Pub Date : 2024-06-30Epub Date: 2024-06-21DOI: 10.21037/tlcr-24-195
Yuchen Zhang, Guangyin Zhao, Chen Xu, Jie Gu, Di Ge
Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with high morbidity and mortality. A combination of systemic therapy and surgery may be a promising modality for the treatment of MPM, but evidence-based medicine is still lacking.
Case description: Here we report a case of MPM. The patient presented to hospital with cough and sputum. After ineffective symptomatic treatment, computed tomography (CT) examination suggested a malignant tumor of pleural origin. Positron emission tomography/computed tomography (PET/CT) examination suggested no lymph node metastasis or distant metastasis. The pathologic diagnosis of MPM was confirmed after CT-guided puncture biopsy. Next, she underwent 3 courses of neoadjuvant chemotherapy combined with dual immunotherapy (carboplatin and pemetrexed combined with anti-CTLA4 and anti-PD-1), resulting in significant tumor shrinkage. After obtaining the patient's consent and completing a preoperative evaluation, we modified the extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) by performing a lower lobe resection and partial pleurectomy of the left lung. Intraoperative rapid frozen pathology suggested that the margins of the tumor were negative and complete resection was achieved. The postoperative pathology report showed 10% residual viable tumor, so the major pathological response (MPR) was achieved after treatment.
Conclusions: MPM might respond well to neoadjuvant chemotherapy and dual immunotherapy, improving the probability of complete surgical resection and attaining an encouraging pathologic response.
{"title":"Major pathological response obtained after neoadjuvant chemotherapy combined with dual immunotherapy for malignant pleural mesothelioma: a case report.","authors":"Yuchen Zhang, Guangyin Zhao, Chen Xu, Jie Gu, Di Ge","doi":"10.21037/tlcr-24-195","DOIUrl":"10.21037/tlcr-24-195","url":null,"abstract":"<p><strong>Background: </strong>Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with high morbidity and mortality. A combination of systemic therapy and surgery may be a promising modality for the treatment of MPM, but evidence-based medicine is still lacking.</p><p><strong>Case description: </strong>Here we report a case of MPM. The patient presented to hospital with cough and sputum. After ineffective symptomatic treatment, computed tomography (CT) examination suggested a malignant tumor of pleural origin. Positron emission tomography/computed tomography (PET/CT) examination suggested no lymph node metastasis or distant metastasis. The pathologic diagnosis of MPM was confirmed after CT-guided puncture biopsy. Next, she underwent 3 courses of neoadjuvant chemotherapy combined with dual immunotherapy (carboplatin and pemetrexed combined with anti-CTLA4 and anti-PD-1), resulting in significant tumor shrinkage. After obtaining the patient's consent and completing a preoperative evaluation, we modified the extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) by performing a lower lobe resection and partial pleurectomy of the left lung. Intraoperative rapid frozen pathology suggested that the margins of the tumor were negative and complete resection was achieved. The postoperative pathology report showed 10% residual viable tumor, so the major pathological response (MPR) was achieved after treatment.</p><p><strong>Conclusions: </strong>MPM might respond well to neoadjuvant chemotherapy and dual immunotherapy, improving the probability of complete surgical resection and attaining an encouraging pathologic response.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-30Epub Date: 2024-06-22DOI: 10.21037/tlcr-24-191
Zelin Ma, Yang Zhang, Han Han, Shengping Wang, Yuan Li, Haiquan Chen
Background: The Japan Clinical Oncology Group (JCOG) 1211 suggested that segmentectomy should be considered as standard treatment for clinical T1N0 (cT1N0) ground glass opacity (GGO). However, over half of patients in JCOG1211 had pre-/minimal invasive adenocarcinoma. This study aims to retrospectively investigate the long-term survival of GGO featured cT1N0 invasive lung adenocarcinoma undergoing segmentectomy or lobectomy.
Methods: This study screened patients with primary cT1N0 lung adenocarcinoma who received segmentectomy or lobectomy from 2010-2020. Prior computed tomography (CT) scans before surgery of all patients were reviewed and the inclusion was confirmed according to tumor diameter and consolidation tumor ratio (CTR). GGO nodules between 2-3 cm with CTR ≤0.5 or ≤2 cm with CTR between 0.25-0.5 were finally included. Patients with pathologically diagnosed pre-/minimally invasive lung adenocarcinoma were excluded. Long-term survivals between segmentectomy group and lobectomy group were compared after propensity score matching (PSM). Recurrence and postoperative complication events were also analyzed.
