Synchronous Multiple Primary Lung Cancer Research Articles

Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

Long-term prognosis analysis of surgical therapy for bilateral synchronous multiple primary lung cancer: a follow-up of 293 cases.

Bilateral synchronous multiple primary lung cancer (BSMPLC) presents significant clinical challenges due to its unique characteristics and prognosis. Understanding the risk factors that influence overall survival (OS) and recurrence-free survival (RFS) is crucial for optimizing therapeutic strategies for BSMPLC patients. We retrospectively analyzed clinical characteristics and treatment outcomes of 293 patients with BSMPLC who underwent surgical treatment between January 2010 and July 2017. The 10-year OS and RFS rates were 96.1% and 92.8%, respectively. Preoperative forced expiratory volume in 1 second (FEV1) ≥70% [hazard ratio (HR), 0.214; 95% confidence interval (CI): 0.053 to 0.857], identical pathology types (HR, 9.726; 95% CI: 1.886 to 50.151), largest pT1 (HR, 7.123; 95% CI: 2.663 to 19.055), and absence of lymphovascular invasion (LVI; HR, 7.021; 95% CI: 1.448 to 34.032) emerged as independent predictors of improved OS. Moreover, the sum of tumor sizes less than or equal to 3 cm (HR, 6.229; 95% CI: 1.411 to 27.502) and absence of pleural invasion (HR, 3.442; 95% CI: 1.352 to 8.759) were identified as independent predictors of enhanced RFS. The presence or absence of residual nodules after bilateral surgery did not influence patients' OS (P=0.987) and RFS (P=0.054). Patients with BSMPLC who underwent surgery generally had a favorable prognosis. Whether or not to remove all nodules bilaterally does not affect the patient's long-term prognosis, suggesting the need for an individualized surgical approach.

Chinese expert consensus: multidisciplinary diagnosis and treatment of multiple ground-glass nodule like lung cancer (2024 edition)

Multiple ground glass nodules (GGN) like lung cancer is a special type of synchronous multiple primary lung cancer, with two or more lesions present simultaneously. It has characteristics such as"indolent"development, less lymph node or distant metastasis, identical or different pathological stages, differential driving gene mutations, diverse imaging manifestations, and good prognosis. In order to standardize the diagnosis and treatment behavior of multiple GGN-like lung cancer, reduce issues such as over diagnosis and insufficient treatment, relevant domestic experts are organized by The Lung Cancer Medical Education Committee of the Chinese Medical Education Association, Lung Cancer Alliance of Chinese Thoracic Surgery, the Society of Tumor Ablation Therapy of the Chinese Anti-Cancer Association, the Tumor Ablation Expert Committee of the Chinese Society of Clinical Oncology, the Tumor Ablation Expert Group of the Chinese College of Interventionalists, The Chinese Expert Consensus:Multidisciplinary Diagnosis and Treatment of Multiple Ground-Glass Nodule Like Lung Cancer (2024 Edition) was discussed and formulated. The main content includes: follow-up strategies, differential diagnosis, diagnosis and staging, treatment methods, and post treatment follow-up for multiple GGN-like lung cancer.

Synchronous multiple neuroendocrine primary lung cancer with endobronchial extension in a never smoker - An unusual manifestation

Synchronous Lung Cancer primaries (SLC) are uncommon, with diverse underlying histology, constituting only a small proportion. The scarcity also poses a challenge in formulating a standardized diagnostic approach. Consequently, the diagnostic and staging challenges for SLC are heightened, particularly when the tumors are located on opposite sides of the chest. We report an exceptionally rare phenomenon in synchronous multiple primary lung cancers with simultaneous occurrence of two neuroendocrine tumors with endobronchial extension, small cell carcinoma and typical carcinoid tumor. Immunohistochemistry proved valuable in confirming the diagnosis. Given the poor prognosis associated with such cases, an accurate diagnosis is crucial for determining appropriate treatment options.

Clinical and pathologic staging accuracy in patients with synchronous multiple primary lung cancers.

