 NSCLC received neoadjuvant treatment based on the results of EBUS‐TBNA. Conclusion: EBUS‐TBNA accurately evaluates station 10/11/12 LNs of both N1 and N3 disease. The diagnostic performances of EBUS‐TBNA for station 10/11/12 LNs seem to be comparable to those of EBUS‐TBNA for mediastinal LNs. [ABSTRACT FROM AUTHOR]

Background: 99mTc bone scintigraphy (BS) is the mainstay and most widely used technique in evaluation of bone metastasis (BM) in China. This study aimed to investigate the value of 99mTc BS in preoperative workup for patients with potentially resectable (cT1−4aN0−3) esophageal squamous cell carcinoma (ESCC). Methods: This prospective cross‐section clinical trial (ChiCTR1800020304) enrolled a total of 385 patients with ESCC diagnosed at thoracic surgery clinic from October 2018 to September 2020. All patients were diagnosed with stage cT1−4aN0−3 and were potential candidates for surgical resection. BS was performed preoperatively and the treatment strategy was changed after confirmation of BM. The primary endpoint was the rate of change of the treatment regimen because of BM, while the secondary endpoint was the rate of positive BS findings. Results: Out of the 385 patients, only two (0.5%) changed their treatment regimen because of BM. The rate of positive BS findings was 1%, while two patients (0.5%) had false‐positive or false‐negative results. The BS diagnostic performance for BM was sensitivity 50%, specificity 99.5%, positive predictive value 50%, negative predictive value 99.5%, and accuracy 99.0%. There was no significant difference in BM in relation to age, sex, tumor location or clinical stage. Conclusion: Our data demonstrated that 99mTc bone scintigraphy does not significantly affect the preoperative workup in patients with potentially resectable ESCC, especially in early clinical stage patients. [ABSTRACT FROM AUTHOR]

Background: To investigate the impact of station 3A lymph node dissection (LND) on overall survival (OS) and disease‐free survival (DFS) in completely resected right‐side non‐small‐cell lung cancer (NSCLC) patients. Methods: A total of 1661 cases with completely resected right‐side NSCLC were included. Propensity score matching (PSM) was performed to minimize selection bias, and a logistic regression model was conducted to investigate the risk factors associated with station 3A lymph node metastasis (LNM). The Kaplan–Meier method and Cox proportional hazards model were used to evaluate the impact of station 3A LND on survival. Results: For the entire cohort, 503 patients (30.3%) underwent station 3A LND. Of those, 11.3% (57/503) presented station 3A LNM. Univariate and multivariate logistic analyses showed that station 10 LNM, tumor location, and the number of resected lymph nodes were independent risk factors associated with station 3A LNM. Before PSM, patients with station 3A LND had worse 5‐year OS (p = 0.002) and DFS (p = 0.011), and more drainage on postoperative day 1 (p = 0.041) than those without. After PSM, however, station 3A LND was not associated with the 5‐year OS (65.7% vs. 63.6%, p = 0.432) or DFS (57.4% vs. 56.0%, p = 0.437). The multivariate analysis further confirmed that station 3A LND was not a prognostic factor (OS, p = 0.361; DFS, p = 0.447). Conclusions: Station 3A LND could not improve long‐term outcomes and it was unnecessary to dissect station 3A lymph nodes during surgery of right‐side NSCLC. [ABSTRACT FROM AUTHOR]

Background Hospitalization expenses for the therapy of lung cancer are not only a direct economic burden on patients, but also the focus of medical insurance departments. Therefore, the method for classifying and analyzing lung cancer hospitalization expenses so as to predict reasonable medical cost has become an issue of common interest for both hospitals and insurance institutions. Methods A C5.0 algorithm is adopted to analyze factors influencing hospitalization expenses of 731 lung cancer patients. A C5.0 algorithm is a data mining method used to classify calculation. Results Increasing the number of input variables leads to variation in the importance of different variables, but length of stay ( LOS), major therapy, and medicine cost are the three variables of greater importance. They are important factors that affect the hospitalization cost of lung cancer patients. In all three calculations, the classification accuracy rate of training and testing partition sets reached 84% and above. The classification accuracy rate reached over 95% after addition of the cost variables. Conclusion The classification rules are proven to be in accordance with actual clinical practice. The model established by the research can also be applied to other diseases in the screening and analysis of disease hospitalization costs according to selected feature variables. [ABSTRACT FROM AUTHOR]