Results: In total, 617 patients were enrolled, 159 received segmentectomy and 458 received lobectomy. Clinicopathological characteristics were well distributed between two groups. With a median follow-up time of 61.1 months (IQR: 42.3-71.7 months), after PSM, the 5-year overall survival rate was 98.8% (97.9-99.6%) for lobectomy and 99.3% (98.2-99.8%) for segmentectomy (P=0.42), the 5-year relapse-free survival rate was 95.3% (92.2-97.6%) for lobectomy and 95.2% for segmentectomy (92.3-98.7%) (P=0.81). The proportion of recurrence was 4.1% for lobectomy and 4.4% for segmentectomy (P=0.89). The proportion of grade 2 and above early postoperative complications was 9.6% for lobectomy and 8.8% for segmentectomy (P=0.86).
Conclusions: For cT1N0 GGO featured invasive lung adenocarcinoma (2 cm < tumor diameter ≤3 cm, CTR ≤0.5 or tumor diameter ≤2 cm, 0.25< CTR ≤0.5), postoperative outcomes between segmentectomy group and lobectomy group were comparable. Concerning minimally invasive surgical strategy, segmentectomy should be confirmed as the standard surgical approach.
{"title":"Segmentectomy versus lobectomy for ground-glass opacity dominant cT1N0 invasive lung adenocarcinoma.","authors":"Zelin Ma, Yang Zhang, Han Han, Shengping Wang, Yuan Li, Haiquan Chen","doi":"10.21037/tlcr-24-191","DOIUrl":"10.21037/tlcr-24-191","url":null,"abstract":"<p><strong>Background: </strong>The Japan Clinical Oncology Group (JCOG) 1211 suggested that segmentectomy should be considered as standard treatment for clinical T1N0 (cT1N0) ground glass opacity (GGO). However, over half of patients in JCOG1211 had pre-/minimal invasive adenocarcinoma. This study aims to retrospectively investigate the long-term survival of GGO featured cT1N0 invasive lung adenocarcinoma undergoing segmentectomy or lobectomy.</p><p><strong>Methods: </strong>This study screened patients with primary cT1N0 lung adenocarcinoma who received segmentectomy or lobectomy from 2010-2020. Prior computed tomography (CT) scans before surgery of all patients were reviewed and the inclusion was confirmed according to tumor diameter and consolidation tumor ratio (CTR). GGO nodules between 2-3 cm with CTR ≤0.5 or ≤2 cm with CTR between 0.25-0.5 were finally included. Patients with pathologically diagnosed pre-/minimally invasive lung adenocarcinoma were excluded. Long-term survivals between segmentectomy group and lobectomy group were compared after propensity score matching (PSM). Recurrence and postoperative complication events were also analyzed.</p><p><strong>Results: </strong>In total, 617 patients were enrolled, 159 received segmentectomy and 458 received lobectomy. Clinicopathological characteristics were well distributed between two groups. With a median follow-up time of 61.1 months (IQR: 42.3-71.7 months), after PSM, the 5-year overall survival rate was 98.8% (97.9-99.6%) for lobectomy and 99.3% (98.2-99.8%) for segmentectomy (P=0.42), the 5-year relapse-free survival rate was 95.3% (92.2-97.6%) for lobectomy and 95.2% for segmentectomy (92.3-98.7%) (P=0.81). The proportion of recurrence was 4.1% for lobectomy and 4.4% for segmentectomy (P=0.89). The proportion of grade 2 and above early postoperative complications was 9.6% for lobectomy and 8.8% for segmentectomy (P=0.86).</p><p><strong>Conclusions: </strong>For cT1N0 GGO featured invasive lung adenocarcinoma (2 cm < tumor diameter ≤3 cm, CTR ≤0.5 or tumor diameter ≤2 cm, 0.25< CTR ≤0.5), postoperative outcomes between segmentectomy group and lobectomy group were comparable. Concerning minimally invasive surgical strategy, segmentectomy should be confirmed as the standard surgical approach.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31Epub Date: 2024-05-17DOI: 10.21037/tlcr-24-40
Takuo Hayashi
{"title":"Genetic diversity in small cell lung carcinoma.","authors":"Takuo Hayashi","doi":"10.21037/tlcr-24-40","DOIUrl":"10.21037/tlcr-24-40","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31Epub Date: 2024-05-24DOI: 10.21037/tlcr-24-352
Wenbin Hu, Jiaming Zhao, Guoxia Wang, Qihao Wang, Mingming Deng, Jie Shen, Paul Hofman, Edyta Maria Urbanska, Eric Santoni-Rugiu, Petros Christopoulos, Robert A Ramirez, Toyoaki Hida, Xiaoqing Lu, Binjun He
Background: The occurrence of pulmonary adenocarcinoma coexisting with atypical carcinoid tumors is a rare phenomenon. The presence of EML4-ALK fusion in an atypical carcinoid component of a histologically mixed tumor is even more uncommon. Due to their infrequency, the origin and pathogenesis of these mixed tumors remain largely unknown. The advances of therapy development in such patients are still limited and there is no standard treatment. We present a case of collision tumor in the lung consisting of atypical carcinoid and adenocarcinoma to better understand the clinical characteristics of this disease.
