Supplementary Figure 1. The TMB distribution of all primary and metastases samples. The total TMB (defined as the number of nonsynonymous mutations) in each group.Supplementary Table 1. The basic clinical information of all patients.

The TMB distribution of all primary and metastases samples. The total TMB (defined as the number of nonsynonymous mutations) in each group.

Dysregulated ARID1A expression is frequently detected in lung adenocarcinoma (LUAD) and mediates significant changes in cancer behaviors and a poor prognosis. ARID1A deficiency in LUAD enhances proliferation and metastasis, which could be induced by activation of the Akt signaling pathway. However, no further exploration of the mechanisms has been performed. Lentivirus was used for the establishment of the ARID1A knockdown (ARID1A-KD) cell line. MTS and migration/invasion assays were used to examine changes in cell behaviors. RNA-seq and proteomics methods were applied. ARID1A expression in tissue samples was determined by IHC. R software was used to construct a nomogram. ARID1A KD significantly promoted the cell cycle and accelerated cell division. In addition, ARID1A KD increased the phosphorylation level of a series of oncogenic proteins, such as EGFR, ErbB2 and RAF1, activated the corresponding pathways and resulted in disease progression. In addition, the bypass activation of the ErbB pathway, the activation of the VEGF pathway and the expression level changes in epithelial–mesenchymal transformation biomarkers induced by ARID1A KD contributed to the insensitivity to EGFR-TKIs. The relationship between ARID1A and the sensitivity to EGFR-TKIs was also determined using tissue samples from LUAD patients. Loss of ARID1A expression influences the cell cycle, accelerates cell division, and promotes metastasis. EGFR-mutant LUAD patients with low ARID1A expression had poor overall survival. In addition, low ARID1A expression was associated with a poor prognosis in EGFR-mutant LUAD patients who received first-generation EGFR-TKI treatment.

Human albumin is essential for indicating the body's overall health. Accurately predicting plasma albumin levels and determining appropriate doses are urgent clinical challenges, particularly in critically ill patients, to maintain optimal blood levels. However, human albumin prediction is non-trivial that has to leverage the dynamics of biochemical markers as well as the experience of treating patients. Moreover, the problem of distribution shift is often encountered in real clinical data, which may lead to a decline in the model prediction performance and reduce the reliability of the model's application. In this paper, we propose a framework named Out-of-Distribution Generalized Dynamic Graph Neural Network for Human Albumin Prediction (DyG-HAP), which is able to provide accurate albumin predictions for Intensity Care Unit (ICU) patients during hospitalization. We first model human albumin prediction as a dynamic graph regression problem to model the dynamics and patient relationship. Then, we propose a disentangled dynamic graph attention mechanism to capture and disentangle the patterns whose relationship to labels under distribution shifts is invariant and variant respectively. Last, we propose an invariant dynamic graph regression method to encourage the model to rely on invariant patterns to make predictions. Moreover, we propose a dataset named Albumin level testing and nutritional dosing data for Intensive Care (ANIC) for evaluation. Extensive experiments demonstrate the superiority of our method compared to several baseline methods in human albumin prediction.

The basic clinical information of all patients.

AbstractBrain metastases (BM) is one of the main reasons for lung cancer-related deaths but lack prediction methods. Many patients with BMs do not benefit from immunotherapy. A comprehensive genomic analysis of matched primary tumors (PT) and their BM lesions may provide new insight into the evolutionary and immune characteristics. To describe evolutionary features and immune characteristic differences, we analyzed whole-exome sequencing data for 28 paired PT and BM samples from 14 patients with non-small cell lung cancer. In addition, we used another 26 matched PT and BM samples as a validation cohort. We found that total mutational signatures were relatively consistent between paired primary and brain metastatic tumors. Nevertheless, the shared mutations of the two lesions were fewer than the mutations present in each of the lesions alone. In the process of BM, driver genes undergo evolutionary branches. Typical driver genes, including EGFR and TP53, appear relatively conserved throughout evolution; however, specific signals are enriched in BM lesions. We found several main characteristics of lung cancer BMs that were different from primary lung cancer, such as genomic instability, novel driver genes, tumor mutation burden, and BM lesion private neoantigens. In addition, the estimated timing of dissemination showed that BMs might occur early in lung cancer.Implications:Mechanistic insight from this study provides new insight into the biology of the metastatic brain process and a new beneficial approach for preventing and treating lung cancer BMs.

