Stage Ⅳb Pulmonary Sarcomatoid Carcinoma with EGFR L861Q KRAS Co-mutation and High PD-L1 Expression Neoadjuvant Immunochemotherapy Combined with Surgery Achieves Near MPR

Stage Ⅳb Pulmonary Sarcomatoid Carcinoma with EGFR L861Q KRAS Co-mutation and High PD-L1 Expression Neoadjuvant Immunochemotherapy Combined with Surgery Achieves Near MPR | 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 Case Report Stage Ⅳb Pulmonary Sarcomatoid Carcinoma with EGFR L861Q KRAS Co-mutation and High PD-L1 Expression Neoadjuvant Immunochemotherapy Combined with Surgery Achieves Near MPR Yu-Tao Pang, Hong-Fei Zhang, Ang Li, Yang Fei Peng, Xiao Yang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8460147/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Pulmonary sarcomatoid carcinoma (PSC) is a rare, highly aggressive non-small cell lung cancer (NSCLC) subtype (0.1%–4% of lung malignancies) [3] . Clinically, it mainly affects smokers, with half diagnosed at advanced stages; pathologically, it is defined by cytokeratin-vimentin co-expression. Molecularly, classical EGFR-sensitive mutations are rare (28%, mostly rare variants like L861Q), while KRAS (22%–34.4%), MET (16%–19%), and TP53 (73.6%–81%) mutations are common [13–17] . Traditional treatments are ineffective (chemotherapy ORR < 10%; surgical 5-year survival 12.6%–16.3%), but immunotherapy (mono/combined with chemotherapy) shows promise (73%–77% with PD-L1 ≥ 50%; ORR 37%–43%) [2, 7, 18–21] . No guidelines exist for PSC with driver mutations (e.g., EGFR/KRAS co-mutation) plus high PD-L1. Methods We retrospectively analyzed clinical, imaging, pathological, and therapeutic data of one PSC patient with informed consent. Results A 62-year-old with stage Ⅳb right upper lung PSC (EGFR L861Q/KRAS co-mutation; PD-L1 TPS 90%) received neoadjuvant "Paclitaxel + Carboplatin + Serplulimab + Denosumab," followed by thoracoscopic lobectomy and postoperative "Furmonertinib + Denosumab." Postoperatively, tumor bed viable cells accounted for 15% (meeting pPR, near MPR [residual < 10%]), with EGFR mutation loss, suggesting treatment-induced clonal evolution. Conclusion Neoadjuvant immunochemotherapy is feasible for PSC with "driver mutation + high PD-L1," providing a clinical reference. It highlights the importance of MDT collaboration and dynamic molecular monitoring in advanced PSC, addressing guideline gaps. Pulmonary Sarcomatoid Carcinoma (PSC) EGFR3.L861Q/KRAS Co-mutation PD-L1 High Expression Neoadjuvant Immunochemotherapy Major Pathological Response (MPR) Case Report Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly aggressive subtype of non-small cell lung cancer (NSCLC). The 2015 World Health Organization (WHO) Classification of Lung Tumors clearly defines it as encompassing five pathological subtypes: carcinosarcoma, spindle cell carcinoma, pleomorphic carcinoma, giant cell carcinoma, and pulmonary blastoma [ 1 ] . Epidemiological data indicate that its proportion among all lung cancers is extremely low: it accounts for less than 1% and 0.4% (3647/878810) in the US National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results (SEER) database, respectively. Additionally, the population incidence rate slowly decreased from 0.120 to 0.092 per 100,000 population between 2004 and 2015 [ 3 – 6 ] . PSC has distinct clinical features. It predominantly affects elderly male smokers and carries an extremely poor prognosis. The overall 1-year, 3-year, and 5-year survival rates are 33.7%, 18.4%, and 14.4%, respectively. Survival time is significantly associated with disease stage: 16.9 months for stage I-II, 5.8 months for stage III, and 5.4 months for stage IV. Among the subtypes, pleomorphic carcinoma has the worst prognosis. Due to the insidious nature of early-stage symptoms, most patients are diagnosed at intermediate or advanced stages, resulting in a narrow therapeutic window [ 2 , 6 – 8 ] . Pathologically, PSC exhibits dual differentiation characteristics of both epithelial and mesenchymal tissues. Its molecular profile is highly unique: the TP53 mutation rate is the highest (73.6%-78.6%), while mutations in CDKN2A (28.6%) and MYC (25.0%) are also relatively common. Among driver mutations, the rate of sensitive EGFR mutations is low (16.0% [9/56] in the Chinese population and 8.8% [11/125] in the Western population, mostly rare types). The KRAS mutation rate ranges from 22% to 34%, and the MET mutation rate from 16% to 19%. Notably, the MET exon 14 skipping mutation accounts for 31.8% of PSC cases in China, which is significantly higher than the 2.62% rate observed in all NSCLC cases [ 13 – 17 ] . Traditional treatments have limited efficacy for PSC. Surgery is the preferred option for early-stage resectable cases and has been confirmed by multivariate analysis as an independent favorable prognostic factor (hazard ratio [HR] 0.40-0.484, P < 0.01), yet long-term survival remains unsatisfactory. The objective response rate (ORR) to chemotherapy is only 8.0%-16.5%, and perioperative (neoadjuvant/adjuvant) chemotherapy may only yield survival benefits for some stage III patients. Although radiotherapy may improve the overall survival (OS) of patients who are inoperable or have locally advanced disease, the efficacy of adjuvant radiotherapy has not been confirmed by large-sample studies [ 2 , 7 , 18 – 21 ] . In recent years, targeted therapy and immunotherapy have brought breakthroughs for PSC. In terms of immunotherapy, 74.2% of PSC patients have a PD-L1 expression level ≥ 50%. Additionally, PSC exhibits high tumor mutation burden (TMB) and a T-cell inflammatory microenvironment, laying the foundation for immunotherapy. Retrospective studies have shown that the ORR of immune checkpoint inhibitors (ICIs) monotherapy ranges from 31.6% to 40.5%, and this rate can increase to 70.2% in patients with high PD-L1 expression. Combinations of ICIs with anti-angiogenic agents (e.g., apatinib) have also shown potential efficacy [ 15 , 21 – 25 ] . Currently, there are no clear clinical guidelines recommending treatment strategies for PSC patients with special molecular characteristics, such as concurrent EGFR/KRAS mutations or MET exon 14 skipping mutations combined with high PD-L1 expression. Most of the existing evidence comes from small-sample cohorts or case reports. Therefore, in clinical practice, individualized treatment plans should be formulated through multidisciplinary team (MDT) collaboration, considering the patient's pathological subtype, molecular profile, clinical stage, and physical function, to maximize survival benefits [9, 10] . This article reports a case of a 62-year-old patient with stage Ⅳb right upper lung sarcomatoid carcinoma (with concurrent EGFR L861Q/KRAS mutations and PD-L1 TPS of 90%) who was treated at our hospital. The patient first received neoadjuvant therapy with "paclitaxel + carboplatin + serplulimab + denosumab," and after disease remission, underwent "video-assisted thoracoscopic right upper lobectomy." Postoperatively, the patient received maintenance therapy with "furmonertinib + denosumab." This treatment achieved a primary tumor shrinkage of over 70%, and only 15% of viable tumor cells remained in the tumor bed of the postoperative specimen, meeting the criteria for partial pathological response (pPR) and approaching major pathological response (MPR, defined as residual tumor cells < 10% in the primary lesion). This successfully converted an unresectable advanced lesion into a radically resected one, with no serious postoperative complications. Additionally, postoperative pathology revealed the disappearance of the EGFR mutation in the patient's tumor lesion after neoadjuvant therapy, suggesting a potential treatment-induced clonal evolution of the tumor. A: Initial CT scan at admission B: Follow-up CT scan after 2 cycles of treatment C: Follow-up CT scan after 4 cycles of treatment A: Bronchoscopy revealed enlargement of the 4R lymph nodeB: Microscopic findings of the lymph node biopsy after pathological staining Case Presentation A 62-year-old female patient presented to our hospital on December 2, 2024, with "cough and expectoration for more than 10 days," without accompanying symptoms such as hemoptysis, chest pain, or fever. A contrast-enhanced chest CT performed at our hospital revealed a 79mm×73mm mass in the right upper lung (Fig. 1 A), accompanied by obstructive pneumonia