Case description: We report an extremely rare case of EML4-ALK rearrangement in a pulmonary atypical carcinoid tumor that coexisting with adenocarcinoma. A 58-year-old woman, who was asymptomatic, underwent pulmonary lobectomy due to the detection of a gradually enlarging solitary pulmonary nodule in the right upper lung. Histological examination of the resected tumor revealed the presence of both atypical carcinoid (approximately 80%) and adenocarcinoma (approximately 20%) components. Metastases by the carcinoid component were observed in mediastinal lymph nodes (station 2R and 4R) and in the primary tumor. Anaplastic lymphoma kinase (ALK) rearrangement was detected in both the primary and metastatic lesions of the carcinoid tumor. Four cycles of chemotherapy with etoposide and carboplatin were dispensed after surgery.
Conclusions: This is the first reported case of coexisting pulmonary adenocarcinoma and atypical carcinoid tumor with an ALK fusion only detected in the carcinoid component. The presence of ALK rearrangement in pulmonary carcinoid tumor is very uncommon, and there is currently no standard treatment for advanced stages. Therefore, comprehensive molecular testing, including ALK rearrangement analysis, should be recommended for mixed tumors exhibiting features of atypical carcinoid. ALK inhibitors could represent a potential treatment strategy for selected patients.
{"title":"A rare case report of a primary lung cancer comprising adenocarcinoma and atypical carcinoid tumor, with the carcinoid component harboring <i>EML4-ALK</i> rearrangement.","authors":"Wenbin Hu, Jiaming Zhao, Guoxia Wang, Qihao Wang, Mingming Deng, Jie Shen, Paul Hofman, Edyta Maria Urbanska, Eric Santoni-Rugiu, Petros Christopoulos, Robert A Ramirez, Toyoaki Hida, Xiaoqing Lu, Binjun He","doi":"10.21037/tlcr-24-352","DOIUrl":"10.21037/tlcr-24-352","url":null,"abstract":"<p><strong>Background: </strong>The occurrence of pulmonary adenocarcinoma coexisting with atypical carcinoid tumors is a rare phenomenon. The presence of <i>EML4-ALK</i> fusion in an atypical carcinoid component of a histologically mixed tumor is even more uncommon. Due to their infrequency, the origin and pathogenesis of these mixed tumors remain largely unknown. The advances of therapy development in such patients are still limited and there is no standard treatment. We present a case of collision tumor in the lung consisting of atypical carcinoid and adenocarcinoma to better understand the clinical characteristics of this disease.</p><p><strong>Case description: </strong>We report an extremely rare case of <i>EML4-ALK</i> rearrangement in a pulmonary atypical carcinoid tumor that coexisting with adenocarcinoma. A 58-year-old woman, who was asymptomatic, underwent pulmonary lobectomy due to the detection of a gradually enlarging solitary pulmonary nodule in the right upper lung. Histological examination of the resected tumor revealed the presence of both atypical carcinoid (approximately 80%) and adenocarcinoma (approximately 20%) components. Metastases by the carcinoid component were observed in mediastinal lymph nodes (station 2R and 4R) and in the primary tumor. Anaplastic lymphoma kinase (<i>ALK</i>) rearrangement was detected in both the primary and metastatic lesions of the carcinoid tumor. Four cycles of chemotherapy with etoposide and carboplatin were dispensed after surgery.</p><p><strong>Conclusions: </strong>This is the first reported case of coexisting pulmonary adenocarcinoma and atypical carcinoid tumor with an <i>ALK</i> fusion only detected in the carcinoid component. The presence of <i>ALK</i> rearrangement in pulmonary carcinoid tumor is very uncommon, and there is currently no standard treatment for advanced stages. Therefore, comprehensive molecular testing, including <i>ALK</i> rearrangement analysis, should be recommended for mixed tumors exhibiting features of atypical carcinoid. <i>ALK</i> inhibitors could represent a potential treatment strategy for selected patients.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31Epub Date: 2024-05-10DOI: 10.21037/tlcr-24-257
Zichen Zhao, Dan Xu, Yan Zhang
{"title":"Synergistic effect of canakinumab with epidermal growth factor receptor tyrosine kinase inhibitors versus with chemotherapy for non-small cell lung cancer.","authors":"Zichen Zhao, Dan Xu, Yan Zhang","doi":"10.21037/tlcr-24-257","DOIUrl":"10.21037/tlcr-24-257","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31Epub Date: 2024-05-24DOI: 10.21037/tlcr-24-85
Xiaojuan Su, Yi Feng, Yi Qu, Dezhi Mu
