Neoadjuvant immunochemotherapy—a promising strategy for primary pulmonary lymphoepithelioma-like carcinoma

Neoadjuvant immunochemotherapy—a promising strategy for primary pulmonary lymphoepithelioma-like carcinoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Neoadjuvant immunochemotherapy—a promising strategy for primary pulmonary lymphoepithelioma-like carcinoma Jiawei Chen, Lei Fan, Hongsheng Deng, Liang Li, Shuben Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4863107/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Dec, 2024 Read the published version in World Journal of Surgical Oncology → Version 1 posted 13 You are reading this latest preprint version Abstract Objective: Neoadjuvant immunochemotherapy becomes a promising choice for patients with locally advanced non-small cell cancer (NSCLC). However, whether neoadjuvant immunochemotherapy impacted the subsequent surgical or pathological outcomes of patients with pulmonary lymphoepithelioma-like carcinoma (PLELC) remains relatively unknown. This study aimed to evaluate the safety and efficacy of neoadjuvant immunochemotherapy in PLELC patients. Methods: A retrospective study was conducted on patients who received neoadjuvant immunochemotherapy in combination with chemotherapy followed by surgery between 2019 and 2022. The clinical records of the patients were analyzed. Results: Out of the 31 patients with PLELC who underwent neoadjuvant therapy followed by surgery, 18 patients (58.0%) experienced downstaging of the tumor. Nineteen patients (61.5%) achieved a partial response, 2 patients (6.4%) achieved a complete response, and 2 (6.4%) had progressive disease. Pathological evaluation of resected specimens revealed that 10 (32.3%) patients achieved major pathological response (MPR), including 2 (6.4%) who achieved complete response (CR). The mean disease-free survival (DFS) was 17.4 months, which was not significantly different from the value in LUSQ patients (15.1 months). Conclusion: Neoadjuvant immunochemotherapy is a safe and effective approach to reduce the extent of tumor, render unresectable to resectable, and offer an opportunity to receive modified surgery, which may be a promising strategy for patients with PLELC. neoadjuvant immunochemotherapy pulmonary lymphoepithelioma-like carcinoma surgery Figures Figure 1 Figure 2 Introduction Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and distinct subtype of lung cancer, accounting for less than 1% of all lung neoplasms 1 . First reported by Begin and colleagues in 1987, LELC was found to be an epithelial neoplasm associated with Epstein‒Barr virus (EBV) infection 2 . In 2015, the World Health Organization (WHO) classified PLELC as a non-small-cell lung cancer (NSCLC) 3 , and in 2021, it was reclassified as a subtype of lung squamous cell carcinom (LUSQ) according to the latest WHO Classification of lung tumors 4 . Currently, there is no standard treatment for PLELC, surgical resection still the cornerstone therapy. However, most patients with PLELC present with non-specific symptoms, leading to diagnostic delay and diagnosing at an unresectable stage. Immune checkpoint inhibitors have been established as the first-line therapy for locally advanced NSCLC. Previous trials 5–7 have demonstrated the benefits of neoadjuvant immunotherapy, including reducing the extent of tumor, eliminating micrometastases and contributing to survival outcomes. Besides, the trial 5 have also shown that neoadjuvant immunochemotherapy leads to superior outcomes in NSCLC, particularly in LUSQ, which exhibits a better tumor response than other subtypes. Given the histologic and genetic similarity between pleomorphic carcinoma of the lung (PLELC) and LUSQ, it is plausible that programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors could be another promising therapeutic option against this rare tumor. Additionally, evidence suggests 8–9 that PLELC has a higher proportion of PD-L1 positive tumor cells than lung adenocarcinoma or squamous cell lung carcinoma, which may provides a possible justification for immunotherapy. Recent studies 10–12 also highlighted the potential benefits of immunotherapy in advanced PLELC, demonstrating a significant improvement in progression-free survival (PFS) outcomes. Notwithstanding, clinical trials of anti-PD-1/PD-L1 therapy in NSCLC have rarely enrolled patients with PLELC due to its rarity, which means that the potential for using neoadjuvant immunotherapy to make initially inoperable advanced PLELC operable and improve long-term survival remains relatively unknown. Herein, we aimed to evaluate the safety and efficacy of neoadjuvant immunochemotherapy in PLELC. In addition, the clinical outcomes of PLELC and LUSQ are compared to enhance our understanding of this uncommon malignancy. Method Between 2019 and 2021, data from patients with PLELC and LUSQ who received neoadjuvant immunotherapy followed by surgery were retrospectively retrieved. All patients underwent standard diagnosis and staging procedures. Computed tomography (CT) scans and 18F-fludeoxyglucose positron emission tomography/CT ( 18 F-FDG PET-CT) were routinely performed to evaluate primary tumors. For any suspicion of metastatic lymph nodes by chest CT or PET/CT, endobronchial ultrasound was subsequently performed for pathological