and atelectasis. The patient was admitted to the thoracic surgery ward of our hospital to clarify the nature of the lesion. After admission, comprehensive blood tests and functional assessments showed no significant abnormalities. Further imaging evaluation, a whole-body PET-CT scan (Fig. 3A), demonstrated: a space-occupying lesion in the right upper lung with surrounding obstructive pneumonia and atelectasis, involvement of mediastinal and hilar lymph nodes, possible bone metastases in the proximal right femur, and undetermined nature of multiple bilateral pulmonary nodules. After evaluating that the patient’s physical condition could tolerate the procedure, a flexible bronchoscopic examination under intravenous anesthesia + transbronchial needle aspiration (TBNA) of the bronchial wall (4R lymph node) was performed on December 5, 2024 (Fig. 2A). Pathological findings indicated: malignant tumor. Microscopically, tumor cells were arranged in nests and sheets, with significant pleomorphism. The tumor cells were epithelioid and large polygonal, with foamy cytoplasm, irregular nuclei, and easily observable mitoses. Abundant inflammatory cells were seen between tumor cells. Combined with the histological morphology and immunohistochemical results, the diagnosis was consistent with sarcomatoid carcinoma (Fig. 2B). Staging of the right lung malignant tumor: T4N2aM1c, stage Ⅳb (ipsilateral mediastinal lymph node metastasis, multiple distant metastases to the femur), with PD-L1 (TPS = 90%). A: Initial PET-CT scan for staging assessment B: Preoperative SPECT/CT scan (bone scan) for staging assessment after neoadjuvant therapy Genetic Testing Results And Treatment Process 1. Genetic Testing Results 1.1 Somatic Variants Two somatic variants were detected in this test, both of which are definite mutations in lung cancer-related driver genes. Details are as follows: EGFR gene: Exon 21, L861Q sensitive mutation, detected Ct value = 29.30. KRAS gene: Exon 2, mutations in G12A/G12V/G12R/G12C/G13C (verified by typing reagents, excluding the G12C mutation), detected Ct value = 28.84. 1.2 Germline Variants No germline variants were detected. Additionally, no pathogenic/potentially pathogenic variants associated with hereditary diseases were identified. 2. Treatment Process On December 11, 2024, January 3, 2025, January 24, 2025, and February 15, 2025, after dynamic monitoring to rule out contraindications, the patient received neoadjuvant chemotherapy combined with immunotherapy and targeted therapy for bone metastases, respectively. The regimens were as follows: Four cycles of neoadjuvant chemotherapy combined with immunotherapy: paclitaxel (albumin-bound) 450mg + carboplatin 550mg + serplulimab 300mg. Three cycles of targeted therapy: denosumab (120mg) to control the risk of bone metastases and regulate the tumor microenvironment. After four cycles of neoadjuvant therapy, a follow-up contrast-enhanced chest CT was performed on April 6, 2025. Comparison with the CT scan on December 4, 2024, showed a significant reduction in the volume of the right upper lung tumor, which now measured approximately 22 mm × 25 mm × 24 mm. The degree of pleural invasion was reduced, and symptoms of obstructive pneumonia improved, indicating a marked therapeutic effect (Fig. 1 C). A follow-up SPECT/CT scan, compared with that on December 3, 2024, revealed increased density of the bone metastatic lesions in the proximal right femur, which was considered a manifestation of bone repair (Fig. 3B). Meanwhile, contrast-enhanced cranial magnetic resonance imaging (MRI) + diffusion-weighted imaging (DWI) showed no obvious abnormalities. Preoperative staging: ycT1cN0M0, stage IA3. After preoperative laboratory tests and pulmonary function assessment revealed no obvious surgical contraindications, the medical team performed video-assisted thoracoscopic right upper lobectomy + hilar and mediastinal lymph node dissection on the patient on April 7, 2025. The operation was smooth, with an intraoperative blood loss of 50ml, and no obvious postoperative complications occurred A: Surgical specimen (right upper lung lobe) with a volume of 111mm×65mm×35mm. A nodule was seen at the cut surface, with a maximum diameter of 28mm. The cut surface was grayish-yellow, firm, with ill-defined borders and visible necrosis. B: Microscopically, focal tumor cells (approximately 5%) were distributed in solid nests. The tumor cells had abundant eosinophilic and foamy cytoplasm with significant nuclear pleomorphism, consistent with sarcomatoid carcinoma changes. C: Microscopic findings of PD-L1 detection Postoperative Pathology 1. Right Upper Lung Lobe Combined with the medical history, morphology, and immunohistochemistry, the findings are consistent with sarcomatoid carcinoma changes (most areas show invasive adenocarcinoma; focal tumor cells are distributed in solid nests. The tumor cells have abundant eosinophilic and foamy cytoplasm with significant nuclear pleomorphism) (Figs. 4 A, 4 B). Maximum diameter of the tumor bed: approximately 2.8 cm. Viable tumor cells in the tumor bed: approximately 15%; necrosis: approximately 20%; fibrous stroma: approximately 65%. No definite vascular tumor thrombus was identified. 2. Mediastinal Lymph Nodes All 12 mediastinal lymph nodes were negative (0/12). Auxiliary Examination: Immunohistochemistry (IHC) Results (Wax blocks 4 + 6): CK(+), CK7(+), TTF-1(+), P40(-), Ki67 (approximately 10%), CK5/6(-), CD68(+), E-ca(+). (Wax blocks 12 + 19): CK(-), LCA(+). (Wax block 28): Vimentin(+), CK7 (focal +). 3. PD-L1 Detection Result PD-L1 expression level in tumor cells: < 1% in the adenocarcinoma area; approximately 40% in the sarcomatoid carcinoma area (Fig. 4 C). 4. Postoperative Genetic Testing No EGFR exon 21 L861Q mutation was detected. KRAS exon 2 mutation persisted. Case Discussion Lung cancer is one of the cancers with the highest global incidence and mortality [1]. Pulmonary sarcomatoid carcinoma (PSC) is a rare, highly aggressive non-small cell lung cancer (NSCLC) subtype, accounting for approximately 0.1%-4% of all lung cancers. Its core pathological feature is dual positivity for cytokeratin (CK) and vimentin. Molecularly, it is characterized by a low incidence of classic sensitive EGFR mutations (only 28%, mostly rare variants like L861Q) and significantly higher mutation rates of KRAS (22%-34.4%) and TP53 (73.6%-81%). The patient in this case had concurrent EGFR L861Q and KRAS mutations—an extremely rare occurrence in PSC with no guideline-recommended regimens—plus initial stage Ⅳb (T4N2aM1c) and PD-L1 TPS of 90%, further highlighting the clinical exploratory value of treatment decisions. Traditional PSC treatments have poor efficacy: chemotherapy achieves an objective response rate (ORR) < 10%, and even with surgery, the 5-year survival rate is only 12.6%-16.3%. Though recent studies show immunotherapy combined with chemotherapy (chemoimmunotherapy, CIT) reaches 37%-43% ORR in PSC patients with PD-L1 ≥ 50%—emerging as a novel therapeutic direction—standard strategies for PSC subtypes with “driver mutations + high PD-L1 expression” remain lacking domestically and internationally, leaving a significant unmet clinical need. However, treatment decisions under such overlapping features face multiple challenges. At initial diagnosis, the patient was stage Ⅳb, with a 79mm×73mm right upper lung lesion, mediastinal lymph node metastasis, and proximal right femoral bone metastasis—classified as “unresectable” per traditional staging. Meanwhile, the molecular interaction of concurrent EGFR/KRAS mutations is unclear: KRAS mutations may weaken EGFR-targeted therapy efficacy via MAPK pathway activation, and the impact of EGFR mutations on the immunotherapeutic tumor microenvironment is understudied. This precludes the direct application of regimens for NSCLC with single driver mutations or high PD-L1 expression. Additionally, the lack of dynamic molecular monitoring during PSC treatment means the risk of tumor clonal evolution is underaddressed, increasing the complexity of treatment planning. The regimen chosen in this case was clearly rational based on cutting-edge evidence: the patient’s PD-L1 TPS of 90% supported CIT. Specifically, chemotherapy (paclitaxel + carboplatin) enhances the immune activation of the PD-1 inhibitor serplulimab by releasing tumor-associated antigens and reducing