背景与目的 小细胞肺癌(small cell lung cancer,SCLC)是一种高度侵袭性的恶性肿瘤,易于早期复发和转移.临床前研究发现,发状分裂相关增强子1(hairy and enhancer of split 1,Hes1)作为碱性螺旋–环–螺旋(basic helix-loop-helix,BHLH)家族的转录抑制因子,不仅可阻止SCLC肿瘤细胞的增殖和迁移,还可抑制神经内分泌转录因子ASCL1的功能.然而,Hes1蛋白表达在SCLC预后中的意义仍不清楚.本研究旨在分析Hes1蛋白在SCLC中的表达模式和预后意义.方法 回顾分析247例手术切除的单纯型SCLC样本,构建组织微阵列(tissue microarray,TMA),采用全自动罗氏免疫组织化学仪检测Hes1蛋白的表达水平.通过Fisher精确检验分析蛋白表达与患者年龄、淋巴结转移、主要细胞形态和肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TILs)等临床病理特征的相关性,并通过Kaplan-Meier曲线及COX回归模型检验其对生存的影响.结果 在247例手术切除的单纯型SCLC患者中,男性有175(70.8％)例;65岁及以下患者有202(81.8％)例;根据美国癌症联合会(american joint committee on cancer,AJCC)癌症分期系统第7版分期,I期有78(31.6％)例,II期有68(27.5％)例,III期有101(40.9％)例.Hes1蛋白表达定位于肿瘤细胞核,Hes1高表达患者占52.2％(129/247),与较低年龄(≤65岁,P=0.014)、无淋巴结转移(P=0.003)、圆形细胞为主的病理形态(P=0.002)及TILs≤30％(P=0.010)呈正相关.Kaplan-Meier分析显示Hes1蛋白高表达患者无病生存期[风险比(hazard ratio,HR)=1.477;95％置信区间(confidence interval,CI):1.025–2.129;P=0.036)显著延长,总生存期(HR=1.181;95％CI:0.778–1.792;P=0.435)也有延长趋势.结论 在局限期单纯型小细胞肺癌中,Hes1蛋白高表达与年龄、淋巴结转移、主要细胞形态和TILs相关,并可能作为SCLC患者预后的潜在生物标志物.

EGFR mutations in non-small cell lung cancer (NSCLC) are associated with a poor response to immune checkpoint inhibitors (ICIs), and only 20