The incidence of synchronous multiple primary lung cancer (SMPLC) is increasing, occurring in up to 20% of lung cancer patients. Accurately identifying SMPLC can be challenging, and failure to recognize SMPLC results in poor outcomes. We sought to assess the staging accuracy of patients with SMPLC at our tertiary institution. We retrospectively reviewed all patients who were evaluated for lung cancer resection between January 2018 to September 2019. Patients with SMPLC were identified using the modified Martini-Melamed criteria. Preoperative imaging, clinical assessment, and pathologic interpretation were reviewed and compared to the final staging assigned by a multidisciplinary lung cancer tumor board to determine accuracy. Out of 227 patients presenting for lung cancer resection, 47 patients with 119 SMPLC were identified, of which 38 (80.9%) were incorrectly staged by at least one report. Incorrect staging was most common by computed tomography (CT) reports (n=33/47, 70.2%), followed by positron emission tomography-CT (PET-CT) reports (n=28/45, 62.2%), surgeons' clinical assessment (n=10/47, 21.3%), and histopathology reports (n=8/47, 17.0%). CT reports, when incorrect, under-staged 97.0% (n=32) of patients. PET-CT reports, when incorrect, over-staged 25.0% (n=7) of patients by reporting the second primary nodule to be "consistent with metastasis". Histopathology reports, when incorrect, over-staged 87.5% (n=7) of patients despite lack of lymph node involvement. Patients with SMPLC are at risk of receiving incorrect treatment based on radiographic and histopathologic staging reports alone. The observed staging inaccuracies are concerning, necessitating increased awareness among physicians caring for lung cancer patients.

Challenges in diagnosis and management of patients with synchronous multiple primary lung cancers

Challenges in diagnosis and management of patients with synchronous multiple primary lung cancers

Contemporary Incidence of Synchronous Multiple Primary Lung Cancers and Survival in the Era of Lung Cancer Screening.

Up to 15% of lung cancer patients have multiple suspicious nodules. While some of these nodules may represent metastatic lung cancer, others represent synchronous multiple primary lung cancer (SMPLC). The incidence of SMPLC ranges from 0.8% to 8.4% and appears to be increasing. Inconsistent identification of SMPLC can be detrimental for patients who are misdiagnosed as having intrapulmonary metastasis and not offered stage-based treatment. We sought to identify the contemporary incidence of SMPLC at a tertiary institution. From January 2018 to September 2019, patients who underwent lung cancer resection were retrospectively reviewed. Patients with SMPLC were identified using the modified Martini-Melamed criteria. During the 21-month period, 227 patients underwent lung cancer resection. There were 47 patients (20.7%) who had 119 pathologically confirmed SMPLC. Most patients had ipsilateral tumors (n = 24, 51.1%) with at least 1 adenocarcinoma (n = 40, 85.1%). Considering histologic subtyping, 38 (80.9%) had histologically distinct tumors. Overall and cancer-specific survival at 4 years was 86% and 90%, respectively. Only patients with 3 or more SMPLC had poor 4-year overall (P = 0.002) and cancer-specific survival (P = 0.043) compared with those with 2 SMPLC. Patient demographics, histology, tumor location, and highest pathologic staging did not affect survival outcomes. Using a strict inclusion criterion, the incidence of SMPLC is higher than previously reported. SMPLC patients have favorable survival outcomes, suggesting that they behave like primary lung cancer, not intrapulmonary metastasis. Awareness of SMPLC by thoracic surgeons is critical in optimizing outcomes in this patient population.

Synchronous lung cancer presenting with small cell carcinoma and squamous cell lung carcinoma: a case report.

Synchronous multiple primary lung cancers are separate tumors presenting at the same time with different histology. We present a rare case of a 64-year-old patient with a combination of small-cell lung carcinoma (SCLC) and squamous carcinoma in two different sites with metastasis of SCLC in the mediastinal lymph node. The SCLC diagnosis was performed via bronchoscopy, and the other diagnosis via CT-guided transthoracic biopsy. It is often difficult to distinguish a synchronous tumor from intrapulmonary metastases. To date, there are no guidelines for the treatment of these cases. The management of synchronous multiple primary lung cancer (SMPLC), mainly surgical with chemotherapy or radiotherapy, must be studied according to the histological type, staging and molecular testing of the tumors. These rare cases of SMPLC require individual treatment and a multidisciplinary approach.