immunosuppressive cells. Denosumab not only prevents bone metastasis-related events but also improves the tumor microenvironment via RANKL-RANK pathway inhibition, synergistically boosting immunoefficacy. Moreover, neoadjuvant therapy—proven to convert unresectable to resectable tumors in oligometastatic advanced NSCLC—provided theoretical support for stage downstaging. Based on this strategy, the patient achieved breakthrough treatment progress. After 4 cycles of neoadjuvant “paclitaxel + carboplatin + serplulimab + denosumab,” the right upper lung tumor shrank from 79mm×73mm to 22mm×25mm×24mm (over 70% shrinkage). The stage was downstaged to IA3 (ycT1cN0M0), and the proximal right femoral bone metastases showed bone repair. Subsequent video-assisted thoracoscopic right upper lobectomy + hilar/mediastinal lymph node dissection was uneventful, with 50ml intraoperative blood loss and no postoperative complications. Postoperative pathology revealed 15% viable tumor cells in the tumor bed—though not meeting the criteria for major pathological response (MPR, residual tumor cells < 10%), it satisfied partial pathological response (pPR), which is significantly superior to that of traditional chemotherapy. Notably, postoperative genetic testing showed loss of the EGFR L861Q mutation with persistent KRAS mutation, suggesting neoadjuvant CIT may induce tumor clonal evolution. This molecular finding provides a key clue for dynamic post-PSC treatment monitoring and a basis for selecting postoperative maintenance therapy (furmonertinib + denosumab). The case’s clinical insights hold practical and exploratory value, reflected in breaking traditional treatment thinking and advancing understanding of molecular mechanisms. Its most valuable decision was abandoning the “target-based treatment” convention. For PSC’s biological uniqueness, a “CIT-first” strategy was established based on three key points: (1) EGFR-TKI efficacy data in PSC are extremely limited, with only 2 retrospective studies reporting < 15% ORR—far lower than that in adenocarcinoma with conventional sensitive EGFR mutations; (2) concurrent KRAS mutations significantly increase EGFR-TKI resistance risk, as in vitro studies confirm KRAS G12C mutations reduce EGFR-TKI tumor cell inhibition by 40%, further weakening targeted therapy potential; (3) the patient’s PD-L1 TPS of 90% confers a clear immunotherapeutic benefit, with a 2-year overall survival (OS) rate of 58%—significantly higher than the 35% with EGFR-TKI monotherapy. Ultimately, 4 cycles of treatment achieved 70% tumor shrinkage and near-MPR, verifying the rationality of this decision and providing a reference pathway for similar rare cases. The postoperative loss of the EGFR L861Q mutation with persistent KRAS mutation is another key insight, whose mechanism requires analysis of tumor biology and detection technology. The most plausible mechanism is treatment-induced clonal selection: neoadjuvant CIT activates anti-tumor immunity to preferentially eliminate more immunogenic EGFR-mutant clones, while KRAS-mutant clones become residual dominant clones due to stronger immune escape. This aligns with the “selective survival of tumor subclones under treatment pressure” theory reported in Nature Cancer (2024). Tumor heterogeneity (preoperative biopsy sampling only EGFR mutation-enriched areas vs. postoperative KRAS-dominant specimens) or differences in detection sensitivity (15% postoperative viable tumor cells possibly below the 5%-10% lower limit of some methods) cannot be fully excluded. This phenomenon highlights the need for dynamic circulating tumor DNA (ctDNA) monitoring during PSC treatment to guide subsequent adjustments (e.g., postoperative furmonertinib maintenance). More importantly, this case provides an innovative direction—“treatment sequencing based on tumor subtype”—for the “high PD-L1 expression + EGFR mutation” population not covered by current NCCN guidelines. Existing guidelines lack recommendations on the priority of immunotherapy vs. targeted therapy for this group. Yet this case suggests sequencing may require individualized adjustment based on NSCLC subtype aggressiveness: for highly aggressive subtypes (e.g., PSC, large-cell carcinoma), prioritizing CIT enables rapid tumor shrinkage, downstaging, and opportunities for radical surgery, while avoiding the insufficient efficacy and resistance risks of targeted therapy; for indolent subtypes (e.g., lung adenocarcinoma), EGFR-TKIs may be prioritized to control progression while preserving quality of life. Though requiring prospective cohort validation, this view fills guideline gaps and provides a clinically valuable entry point for optimizing individualized strategies. This single-case report has limitations: individual differences cannot be ruled out, requiring multicenter prospective studies to verify regimen efficacy and safety; postoperative follow-up is < 6 months, necessitating long-term observation of recurrence, metastasis, and potential resistance related to residual KRAS mutations; the mechanism of EGFR L861Q loss remains unclear, requiring follow-up basic research (e.g., single-cell sequencing) to elucidate CIT-induced tumor clonal evolution. Declarations Funding This work was supported by the Key Clinical Projects of Affiliated Hospital of Guangdong Medical University (LCYJ2022DL003) and the Supported Projects of Zhanjiang (2021A05076). Conflicts of interest/Competing interests The authors have no conflicts of interest to declare that are relevant to the content of this article. CARE Guidelines Compliance This case report strictly adheres to the CARE (Case Report) Guidelines to ensure transparency, completeness, and methodological rigor. Informed Consent Written informed consent was obtained from the patient for the publication of this case report and accompanying images, in compliance with the Declaration of Helsinki. The patient was fully informed of the purpose of the study, the use of clinical data, imaging materials, and pathological findings in the publication, and voluntarily provided written consent for both participation in the study and the publication of de-identified personal and clinical information. Relevant consent documents are available from the corresponding author upon reasonable request by the editorial office. Author contribution Z.L., J.C., and Z.H. contributed to the conception or design of the work. H.F.Z., A.L., and Y.T.P. contributed to the acquisition and analysis of data for the work., Y.T.P. are responsible for the interpretation of data. Y.T.P. drafted the manuscript. F.S.L. and Z.H. critically revised the manuscript. All authors read and approved the final manuscript. Data availability statement The data that support the findings of this study are available from the corresponding author upon reasonable request. Clinical trial number Not applicable. Ethics declaration This study is a retrospective clinical analysis. All experimental protocols have been approved by the Ethics Committee of Affiliated Hospital of Guangdong Medical University. The study strictly adheres to the principles of the Declaration of Helsinki, and all clinical diagnosis and treatment procedures, data collection methods, and detection techniques employed are covered by the ethical approval. Consent for publication Written informed consent was obtained from the patient for participation in the study and for publication of this case report and any accompanying images. References W. D. Travis, E. Brambilla, and A. G. Nicholson, “The 2015 world health organization classification of lung tumors,”Journal of Thoracic Oncology, vol. 10, no. 9, pp. 1243–1260,2015. Y. Lin, H. Yang, and Q. Cai, “Characteristics and prognostic analysis of 69 patients with pulmonary sarcomatoid carci-noma,” American Journal of Clinical Oncology, vol. 39, no. 3,pp. 215–222, 2016. H. M. Abdallah, D. Martinez-Meehan, and W. Lutfi, “Adjuvant chemotherapy for pulmonary sarcomatoid carcinoma:a retrospective analysis of the national cancer database,” TheJournal of Thoracic and Cardiovascular Surgery, vol. S0022-5223, no. 21, p. 180, 2021. C. E. Steuer, M. Behera, and Y. Liu, “Pulmonary sarcomatoid carcinoma: an analysis of the national cancer data base,”Clinical Lung Cancer, vol. 18, no. 3, pp. 286–292, 2017. S. Yendamuri, L. Caty, M. Pine et al., “Outcomes of sarcomatoid carcinoma of the lung: a