e21100 Background: Epidermal growth factor receptor ( EGFR)-mutated lung adenocarcinoma (LUAD) could benefit from EGFR-TKIs (tyrosine kinase inhibitors) treatment, but drug resistance seems to be inevitable. Small cell lung cancer (SCLC) transformation counts for 3-15% of the resistance mechanism, and was amply studied at genomics level but rarely at transcriptional level. Methods: The expression of 730 mRNAs were investigated by Nanostring nCounter Pancancer Pathway Panel on 72 formalin-fixed and paraffin-embedded (FFPE) samples from 27 EGFR-mutated LUAD patients with SCLC transformation after EGFR-TKIs therapy (19 LUAD samples before transformation, LUAD-BT; 21 SCLC samples after transformation, SCLC-AT), 12 EGFR-mutated LUAD patients never SCLC transformed after EGFR-TKIs therapy (12 samples, LUAD-NT) and 20 stage IIĨIV primary SCLC patients (20 samples, SCLC-P). For patients enrolled in LUAD-NT group, tissue biopsies were performed at least twice, which were all diagnosed as pure LUAD, and the overall survival (OS) since first line therapy was longer than the median transformation time (mTt) of SCLC-transformed patients in our study. mRNA expression patterns and biological pathway scores were compared among four groups. The candidate predictive biomarkers from mRNA expression pattern analysis were validated by area under curve (AUC) of receiver operating characteristic curve (ROC) and the logarithm of fold change to the base 2 (log2FC). Results: On the last day of follow up (1st February 2022), the shortest OS of LUAD-NT patients was 28.4 months, whereas the mTt was 27.5 months. Among four groups, LUAD-NT and LUAD-BT showed the most similar mRNA expression patterns, and SCLC-P were significantly different from the others. 8.6% (63/730) mRNA showed significant downregulation after SCLC transformation, while 3.6% (26/730) showed significant upregulation ( p value adjusted by Benjamin & Hochberg’s method < 0.05, SCLC-AT vs LUAD-BT). In pathway enrichment analysis, the score of RAS and TGF-β pathways were significantly lower in SCLC-AT than LUAD-BT. Compared with SCLC-P, 6 upregulated mRNAs in SCLC-AT were observed (log2FC > 2, AUC > 0.85 and each raw p value < 0.05), including AR, COL5A1, GHR, HMGA2, IGFBP3 and IL6R, which could be further validated as diagnostic markers in a larger cohort. Moreover, compared with LUAD-NT, 4 mRNAs ( BRIP1, CCNE2, CDKN2A and MCM2) were found to be significantly upregulated (log2FC > 1, AUC > 0.75 and each raw p value < 0.05) in LUAD-BT, indicating the predictive value of SCLC transformation. Conclusions: The transformation of LUAD to SCLC may be promoted by transcriptional events. We also described some significantly different expressed mRNAs that could candidate as predictive or diagnostic markers for SCLC transformation, which should be further validated in a larger cohort.

Objective: Continuation of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has shown potential in prolonging survival in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutation who had gradual progression at initial targeting therapy. However, it remains unknown whether the combination of bevacizumab and continuation of EGFR-TKIs would benefit this subpopulation. This study retrospectively explored the effect of bevacizumab combined with EGFR-TKIs in NSCLC beyond gradual progression in the real-world setting. Methods: The records of 48 patients were reviewed who received bevacizumab and continuation of EGFR-TKIs beyond gradual progression at initial targeting therapy. The response to the treatment and post progression survival (PPS) were reviewed and analyzed. Results: The median PPS was 11.4 months (95% CI 7.368???15.492) for all patients included at the median follow-up time of 17.3 months. The objective response rate (ORR) was 8.3%, and the disease control rate (DCR) was 86.1% (with 3 partial response and 28 stable disease) in 36 patients who were evaluable for response with at least one measurable lesion. Univariate Cox analysis showed that age <60, male sex, and EGFR exon19 deletion mutation were associated with longer PPS (P<0.05). Patients harboring EGFR exon19 deletion mutation had significantly longer PPS than those with EGFR exon21 L858R mutation, with an mPPS of 15.5 months and 5.7 months, respectively (HR=0.251, 95% CI 0.112???0.561, P=0.019). Multivariate Cox analysis indicated that age <60 and EGFR exon19 deletion mutation were associated with longer PPS (P<0.05). Conclusion: Continuation of EGFR-TKI with the combination of bevacizumab is a reasonable strategy in NSCLC patients beyond gradual progression in previous EGFR-TKI treatment. Younger patients with EGFR exon19 deletion mutation may benefit more from the combination

Abstract 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‐foot‐skin 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.