Sublobar resection versus lobectomy in the treatment of synchronous multiple primary lung cancer

ObjectiveAlthough synchronous multiple primary lung cancers (sMPLCs) are common in clinical practice, the choice of surgical modalities for the main lesion is still at the stage of exploration. This study is designed to analyze the prognosis of sMPLCs and single primary lung cancers with similar tumor stages and to explore whether sublobar resection has a similar prognosis as lobectomy for sMPLCs.MethodsOne-hundred forty-one cases of sMPLCs were selected, including the following: 65 cases underwent lobectomy for main lesions, and 76 cases underwent sublobar resection for main lesions. One thousand one hundred forty-four cases of single primary lung cancer were matched at 1:1 by propensity score matching. Then, the patients with sMPLCs were divided into a lobectomy group and a sublobar group according to the first tumor stage. Ninety-eight cases of patients with sMPLCs were matched. The short-term perioperative effect, 5-year disease-free survival (DFS) rate, and 5-year overall survival (OS) rate between the two groups were compared.ResultsThere was no significant difference in OS between sMPLCs and single primary lung cancer after lobectomy (77.1% vs. 77.2%, P = 0.157) and sublobar resection (98.7% vs. 90.7%, P = 0.309). There was no significant difference in OS (86.7% vs. 83.9%, P = 0.482) or DFS (67.6 vs. 87.7%, P = 0.324) between the lobectomy group and sublobar group with sMPLCs. The sublobar resection group obtained a lower incidence of postoperative complications (40.8% vs. 16.3%, P = 0.007) and shorter postoperative hospital stay (11.22 vs. 9.27, P = 0.049).ConclusionThe prognosis of patients with sMPLCs generally depends on the main tumor state, which has no statistical difference regardless of sublobar resection or lobectomy, and the perioperative period of sublobar resection is safer than that of lobectomy.

Real-world comprehensive diagnosis and "Surgery + X" treatment strategy of early-stage synchronous multiple primary lung cancer.

Diagnosing and treating synchronous multiple primary lung cancers (sMPLC) are complex and challenging. This study aimed to report real-world data on the comprehensive diagnosis and treatment of patients with early-stage sMPLC. A single-center cohort study was carried out and a large number of patients with early-stage sMPLC were included. A single- or two-stage surgery was performed to remove the primary and co-existing lesions. The "X" strategies, including ablation, SBRT, and EGFR-TKIs treatment, were applied to treat the high-risk residual lesions. Wide panel-genomic sequencing was performed to assess the genetic heterogeneity of the co-existing lesions. A total of 465 early-stage sMPLC patients with 1198 resected lesions were included. Despite most patients being histologically different or harboring different genetic alternations, about 7.5% of the patients had the same histological type and driver gene mutation changes, comprehensive re-evaluation is thus needed. The "Surgery + X" strategy showed remarkable efficacy and safety in treating multiple lesions. Follow-up data revealed that the T2 stage (p = 0.014) and the solid presence of a primary lesion (p < 0.001) were significantly related to tumor recurrence. And a T2-stage primary tumor had a significantly higher rate of developing new lesions after the initial surgery (p < 0.001). In real-world practice, histopathological and radiological evaluation combined with genetic analyses could be a robust diagnostic approach for sMPLC. The "Surgery + X" treatment strategy showed remarkable efficacy, superiority, and safety in the clinical treatment of early-stage sMPLC.

ASO Author Reflections: CT-Based Prognostic Score as an Indicator for Predicting the Survival of Patients with Synchronous Multiple Primary Lung Cancer.

ASO Author Reflections: CT-Based Prognostic Score as an Indicator for Predicting the Survival of Patients with Synchronous Multiple Primary Lung Cancer.

CT-based decision tree model for predicting EGFR mutation status in synchronous multiple primary lung cancers.