surveillance, epidemiology,and end results database analysis,” Surgery, vol. 152, no. 3,pp. 397–402, 2012. M. Chen, Q. Yang, and Z. Xu, “Survival analysis and pre-diction model for pulmonary sarcomatoid carcinoma basedon SEER database,” Frontiers in Oncology, vol. 11, Article ID630885, 2021. K. Maneenil, Z. Xue, and M. Liu, “Sarcomatoid carcinoma ofthe lung: the Mayo clinic experience in 127 patients,” Clinical Lung Cancer, vol. 19, no. 3, pp. e323–e333, 2018. C. E. Steuer, M. Behera, and Y. Liu, “Pulmonary sarcomatoid carcinoma: an analysis of the national cancer data base,”Clinical Lung Cancer, vol. 18, no. 3, pp. 286–292, 2016.8 Journal of Oncology U.S. National Library of Medicine, “Clinical trials on pulmonary sarcomatoid carcinoma,” U.S. National Library ofMedicine, Bethesda, MD, USA, 2021. National Comprehensive Cancer Network, 2021, NCCN Guidelines, Non-Small Cell Lung Cancer. R. J. ´Avila Mart´ınez, C. Marr´on Fern´andez, and F. Hermoso Alarza, “Carcinomas sarcomatoides pulmonares primarios,”Archivos de Bronconeumolog´ıa, vol. 49, no. 9, pp. 405–407,2013. Schrock A B, Li S D, Frampton G M. Pulmonary sarcomatoid carcinomas commonly harbor either potentially targetable genomic alterations or high tumor mutational burden as observed by comprehensive genomic profiling[J]. Journal of Thoracic Oncology, 2017, 12(6): 932-942. Zhou F, Huang Y, Cai W. The genomic and immunologic profiles of pure pulmonary sarcomatoid carcinoma in Chinese patients[J]. Lung Cancer, 2021, 153: 66-72. Yang Z, Xu J, Li L. Integrated molecular characterization reveals potential therapeutic strategies for pulmonary sarcomatoid carcinoma[J]. Nature Communications, 2020, 11(1): 1-12. Tong J H, Yeung S F, Chan A W H. MET amplification and exon 14 splice site mutation define unique molecular subgroups of non-small cell lung carcinoma with poor prognosis[J]. Clinical Cancer Research, 2016, 22(12): 3048-3056. Liu X, Jia Y, Stoopler M B. Next-Generation sequencing of pulmonary sarcomatoid carcinoma reveals high frequency of actionable MET gene mutations[J]. Journal of Clinical Oncology, 2016, 34(8): 794-802. Zeng Q, Li J, Sun N. Preoperative systemic immune-inflammation index predicts survival and recurrence in patients with resected primary pulmonary sarcomatoid carcinoma[J]. Translational Lung Cancer Research, 2021, 10(1): 18-31. Gang J, Yan Q, Xiang S. Clinicopathological characteristics and prognostic factors of pulmonary sarcomatoid carcinoma: a large population analysis[J]. Annals of Translational Medicine, 2021, 9(2): 121 .[20] Sun L, Dai J, Chen Y. Pulmonary sarcomatoid carcinoma: experience from SEER database and Shanghai pulmonary hospital[J]. The Annals of Thoracic Surgery, 2020, 110(2): 406-413. Vieira T, Girard N, Ung M. Efficacy of first-line chemotherapy in patients with advanced lung sarcomatoid carcinoma[J]. Journal of Thoracic Oncology, 2013, 8(12): 1574-1577. Babacan N A, Pina I B, Signorelli D. Relationship between programmed death receptor-ligand 1 expression and response to checkpoint inhibitor immunotherapy in pulmonary sarcomatoid carcinoma: a pooled analysis[J]. Clinical Lung Cancer, 2020, 21(5): e456-e463. Domblides C, Leroy K, Monnet I. Efficacy of immune checkpoint inhibitors in lung sarcomatoid carcinoma[J]. Journal of Thoracic Oncology, 2020, 15(5): 860-866. Manglaviti S, Brambilla M, Signorelli D. Immune-checkpoint inhibitors in advanced non-small cell lung cancer with uncommon histology[J]. Clinical Lung Cancer, 2021, 23(1): e17-e28. Zhao S, Ren S, Jiang T. Low-dose apatinib optimizes tumor microenvironment and potentiates antitumor effect of PD-1/PD-L1 blockade in lung cancer[J]. Cancer Immunology Research, 2019, 7(4): 640-643. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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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He","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIie3Qr4/CMBTA8UeWFNOjtssdI/wHJSRT98e0WTI1EuQEYsnIJu6n3P0Xk8g1S3qm5yd36uzmUHB4CB0O0Y9+37TvAVjWHUIklW0XP3tknMuWxxtzMqEqWBQ6XLqvOmCtVubEg8h/fMhqUTbcd3+3zoCPgeJugRxRVjyMRYKA5C/8euKkFeswWn5VUjVi9wRU/5TGV0RB8fRdJmEjNAJGV6YkYjVmdJTU4K9F5gxKFinmbP6pwIdhyenIo6LipyPjgHKtsHGX2Uf6ve8PR4/M/mS/jzceyd+uJ2fwbeOWZVnWRf8kvVAzzL6ggAAAAABJRU5ErkJggg==","orcid":"","institution":"Affiliated Hospital of Guangdong Medical University","correspondingAuthor":true,"prefix":"","firstName":"zhan","middleName":"","lastName":"He","suffix":""}],"badges":[],"createdAt":"2025-12-27 09:53:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8460147/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8460147/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101459896,"identity":"f745f154-ff0d-4ead-8bab-4f1302d075f3","added_by":"auto","created_at":"2026-01-30 01:33:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":636281,"visible":true,"origin":"","legend":"\u003cp\u003eImaging changes of the patient during neoadjuvant therapy\u003c/p\u003e\n\u003cp\u003eA: Initial CT scan at admission B: Follow-up CT scan after 2 cycles of treatment\u003c/p\u003e\n\u003cp\u003eC: Follow-up CT scan after 4 cycles of treatment\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8460147/v1/815baeed2dd6ac8fcd7e97e3.png"},{"id":101459894,"identity":"e2ea80cd-7698-47fd-8597-f57c38ea1565","added_by":"auto","created_at":"2026-01-30 01:33:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1044832,"visible":true,"origin":"","legend":"\u003cp\u003eBronchoscopy and biopsy pathological examination of the patient\u003c/p\u003e\n\u003cp\u003eA: Bronchoscopy revealed enlargement of the 4R lymph nodeB: Microscopic findings of the lymph node biopsy after pathological staining\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8460147/v1/2c3e8adfb07027dbad4bbd83.png"},{"id":101751935,"identity":"d8faea7a-3645-4409-9cf5-6feba29d6c9e","added_by":"auto","created_at":"2026-02-03 10:24:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":672272,"visible":true,"origin":"","legend":"\u003cp\u003ePET-CT and SPECT/CT images of the patient\u003c/p\u003e\n\u003cp\u003eA: Initial PET-CT scan for staging assessment\u003c/p\u003e\n\u003cp\u003eB: Preoperative SPECT/CT scan (bone scan) for staging assessment after neoadjuvant therapy\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8460147/v1/002c9cbdd720a2c1918d2757.png"},{"id":101459897,"identity":"84ecc3e6-6d2d-4898-99d8-3750514f7bac","added_by":"auto","created_at":"2026-01-30 01:33:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2020923,"visible":true,"origin":"","legend":"\u003cp\u003ePostoperative Specimen and Microscopic Pathological Findings\u003c/p\u003e\n\u003cp\u003eA: Surgical specimen (right upper lung lobe) with a volume of 111mm×65mm×35mm. A nodule was seen at the cut surface, with a maximum diameter of 28mm. The cut surface was grayish-yellow, firm, with ill-defined borders and visible necrosis.\u003c/p\u003e\n\u003cp\u003eB: Microscopically, focal tumor cells (approximately 5%) were distributed in solid nests. The tumor cells had abundant eosinophilic and foamy cytoplasm with significant nuclear pleomorphism, consistent with sarcomatoid carcinoma changes.\u003c/p\u003e\n\u003cp\u003eC: Microscopic findings of PD-L1 detection\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8460147/v1/29d2efd9ea1ec93384f57ed4.png"},{"id":102906129,"identity":"c016da5b-077e-4363-9d83-da185945fef9","added_by":"auto","created_at":"2026-02-18 09:12:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8404942,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8460147/v1/a4d24fc5-155a-4c90-a26d-7d65de44bbd6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Stage Ⅳb Pulmonary Sarcomatoid Carcinoma with EGFR L861Q KRAS Co-mutation and High PD-L1 Expression Neoadjuvant Immunochemotherapy Combined with Surgery Achieves Near MPR","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePulmonary sarcomatoid carcinoma (PSC) is a rare and highly aggressive subtype of non-small cell lung cancer (NSCLC). The 2015 World Health Organization (WHO) Classification of Lung Tumors clearly defines it as encompassing five pathological subtypes: carcinosarcoma, spindle cell carcinoma, pleomorphic carcinoma, giant cell carcinoma, and pulmonary blastoma \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Epidemiological data indicate that its proportion among all lung cancers is extremely low: it accounts for less than 1% and 0.4% (3647/878810) in the US