Purpose After progression to immunotherapy, the standard of care for non-small cell lung cancer (NSCLC) was limited. Administration of the same or different immune checkpoint inhibitors (i.e., ICI rechallenge) may serve as a novel option. The present study aimed to evaluate the efficacy of ICI rechallenge for NSCLC and explore prognostic factors. Methods In this retrospective cohort study, data of advanced or metastatic NSCLC patients rechallenged with ICI at the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College between December 2018 and June 2021 were retrieved. Progression-free, overall survivals (PFS; OS), etc. were calculated. Subgroup analyses were conducted according to baseline characteristics, prior treatment results, etc. for prognostic factor exploration using the Cox model. Results Forty patients were included. Median age was 59 years. Thirty-one (78%) were male. Twenty-seven (68%) were smokers. Adenocarcinoma (28 [70%]) was the major histological subtype. Median PFS of patients receiving initial ICI was 5.7 months. The most common rechallenge regimens were ICI plus chemotherapy and/or angiogenesis inhibitor (93%). Seventeen (43%) were rechallenged with another ICI. Median PFS for ICI rechallenge was 6.8 months (95% CI 5.8–7.8). OS was immature. Tendencies for longer PFS were observed in nonsmoker or patients with adenocarcinoma, response of stable/progressive disease in initial immunotherapy, or whose treatment lines prior to ICI rechallenge were one/two. However, all results of prognostic factors were nonsignificant. Conclusion ICI rechallenge may be an option for NSCLC after progress to immunotherapy. Further studies to confirm the efficacy and investigate prognostic factors are warranted.

Objective: Osimertinib is the standard targeted strategy for lung adenocarcinoma patients harboring epidermal growth factor receptor (EGFR)-activating mutation who have achieved acquired mutation T790M beyond progression of first-line EGFR-tyrosine kinase inhibitor (TKI). In a real world setting, the efficacy for osimertinib as a subsequent treatment beyond first-generation EGFR-TKI progression under complex circumstances such as different T790M mutation status is still worth exploring. Methods: Records of 84 lung adenocarcinoma patients with an EGFR sensitive mutation who received first-generation EGFR-TKI as first-line therapy and sequenced by osimertinib after progression were retrospectively reviewed in this study. The assessment of efficacy of subsequent osimertinib treatment was evaluated by progression free survival (PFS), objective response rate (ORR), complete response (CR), partial response (PR), disease control rate (DCR) and stable disease (SD) rates. Relationship between PFS and clinicopathological characteristics was analyzed using univariate analysis. Results: Until the median follow-up time of 23.7 months (IQR 10.8-29.0 months), the median PFS (mPFS) of subsequent osimertinib was 17.0 months (HR 1.744, 95% CI, 13.547-20.382). Among 60 patients who had at least one measurable lesion, 35.0% of patients (21/60) had PR to osimertinib, and 63.3% patients (38/60) had SD during osimertinib treatment. The ORR was 35.0%, and the DCR was 98.3%. Patients with acquired T790M mutation which was detected by NGS or ddPCR assay had an mPFS of 17.0 months (HR = 1.032, 95% CI, 14.941-18.987), while the remaining 17 patients who had negative or unknown T790M mutation status had an mPFS of 23.5 months (HR = 9.404, 95% CI, 5.068-41.932). No significant difference was observed in those with and without T790M mutation (P = 0.704). Conclusion: Osimertinib may serve as an alternative subsequent choice after progression of first-generation EGFR-TKI in EGFR-mutated lung adenocarcinoma and may represent a potential treatment option for selected T790M-negative patients.

1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2Department of Medical Oncology, Beijing Chaoyang Sanhuan Hospital, Beijing, 100021, People’s Republic of China; 3Department of Medical Oncology, Cancer Hospital of Huanxing, Beijing, 100021, People’s Republic of China