confirmation of N stage in these cases. Metastatic disease was assessed with brain magnetic resonance imaging and positron emission tomography. Specimens for cytological and histological characterization were collected via bronchoscopy or subcutaneous needle biopsy before treatment. The preoperative and postoperative staging was evaluated in accordance with the 8th American Joint Committee on Cancer (AJCC) lung cancer manuals on the tumor–node–metastasis (TNM) staging system 13 . Responses were evaluated by specialists according to the Response Evaluation Criteria In Solid Tumors (RECIST) 14 . Patient characteristics were reported as frequencies and percentages for categorical variables and as medians and interquartile ranges for continuous variables. The Kaplan–Meier method was used to analyze disease-free survival (DFS), which was compared using the log-rank test. Statistical analysis was performed using SPSS version 25.0 (IBM Corp., New York, NY, USA). A P value less than 0.05 was considered statistically significant. Result Patient characteristics We analyzed patient data that met the eligibility criteria for receiving neoadjuvant immunotherapy followed by surgery. The study included 31 patients, predominantly female (n = 19, 61.3%), with a mean age of 56.8 years. All patients were at stage II-III, with 19 cases (64.5%) classified as N2 disease. The majority of patients (n = 28, 90.3%) underwent 2–4 cycles of preoperative immunochemotherapy. In all cases, surgery was performed, resulting in R0 resection. The mean tumor diameter prior to immunochemotherapy was 5.9 cm (range, 2.7 to 11.9 cm). Table 1 summarizes the detailed baseline characteristics of the patients. Table 1 Clinical demographics of patients who received neoadjuvant therapy followed by surgery Covariate n = 31 Age Mean (min, max) 56.8 (41,72) Sex female 19 (61.3%) male 12 (38.7%) RECIST1.1 Mean (min, max) 5.9 (2.7,11.9) Pre T 1 1 (3.4) 2 13 (44.8) 3 5 (16.1) 4 12 (35.7) Pre N 0 4 (12.9%) 1 8 (25.8%) 2 19 (64.5%) Pre stage 2a 1 (3.2%) 2b 3 (9.6%) 3a 16 (51.6%) 3b 11 (35.4%) Cycles 2 16 (51.6%) 3 8 (25.8%) 4 4 (12.9%) >4 3 (9.7%) Preoperative outcomes Of the 31 patients who underwent neoadjuvant immunochemotherapy followed by surgery, 26 (83.8%) underwent lobectomy, 4 (12.9%) underwent sleeve lobectomy, and 1 (3.2%) received lung autotransplantation. In total, 30 (96.8%) received video-assisted thoracic surgery (VATS). Due to dense adhesions and pulmonary artery hemorrhage, 2 case converted to thoracotomy. The mean operating time was 199.7 min (range, 105 to 595 min). The mean intraoperative bleeding volume was 44.8 mL (range, 10 to 200 mL). Patients had an average postoperative hospital stay of 5.5 days (range, 2 to 10 days). Seven patients (22.6%) experienced pneumonia. No serious postoperative complication was observed. The 90-day mortality was 0. (Table 2 ). Table 2 Surgical and pathological outcomes of patients who received neoadjuvant therapy followed by surgery Covariate n = 31 Post stage TxN0M0 2 (6.4%) 1b 1 (3.2%) 2a 1 (3.2%) 2b 7 (22.5%) 3a 19 (61.2%) 3b 1 (3.2%) Downstage No 13 (42.0%) Yes 18 (58.0%) ORR No 10 (27.6%) Yes 21 (72.4%) Radiologic response Unknown 1 (3.2%) CR 2 (6.4%) PD 2 (6.4%) PR 19 (61.5%) SD 7 (22.5%) Type of Surgery Lobectomy 26 (83.8%) Sleeve lobectomy 4 (12.9%) Lung autotransplantation 1 (3.2%) Days (d) Mean (min, max) 5.5 ( 2 , 10 ) Surgery time (min) Mean (min, max) 199.7 (105,595) Blood loss (ml) Mean ((min, max) 44.8 (10,200) Volume of drainage (ml) Mean (min, max) 646.1 (220,1200) DFS (months) Mean (min, max) 17.4 (5,40) Pathological valuation MPR 10 (32.3%) pCR 2 (6.4%) Treatment response Radiographic response evaluation based on the RECIST 14 standard was available for all patients. After neoadjuvant treatment, 2 (6.4%) achieved complete response (CR), 19 (61.5%) patients achieved partial response (PR), and 2 (6.4%) had progressed disease (PD), corresponding to an overall response rate (ORR) of 72.4% (n = 21). One case was not feasible to evaluate the response of the target lesions radiologically due to pneumonia and dense lung consolidation. Seven patients achieved stable disease (SD), which resulted in a disease control rate (DCR) of 90.3% (n = 28). (Table 2 ) Postoperative pathological evaluation revealed 10 (32.3%) patients achieved major pathological response (MPR), including 2 (6.4%) achieved pathological complete response (pCR). Lymph node positive was confirmed in 11 (35.5%) patients. (Table 2 ) The media follow-up time was 16 months (range, 3m to 40m). All patients received adjuvant treatment. Thirty patients remaining alive during the follow-up period. Tumor-related causes of death were no observed, only one patients died for Covid-19. The maen disease-free survival (DFS) was 17.4 months. And the 1-year disease-free survival (DFS) rate was 96.8%. Recurrence was documented in 4 patients. (Fig. 2 ) The multivariable regression analysis, which adjusted for confounders such as tumor size and stage, showed that tumor type significantly impacted pathological outcomes after neoadjuvant immunochemotherapy. The pathological regression was better in LUSQ than PLELC, with a slightly higher proportion of LUSQ patients achieving pCR and MPR (p < 0.01). However, there was no difference in DFS between LUSQ and PLELC (p = 0.54) (Table 3 ). Table 