National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results (SEER) database, respectively. Additionally, the population incidence rate slowly decreased from 0.120 to 0.092 per 100,000 population between 2004 and 2015 \u003csup\u003e[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePSC has distinct clinical features. It predominantly affects elderly male smokers and carries an extremely poor prognosis. The overall 1-year, 3-year, and 5-year survival rates are 33.7%, 18.4%, and 14.4%, respectively. Survival time is significantly associated with disease stage: 16.9 months for stage I-II, 5.8 months for stage III, and 5.4 months for stage IV. Among the subtypes, pleomorphic carcinoma has the worst prognosis. Due to the insidious nature of early-stage symptoms, most patients are diagnosed at intermediate or advanced stages, resulting in a narrow therapeutic window\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Pathologically, PSC exhibits dual differentiation characteristics of both epithelial and mesenchymal tissues. Its molecular profile is highly unique: the TP53 mutation rate is the highest (73.6%-78.6%), while mutations in CDKN2A (28.6%) and MYC (25.0%) are also relatively common. Among driver mutations, the rate of sensitive EGFR mutations is low (16.0% [9/56] in the Chinese population and 8.8% [11/125] in the Western population, mostly rare types). The KRAS mutation rate ranges from 22% to 34%, and the MET mutation rate from 16% to 19%. Notably, the MET exon 14 skipping mutation accounts for 31.8% of PSC cases in China, which is significantly higher than the 2.62% rate observed in all NSCLC cases \u003csup\u003e[\u003cspan additionalcitationids=\"CR14 CR15 CR16\" citationid=\"CR12\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTraditional treatments have limited efficacy for PSC. Surgery is the preferred option for early-stage resectable cases and has been confirmed by multivariate analysis as an independent favorable prognostic factor (hazard ratio [HR] 0.40-0.484, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), yet long-term survival remains unsatisfactory. The objective response rate (ORR) to chemotherapy is only 8.0%-16.5%, and perioperative (neoadjuvant/adjuvant) chemotherapy may only yield survival benefits for some stage III patients. Although radiotherapy may improve the overall survival (OS) of patients who are inoperable or have locally advanced disease, the efficacy of adjuvant radiotherapy has not been confirmed by large-sample studies \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn recent years, targeted therapy and immunotherapy have brought breakthroughs for PSC. In terms of immunotherapy, 74.2% of PSC patients have a PD-L1 expression level\u0026thinsp;\u0026ge;\u0026thinsp;50%. Additionally, PSC exhibits high tumor mutation burden (TMB) and a T-cell inflammatory microenvironment, laying the foundation for immunotherapy. Retrospective studies have shown that the ORR of immune checkpoint inhibitors (ICIs) monotherapy ranges from 31.6% to 40.5%, and this rate can increase to 70.2% in patients with high PD-L1 expression. Combinations of ICIs with anti-angiogenic agents (e.g., apatinib) have also shown potential efficacy \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22 CR23 CR24\" citationid=\"CR19\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCurrently, there are no clear clinical guidelines recommending treatment strategies for PSC patients with special molecular characteristics, such as concurrent EGFR/KRAS mutations or MET exon 14 skipping mutations combined with high PD-L1 expression. Most of the existing evidence comes from small-sample cohorts or case reports. Therefore, in clinical practice, individualized treatment plans should be formulated through multidisciplinary team (MDT) collaboration, considering the patient's pathological subtype, molecular profile, clinical stage, and physical function, to maximize survival benefits \u003csup\u003e[9, 10]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis article reports a case of a 62-year-old patient with stage Ⅳb right upper lung sarcomatoid carcinoma (with concurrent EGFR L861Q/KRAS mutations and PD-L1 TPS of 90%) who was treated at our hospital. The patient first received neoadjuvant therapy with \"paclitaxel\u0026thinsp;+\u0026thinsp;carboplatin\u0026thinsp;+\u0026thinsp;serplulimab\u0026thinsp;+\u0026thinsp;denosumab,\" and after disease remission, underwent \"video-assisted thoracoscopic right upper lobectomy.\" Postoperatively, the patient received maintenance therapy with \"furmonertinib\u0026thinsp;+\u0026thinsp;denosumab.\" This treatment achieved a primary tumor shrinkage of over 70%, and only 15% of viable tumor cells remained in the tumor bed of the postoperative specimen, meeting the criteria for partial pathological response (pPR) and approaching major pathological response (MPR, defined as residual tumor cells\u0026thinsp;\u0026lt;\u0026thinsp;10% in the primary lesion). This successfully converted an unresectable advanced lesion into a radically resected one, with no serious postoperative complications. Additionally, postoperative pathology revealed the disappearance of the EGFR mutation in the patient's tumor lesion after neoadjuvant therapy, suggesting a potential treatment-induced clonal evolution of the tumor.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA: Initial CT scan at admission B: Follow-up CT scan after 2 cycles of treatment\u003c/p\u003e \u003cp\u003eC: Follow-up CT scan after 4 cycles of treatment\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA: Bronchoscopy revealed enlargement of the 4R lymph nodeB: Microscopic findings of the lymph node biopsy after pathological staining\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 62-year-old female patient presented to our hospital on December 2, 2024, with \"cough and expectoration for more than 10 days,\" without accompanying symptoms such as hemoptysis, chest pain, or fever. A contrast-enhanced chest CT performed at our hospital revealed a 79mm\u0026times;73mm mass in the right upper lung (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA), accompanied by obstructive pneumonia and atelectasis. The patient was admitted to the thoracic surgery ward of our hospital to clarify the nature of the lesion.\u003c/p\u003e \u003cp\u003eAfter admission, comprehensive blood tests and functional assessments showed no significant abnormalities. Further imaging evaluation, a whole-body PET-CT scan (Fig.\u0026nbsp;3A), demonstrated: a space-occupying lesion in the right upper lung with surrounding obstructive pneumonia and atelectasis, involvement of mediastinal and hilar lymph nodes, possible bone metastases in the proximal right femur, and undetermined nature of multiple bilateral pulmonary nodules.\u003c/p\u003e \u003cp\u003eAfter evaluating that the patient\u0026rsquo;s physical condition could tolerate the procedure, a flexible bronchoscopic examination under intravenous anesthesia\u0026thinsp;+\u0026thinsp;transbronchial needle aspiration (TBNA) of the bronchial wall (4R lymph node) was performed on December 5, 2024 (Fig.\u0026nbsp;2A). Pathological findings indicated: malignant tumor. Microscopically, tumor cells were arranged in nests and sheets, with significant pleomorphism. The tumor cells were epithelioid and large polygonal, with foamy cytoplasm, irregular nuclei, and easily observable mitoses. Abundant inflammatory cells were seen between tumor cells. Combined with the histological morphology and immunohistochemical results, the diagnosis was consistent with sarcomatoid carcinoma (Fig.\u0026nbsp;2B).\u003c/p\u003e \u003cp\u003eStaging of the right lung malignant tumor: T4N2aM1c, stage Ⅳb (ipsilateral mediastinal lymph node metastasis, multiple distant metastases to the femur), with PD-L1 (TPS\u0026thinsp;=\u0026thinsp;90%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA: Initial PET-CT scan for staging assessment\u003c/p\u003e \u003cp\u003eB: Preoperative SPECT/CT scan (bone scan) for staging assessment after neoadjuvant therapy\u003c/p\u003e"},{"header":"Genetic Testing Results And Treatment Process","content":"\u003ch3\u003e1. Genetic Testing Results\u003c/h3\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e1.1 Somatic Variants\u003c/h2\u003e \u003cp\u003eTwo somatic variants were detected in this test, both of which are definite mutations in lung cancer-related driver genes. Details are as follows:\u003c/p\u003e \u003cp\u003eEGFR gene: Exon 21, L861Q sensitive mutation, detected Ct value = 29.30.