ARID1A is a key component of the SWI/SNF chromatin remodeling complexes which is important for the maintaining of biological processes of cells. Recent studies had uncovered the potential role of ARID1A alterations or expression loss in the therapeutic sensitivity of cancers, but the studies in this field requires to be further summarized and discussed. Therefore, we proposed a series of mechanisms related to the resistance to EGFR-TKIs induced by ARID1A alterations or expression loss and the potential therapeutic strategies to overcome the resistance based on published studies. It suggested that ARID1A alterations or expression loss might be the regulators in PI3K/Akt, JAK/STAT and NF-κB signaling pathways which are strongly associated with the resistance to EGFR-TKIs in NSCLC patients harboring sensitive EGFR mutations. Besides, ARID1A alterations or expression loss could lead to the resistance to EGFR-TKIs via a variety of processes during the tumorigenesis and development of cancers, including epithelial to mesenchymal transition, angiogenesis and the inhibition of apoptosis. Based on the potential mechanisms related to ARID1A, we summarized that the small molecular inhibitors targeting ARID1A or PI3K/Akt pathway, the anti-angiogenic therapy and immune checkpoint inhibitors could be used for the supplementary treatment for EGFR-TKIs among NSCLC patients harboring the concomitant alterations of sensitive EGFR mutations and ARID1A.

Abstract Objective Small cell lung cancer (SCLC) is one of the most aggressive malignancies characterized by neuroendocrine (NE) differentiation. The Delta‐like protein 3 (DLL3), as a direct downstream target of ASCL1, is involved in NE differentiation and carcinogenesis of SCLC. This study aims to investigate the relationship between ASCL1 and DLL3 expressions and their clinicopathological implications in SCLC. Methods A total of 247 surgically resected pure SCLC samples with limited clinical stage and follow‐up data were retrieved in this retrospective study. ASCL1 and DLL3 protein expression was detected by immunohistochemistry staining. The correlations between ASCL1 and DLL3 expressions, as well as their clinicopathological features, were analyzed by χ2 tests. Disease‐free survival (DFS) and overall survival (OS) in SCLC patients with ASCL1/DLL3 low and high expressions were compared by the Kaplan‐Meier method and log‐rank tests. Results ASCL1 high expression was detected in 105 (42.5%) patients. Its expression was positively correlated with the clinical stage (p = 0.02) and nerve invasion (p = 0.03). DLL3 high expression was observed in 188 (72.8%) patients and was correlated with vascular invasion (p = 0.04). ASCL1 expression was positively associated with DLL3 expression (p = 0.03). In addition, DLL3 expression has a strong correlation with the expression of thyroid transcription factor‐1 (TTF1) and conventional NE markers. Conclusion ASCL1 and DLL3 were highly expressed in SCLC tumor samples, and a positive correlation between these two markers was observed. Co‐analysis of ASCL1 and DLL3 may identify a distinct SCLC subgroup benefit from targeted therapy. Therefore, ASCL1 and DLL3 could be potential biomarkers served for the selection of related patients.

Background The purpose of this study was to compare the efficacy of osimertinib (OSI) versus afatinib (AFA) in patients with T790M-positive, non-small-cell lung cancer (NSCLC) and multiple central nervous system (CNS) metastases after failure of initial epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. Methods Consecutive patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment were retrospectively identified from our medical institution during 2016–2018 and underwent either oral 80 daily OSI or oral 40 daily AFA every 3 weeks for up to 6 cycles, until disease progression, intolerable adverse events (AEs), or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS). Results The cohort consisted of 124 patients (OSI: n = 60, mean age = 64.24 years [SD: 12.33]; AFA: n = 64, mean age = 64.13 years [SD: 13.72]). After a median follow-up of 24 months (range, 3 to 28), a significant improvement in OS was detected (hazard ratio [HR] 0.59, 95% confidence interval [CI], 0.39–0.91; p = 0.0160; median, 13.7 months [95% CI, 11.1–14.8] for OSI vs 9.6 months [95% CI, 8.4–10.2] for AFA). The median duration of PFS was significantly longer with OSI than with AFA (HR 0.62; 95% CI, 0.41–0.91; p = 0.014; median, 4.5 months [95% CI, 3.5–5.7] vs 3.9 months [95% CI, 3.1–4.8]). The proportion of grade 3 or higher adverse events (AEs) was lower with OSI (22.4%) than with AFA (39.4%). Conclusions In patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment, OSI may be associated with significantly improved survival benefit compared with AFA, with a controllable tolerability profile.