3 Multivariable regression analysis was performed to adjust for confounders, including tumor size and stage, between PLELC and LUSQ Covariate LUSQ (n = 31) PLELC (n = 31) p value Radiologic response 0.11 Unknown 0 (0) 1 (3%) CR 0 (0) 2 (6%) PD 0 (0) 2 (6%) PR 17 (55%) 19 (61%) SD 14 (45%) 7 (23%) Pathological valuation < 0.01 Unknown 12 (39%) 21 (68%) MPR 7 (23%) 8 (26%) pCR 12 (39%) 2 (6%) DFS 0.54 Mean (min, max) 15.1 (1,29) 17.4 (5,40) Discussion PLELC is a rare malignancy with few recognized treatment options that have been demonstrated to improve patient outcomes. Surgical resection is generally recommended for PLELC. However, due to the growth of the tumor, systemic chemotherapy and radiotherapy remain the current focus of treatment for patients with locally advanced PLELC 15 . The function of neoadjuvant immunochemotherapy in treating PLELC remains uncertain. This retrospective study aimed to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with PLELC . Checkmate-816 trial 5 confirmed that neoadjuvant immunochemotherapy contributed to NSCLC both pathological and survival outcomes with considerable toxic side effects. Besides, the trial showed that patients with locally advanced stages might also experience benefit from neoadjuvant immunochemotherapy. Deng and coworker 16 indicated that the addition of radical surgery after immunochemotherapy in initially unresectable stage IIIB NSCLC was favorably associated with longer DFS/PFS (27.5 months vs. 16.7 months) compared to those without. In our study, totally 19 patients achieved partial response according to RECIST, including 9 with IIIB, which were rendered unresectable to resectable. Besides, neoadjuvant immunochemotherapy offers an opportunity for patients with compromised lung function to receive modified surgical interventions. No severe adverse events occurred during treatment. During the follow-up period, the maen disease-free survival (DFS) was 17.4 months. And the 1-year disease-free survival (DFS) rate was 96.8%. Only 4 patients experience recurrence, including 2 distant and 2 local recurrence. ( Fig. 1 ) The safety and feasibility of neoadjuvant immunochemotherapy followed by surgery have been well confirmed 17–19 . In our study, VATS was attempted in 30 patients, only 2 patients converted to thoracotomy. Five patients safely underwent modified surgical procedure to avoid pneumonectomy, including lung autotransplantation (n = 1) and sleeve lobectomy (n = 4). Seven patients (22.6%) experienced immune-related pneumonitis. No surgery-related complication was observed. Previous studies 5, 9 showed that several factor may associated with better outcomes to neoadjuvant immunochemotherapy, including type of NSCLC and PD-L1 expression. Patients with LUSQ and/or high PD-L1 expression may achieved better response to immunochemotherapy. Jiang and colleges 8 showed that PLELC has a higher expression of PD-L1 than other NSCLC subtypes. Furthermore, the association of PLELC with EBV infection may contribute to its sensitivity to immunotherapy 2 , which may render PLELC responsive to neoadjuvant immunochemotherapy. In our study, 32.3% (n = 10) of patients experiencing major pathologic response (MPR), including 6.4% with pathologic complete response (pCR). The mean DFS was 17.4 months. Although, LUSQ demonstrated higher response rate than PLELC (p < 0.01), no statistically significant difference was detected between these cancers in terms of DFS (p = 0.54). These findings provide support for the idea that neoadjuvant immunochemotherapy may be beneficial for survival outcomes in PLELC. Despite being one of the large series on neoadjuvant immunochemotherapy followed by surgery, this retrospective study is not without limitations. First, it is subject to potential selection bias, and its sample size is small, which may compromise the statistical power of the analysis. Furthermore, this study lacked long-term outcomes and the exploration of potential biomarkers, which may have provided a more comprehensive understanding of the treatment's efficacy. Further research is needed in prospective observational studies to confirm these findings and strengthen our understanding of the unique immunobiology driving PLELC. Conclusion Neoadjuvant immunochemotherapy is safe and effective for patients with locally advanced PLELC, reducing the extent of tumor, rendering unresectable to resectable, and contributing to survival outcomes. Neoadjuvant immunochemotherapy may be a promising strategy for patients with PLELC. Declarations Ethics approval and consent to participate Informed Consent Statement: A waiver of consent was was granted by the the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University, due to the retrospective nature of the study making consent impractical and contacting patients to obtain consent would pose a greater risk than the waiver. The study was approved by the the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. Consent for publication No applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding authors upon reasonable request. Competing interest None. Funding None. Acknowledements No applicable References Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB et al. 