Background: Genomic testing is the cornerstone of the treatment of patients with non‐small‐cell lung cancer. However, comprehensive molecular testing of small specimens may be inadequate due to limited tissue. Liquid biopsy has emerged as a new method of genotyping. In this study, we evaluate the feasibility of using supernatants from core needle biopsy samples of lung adenocarcinoma for genomic testing. Methods: Core needle biopsy specimens and their supernatants were collected from patients (n = 48) with lung adenocarcinoma. Genomic testing results of the supernatant samples were compared with results derived from paired tissue samples from the same patient. Result: All 48 supernatant samples yield adequate cell‐free DNA, but the concentration of cell‐free RNA did not meet the criteria for analysis. The concordance rate between the genomic testing results of supernatants and the corresponding tissue samples was 95.8% (kappa = 0.899). The coincidence rate of detectable mutations at the DNA level in the supernatants was up to 100%. Conclusion: Core needle biopsy supernatants can provide a valuable specimen source for genotyping pulmonary adenocarcinoma. However, the method of preserving and extracting RNA from supernatant specimens needs further improvement. [ABSTRACT FROM AUTHOR]

Objectives: Breast and ovarian cancer account for over 30% of malignant pleural effusions (MPEs). Treatment of the metastatic disease requires control of the MPE. Even though primarily symptomatic, the treatment of the MPE can potentially affect the oncological course of the disease. The aim of this review is to analyze the effectiveness of intrathoracic chemotherapy in the treatment of MPE caused by breast and ovarian cancer. Methods: A systematic literature research was conducted up until May 2021. Studies published in English on patients undergoing either surgical or interventional intrapleural chemotherapy were included. Results: Thirteen studies with a total of 497 patients were included. Analysis was performed on 169 patients with MPE due to breast cancer and eight patients with MPE secondary to ovarian cancer. The pooled success rates of intrathoracic chemotherapy for controlling the MPE were 59.1% and 87.5%, respectively. A survival analysis was not possible with the available data. The overall toxicity of the treatment was low. Conclusions: Intrathoracic chemotherapy achieves symptomatic control of the MPE in 59.1% of patients with metastatic breast cancer and 87.5% of patients with metastatic ovarian cancer. This is inferior to other forms of surgical pleurodesis. Data from small case series and studies on intraperitoneal chemotherapy show promising results. However, formal oncological studies on the use of intrathoracic chemotherapy for metastatic breast or ovarian cancer are lacking. Further prospective pilot studies are needed to assess the therapeutic oncological effects of this treatment. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung abnormality (ILA) is closely related to lung cancer. This study aimed to assess whether the presence of ILA is associated with the clinicoradiological features of elderly patients (≥70 years) with early‐stage non‐small cell lung cancer (NSCLC). Methods: Elderly patients who underwent surgical resection for stage I or II NSCLC with preserved lung function between 2012 and 2019 were retrospectively identified. ILA was evaluated using a three‐point scale. Univariate analyses were performed for clinicoradiological features based on the presence of ILA. Logistic and linear regression analyses were performed for cancer staging and tumor size, respectively. Results: A total of 254 patients were evaluated. The presence of ILA (score = 2) was significantly associated with male sex, current or former smoker status, higher pack‐years of smoking, low forced expiratory volume in one second/forced vital capacity ratios and diffusing capacity of the lung for carbon monoxide, and presence of emphysema (≥5%). Tumor characteristics, such as lower lobe and outer one‐third location, squamous cell carcinoma, and higher cancer stage (stage II) were significantly associated with ILA. The presence of ILA independently predicted a higher cancer stage (adjusted odds ratio, 1.81; 95% confidence interval, 1.10–2.96; p = 0.02) and a larger tumor size in linear regression analysis (p = 0.04). Conclusions: Patients with ILA showed clinicoradiological features similar to those of idiopathic pulmonary fibrosis in elderly patients with early‐stage NSCLC. Identifying the clinical implications of ILA in early‐stage lung cancer will guide clinicians in providing appropriate management for these patients. [ABSTRACT FROM AUTHOR]