\u003c/p\u003e \u003cp\u003eKRAS gene: Exon 2, mutations in G12A/G12V/G12R/G12C/G13C (verified by typing reagents, excluding the G12C mutation), detected Ct value = 28.84.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e1.2 Germline Variants\u003c/h2\u003e \u003cp\u003eNo germline variants were detected. Additionally, no pathogenic/potentially pathogenic variants associated with hereditary diseases were identified.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e2. Treatment Process\u003c/h3\u003e\n\u003cp\u003eOn December 11, 2024, January 3, 2025, January 24, 2025, and February 15, 2025, after dynamic monitoring to rule out contraindications, the patient received neoadjuvant chemotherapy combined with immunotherapy and targeted therapy for bone metastases, respectively.\u003c/p\u003e \u003cp\u003eThe regimens were as follows:\u003c/p\u003e \u003cp\u003eFour cycles of neoadjuvant chemotherapy combined with immunotherapy: paclitaxel (albumin-bound) 450mg + carboplatin 550mg + serplulimab 300mg.\u003c/p\u003e \u003cp\u003eThree cycles of targeted therapy: denosumab (120mg) to control the risk of bone metastases and regulate the tumor microenvironment.\u003c/p\u003e \u003cp\u003eAfter four cycles of neoadjuvant therapy, a follow-up contrast-enhanced chest CT was performed on April 6, 2025. Comparison with the CT scan on December 4, 2024, showed a significant reduction in the volume of the right upper lung tumor, which now measured approximately 22 mm × 25 mm × 24 mm. The degree of pleural invasion was reduced, and symptoms of obstructive pneumonia improved, indicating a marked therapeutic effect (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003eA follow-up SPECT/CT scan, compared with that on December 3, 2024, revealed increased density of the bone metastatic lesions in the proximal right femur, which was considered a manifestation of bone repair (Fig.\u0026nbsp;3B).\u003c/p\u003e \u003cp\u003eMeanwhile, contrast-enhanced cranial magnetic resonance imaging (MRI) + diffusion-weighted imaging (DWI) showed no obvious abnormalities.\u003c/p\u003e \u003cp\u003ePreoperative staging: ycT1cN0M0, stage IA3.\u003c/p\u003e \u003cp\u003e\u003c/p\u003e\u003cp\u003eAfter preoperative laboratory tests and pulmonary function assessment revealed no obvious surgical contraindications, the medical team performed video-assisted thoracoscopic right upper lobectomy + hilar and mediastinal lymph node dissection on the patient on April 7, 2025. The operation was smooth, with an intraoperative blood loss of 50ml, and no obvious postoperative complications occurred\u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003eA: Surgical specimen (right upper lung lobe) with a volume of 111mm×65mm×35mm. A nodule was seen at the cut surface, with a maximum diameter of 28mm. The cut surface was grayish-yellow, firm, with ill-defined borders and visible necrosis.\u003c/p\u003e \u003cp\u003eB: Microscopically, focal tumor cells (approximately 5%) were distributed in solid nests. The tumor cells had abundant eosinophilic and foamy cytoplasm with significant nuclear pleomorphism, consistent with sarcomatoid carcinoma changes.\u003c/p\u003e \u003cp\u003eC: Microscopic findings of PD-L1 detection\u003c/p\u003e\n\n "},{"header":"Postoperative Pathology","content":"\u003ch3\u003e1. Right Upper Lung Lobe\u003c/h3\u003e\u003cp\u003eCombined with the medical history, morphology, and immunohistochemistry, the findings are consistent with sarcomatoid carcinoma changes (most areas show invasive adenocarcinoma; focal tumor cells are distributed in solid nests. The tumor cells have abundant eosinophilic and foamy cytoplasm with significant nuclear pleomorphism) (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003eA, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003eB).\u003c/p\u003e\u003cp\u003eMaximum diameter of the tumor bed: approximately 2.8 cm.\u003c/p\u003e\u003cp\u003eViable tumor cells in the tumor bed: approximately 15%; necrosis: approximately 20%; fibrous stroma: approximately 65%.\u003c/p\u003e\u003cp\u003eNo definite vascular tumor thrombus was identified.\u003c/p\u003e\n\u003ch3\u003e2. Mediastinal Lymph Nodes\u003c/h3\u003e\n\u003cp\u003eAll 12 mediastinal lymph nodes were negative (0/12).\u003c/p\u003e \u003cp\u003eAuxiliary Examination: Immunohistochemistry (IHC) Results\u003c/p\u003e \u003cp\u003e(Wax blocks 4\u0026thinsp;+\u0026thinsp;6): CK(+), CK7(+), TTF-1(+), P40(-), Ki67 (approximately 10%), CK5/6(-), CD68(+), E-ca(+).\u003c/p\u003e \u003cp\u003e(Wax blocks 12\u0026thinsp;+\u0026thinsp;19): CK(-), LCA(+).\u003c/p\u003e \u003cp\u003e(Wax block 28): Vimentin(+), CK7 (focal +).\u003c/p\u003e\n\u003ch3\u003e3. PD-L1 Detection Result\u003c/h3\u003e\n\u003cp\u003ePD-L1 expression level in tumor cells: \u0026lt; 1% in the adenocarcinoma area; approximately 40% in the sarcomatoid carcinoma area (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003eC).\u003c/p\u003e\n\u003ch3\u003e4. Postoperative Genetic Testing\u003c/h3\u003e\n\u003cp\u003eNo EGFR exon 21 L861Q mutation was detected.\u003c/p\u003e \u003cp\u003eKRAS exon 2 mutation persisted.\u003c/p\u003e"},{"header":"Case Discussion","content":"\u003cp\u003eLung cancer is one of the cancers with the highest global incidence and mortality [1]. Pulmonary sarcomatoid carcinoma (PSC) is a rare, highly aggressive non-small cell lung cancer (NSCLC) subtype, accounting for approximately 0.1%-4% of all lung cancers. Its core pathological feature is dual positivity for cytokeratin (CK) and vimentin. Molecularly, it is characterized by a low incidence of classic sensitive EGFR mutations (only 28%, mostly rare variants like L861Q) and significantly higher mutation rates of KRAS (22%-34.4%) and TP53 (73.6%-81%). The patient in this case had concurrent EGFR L861Q and KRAS mutations\u0026mdash;an extremely rare occurrence in PSC with no guideline-recommended regimens\u0026mdash;plus initial stage Ⅳb (T4N2aM1c) and PD-L1 TPS of 90%, further highlighting the clinical exploratory value of treatment decisions.\u003c/p\u003e \u003cp\u003eTraditional PSC treatments have poor efficacy: chemotherapy achieves an objective response rate (ORR)\u0026thinsp;\u0026lt;\u0026thinsp;10%, and even with surgery, the 5-year survival rate is only 12.6%-16.3%. Though recent studies show immunotherapy combined with chemotherapy (chemoimmunotherapy, CIT) reaches 37%-43% ORR in PSC patients with PD-L1\u0026thinsp;\u0026ge;\u0026thinsp;50%\u0026mdash;emerging as a novel therapeutic direction\u0026mdash;standard strategies for PSC subtypes with \u0026ldquo;driver mutations\u0026thinsp;+\u0026thinsp;high PD-L1 expression\u0026rdquo; remain lacking domestically and internationally, leaving a significant unmet clinical need.\u003c/p\u003e \u003cp\u003eHowever, treatment decisions under such overlapping features face multiple challenges. At initial diagnosis, the patient was stage Ⅳb, with a 79mm\u0026times;73mm right upper lung lesion, mediastinal lymph node metastasis, and proximal right femoral bone metastasis\u0026mdash;classified as \u0026ldquo;unresectable\u0026rdquo; per traditional staging. Meanwhile, the molecular interaction of concurrent EGFR/KRAS mutations is unclear: KRAS mutations may weaken EGFR-targeted therapy efficacy via MAPK pathway activation, and the impact of EGFR mutations on the immunotherapeutic tumor microenvironment is understudied. This precludes the direct application of regimens for NSCLC with single driver mutations or high PD-L1 expression. Additionally, the lack of dynamic molecular monitoring during PSC treatment means the risk of tumor clonal evolution is underaddressed, increasing the complexity of treatment planning.\u003c/p\u003e \u003cp\u003eThe regimen chosen in this case was clearly rational based on cutting-edge evidence: the patient\u0026rsquo;s PD-L1 TPS of 90% supported CIT. Specifically, chemotherapy (paclitaxel\u0026thinsp;+\u0026thinsp;carboplatin) enhances the immune activation of the PD-1 inhibitor serplulimab by releasing tumor-associated antigens and reducing immunosuppressive cells. Denosumab not only prevents bone metastasis-related events but also improves the tumor microenvironment via RANKL-RANK pathway inhibition, synergistically boosting immunoefficacy. Moreover, neoadjuvant therapy\u0026mdash;proven to convert unresectable to resectable tumors in oligometastatic advanced NSCLC\u0026mdash;provided theoretical support for stage downstaging.