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Cite Share Download PDF Status: Published Journal Publication published 20 Dec, 2024 Read the published version in World Journal of Surgical Oncology → Version 1 posted Editorial decision: Revision requested 08 Nov, 2024 Reviews received at journal 06 Nov, 2024 Reviews received at journal 06 Nov, 2024 Reviewers agreed at journal 29 Oct, 2024 Reviewers agreed at journal 27 Oct, 2024 Reviewers agreed at journal 25 Oct, 2024 Reviews received at journal 20 Aug, 2024 Reviewers agreed at journal 15 Aug, 2024 Reviewers agreed at journal 14 Aug, 2024 Reviewers invited by journal 12 Aug, 2024 Editor assigned by journal 11 Aug, 2024 Submission checks completed at journal 06 Aug, 2024 First submitted to journal 05 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4863107","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":344211270,"identity":"854500f2-1c88-468b-bc6b-4b89273a1cf6","order_by":0,"name":"Jiawei Chen","email":"","orcid":"","institution":"the First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jiawei","middleName":"","lastName":"Chen","suffix":""},{"id":344211271,"identity":"0117f41a-a75d-41bf-96d2-f0540ebb9ee6","order_by":1,"name":"Lei Fan","email":"","orcid":"","institution":"the First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Fan","suffix":""},{"id":344211272,"identity":"d23c7f62-3237-4108-b721-c30b9245a694","order_by":2,"name":"Hongsheng Deng","email":"","orcid":"","institution":"the First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hongsheng","middleName":"","lastName":"Deng","suffix":""},{"id":344211273,"identity":"ceddcb2e-58ff-4534-ae92-f8056f6abdbb","order_by":3,"name":"Liang Li","email":"","orcid":"","institution":"Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University)","correspondingAuthor":false,"prefix":"","firstName":"Liang","middleName":"","lastName":"Li","suffix":""},{"id":344211274,"identity":"920a51ff-cb8e-4ce7-8be5-dbbaa828ce7c","order_by":4,"name":"Shuben Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIie3RMQ6CMBSA4ZomuFRZayR4BQwJq1dpl06YODIw2GBgEGX1GI6OJCR1ee6MeAPdHFVWDcXNof/cL6+vRchk+sMsu2hK5sXEHkrZsCjWkzGFQXOLlDvJq8prQOmJi0I8PwD2vVqIyXWDe1wMXdR0lFp8DRBEfG0hO9uyboL34kUcLrM8qPnJQRQuR82UMminJAReBCzk0aWOsDfBPKVhsOIp7kNCv12fUCFQP0IVbx+ZkqqiDBTR7jIrkrL9ysVZyvsjil0723WTj8hvx00mk8n0tSfmkk0plDzBbgAAAABJRU5ErkJggg==","orcid":"","institution":"the First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":true,"prefix":"","firstName":"Shuben","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2024-08-05 15:36:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4863107/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4863107/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12957-024-03617-w","type":"published","date":"2024-12-20T15:57:24+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66123204,"identity":"39dbd022-4a30-48cf-8aaa-b77311ca8c11","added_by":"auto","created_at":"2024-10-08 02:24:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":18816,"visible":true,"origin":"","legend":"\u003cp\u003eClinical stage of patients before and after neoadjuvant immunochemotherapy\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4863107/v1/b5efea2fd84f563694e5b23c.jpg"},{"id":66123205,"identity":"dc07127c-b39f-4996-8f33-153823cecce4","added_by":"auto","created_at":"2024-10-08 02:24:24","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":23752,"visible":true,"origin":"","legend":"\u003cp\u003eExtended Kaplan–Meier curve for DFS of patients with PLELC\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4863107/v1/bfd63e364e35d926691ed1c1.jpg"},{"id":72202058,"identity":"e0973bbf-1630-43f0-b110-2c1b5d9798cf","added_by":"auto","created_at":"2024-12-23 16:14:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":542013,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4863107/v1/00bcc2b5-017b-450f-b37b-b950201e325d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neoadjuvant immunochemotherapy—a promising strategy for primary pulmonary lymphoepithelioma-like carcinoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and distinct subtype of lung cancer, accounting for less than 1% of all lung neoplasms\u003csup\u003e1\u003c/sup\u003e. First reported by Begin and colleagues in 1987, LELC was found to be an epithelial neoplasm associated with Epstein‒Barr virus (EBV) infection\u003csup\u003e2\u003c/sup\u003e. In 2015, the World Health Organization (WHO) classified PLELC as a non-small-cell lung cancer (NSCLC)\u003csup\u003e3\u003c/sup\u003e, and in 2021, it was reclassified as a subtype of lung squamous cell carcinom (LUSQ) according to the latest WHO Classification of lung tumors\u003csup\u003e4\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCurrently, there is no standard treatment for PLELC, surgical resection still the cornerstone therapy. However, most patients with PLELC present with non-specific symptoms, leading to diagnostic delay and diagnosing at an unresectable stage.