Background: We investigated whether adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers affected survival of patients with the early stage of large‐cell neuroendocrine cancer. Methods: This was a retrospective multicenter study including consecutive patients undergoing resection of node negative large‐cell neuroendocrine carcinoma. Five‐year survival and disease‐free survival rate were evaluated by the Kaplan–Meier method and the log‐rank test in relation to adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers (synaptophysin, chromogranin A, and neuron‐specific enolase). Results: Our study population included 117 patients; 47 (40%) of these received adjuvant chemotherapy. Patients treated with adjuvant chemotherapy had better survival (74% vs. 45%, p = 0.002) and disease‐free survival (79% vs. 40%, p = 0.001) in all cases except patients with tumor <20 mm (79.5% vs. 57.4%, p = 0.43). Lobectomy compared to sublobar resection was associated with better survival (67% vs. 0.1%, p < 0.0001) and disease‐free survival (65% vs. 0.1%, p < 0.0001) also in patients with tumor <20 mm (79% vs. 28%, p = 0.001). Patients with triple‐positive neuroendocrine markers had better survival (79% vs. 35%, p = 0.0001) and disease‐free survival (69% vs. 42%, p = 0.0008). Regression analysis showed that tumor size <20 mm, lobectomy, adjuvant chemotherapy, and triple‐positive immunistochemical neuroendocrine markers were significant favorable prognostic factors for survival outcomes. Conclusions: Lobectomy seems to be the management of choice in patients with large‐cell neuroendocrine cancer <20 mm while adjuvant chemotherapy should be administered only in patients with tumor >20 mm. [ABSTRACT FROM AUTHOR]

Background: Early identification of the malignant propensity of pulmonary ground-glass nodules (GGNs) can relieve the pressure from tracking lesions and personalized treatment adaptation. The purpose of this study was to develop a deep learning-based method using sequential computed tomography (CT) imaging for diagnosing pulmonary GGNs. Methods: This diagnostic study retrospectively enrolled 762 patients with GGNs from West China Hospital of Sichuan University between July 2009 and March 2019. All patients underwent surgical resection and at least two consecutive timepoint CT scans. We developed a deep learning-based method to identify GGNs using sequential CT imaging on a training set consisting of 1524 CT sections from 508 patients and then evaluated 256 patients in the testing set. Afterwards, an observer study was conducted to compare the diagnostic performance between the deep learning model and two trained radiologists in the testing set. We further performed stratified analysis to further relieve the impact of histological types, nodule size, time interval between two CTs, and the component of GGNs. Receiver operating characteristic (ROC) analysis was used to assess the performance of all models. Results: The deep learning model that used integrated DL-features from initial and follow-up CT images yielded the best diagnostic performance, with an area under the curve of 0.841. The observer study showed that the accuracies for the deep learning model, junior radiologist, and senior radiologist were 77.17%, 66.89%, and 77.03%, respectively. Stratified analyses showed that the deep learning model and radiologists exhibited higher performance in the subgroup of nodule sizes larger than 10 mm. With a longer time interval between two CTs, the deep learning model yielded higher diagnostic accuracy, but no general rules were yielded for radiologists. Different densities of components did not affect the performance of the deep learning model. In contrast, the radiologists were affected by the nodule component. Conclusions: Deep learning can achieve diagnostic performance on par with or better than radiologists in identifying pulmonary GGNs. [ABSTRACT FROM AUTHOR]