Non-small cell lung cancer (NSCLC) is a malignant cancer that with high incidence, recurrence, and mortality rates in human beings, posing significant threats to human health. Moreover, effective early diagnosis of NSCLC remains limited primarily by the lack of accurate biomarkers. Therefore, there is an urgent need to understand the mechanisms underlying NSCLC pathogenesis and treatment failure. Methyltransferase-like 3 (METTL3) is a prototypical member of a family of which its members transfer methyl groups. It has been implicated in modulating the pathogenesis of NSCLC, as well as conferring resistance to NSCLC therapeutics. The targeting of METTL3 for NSCLC treatment has been reported. However, the relationship between METTL3 and NSCLC remains to be demonstrated. In this review, we discuss relevant interrelationships by summarising the studies on METTL3 in NSCLC pathogenesis, therapeutic resistance, and clinical applications. Current research suggests that the upregulation of METTL3 expression propels the tumorigenesis, progression, and treatment resistance of NSCLC. Therefore, we propose that METTL3 is an excellent candidate biomarker for NSCLC diagnosis and prognosis. Therapeutic targeting of METTL3 has significant potential for NSCLC treatment. This review provides a summary of the association between METTL3 and NSCLC, which would be a valuable reference for both basic and clinical research.
{"title":"Association between methyltransferase-like 3 and non-small cell lung cancer: pathogenesis, therapeutic resistance, and clinical applications.","authors":"Xiaojuan Su, Yi Feng, Yi Qu, Dezhi Mu","doi":"10.21037/tlcr-24-85","DOIUrl":"10.21037/tlcr-24-85","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is a malignant cancer that with high incidence, recurrence, and mortality rates in human beings, posing significant threats to human health. Moreover, effective early diagnosis of NSCLC remains limited primarily by the lack of accurate biomarkers. Therefore, there is an urgent need to understand the mechanisms underlying NSCLC pathogenesis and treatment failure. Methyltransferase-like 3 (METTL3) is a prototypical member of a family of which its members transfer methyl groups. It has been implicated in modulating the pathogenesis of NSCLC, as well as conferring resistance to NSCLC therapeutics. The targeting of METTL3 for NSCLC treatment has been reported. However, the relationship between METTL3 and NSCLC remains to be demonstrated. In this review, we discuss relevant interrelationships by summarising the studies on METTL3 in NSCLC pathogenesis, therapeutic resistance, and clinical applications. Current research suggests that the upregulation of METTL3 expression propels the tumorigenesis, progression, and treatment resistance of NSCLC. Therefore, we propose that METTL3 is an excellent candidate biomarker for NSCLC diagnosis and prognosis. Therapeutic targeting of METTL3 has significant potential for NSCLC treatment. This review provides a summary of the association between METTL3 and NSCLC, which would be a valuable reference for both basic and clinical research.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31Epub Date: 2024-05-24DOI: 10.21037/tlcr-23-739
Yicong Lin, Yue Wang, Qianqian Xue, Qiang Zheng, Lijun Chen, Yan Jin, Ziling Huang, Yuan Li
Background: The tumor microenvironment (TME) plays an important role in tumor progression and immunotherapy responses in non-small cell lung cancer (NSCLC). The programmed cell death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) checkpoint is a central mediator of immunosuppression in the TME. However, there is still a need to identify additional biomarkers that could reflect the difference in TME and PD-L1 expression in NSCLC patients. To this end, we focused on the expression of G-protein-coupled receptor family C group 5 type A (GPRC5A) in NSCLC. GPRC5A, is a retinoic acid-inducible gene that plays multiple roles in NSCLC. However, little is known about the role of GPRC5A in regulating the TME and PD-L1. Our objective was to describe the critical role of GPRC5A expression in NSCLC in the setting of immune cell infiltration.
Methods: We identified the relationship between GPRC5A expression and the clinicopathologic characteristics of NSCLC patients in the Fudan University Shanghai Cancer Center (FUSCC) cohort. Furthermore, we validated GPRC5A as a predictive biomarker by using public databases to reveal the relationship between GPRC5A expression and immune cell infiltration. To correlate the expression of GPRC5A with the spatial distribution of PD-L1 in NSCLC samples, we performed multiplex immunohistochemistry (mIHC).