\u003c/p\u003e \u003cp\u003eImmune checkpoint inhibitors have been established as the first-line therapy for locally advanced NSCLC. Previous trials\u003csup\u003e5\u0026ndash;7\u003c/sup\u003e have demonstrated the benefits of neoadjuvant immunotherapy, including reducing the extent of tumor, eliminating micrometastases and contributing to survival outcomes. Besides, the trial\u003csup\u003e5\u003c/sup\u003e have also shown that neoadjuvant immunochemotherapy leads to superior outcomes in NSCLC, particularly in LUSQ, which exhibits a better tumor response than other subtypes. Given the histologic and genetic similarity between pleomorphic carcinoma of the lung (PLELC) and LUSQ, it is plausible that programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors could be another promising therapeutic option against this rare tumor. Additionally, evidence suggests\u003csup\u003e8\u0026ndash;9\u003c/sup\u003e that PLELC has a higher proportion of PD-L1 positive tumor cells than lung adenocarcinoma or squamous cell lung carcinoma, which may provides a possible justification for immunotherapy. Recent studies\u003csup\u003e10\u0026ndash;12\u003c/sup\u003e also highlighted the potential benefits of immunotherapy in advanced PLELC, demonstrating a significant improvement in progression-free survival (PFS) outcomes.\u003c/p\u003e \u003cp\u003eNotwithstanding, clinical trials of anti-PD-1/PD-L1 therapy in NSCLC have rarely enrolled patients with PLELC due to its rarity, which means that the potential for using neoadjuvant immunotherapy to make initially inoperable advanced PLELC operable and improve long-term survival remains relatively unknown.\u003c/p\u003e \u003cp\u003eHerein, we aimed to evaluate the safety and efficacy of neoadjuvant immunochemotherapy in PLELC. In addition, the clinical outcomes of PLELC and LUSQ are compared to enhance our understanding of this uncommon malignancy.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eBetween 2019 and 2021, data from patients with PLELC and LUSQ who received neoadjuvant immunotherapy followed by surgery were retrospectively retrieved. All patients underwent standard diagnosis and staging procedures. Computed tomography (CT) scans and 18F-fludeoxyglucose positron emission tomography/CT (\u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT) were routinely performed to evaluate primary tumors. For any suspicion of metastatic lymph nodes by chest CT or PET/CT, endobronchial ultrasound was subsequently performed for pathological confirmation of N stage in these cases. Metastatic disease was assessed with brain magnetic resonance imaging and positron emission tomography. Specimens for cytological and histological characterization were collected via bronchoscopy or subcutaneous needle biopsy before treatment.\u003c/p\u003e \u003cp\u003eThe preoperative and postoperative staging was evaluated in accordance with the 8th American Joint Committee on Cancer (AJCC) lung cancer manuals on the tumor\u0026ndash;node\u0026ndash;metastasis (TNM) staging system\u003csup\u003e13\u003c/sup\u003e. Responses were evaluated by specialists according to the Response Evaluation Criteria In Solid Tumors (RECIST)\u003csup\u003e14\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePatient characteristics were reported as frequencies and percentages for categorical variables and as medians and interquartile ranges for continuous variables. The Kaplan\u0026ndash;Meier method was used to analyze disease-free survival (DFS), which was compared using the log-rank test. Statistical analysis was performed using SPSS version 25.0 (IBM Corp., New York, NY, USA). A P value less than 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Result","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003e We analyzed patient data that met the eligibility criteria for receiving neoadjuvant immunotherapy followed by surgery. The study included 31 patients, predominantly female (n\u0026thinsp;=\u0026thinsp;19, 61.3%), with a mean age of 56.8 years. All patients were at stage II-III, with 19 cases (64.5%) classified as N2 disease. The majority of patients (n\u0026thinsp;=\u0026thinsp;28, 90.3%) underwent 2\u0026ndash;4 cycles of preoperative immunochemotherapy. In all cases, surgery was performed, resulting in R0 resection. The mean tumor diameter prior to immunochemotherapy was 5.9 cm (range, 2.7 to 11.9 cm). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the detailed baseline characteristics of the patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical demographics of patients who received neoadjuvant therapy followed by surgery\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCovariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (min, max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56.8 (41,72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003efemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (61.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (38.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRECIST1.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (min, max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.9 (2.7,11.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre T\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (44.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (16.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (35.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre N\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (25.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (64.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre stage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (9.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (51.