Background: There is a need for the development of therapies to delay cancer progression and prolong survival after initial chemotherapy for the treatment of small cell lung cancer (SCLC). Since apatinib has been found to exert promising effects on cancer patients after standard first-line chemotherapy, this study aimed to investigate apatinib as a maintenance treatment following first-line chemotherapy in extensive disease (ED)-SCLC. Methods: The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints included toxicity and safety. Apatinib (250 mg/day) was administered during the chemotherapy interval and as maintenance therapy after 4-6 cycles until the patient's disease progressed, the patient died, or became intolerant to the drug's toxicity. Results: The patients who received apatinib maintenance treatment had a median PFS of 3.7 months (95% CI: 1.3-6.2 months). The median OS was 16.3 months (95% CI: 9.7-22.8 months). The objective response rate and disease control rate were 50.0% and 66.7%, respectively. Two patients required dose reduction due to adverse effects (AEs). The most common AEs included hypertension (n = 4, 33.3%) and hand-footskin reaction (n = 2, 16.7%). One patient developed diarrhea, while another patient developed hemoptysis. The most serious AE was intestinal obstruction. Conclusions: Apatinib maintenance therapy showed promising efficacy and safety to extend the OS/PFS of patients with ED-SCLC, thus making it a potent therapeutic option in future clinical practice. Given the small sample size of this study, further studies with large sample sizes are needed to validate the findings of the present study. [ABSTRACT FROM AUTHOR]

Background: Studies on the clinical implication of hospital selection for patients with lung cancer are few. Therefore, this study aimed to analyze 2005–2016 data from the Korean national database to assess annual trends of lung cancer surgery and clinical outcomes according to hospital selection. Methods: Data of 212 554 patients with lung cancer who underwent upfront surgery were screened. Trends according to sex, age, residence, and income were examined. Descriptive statistics were performed, and ptrend values were estimated. The association between survival and hospital selection was assessed using the log‐rank test. A multivariate Cox regression analysis was also performed. Results: A total of 49 021 patients were included in this study. Surgery was prevalent among men, patients aged 61–75 years, capital area residents, and high‐income patients. However, with the increasing rate of surgery among women, patients aged ≥76 years, city residents, and middle‐income patients, the current distribution of lung cancer surgery could change. The rate of lobectomy among these groups increased. All patients, except those in capital areas, preferred a hospital outside their area of residence (HOR); the number of patients with this tendency also increased. However, this trend was not observed among low‐income patients and those aged ≥76 years. There were significant differences in survival according to hospital selection. Conclusions: The trend of lung cancer surgery is changing. The current medical system is effective in providing lobectomy for patients including women, aged ≥76 years, city residents, and middle‐income. Increasing tendency to choose an HOR requires further study. [ABSTRACT FROM AUTHOR]

Long non‐coding RNAs (LncRNAs), which are more than 200 nucleotides in length and with limited protein‐coding potential, play vital roles in the pathogenesis, tumorigenesis, and angiogenesis of cancers. Aberrant expression of lncRNAs has been detected in various carcinomas and may be correlated with oncogenesis by affecting related genes expression. Recently, an increasing number of studies have reported on long intergenic non‐protein coding RNA 460 (LINC00460) in human tumor fields. LINC00460 is upregulated in diverse cancer tissues and cells. The upregulated expression level of LINC00460 is correlated with larger tumor size, tumor node metastasis (TNM) stage, lymph node metastasis, and shorter overall survival. The regulatory mechanism of LINC00460 was complex and diverse. LINC00460 could act as a competitive endogenous RNA (ceRNA), directly bind with proteins or regulate multiple pathways, which affected tumor progression. Moreover, LINC00460 was also identified to increase drug resistance, and therefore, weaken the effectiveness of tumor treatment. It has become increasingly important to investigate the roles of LINC00460 in various cancers by different mechanisms. Therefore, a more comprehensive understanding of LINC00460 is crucial to expound on the cellular function and molecular mechanism of human cancers. In this review, we refer to studies concerning LINC00460 and provide the basis for the evaluation of LINC00460 as a predicted biomarker or potential therapeutic target in malignancies, and also provide ideas for the future research of lncRNAs similar to LINC00460. [ABSTRACT FROM AUTHOR]