Results: Low GPRC5A expression is associated with earlier pathological stage (pStage). Analysis of immune cell infiltration indicates there is a relationship between low GPRC5A expression and increased infiltration of CD8+ T cells, activated CD4+ T cells, and M1 macrophages within the TME. Furthermore, low GPRC5A expression is associated with an increased immunophenotype score (IPS) in NSCLC. Additionally, analysis of mIHC reveals there is a correlation between low GPRC5A expression and spatial distribution of tumoral PD-L1 expression.
Conclusions: Our study revealed the relationship between low expression of GPRC5A and earlier pStage in NSCLC. Furthermore, we observed that low expression of GPRC5A is associated with increased infiltration of immune cells, higher IPS, and spatial distribution of PD-L1-positive tumor cells. Therefore, we speculate that low expression of GPRC5A is associated with immunotherapy, but further validation is still required.
{"title":"<i>GPRC5A</i> is a potential prognostic biomarker and correlates with immune cell infiltration in non-small cell lung cancer.","authors":"Yicong Lin, Yue Wang, Qianqian Xue, Qiang Zheng, Lijun Chen, Yan Jin, Ziling Huang, Yuan Li","doi":"10.21037/tlcr-23-739","DOIUrl":"10.21037/tlcr-23-739","url":null,"abstract":"<p><strong>Background: </strong>The tumor microenvironment (TME) plays an important role in tumor progression and immunotherapy responses in non-small cell lung cancer (NSCLC). The programmed cell death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) checkpoint is a central mediator of immunosuppression in the TME. However, there is still a need to identify additional biomarkers that could reflect the difference in TME and PD-L1 expression in NSCLC patients. To this end, we focused on the expression of G-protein-coupled receptor family C group 5 type A (<i>GPRC5A</i>) in NSCLC. <i>GPRC5A</i>, is a retinoic acid-inducible gene that plays multiple roles in NSCLC. However, little is known about the role of <i>GPRC5A</i> in regulating the TME and PD-L1. Our objective was to describe the critical role of <i>GPRC5A</i> expression in NSCLC in the setting of immune cell infiltration.</p><p><strong>Methods: </strong>We identified the relationship between GPRC5A expression and the clinicopathologic characteristics of NSCLC patients in the Fudan University Shanghai Cancer Center (FUSCC) cohort. Furthermore, we validated <i>GPRC5A</i> as a predictive biomarker by using public databases to reveal the relationship between <i>GPRC5A</i> expression and immune cell infiltration. To correlate the expression of GPRC5A with the spatial distribution of PD-L1 in NSCLC samples, we performed multiplex immunohistochemistry (mIHC).</p><p><strong>Results: </strong>Low GPRC5A expression is associated with earlier pathological stage (pStage). Analysis of immune cell infiltration indicates there is a relationship between low <i>GPRC5A</i> expression and increased infiltration of CD8<sup>+</sup> T cells, activated CD4<sup>+</sup> T cells, and M1 macrophages within the TME. Furthermore, low <i>GPRC5A</i> expression is associated with an increased immunophenotype score (IPS) in NSCLC. Additionally, analysis of mIHC reveals there is a correlation between low GPRC5A expression and spatial distribution of tumoral PD-L1 expression.</p><p><strong>Conclusions: </strong>Our study revealed the relationship between low expression of GPRC5A and earlier pStage in NSCLC. Furthermore, we observed that low expression of <i>GPRC5A</i> is associated with increased infiltration of immune cells, higher IPS, and spatial distribution of PD-L1-positive tumor cells. Therefore, we speculate that low expression of <i>GPRC5A</i> is associated with immunotherapy, but further validation is still required.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31Epub Date: 2024-05-29DOI: 10.21037/tlcr-23-816
Natthaya Triphuridet, Misako Nagasaka, Elaine Shum, Sai-Hong Ignatius Ou
Background: We previously demonstrated in a meta-analysis there was no difference in risk ratio (RR) of lung cancer detected by low-dose computed tomography (LDCT) screening among female never-smokers (NS) and male ever-smokers (ES) in Asia. LDCT screening significantly decreased lung cancer death among Asian NS compared to Asian ES (RR =0.27, P<0.001).
Methods: We investigated if race, age at diagnosis, and histology further differentiate lung cancer diagnosed by LDCT among in NS and ES using the 14 studies from our previous meta-analysis.