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (35.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCycles\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (51.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (25.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (9.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePreoperative outcomes\u003c/h2\u003e \u003cp\u003eOf the 31 patients who underwent neoadjuvant immunochemotherapy followed by surgery, 26 (83.8%) underwent lobectomy, 4 (12.9%) underwent sleeve lobectomy, and 1 (3.2%) received lung autotransplantation. In total, 30 (96.8%) received video-assisted thoracic surgery (VATS). Due to dense adhesions and pulmonary artery hemorrhage, 2 case converted to thoracotomy. The mean operating time was 199.7 min (range, 105 to 595 min). The mean intraoperative bleeding volume was 44.8 mL (range, 10 to 200 mL). Patients had an average postoperative hospital stay of 5.5 days (range, 2 to 10 days). Seven patients (22.6%) experienced pneumonia. No serious postoperative complication was observed. The 90-day mortality was 0. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSurgical and pathological outcomes of patients who received neoadjuvant therapy followed by surgery\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCovariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost stage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTxN0M0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (22.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (61.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDownstage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (42.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (58.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eORR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (27.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (72.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRadiologic response\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (61.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (22.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of Surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (83.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSleeve lobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung autotransplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDays (d)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (min, max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.5 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery time (min)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (min, max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e199.7 (105,595)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBlood loss (ml)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean ((min, max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.8 (10,200)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVolume of drainage (ml)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (min, max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e646.1 (220,1200)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDFS (months)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (min, max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.4 (5,40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathological valuation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMPR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (32.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eTreatment response\u003c/h2\u003e \u003cp\u003eRadiographic response evaluation based on the RECIST\u003csup\u003e14\u003c/sup\u003e standard was available for all patients. After neoadjuvant treatment, 2 (6.4%) achieved complete response (CR), 19 (61.5%) patients achieved partial response (PR), and 2 (6.4%) had progressed disease (PD), corresponding to an overall response rate (ORR) of 72.4% (n\u0026thinsp;=\u0026thinsp;21). One case was not feasible to evaluate the response of the target lesions radiologically due to pneumonia and dense lung consolidation. Seven patients achieved stable disease (SD), which resulted in a disease control rate (DCR) of 90.3% (n\u0026thinsp;=\u0026thinsp;28). (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePostoperative pathological evaluation revealed 10 (32.3%) patients achieved major pathological response (MPR), including 2 (6.4%) achieved pathological complete response (pCR). Lymph node positive was confirmed in 11 (35.5%) patients. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe media follow-up time was 16 months (range, 3m to 40m). All patients received adjuvant treatment. Thirty patients remaining alive during the follow-up period. Tumor-related causes of death were no observed, only one patients died for Covid-19. The maen disease-free survival (DFS) was 17.4 months. And the 1-year disease-free survival (DFS) rate was 96.8%. Recurrence was documented in 4 patients. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe multivariable regression analysis, which adjusted for confounders such as tumor size and stage, showed that tumor type significantly impacted pathological outcomes after neoadjuvant immunochemotherapy. The pathological regression was better in LUSQ than PLELC, with a slightly higher proportion of LUSQ patients achieving pCR and MPR (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). However, there was no difference in DFS between LUSQ and PLELC (p\u0026thinsp;=\u0026thinsp;0.54) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable regression analysis was performed to adjust for confounders, including tumor size and stage, between PLELC and LUSQ\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCovariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLUSQ (n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePLELC (n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRadiologic response\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathological valuation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMPR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDFS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (min, max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.1 (1,29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.4 (5,40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePLELC is a rare malignancy with few recognized treatment options that have been demonstrated to improve patient outcomes. Surgical resection is generally recommended for PLELC. However, due to the growth of the tumor, systemic chemotherapy and radiotherapy remain the current focus of treatment for patients with locally advanced PLELC\u003csup\u003e15\u003c/sup\u003e. The function of neoadjuvant immunochemotherapy in treating PLELC remains uncertain. This retrospective study aimed to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with PLELC .\u003c/p\u003e \u003cp\u003eCheckmate-816 trial\u003csup\u003e5\u003c/sup\u003e confirmed that neoadjuvant immunochemotherapy contributed to NSCLC both pathological and survival outcomes with considerable toxic side effects. Besides, the trial showed that patients with locally advanced stages might also experience benefit from neoadjuvant immunochemotherapy. Deng and coworker\u003csup\u003e16\u003c/sup\u003e indicated that the addition of radical surgery after immunochemotherapy in initially unresectable stage IIIB NSCLC was favorably associated with longer DFS/PFS (27.5 months vs. 16.7 months) compared to those without. In our study, totally 19 patients achieved partial response according to RECIST, including 9 with IIIB, which were rendered unresectable to resectable. Besides, neoadjuvant immunochemotherapy offers an opportunity for patients with compromised lung function to receive modified surgical interventions. No severe adverse events occurred during treatment. During the follow-up period, the maen disease-free survival (DFS) was 17.4 months. And the 1-year disease-free survival (DFS) rate was 96.8%. Only 4 patients experience recurrence, including 2 distant and 2 local recurrence. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe safety and feasibility of neoadjuvant immunochemotherapy followed by surgery have been well confirmed\u003csup\u003e17\u0026ndash;19\u003c/sup\u003e. In our study, VATS was attempted in 30 patients, only 2 patients converted to thoracotomy. Five patients safely underwent modified surgical procedure to avoid pneumonectomy, including lung autotransplantation (n\u0026thinsp;=\u0026thinsp;1) and sleeve lobectomy (n\u0026thinsp;=\u0026thinsp;4). Seven patients (22.6%) experienced immune-related pneumonitis. No surgery-related complication was observed.\u003c/p\u003e \u003cp\u003ePrevious studies\u003csup\u003e5, 9\u003c/sup\u003e showed that several factor may associated with better outcomes to neoadjuvant immunochemotherapy, including type of NSCLC and PD-L1 expression. Patients with LUSQ and/or high PD-L1 expression may achieved better response to immunochemotherapy. Jiang and colleges\u003csup\u003e8\u003c/sup\u003e showed that PLELC has a higher expression of PD-L1 than other NSCLC subtypes. Furthermore, the association of PLELC with EBV infection may contribute to its sensitivity to immunotherapy\u003csup\u003e2\u003c/sup\u003e, which may render PLELC responsive to neoadjuvant immunochemotherapy. In our study, 32.3% (n\u0026thinsp;=\u0026thinsp;10) of patients experiencing major pathologic response (MPR), including 6.4% with pathologic complete response (pCR). The mean DFS was 17.4 months. Although, LUSQ demonstrated higher response rate than PLELC (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), no statistically significant difference was detected between these cancers in terms of DFS (p\u0026thinsp;=\u0026thinsp;0.54). These findings provide support for the idea that neoadjuvant immunochemotherapy may be beneficial for survival outcomes in PLELC.\u003c/p\u003e \u003cp\u003eDespite being one of the large series on neoadjuvant immunochemotherapy followed by surgery, this retrospective study is not without limitations. First, it is subject to potential selection bias, and its sample size is small, which may compromise the statistical power of the analysis. Furthermore, this study lacked long-term outcomes and the exploration of potential biomarkers, which may have provided a more comprehensive understanding of the treatment's efficacy. Further research is needed in prospective observational studies to confirm these findings and strengthen our understanding of the unique immunobiology driving PLELC.