The current study aimed to construct a computed tomography (CT)-based decision tree algorithm (DTA) model to predict the epidermal growth factor receptor (EGFR) mutation status in synchronous multiple primary lung cancers (SMPLCs). The demographic and CT findings of 85 patients with molecular profiling for surgically resected SMPLCs were reviewed retrospectively. Least absolute shrinkage and selection operator (LASSO) regression was used to select the potential predictors of EGFR mutation, and a CT-DTA model was developed. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to assess the performance of this CT-DTA model. The CT-DTA model was applied to predict the EGFR mutant that had ten binary split, of which eight parameters to accurately categorize the lesions as follows: the presence of bubble-like vacuole sign (19.4% importance in the development of the model), presence of air bronchogram sign (17.4% importance), smoking status (15.7% importance), types of the lesions (14.8% importance), histology (12.6% importance), presence of pleural indentation sign (7.6% importance), gender (6.9% importance), and presence of lobulation sign (5.6% importance). The ROC analysis achieved an area under the curve (AUC) of 0.854. Multivariate logistic regression analysis demonstrated that this CT-DTA model was an independent predictor of EGFR mutation (P<0.001). CT-DTA model is a simple tool to predict the status of EGFR mutation in SMPLC patients and could be considered for treatment decision-making.

A Novel Prognostic Score Based on Multiple Quantitative Parameters of Chest CT for Patients with Synchronous Multiple Primary Lung Cancer: Is Solid Component Size a Better Prognostic Indicator?

There is no simple and definitive way to predict the prognosis of synchronous multiple primary lung cancer (SMPLC). In this study, we developed a clinical prognostic score for predicting the survival of patients with SMPLC. This study included 206 patients with SMPLC between 2011 and 2020 at three hospitals. Kaplan-Meier analysis was used to determine the optimal cutoff values for the quantitative chest computed tomography (CT) parameters. Multivariable Cox proportional hazards regression was carried out to identify independent prognostic factors for predicting overall survival (OS) and disease-free survival (DFS). The time-dependent receiver operating characteristic curve was analyzed to evaluate the prognostic performance. A CT-based prognostic score (CTPS) comprising six chest CT parameters was developed. Compared with T stage, CTPS had a higher prediction accuracy for OS and DFS. All C-indices of the model reached a satisfactory level in both the development and validation cohorts. Significant differences in the OS and DFS curves were observed when the patients were stratified into different risk groups. The high-risk group (CTPS of 5-6) had poorer survival than the low-risk group (CTPS of 0-4). The developed CTPS and the corresponding risk stratification system are valid for predicting the survival of patients with SMPLC.

Treatments and whole exon sequencing of a case with multiple primary lung cancer

IntroductionThe number of patients with synchronous multiple primary lung cancer (sMPLC) has increased recently. However, diagnosing and selecting the appropriate therapeutic strategy for this type of disease is not simple.Case presentationThis report presented a case of sMPLC with lymph node metastasis. With no smoking and cancer history, this patient had seven nodules in the right lung and underwent single-portal video-assisted thoracoscopic surgery (VATS). In addition, she received four cycles of chemotherapy after the operation. Whole exon sequencing (WES) was performed in five resected tissue samples (four tumors and one lymph node). We conducted genomic profiling and clone evolution analysis of the five samples. Gene detection helped to confirm that the metastasis lymph node was transferred from one nodule. There was apparent heterogeneity of gene mutations among the five samples of the patient, with only one shared “neurofilament heavy polypeptide” (NEFH) mutation. A dominant substitution of C > T/G > A was found in all the samples. Pyclone model was used to calculate all tissues' cellular prevalence (CP) values, and NEFH mutations were thought to be the ancestral clones. During the follow-up period, residual lesions showed no apparent changes and limited response to chemotherapy.ConclusionsThis report showed an essential role in genomic detection and selecting the appropriate treatment of sMPLC. Surgery remains the primary treatment strategy for this type of disease, and the occurrence and development of sMPLC need more in-depth research.

Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer

BackgroundTo explore the possible carcinogenesis and help better diagnose and treat patients with synchronous multiple primary lung cancers (sMPLC), we systematically investigated the genetic and DNA methylation profiles of early-stage sMPLC and single primary lung cancer (SPLC) and explored the immune profiles in the tumor microenvironment.MethodsHundred and ninety-one patients with 191 nodules in the SPLC group and 132 patients with 295 nodules in the sMPLC group were enrolled. All the samples were subjected to wide panel-genomic sequencing. Genome-wide DNA methylation was assessed using the Infinium Human Methylation 850 K BeadChip. RNA-seq and CIBERSORT analyses were performed to identify the immune characteristics in these two groups.ResultsLesions from sMPLC patients had lower TMB levels than that from SPLC patients. sMPLC had a similar genetic mutational landscape with SPLC, despite some subgroup genetic discrepancies. Distinct DNA methylation patterns were identified between the two groups. The differentially methylated genes were related to immune response pathways. RNA-seq analyses revealed more immune-related DEGs in sMPLC. Accordingly, more immune-related biological processes and pathways were identified in sMPLC. Aberrant DNA methylation was associated with the abnormal expression of immune-related genes. CIBERSORT analysis revealed the infiltration of immune cells was different between the two groups.ConclusionOur study for the first time demonstrated genetic, epigenetic, and immune profile discrepancies between sMPLC and SPLC. Relative to the similar genetic mutational landscape, the DNA methylation patterns and related immune profiles were significantly different between sMPLC and SPLC, indicating their essential roles in the initiation and development of sMPLC.

Osimertinib showed efficacy on contralateral multiple ground-glass nodules after segmentectomy for lung adenocarcinoma harboring primary EGFR-T790M mutation: a case report and review of the literature

BackgroundMultiple ground-glass nodules (mGGNs) in the lung has been defined as synchronous multiple primary lung cancer (SMPLC), it is has been very difficult challenging to differentiate SMPLC from intrapulmonary metastases, and its treatment remains controversial.Case presentationWe report a case simultaneously involving mGGNs and lung adenocarcinoma harboring primary EGFR-T790M mutation, in which the patient underwent the radical resection of lesions in the left upper lung, and continued the osimertinib treatment for the residual mGGNs in all lobes of the right lung. These mGGNs displayed different responses to osimertinib.ConclusionsWe reported a successful strategy on the postoperative treatment for mGGNs. For those that cannot be completely resected, the chemotherapy, radiotherapy, stereotactic body radiation therapy, immunotherapy and targeted therapy have been performed instead. The EGFR-TKI therapy strategy showed significant advantages, but how to achieve even better therapeutic effect needs more researches.

Small nodules (≤ 6 mm in diameter) of multiple primary lung cancers: prevalence and management

BackgroundSynchronous multiple primary lung cancers associated with small non-dominant nodules are commonly encountered. However, the incidence, follow-up, and treatment of small non-dominant tumors have been but little studied. We explored the prevalence and management of small non-dominant tumors and factors associated with interval growth.MethodsThis observational, consecutive, retrospective single-center study enrolled patients diagnosed with synchronous multiple primary lung cancers and small non-dominant tumors (≤ 6 mm in diameter) who underwent resection of the dominant tumor. The incidence, follow-up, and management of small non-dominant tumors and predictors of nodule growth were analyzed.ResultsThere were 88 patients (12% of all lung cancer patients) with pathological diagnoses of synchronous multiple primary lung cancers. A total of 131 (18%) patients were clinically diagnosed with at least one small (≤ 6 mm in diameter) multiple primary lung cancer non-dominant tumor. 94 patients with 125 small-nodule non-dominant tumors clinically diagnosed as multiple primary lung cancers were followed-up for at least 6 months. A total of 29 (29/125, 23.2%) evidenced small pulmonary nodules (≤ 6 mm in diameter) that exhibited interval growth on follow-up computed tomography (CT). On multivariate analysis, a part-solid nodule (compared to a pGGN) (OR 1.23; 95% CI 1.08–1.40) or a solid nodule (compared to a pGGN) (OR 3.50; 95% CI 1.94–6.30) predicted small nodule interval growth.ConclusionWe found a relatively high incidence of multiple primary lung cancers with small non-dominant tumors exhibiting interval growth on follow-up CT, suggesting that resection of non-dominant tumors at the time of dominant tumor resection, especially when the nodules are part-solid or solid, is the optimal treatment.

V7 ENB-guided thoracoscopic sublobectomy for stage IA synchronous multiple primary lung cancer.