Results: Twelve publications reported relevant data utilized in this study. From five Asian and one international studies, Asian ES had similar risk of lung cancer diagnosed at baseline screening as Asian NS [RR =0.96; 95% confidence interval (CI): 0.74-1.24] but among non-Asian ES had a 4.56 times significantly higher risk than non-Asian NS (RR =4.56; 95% CI: 2.85-7.28). The baseline incidence of lung cancer in never-smoker (LCINS) was approximately 2.3 times higher among Asian NS than non-Asian NS (0.62% vs. 0.27%, P=0.001). Asian ES had about half the baseline incidence of lung cancer diagnosed as non-Asian ES (0.65% vs. 1.26%). LCINS was diagnosed at 1.98 years younger than ES (95% CI: -3.38 to -0.58) (four studies) and exhibited a higher proportion of adenocarcinoma (ADC) (96.58% vs. 70.37%).
Conclusions: Among normal-risk individuals, LCINS had a significantly higher likelihood of being diagnosed among Asians than non-Asians, predominantly manifesting as ADC and diagnosed approximately 2 years younger than ES suggesting that the age limit to initiate lung cancer screening in NS may be set lower compared to LDCT lung cancer screening among ES.
背景:我们曾在一项荟萃分析中证实,在亚洲,低剂量计算机断层扫描(LDCT)筛查在女性从不吸烟者(NS)和男性曾经吸烟者(ES)中发现肺癌的风险比(RR)没有差异。低剂量计算机断层扫描(LDCT)筛查大大降低了亚洲女性从不吸烟者(NS)与亚洲男性从不吸烟者(ES)的肺癌死亡率(RR =0.27,PM 方法:我们利用之前荟萃分析中的 14 项研究,调查了种族、诊断年龄和组织学是否能进一步区分通过 LDCT 诊断的 NS 和 ES 肺癌:本研究使用了 12 篇文献的相关数据。从 5 项亚洲研究和 1 项国际研究中可以看出,亚裔 ES 在基线筛查中确诊肺癌的风险与亚裔 NS 相似 [RR =0.96;95% 置信区间 (CI):0.74-1.24],但非亚裔 ES 的风险比非亚裔 NS 高 4.56 倍(RR =4.56;95% CI:2.85-7.28)。亚裔 NS 的从不吸烟者肺癌基线发病率(LCINS)是非亚裔 NS 的约 2.3 倍(0.62% 对 0.27%,P=0.001)。亚裔 ES 的肺癌诊断基线发病率约为非亚裔 ES 的一半(0.65% 对 1.26%)。LCINS的诊断年龄比ES小1.98岁(95% CI:-3.38至-0.58)(四项研究),腺癌(ADC)的比例更高(96.58%对70.37%):结论:在正常风险人群中,亚洲人确诊为LCINS的可能性明显高于非亚洲人,主要表现为ADC,确诊年龄比ES年轻约2岁。
{"title":"Race, age at diagnosis and histological characteristics of lung cancer in never-smokers (LCINS) and ever-smokers in low-dose computed tomography (LDCT) screening: a systematic review and meta-analysis.","authors":"Natthaya Triphuridet, Misako Nagasaka, Elaine Shum, Sai-Hong Ignatius Ou","doi":"10.21037/tlcr-23-816","DOIUrl":"10.21037/tlcr-23-816","url":null,"abstract":"<p><strong>Background: </strong>We previously demonstrated in a meta-analysis there was no difference in risk ratio (RR) of lung cancer detected by low-dose computed tomography (LDCT) screening among female never-smokers (NS) and male ever-smokers (ES) in Asia. LDCT screening significantly decreased lung cancer death among Asian NS compared to Asian ES (RR =0.27, P<0.001).</p><p><strong>Methods: </strong>We investigated if race, age at diagnosis, and histology further differentiate lung cancer diagnosed by LDCT among in NS and ES using the 14 studies from our previous meta-analysis.</p><p><strong>Results: </strong>Twelve publications reported relevant data utilized in this study. From five Asian and one international studies, Asian ES had similar risk of lung cancer diagnosed at baseline screening as Asian NS [RR =0.96; 95% confidence interval (CI): 0.74-1.24] but among non-Asian ES had a 4.56 times significantly higher risk than non-Asian NS (RR =4.56; 95% CI: 2.85-7.28). The baseline incidence of lung cancer in never-smoker (LCINS) was approximately 2.3 times higher among Asian NS than non-Asian NS (0.62% <i>vs.</i> 0.27%, P=0.001). Asian ES had about half the baseline incidence of lung cancer diagnosed as non-Asian ES (0.65% <i>vs.</i> 1.26%). LCINS was diagnosed at 1.98 years younger than ES (95% CI: -3.38 to -0.58) (four studies) and exhibited a higher proportion of adenocarcinoma (ADC) (96.58% <i>vs.</i> 70.37%).</p><p><strong>Conclusions: </strong>Among normal-risk individuals, LCINS had a significantly higher likelihood of being diagnosed among Asians than non-Asians, predominantly manifesting as ADC and diagnosed approximately 2 years younger than ES suggesting that the age limit to initiate lung cancer screening in NS may be set lower compared to LDCT lung cancer screening among ES.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31Epub Date: 2024-05-29DOI: 10.21037/tlcr-23-641
Kevin V Chaung, Michael Z Kharouta, Andrew J Gross, Pingfu Fu, Mitchell Machtay, Tiffany R Hodges, Andrew E Sloan, Tithi Biswas, Afshin Dowlati, Serah Choi