\u003c/p\u003e \u003cp\u003eBased on this strategy, the patient achieved breakthrough treatment progress. After 4 cycles of neoadjuvant \u0026ldquo;paclitaxel\u0026thinsp;+\u0026thinsp;carboplatin\u0026thinsp;+\u0026thinsp;serplulimab\u0026thinsp;+\u0026thinsp;denosumab,\u0026rdquo; the right upper lung tumor shrank from 79mm\u0026times;73mm to 22mm\u0026times;25mm\u0026times;24mm (over 70% shrinkage). The stage was downstaged to IA3 (ycT1cN0M0), and the proximal right femoral bone metastases showed bone repair. Subsequent video-assisted thoracoscopic right upper lobectomy\u0026thinsp;+\u0026thinsp;hilar/mediastinal lymph node dissection was uneventful, with 50ml intraoperative blood loss and no postoperative complications.\u003c/p\u003e \u003cp\u003ePostoperative pathology revealed 15% viable tumor cells in the tumor bed\u0026mdash;though not meeting the criteria for major pathological response (MPR, residual tumor cells\u0026thinsp;\u0026lt;\u0026thinsp;10%), it satisfied partial pathological response (pPR), which is significantly superior to that of traditional chemotherapy. Notably, postoperative genetic testing showed loss of the EGFR L861Q mutation with persistent KRAS mutation, suggesting neoadjuvant CIT may induce tumor clonal evolution. This molecular finding provides a key clue for dynamic post-PSC treatment monitoring and a basis for selecting postoperative maintenance therapy (furmonertinib\u0026thinsp;+\u0026thinsp;denosumab).\u003c/p\u003e \u003cp\u003eThe case\u0026rsquo;s clinical insights hold practical and exploratory value, reflected in breaking traditional treatment thinking and advancing understanding of molecular mechanisms. Its most valuable decision was abandoning the \u0026ldquo;target-based treatment\u0026rdquo; convention. For PSC\u0026rsquo;s biological uniqueness, a \u0026ldquo;CIT-first\u0026rdquo; strategy was established based on three key points: (1) EGFR-TKI efficacy data in PSC are extremely limited, with only 2 retrospective studies reporting\u0026thinsp;\u0026lt;\u0026thinsp;15% ORR\u0026mdash;far lower than that in adenocarcinoma with conventional sensitive EGFR mutations; (2) concurrent KRAS mutations significantly increase EGFR-TKI resistance risk, as in vitro studies confirm KRAS G12C mutations reduce EGFR-TKI tumor cell inhibition by 40%, further weakening targeted therapy potential; (3) the patient\u0026rsquo;s PD-L1 TPS of 90% confers a clear immunotherapeutic benefit, with a 2-year overall survival (OS) rate of 58%\u0026mdash;significantly higher than the 35% with EGFR-TKI monotherapy. Ultimately, 4 cycles of treatment achieved 70% tumor shrinkage and near-MPR, verifying the rationality of this decision and providing a reference pathway for similar rare cases.\u003c/p\u003e \u003cp\u003eThe postoperative loss of the EGFR L861Q mutation with persistent KRAS mutation is another key insight, whose mechanism requires analysis of tumor biology and detection technology. The most plausible mechanism is treatment-induced clonal selection: neoadjuvant CIT activates anti-tumor immunity to preferentially eliminate more immunogenic EGFR-mutant clones, while KRAS-mutant clones become residual dominant clones due to stronger immune escape. This aligns with the \u0026ldquo;selective survival of tumor subclones under treatment pressure\u0026rdquo; theory reported in Nature Cancer (2024). Tumor heterogeneity (preoperative biopsy sampling only EGFR mutation-enriched areas vs. postoperative KRAS-dominant specimens) or differences in detection sensitivity (15% postoperative viable tumor cells possibly below the 5%-10% lower limit of some methods) cannot be fully excluded. This phenomenon highlights the need for dynamic circulating tumor DNA (ctDNA) monitoring during PSC treatment to guide subsequent adjustments (e.g., postoperative furmonertinib maintenance).\u003c/p\u003e \u003cp\u003eMore importantly, this case provides an innovative direction\u0026mdash;\u0026ldquo;treatment sequencing based on tumor subtype\u0026rdquo;\u0026mdash;for the \u0026ldquo;high PD-L1 expression\u0026thinsp;+\u0026thinsp;EGFR mutation\u0026rdquo; population not covered by current NCCN guidelines. Existing guidelines lack recommendations on the priority of immunotherapy vs. targeted therapy for this group. Yet this case suggests sequencing may require individualized adjustment based on NSCLC subtype aggressiveness: for highly aggressive subtypes (e.g., PSC, large-cell carcinoma), prioritizing CIT enables rapid tumor shrinkage, downstaging, and opportunities for radical surgery, while avoiding the insufficient efficacy and resistance risks of targeted therapy; for indolent subtypes (e.g., lung adenocarcinoma), EGFR-TKIs may be prioritized to control progression while preserving quality of life. Though requiring prospective cohort validation, this view fills guideline gaps and provides a clinically valuable entry point for optimizing individualized strategies.\u003c/p\u003e \u003cp\u003eThis single-case report has limitations: individual differences cannot be ruled out, requiring multicenter prospective studies to verify regimen efficacy and safety; postoperative follow-up is \u0026lt;\u0026thinsp;6 months, necessitating long-term observation of recurrence, metastasis, and potential resistance related to residual KRAS mutations; the mechanism of EGFR L861Q loss remains unclear, requiring follow-up basic research (e.g., single-cell sequencing) to elucidate CIT-induced tumor clonal evolution.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Key Clinical Projects of Affiliated Hospital of Guangdong Medical University (LCYJ2022DL003) and the Supported Projects of Zhanjiang (2021A05076).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest/Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare that are relevant to the content of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCARE Guidelines Compliance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report strictly adheres to the CARE (Case Report) Guidelines to ensure transparency, completeness, and methodological rigor.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for the publication of this case report and accompanying images, in compliance with the Declaration of Helsinki. The patient was fully informed of the purpose of the study, the use of clinical data, imaging materials, and pathological findings in the publication, and voluntarily provided written consent for both participation in the study and the publication of de-identified personal and clinical information. Relevant consent documents are available from the corresponding author upon reasonable request by the editorial office.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZ.L., J.C., and Z.H. contributed to the conception or design of the work. H.F.Z., A.L., and Y.T.P. contributed to the acquisition and analysis of data for the work., Y.T.P. are responsible for the interpretation of data. Y.T.P. drafted the manuscript. F.S.L. and Z.H. critically revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a retrospective clinical analysis. All experimental protocols have been approved by the Ethics Committee of Affiliated Hospital of Guangdong Medical University. The study strictly adheres to the principles of the Declaration of Helsinki, and all clinical diagnosis and treatment procedures, data collection methods, and detection techniques employed are covered by the ethical approval.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for participation in the study and for publication of this case report and any accompanying images.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eW. D. Travis, E. Brambilla, and A. G. Nicholson, \u0026ldquo;The 2015 world health organization classification of lung tumors,\u0026rdquo;Journal of Thoracic Oncology, vol. 10, no. 9, pp. 1243\u0026ndash;1260,2015.\u003c/li\u003e\n\u003cli\u003eY. Lin, H. Yang, and Q. Cai, \u0026ldquo;Characteristics and prognostic analysis of 69 patients with pulmonary sarcomatoid carci-noma,\u0026rdquo; American Journal of Clinical Oncology, vol. 39, no. 3,pp. 215\u0026ndash;222, 2016.