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e Neoadjuvant immunochemotherapy is safe and effective for patients with locally advanced PLELC, reducing the extent of tumor, rendering unresectable to resectable, and contributing to survival outcomes. Neoadjuvant immunochemotherapy may be a promising strategy for patients with PLELC.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed Consent Statement: A waiver of consent was was granted by the the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University,\u0026nbsp;due to the retrospective nature of the study making consent impractical and contacting patients to obtain consent would pose a greater risk than the waiver. The study was approved by the the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding authors upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTravis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB et al. 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Ann Thorac Surg. 2022;114(4):1505\u0026ndash;15. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.athoracsur.2021.06.069\u003c/span\u003e\u003cspan address=\"10.1016/j.athoracsur.2021.06.069\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"neoadjuvant immunochemotherapy, pulmonary lymphoepithelioma-like carcinoma, surgery","lastPublishedDoi":"10.21203/rs.3.rs-4863107/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4863107/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective:\u003c/h2\u003e \u003cp\u003e Neoadjuvant immunochemotherapy becomes a promising choice for patients with locally advanced non-small cell cancer (NSCLC). However, whether neoadjuvant immunochemotherapy impacted the subsequent surgical or pathological outcomes of patients with pulmonary lymphoepithelioma-like carcinoma (PLELC) remains relatively unknown. This study aimed to evaluate the safety and efficacy of neoadjuvant immunochemotherapy in PLELC patients.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eA retrospective study was conducted on patients who received neoadjuvant immunochemotherapy in combination with chemotherapy followed by surgery between 2019 and 2022. The clinical records of the patients were analyzed.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eOut of the 31 patients with PLELC who underwent neoadjuvant therapy followed by surgery, 18 patients (58.0%) experienced downstaging of the tumor. Nineteen patients (61.5%) achieved a partial response, 2 patients (6.4%) achieved a complete response, and 2 (6.4%) had progressive disease. Pathological evaluation of resected specimens revealed that 10 (32.3%) patients achieved major pathological response (MPR), including 2 (6.4%) who achieved complete response (CR). The mean disease-free survival (DFS) was 17.4 months, which was not significantly different from the value in LUSQ patients (15.1 months).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eNeoadjuvant immunochemotherapy is a safe and effective approach to reduce the extent of tumor, render unresectable to resectable, and offer an opportunity to receive modified surgery, which may be a promising strategy for patients with PLELC.\u003c/p\u003e","manuscriptTitle":"Neoadjuvant immunochemotherapy—a promising strategy for primary pulmonary lymphoepithelioma-like carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-08 02:24:18","doi":"10.21203/rs.3.rs-4863107/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-08T14:04:56+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-06T18:06:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-06T08:30:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222958871143761071813725096487337766330","date":"2024-10-29T13:29:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"137603430410625992334584479968963682728","date":"2024-10-28T02:42:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"19289630894236380996641416911738953267","date":"2024-10-25T11:15:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-20T08:30:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"126074572896109550121991339626105240273","date":"2024-08-15T13:16:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"18853857970583513957260171281829285593","date":"2024-08-14T16:34:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-13T01:50:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-11T14:53:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-06T06:31:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"World Journal of Surgical Oncology","date":"2024-08-05T15:33:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9d14c62e-6b1d-428e-8ac5-f28f2ff95573","owner":[],"postedDate":"October 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-23T16:06:40+00:00","versionOfRecord":{"articleIdentity":"rs-4863107","link":"https://doi.org/10.1186/s12957-024-03617-w","journal":{"identity":"world-journal-of-surgical-oncology","isVorOnly":false,"title":"World Journal of Surgical Oncology"},"publishedOn":"2024-12-20 15:57:24","publishedOnDateReadable":"December 20th, 2024"},"versionCreatedAt":"2024-10-08 02:24:18","video":"","vorDoi":"10.1186/s12957-024-03617-w","vorDoiUrl":"https://doi.org/10.1186/s12957-024-03617-w","workflowStages":[]},"version":"v1","identity":"rs-4863107","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4863107","identity":"rs-4863107","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}