Background: Non‐small cell lung cancer (NSCLC) is the leading cause of cancer‐related mortality worldwide. It is advisable to select the appropriate treatment based on characteristics of the cancer such as pathology, mutations, and programmed death‐ligand 1 (PD‐L1) levels. In this study, by remarking squamous NSCLC with low PD‐L1 expression without mutations, we investigated the efficacy and safety of regimens that included molecularly targeted drugs such as immune checkpoint inhibitors (ICIs) through a network meta‐analysis. Methods: Databases were searched systematically to identify appropriate articles, in which randomized trials with incurable squamous NSCLC were described. Suitable studies were manually checked by two reviewers. A random model network meta‐analysis was conducted, in which the primary outcome was the overall survival rate. Results: We identified 48 studies, which included 16 391 patients. When a platinum + third‐generation cytotoxic agent regimen (platinum regimen) was a reference, the platinum regimen + pembrolizumab (Pemb) yielded the best results in regard to the overall survival rate when compared with chemotherapy (hazard ratio [HR] = 0.57, 95% confidence interval [CI] = 0.36–0.90, p = 0.016) followed by the platinum regimen + nivolumab (Niv) + ipilimumab (Ipi) (HR = 0.61, 95% CI = 0.44–0.84, p = 0.003). However, the efficacy of ICI monotherapy was not statistically different from that of the platinum regimen. Conclusions: The combination therapies, which were the platinum regimen + Pemb and the platinum regimen + Niv + Ipi, rather than ICI monotherapy were effective first‐line agents for treating squamous NSCLC with low PD‐L1 levels. [ABSTRACT FROM AUTHOR]

Background: Inflammation‐nutritional markers of peripheral blood are easily assessed and can predict survival. The aim of this study was to investigate the association between inflammation‐nutritional parameters and survival of anti‐programmed death‐1 (PD‐1) therapy in non‐small‐cell lung cancer (NSCLC) patients. Methods: We performed a retrospective study from March 2017 to April 2020 in advanced NSCLC patients treated with PD‐1 inhibitors. Univariable and multivariable analyses were conducted to evaluate the relationship between peripheral blood parameters (absolute lymphocyte count [ALC], absolute neutrophil count [ANC], absolute monocyte count [AMC], absolute eosinocyte count [AEC], lactic dehydrogenase [LDH], plasma‐albumin [ALB], neutrophil/lymphocyte ratio [NLR], and platelet/lymphocyte ratio [PLR]) measured before therapy initiation and prognosis. Results: Among 184 evaluable patients, 134 (72.8%) were male and the median age was 58 years (range 33–87) with 31 (16.8%) ≥70 years. An elevated ANC (≥7500/ul), NLR (≥5), and PLR (≥200) was significantly associated with worse objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS), while increased ALC (≥1000/ul) and ALB (≥3.5 g/dl) could significantly improve survival in terms of ORR, PFS, and OS. In multivariate analyses, higher AEC (≥150/ul) and AMC (≥650/ul) could significantly decrease the risk of death (hazard ratio [HR] 0.363, 95% confidence interval [CI] 0.141–0.931, p = 0.035; HR 0.370, 95% CI 0.203–0.675, p = 0.001). A higher NLR and PLR, and lower ALB were independent predictors of poor prognosis for OS (HR 1.964, 95% CI 1.027–3.755, p = 0.041; HR 4.255, 95% CI 2.364–7.658, p = 0.000; HR 1.962, 95% CI 1.213–3.174, p = 0.006, respectively). Conclusion: Our research illustrated that pretreatment AEC, AMC, ALB, NLR, and PLR are independent predictors for survival in advanced NSCLC patients treated with PD‐1 inhibitors. [ABSTRACT FROM AUTHOR]