\u003c/li\u003e\n\u003cli\u003eH. M. Abdallah, D. Martinez-Meehan, and W. Lutfi, \u0026ldquo;Adjuvant chemotherapy for pulmonary sarcomatoid carcinoma:a retrospective analysis of the national cancer database,\u0026rdquo; TheJournal of Thoracic and Cardiovascular Surgery, vol. S0022-5223, no. 21, p. 180, 2021.\u003c/li\u003e\n\u003cli\u003eC. E. Steuer, M. Behera, and Y. Liu, \u0026ldquo;Pulmonary sarcomatoid carcinoma: an analysis of the national cancer data base,\u0026rdquo;Clinical Lung Cancer, vol. 18, no. 3, pp. 286\u0026ndash;292, 2017.\u003c/li\u003e\n\u003cli\u003eS. Yendamuri, L. Caty, M. Pine et al., \u0026ldquo;Outcomes of sarcomatoid carcinoma of the lung: a surveillance, epidemiology,and end results database analysis,\u0026rdquo; Surgery, vol. 152, no. 3,pp. 397\u0026ndash;402, 2012.\u003c/li\u003e\n\u003cli\u003eM. Chen, Q. Yang, and Z. Xu, \u0026ldquo;Survival analysis and pre-diction model for pulmonary sarcomatoid carcinoma basedon SEER database,\u0026rdquo; Frontiers in Oncology, vol. 11, Article ID630885, 2021.\u003c/li\u003e\n\u003cli\u003eK. Maneenil, Z. Xue, and M. Liu, \u0026ldquo;Sarcomatoid carcinoma ofthe lung: the Mayo clinic experience in 127 patients,\u0026rdquo; Clinical Lung Cancer, vol. 19, no. 3, pp. e323\u0026ndash;e333, 2018.\u003c/li\u003e\n\u003cli\u003eC. E. Steuer, M. Behera, and Y. Liu, \u0026ldquo;Pulmonary sarcomatoid carcinoma: an analysis of the national cancer data base,\u0026rdquo;Clinical Lung Cancer, vol. 18, no. 3, pp. 286\u0026ndash;292, 2016.8 Journal of Oncology\u003c/li\u003e\n\u003cli\u003eU.S. National Library of Medicine, \u0026ldquo;Clinical trials on pulmonary sarcomatoid carcinoma,\u0026rdquo; U.S. National Library ofMedicine, Bethesda, MD, USA, 2021.\u003c/li\u003e\n\u003cli\u003eNational Comprehensive Cancer Network, 2021, NCCN Guidelines, Non-Small Cell Lung Cancer.\u003c/li\u003e\n\u003cli\u003eR. J. \u0026acute;Avila Mart\u0026acute;ınez, C. Marr\u0026acute;on Fern\u0026acute;andez, and F. Hermoso Alarza, \u0026ldquo;Carcinomas sarcomatoides pulmonares primarios,\u0026rdquo;Archivos de Bronconeumolog\u0026acute;ıa, vol. 49, no. 9, pp. 405\u0026ndash;407,2013.\u003c/li\u003e\n\u003cli\u003eSchrock A B, Li S D, Frampton G M. Pulmonary sarcomatoid carcinomas commonly harbor either potentially targetable genomic alterations or high tumor mutational burden as observed by comprehensive genomic profiling[J]. Journal of Thoracic Oncology, 2017, 12(6): 932-942.\u003c/li\u003e\n\u003cli\u003eZhou F, Huang Y, Cai W. The genomic and immunologic profiles of pure pulmonary sarcomatoid carcinoma in Chinese patients[J]. Lung Cancer, 2021, 153: 66-72.\u003c/li\u003e\n\u003cli\u003eYang Z, Xu J, Li L. Integrated molecular characterization reveals potential therapeutic strategies for pulmonary sarcomatoid carcinoma[J]. Nature Communications, 2020, 11(1): 1-12.\u003c/li\u003e\n\u003cli\u003eTong J H, Yeung S F, Chan A W H. MET amplification and exon 14 splice site mutation define unique molecular subgroups of non-small cell lung carcinoma with poor prognosis[J]. Clinical Cancer Research, 2016, 22(12): 3048-3056.\u003c/li\u003e\n\u003cli\u003eLiu X, Jia Y, Stoopler M B. Next-Generation sequencing of pulmonary sarcomatoid carcinoma reveals high frequency of actionable MET gene mutations[J]. Journal of Clinical Oncology, 2016, 34(8): 794-802.\u003c/li\u003e\n\u003cli\u003eZeng Q, Li J, Sun N. Preoperative systemic immune-inflammation index predicts survival and recurrence in patients with resected primary pulmonary sarcomatoid carcinoma[J]. Translational Lung Cancer Research, 2021, 10(1): 18-31.\u003c/li\u003e\n\u003cli\u003eGang J, Yan Q, Xiang S. Clinicopathological characteristics and prognostic factors of pulmonary sarcomatoid carcinoma: a large population analysis[J]. Annals of Translational Medicine, 2021, 9(2): 121\u003c/li\u003e\n\u003cli\u003e.[20] Sun L, Dai J, Chen Y. Pulmonary sarcomatoid carcinoma: experience from SEER database and Shanghai pulmonary hospital[J]. The Annals of Thoracic Surgery, 2020, 110(2): 406-413.\u003c/li\u003e\n\u003cli\u003eVieira T, Girard N, Ung M. Efficacy of first-line chemotherapy in patients with advanced lung sarcomatoid carcinoma[J]. Journal of Thoracic Oncology, 2013, 8(12): 1574-1577.\u003c/li\u003e\n\u003cli\u003eBabacan N A, Pina I B, Signorelli D. Relationship between programmed death receptor-ligand 1 expression and response to checkpoint inhibitor immunotherapy in pulmonary sarcomatoid carcinoma: a pooled analysis[J]. Clinical Lung Cancer, 2020, 21(5): e456-e463.\u003c/li\u003e\n\u003cli\u003eDomblides C, Leroy K, Monnet I. Efficacy of immune checkpoint inhibitors in lung sarcomatoid carcinoma[J]. Journal of Thoracic Oncology, 2020, 15(5): 860-866.\u003c/li\u003e\n\u003cli\u003eManglaviti S, Brambilla M, Signorelli D. Immune-checkpoint inhibitors in advanced non-small cell lung cancer with uncommon histology[J]. Clinical Lung Cancer, 2021, 23(1): e17-e28.\u003c/li\u003e\n\u003cli\u003eZhao S, Ren S, Jiang T. Low-dose apatinib optimizes tumor microenvironment and potentiates antitumor effect of PD-1/PD-L1 blockade in lung cancer[J]. Cancer Immunology Research, 2019, 7(4): 640-643.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Pulmonary Sarcomatoid Carcinoma (PSC), EGFR3.L861Q/KRAS Co-mutation, PD-L1 High Expression, Neoadjuvant Immunochemotherapy, Major Pathological Response (MPR), Case Report","lastPublishedDoi":"10.21203/rs.3.rs-8460147/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8460147/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground Pulmonary sarcomatoid carcinoma (PSC) is a rare, highly aggressive non-small cell lung cancer (NSCLC) subtype (0.1%–4% of lung malignancies)\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e[3]\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e. Clinically, it mainly affects smokers, with half diagnosed at advanced stages; pathologically, it is defined by cytokeratin-vimentin co-expression. Molecularly, classical EGFR-sensitive mutations are rare (28%, mostly rare variants like L861Q), while KRAS (22%–34.4%), MET (16%–19%), and TP53 (73.6%–81%) mutations are common\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e[13–17]\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e. Traditional treatments are ineffective (chemotherapy ORR \u0026lt; 10%; surgical 5-year survival 12.6%–16.3%), but immunotherapy (mono/combined with chemotherapy) shows promise (73%–77% with PD-L1 ≥ 50%; ORR 37%–43%)\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e[2, 7, 18–21]\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e. No guidelines exist for PSC with driver mutations (e.g., EGFR/KRAS co-mutation) plus high PD-L1.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods We retrospectively analyzed clinical, imaging, pathological, and therapeutic data of one PSC patient with informed consent.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults A 62-year-old with stage Ⅳb right upper lung PSC (EGFR L861Q/KRAS co-mutation; PD-L1 TPS 90%) received neoadjuvant \"Paclitaxel + Carboplatin + Serplulimab + Denosumab,\" followed by thoracoscopic lobectomy and postoperative \"Furmonertinib + Denosumab.\" Postoperatively, tumor bed viable cells accounted for 15% (meeting pPR, near MPR [residual \u0026lt; 10%]), with EGFR mutation loss, suggesting treatment-induced clonal evolution.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion Neoadjuvant immunochemotherapy is feasible for PSC with \"driver mutation + high PD-L1,\" providing a clinical reference. It highlights the importance of MDT collaboration and dynamic molecular monitoring in advanced PSC, addressing guideline gaps.\u003c/strong\u003e\u003c/p\u003e","manuscriptTitle":"Stage Ⅳb Pulmonary Sarcomatoid Carcinoma with EGFR L861Q KRAS Co-mutation and High PD-L1 Expression Neoadjuvant Immunochemotherapy Combined with Surgery Achieves Near MPR","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-30 01:33:44","doi":"10.21203/rs.3.rs-8460147/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9e6a2a0a-84c0-4051-a18a-49d0935f8c1f","owner":[],"postedDate":"January 30th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-18T09:11:21+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-30 01:33:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8460147","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8460147","identity":"rs-8460147","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}