The objective of this study was to analyze the clinical and pathological characteristics of patients with small cell lung cancer (SCLC) after curative surgery and to explore prognostic factors for disease-free survival (DFS) and overall survival (OS). Clinical data of 247 patients were collected, and clinicopathological features were retrieved, including gender, age, smoking history, tumor location, and distant metastasis. Histopathological features were also reviewed by three pathologists, including primary tumor (T), lymph node metastasis (N), pleural invasion, bronchial invasion, nerve invasion, spread through air spaces (STAS), tumor thrombosis, major cell shape (round Vs. spindle), tumor necrosis, stromal fibrosis, and tumor-infiltrating lymphocytes (TILs). Immunohistochemical staining of neuroendocrine markers (CD56, synapsin, chromogranin A) was also reviewed. All patients were followed up for recurrence, distant metastasis, and survival. Kaplan-Meier curves and log-rank tests were applied for survival analysis. The median DFS was 98 months, and the 1-year, 3-year, and 5-year DFS rates were 70.9%, 54.4%, and 52.2%, respectively. The median OS was not reached, and the 1-year, 3-year, and 5-year survival rates were 94.2%, 72.3%, and 65.4%, respectively. Univariate analysis revealed clinicopathological features with DFS (gender, smoking history, primary tumor, regional lymph node metastasis, major cell shape, and TILs) and OS (age, primary tumor, regional lymph node metastasis, distant metastasis, nerve invasion, major cell shape, and TILs). Multivariate analysis revealed DFS-related factors (smoking history, regional lymph node metastasis and major cell shape) and OS-related factors (age, primary tumor, distant metastasis in the brain, liver, bone, nerve invasion, and TILs). Age more than 65 years, smoking, advanced stage (T and N), distant metastasis, nerve invasion, major cell shape as spindle and TILs >30% were negatively correlated with survival. Neuroendocrine immunostaining markers showed no correlation with survival. Of interest, spindle cell type and TILs >30% are revealed as independent negative prognostic factors, and further molecular mechanisms need to be explored.

Background Histologically, SCLC are classified as pure (P‐SCLC) and combined subtypes (C‐SCLC). Currently, few studies compare the clinicopathological characteristics and explore the treatment strategies applied to them. Methods Between July 2005 and April 2016, the clinical records of 297 postoperative patients with pathologically confirmed SCLC were retrospectively analyzed. Kaplan‐Meier method and Cox regression model were separately used for stratified univariate and multivariate survival analysis. Results A total of 46 cases (15.5%) of C‐SCLCs and 251 cases (85.5%) of pure SCLCs (P‐SCLCs) were included in this study. The average age of C‐SCLCs was a little higher than that of P‐SCLCs (59.65 ± 8.72 vs. 56.56 ± 10.12; P = 0.053). More patients had a history of smoking in C‐SCLC (78.3% vs. 63.3%; P = 0.074). The five‐year overall survival (OS) rate for P‐SCLCs and C‐SCLCs was 65.1% and 56.7%, respectively ( P = 0.683). For P‐SCLC, stage and an intervention of prophylactic cranial irradiation (PCI) were independent factors that affected OS. In C‐SCLCs cases, performing sublobectomy was an independent risk factor for poor prognosis. Conclusions We identified no significant difference in clinical characteristics and outcome between C‐SCLCs and P‐SCLCs. However, the factors affecting the prognosis of the two subtypes were slightly inconsistent. For C‐SCLCs, the extent of resection had a greater impact on survival, and lobectomy combined with systemic lymph node dissection should therefore be performed as extensively as possible. In addition, PCI was beneficial in improving the SCLC OS rate. Key points This study demonstrated the prognosis of C‐SCLCs did not significantly differ from that of P‐SCLCs, but was more susceptible to the extent of resection. Patients with C‐SCLC who underwent limited resection had a significantly increased risk of shorter OS. This study highlighted the importance of performing lobectomy for resectable C‐SCLC patients. This study also proved the benefit of PCI in improving the OS rate for both P‐SCLC and C‐SCLC patients.