Objective: Currently, several immune checkpoint inhibitors (ICIs) treatment for advanced non‐small‐cell lung cancer (NSCLC) have been investigated; their overall efficacy and safety remain unclear. Methods: We searched electronic databases such as PubMed, EMBASE, and the Cochrane library. The randomized controlled trials (RCTs) that compared ICIs with or without chemotherapy to chemotherapy in advanced NSCLC. We collected and compaired thier parameters, including overall survival (OS), progression‐free survival (PFS), objective response rate (ORR), and treatment‐related adverse events (TRAEs) of grade ≥3. Results: A total of 15 RCTs involving 8869 patients with NSCLC were included. Pembrolizumab plus platinum‐based chemotherapy had higher OS and PFS than platinum‐based chemotherapy (hazard ratio [HR] 0.55, 95% CI 0.46–0.67; HR 0.54, 95% CI 0.41–0.70, respectively). Pembrolizumab plus platinum‐based chemotherapy had higher ranked ORR than platinum‐based chemotherapy (odds ratio [OR] 2.92, 95% CI 1.99–4.22). In terms of OS, atezolizumab, pembrolizumab plus platinum‐based chemotherapy, and nivolumab plus ipilimumab ranked as the best treatments for patients with programmed death‐ligand 1 (PD‐L1) expression levels of ≥50%, 1–49%, and <1%, respectively. In terms of PFS, pembrolizumab plus platinum‐based chemotherapy ranked as the best treatment for patients with any PD‐L1 expression levels. However, ipilimumab plus platinum‐based chemotherapy, nivolumab plus platinum‐based chemotherapy, and atezolizumab plus platinum‐based chemotherapy have higher TRAEs of grade ≥3 than platinum‐based chemotherapy. Conclusions: Pembrolizumab plus platinum‐based chemotherapy prevailed in rank in OS, PFS, and ORR benefit. The TRAEs of pembrolizumab plus platinum‐based chemotherapy were more than ICI monotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The risk of cancer treatment‐related acute exacerbation (AE) in patients with lung cancer and mild interstitial lung disease (ILD) on imaging, classified as indeterminate for usual interstitial pneumonia (UIP), has not previously been clarified. Methods: We retrospectively reviewed the clinical records of 27 patients with lung cancer and ILD who were diagnosed and treated from April 2016 to March 2021. Results: Among the 27 patients, 21 were classified as indeterminate for UIP and six as UIP/probable UIP; furthermore, 10 (46.6%) and three (50%) patients from each group, respectively, developed treatment‐related AEs. No significant difference was observed regarding the incidence of AEs between the two groups. However, significantly more patients in the AE group received immune checkpoint inhibitors (ICIs) compared to the non‐AE group (p = 0.021). Multivariate analysis revealed that the use of ICIs was a significant independent risk factor for treatment‐related AEs. Conclusions: Lung cancer patients with mild ILD suggestive of indeterminate for UIP and UIP patterns are at an increased risk for treatment‐related AEs. Furthermore, ICI use is an independent risk factor for AEs in patients with lung cancer complicated by ILD, and ICIs should be used with great caution. [ABSTRACT FROM AUTHOR]

Objectives: Various drug‐sensitivity markers have been reported to be associated with tumor progression and chemotherapy resistance. Detailed expression profiles of sensitivity markers for cytotoxic chemotherapy in pulmonary large cell neuroendocrine carcinoma (LCNEC) remain unclear. Herein, we aimed to clarify the correlation between the expression of drug‐sensitivity markers and clinicopathological features, prognostic impact, and status of tumor immunity in patients with LCNEC. Methods: We retrospectively analyzed the correlation between clinicopathological features and the expression of drug‐sensitivity‐related markers, including vascular endothelial growth factor 2 (VEGFR2), thymidylate synthase (TS), tubulin beta 3 class III (TUBB3), topoisomerase I (Topo‐I), and Topo‐II in 92 surgically resected LCNEC samples. Furthermore, we examined the prognostic significance of expression of these and their correlation with the immune cell status. Results: Overall, high expression of TS, TUBB3, VEGFR2, Topo‐I, and Topo‐II was detected in 50 (54%), 31 (34%), 23 (25%), 65 (71%), and 36 (39%) samples, respectively. Univariate and multivariate analyses revealed that advanced pathological T and N factors, positive lymphatic permeation, and Topo‐II expression were independent unfavorable prognosticators for recurrence‐free survival, and advanced pathological T and N factors, Topo‐II positive expression, and TS positive expression were independent unfavorable prognosticators for overall survival. In terms of correlation with immune cell status, higher expression of VEGFR2 was closely linked to negative PD‐L1 expression. Conclusions: These findings suggest that elevated Topo‐II and TS expression may contribute to poor outcomes through protumoral biology in patients with LCNEC, and elevated VEGFR2 expression might negatively impact tumor immune reactions in LCNEC. [ABSTRACT FROM AUTHOR]