Small cell lung cancer (SCLC) has a propensity for brain metastases, which is associated with poor prognosis. We sought to determine predictors of overall survival (OS) and brain progression-free survival (bPFS) in SCLC patients with synchronous brain metastases at the time of initial SCLC diagnosis. A total of 107 SCLC patients with synchronous brain metastases treated at a single institution were included in this retrospective analysis. These patients had brain lesions present on initial staging imaging. Survival was estimated using the Kaplan-Meier method with log-rank test. Factors predictive of OS and bPFS were analyzed using Cox proportional hazards regression model. Median OS for the entire cohort was 9 months (interquartile range, 4.2-13.8 months) and median bPFS was 7.3 months (interquartile range, 3.5-11.1 months). OS was 30.3% at 1 year and 14.4% at 2 years, while bPFS was 22.0% at 1 year and 6.9% at 2 years. The median number of brain lesions at diagnosis was 3 (interquartile range, 2-8), and the median size of the largest metastasis was 2.0 cm (interquartile range, 1.0-3.3 cm). Increased number of brain lesions was significantly associated with decreased OS. Patients who received both chemotherapy and whole brain radiation therapy (WBRT) had improved OS (P=0.02) and bPFS (P=0.005) compared to those who had either chemotherapy or WBRT alone. There was no significant difference in OS or bPFS depending on the sequence of therapy or the dose of WBRT. Thirteen patients underwent upfront brain metastasis resection, which was associated with improved OS (P=0.02) but not bPFS (P=0.09) compared to those who did not have surgery. The combination of chemotherapy and WBRT was associated with improved OS and bPFS compared to either modality alone. Upfront brain metastasis resection was associated with improved OS but not bPFS compared to those who did not have surgery.
{"title":"Outcomes of initial therapy for synchronous brain metastases from small cell lung cancer: a single-institution retrospective analysis.","authors":"Kevin V Chaung, Michael Z Kharouta, Andrew J Gross, Pingfu Fu, Mitchell Machtay, Tiffany R Hodges, Andrew E Sloan, Tithi Biswas, Afshin Dowlati, Serah Choi","doi":"10.21037/tlcr-23-641","DOIUrl":"10.21037/tlcr-23-641","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) has a propensity for brain metastases, which is associated with poor prognosis. We sought to determine predictors of overall survival (OS) and brain progression-free survival (bPFS) in SCLC patients with synchronous brain metastases at the time of initial SCLC diagnosis. A total of 107 SCLC patients with synchronous brain metastases treated at a single institution were included in this retrospective analysis. These patients had brain lesions present on initial staging imaging. Survival was estimated using the Kaplan-Meier method with log-rank test. Factors predictive of OS and bPFS were analyzed using Cox proportional hazards regression model. Median OS for the entire cohort was 9 months (interquartile range, 4.2-13.8 months) and median bPFS was 7.3 months (interquartile range, 3.5-11.1 months). OS was 30.3% at 1 year and 14.4% at 2 years, while bPFS was 22.0% at 1 year and 6.9% at 2 years. The median number of brain lesions at diagnosis was 3 (interquartile range, 2-8), and the median size of the largest metastasis was 2.0 cm (interquartile range, 1.0-3.3 cm). Increased number of brain lesions was significantly associated with decreased OS. Patients who received both chemotherapy and whole brain radiation therapy (WBRT) had improved OS (P=0.02) and bPFS (P=0.005) compared to those who had either chemotherapy or WBRT alone. There was no significant difference in OS or bPFS depending on the sequence of therapy or the dose of WBRT. Thirteen patients underwent upfront brain metastasis resection, which was associated with improved OS (P=0.02) but not bPFS (P=0.09) compared to those who did not have surgery. The combination of chemotherapy and WBRT was associated with improved OS and bPFS compared to either modality alone. Upfront brain metastasis resection was associated with improved OS but not bPFS compared to those who did not have surgery.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31Epub Date: 2024-05-21DOI: 10.21037/tlcr-24-33
Laduona Wang, Yijun Wu, Kai Kang, Xuanwei Zhang, Ren Luo, Zegui Tu, Yue Zheng, Guo Lin, Hui Wang, Min Tang, Min Yu, Bingwen Zou, Ruizhan Tong, Linglu Yi, Feifei Na, Jianxin Xue, Zhuoran Yao, You Lu
Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors have shown significant activity against several solid tumors by reducing the phosphorylation of the canonical CDK4/6 substrate retinoblastoma (Rb) protein, while the anti-tumor effect of CDK4/6 inhibitors on Rb-deficient tumors is not clear. Most small cell lung cancers (SCLCs) are Rb-deficient and show very modest response to immune checkpoint blockade (ICB) despite recent advances in the use of immunotherapy. Here, we aimed to investigate the direct effect of CDK4/6 inhibition on SCLC cells and determine its efficacy in combination therapy for SCLC.