An increasing number of patients are being diagnosed with synchronous multiple primary lung cancer (SMPLC) with the popularization of lung cancer screening programs. However, a strategy for accurate location and suitable surgery therapy is still lacking. The present study aimed to explore the accuracy and feasibility of electromagnetic navigation bronchoscopy (ENB)-guided thoracoscopic sublobectomy for stage IA SMPLC. Patients with SMPLC who underwent ENB-guided sublobectomy from January 2020 to June 2022 were enrolled in this study. The analysis of localization accuracy of ENB and surgical outcome was conducted. Overall, 138 patients with 353 malignant nodules were enrolled. The tumor size was 0.7cm (range from 0.5 to 1.1cm). ENB localization was performed on 162 nodules, and a customized scoring system was developed to evaluate localization accuracy. The success rate of localization was 98.3% (178/181). Notably, localization accuracy was positively correlated with bronchial signs (p < 0.01) and negatively correlated with the distance from the nodule to the pleura (p=0.02). All nodules were completely resected. Operation time, drainage volume on the third postoperative day, and catheter time were significantly correlated with the resected lesion numbers (p=0.009, p=0.004, and p=0.01, respectively). ENB-guided uniportal video-assisted thoracoscopic sublobectomy provides accurate preoperative localization and avoids unnecessary lung resection of patients with stage IA SMPLC. However, complete resection of multilocation nodules (more than four lesions) increases the risk of postoperative complications. A new combined treatment strategy for SMPLC should be explored.

Sequential bronchoplastic upper lobectomy as a surgical component of multimodal treatment for synchronous bilateral multiple primary non-small cell lung cancer

Relevance. Lung cancer (LC) is the leading cause of cancer-related death worldwide including Russia. Surgery remains the standard of care for early non-small cell lung cancer (NSCLC). However, as the disease progresses, the risk of metastasis increases, and the effectiveness of surgical intervention decreases. The treatment strategy for patients presenting with a single NSCLC has long been developed. However, for patients with two or more tumors, especially in both lungs, the correct choice is determined by many additional factors. Currently, the view on the surgical treatment for synchronous multiple primary NSCLC has changed dramatically. However, patients with locally advanced synchronous NSCLC often receive conservative treatment, and for those who do undergo surgery, the prognostic factors are unclear. The disease prognosis in patients after surgical treatment for bilateral synchronous multiple primary NSCLC has now been proven to be favorable. Pneumonectomy is believed to have no any negative effect on survival; however, several authors reported on a 1.5-2-fold increase in postoperative mortality in a series of surgeries for synchronous NSCLC. Case description. We herein report a case in which extended bronchoplastic upper lobectomy was successfully applied in the treatment of a patient with bilateral synchronous NSCLC. Our experience demonstrates that the sequential application of modern therapeutic modalities results in satisfactory long-term outcomes in the treatment of locally advanced LC.Conclusion. Due to its uniqueness, this clinical case will be useful for developing treatment strategy for synchronous locally advanced NSCLC as well as for improving the quality of life of patients and increasing their survival.

Abstract 5231: Case report: dramatic response to Crizotinib in a patient with synchronous multiple primary lung cancer positive for a novel ARL1-MET fusion

Abstract Background: With the use of high-resolution chest imaging system, an increasing number of lung cancer patients are being diagnosed with multiple primary lung cancer (MPLC). Although surgery is considered as the first choice of treatment for early MPLC, targeted therapy is essential in the management of unresectable MPLC. To date, the driver oncogenes reported in the patients with MPLC are limited, and MET fusion has not yet been reported in MPLC. Case presentation: In this case, we reported a female patient with simultaneous MPLC (sMPLC). A novel ARL1-MET fusion was detected in her right lung tumor tissues using next-generation sequencing (NGS). The patient achieved about 5-month progressive-free survival (PFS) after receiving Crizotinib for the unresectable right lung malignancies. Conclusion: To the best of our knowledge, this case provided the first clinical evidence that the novel ARL1-MET fusion might be an actionable mutation in sMPLC. Citation Format: Qing Ma, Lingping Kong, Diansheng Zhong. Case report: dramatic response to Crizotinib in a patient with synchronous multiple primary lung cancer positive for a novel ARL1-MET fusion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5231.