Methods: The immediate impact of CDK4/6 inhibitor abemaciclib on cell cycle, cell viability and apoptosis in four SCLC cell lines was initially checked. To explore the effect of abemaciclib on double-strand DNA (ds-DNA) damage induction and the combination impact of abemaciclib coupled with radiotherapy (RT), western blot, immunofluorescence (IF) and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. An Rb-deficient immunocompetent murine SCLC model was established to evaluate efficacy of abemaciclib in combination therapy. Histological staining, flow cytometry analysis and RNA sequencing were performed to analyze alteration of infiltrating immune cells in tumor microenvironment (TME).
Results: Here, we demonstrated that abemaciclib induced increased ds-DNA damage in Rb-deficient SCLC cells. Combination of abemaciclib and RT induced more cytosolic ds-DNA, and activated the STING pathway synergistically. We further showed that combining low doses of abemaciclib with low-dose RT (LDRT) plus anti-programmed cell death protein-1 (anti-PD-1) antibody substantially potentiated CD8+ T cell infiltration and significantly inhibited tumor growth and prolonged survival in an Rb-deficient immunocompetent murine SCLC model.
Conclusions: Our results define previously uncertain DNA damage-inducing properties of CDK4/6 inhibitor abemaciclib in Rb-deficient SCLCs, and demonstrate that low doses of abemaciclib combined with LDRT inflame the TME and enhance the efficacy of anti-PD-1 immunotherapy in SCLC model, which represents a potential novel therapeutic strategy for SCLC.
{"title":"CDK4/6 inhibitor abemaciclib combined with low-dose radiotherapy enhances the anti-tumor immune response to PD-1 blockade by inflaming the tumor microenvironment in Rb-deficient small cell lung cancer.","authors":"Laduona Wang, Yijun Wu, Kai Kang, Xuanwei Zhang, Ren Luo, Zegui Tu, Yue Zheng, Guo Lin, Hui Wang, Min Tang, Min Yu, Bingwen Zou, Ruizhan Tong, Linglu Yi, Feifei Na, Jianxin Xue, Zhuoran Yao, You Lu","doi":"10.21037/tlcr-24-33","DOIUrl":"10.21037/tlcr-24-33","url":null,"abstract":"<p><strong>Background: </strong>Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors have shown significant activity against several solid tumors by reducing the phosphorylation of the canonical CDK4/6 substrate retinoblastoma (Rb) protein, while the anti-tumor effect of CDK4/6 inhibitors on Rb-deficient tumors is not clear. Most small cell lung cancers (SCLCs) are Rb-deficient and show very modest response to immune checkpoint blockade (ICB) despite recent advances in the use of immunotherapy. Here, we aimed to investigate the direct effect of CDK4/6 inhibition on SCLC cells and determine its efficacy in combination therapy for SCLC.</p><p><strong>Methods: </strong>The immediate impact of CDK4/6 inhibitor abemaciclib on cell cycle, cell viability and apoptosis in four SCLC cell lines was initially checked. To explore the effect of abemaciclib on double-strand DNA (ds-DNA) damage induction and the combination impact of abemaciclib coupled with radiotherapy (RT), western blot, immunofluorescence (IF) and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. An Rb-deficient immunocompetent murine SCLC model was established to evaluate efficacy of abemaciclib in combination therapy. Histological staining, flow cytometry analysis and RNA sequencing were performed to analyze alteration of infiltrating immune cells in tumor microenvironment (TME).</p><p><strong>Results: </strong>Here, we demonstrated that abemaciclib induced increased ds-DNA damage in Rb-deficient SCLC cells. Combination of abemaciclib and RT induced more cytosolic ds-DNA, and activated the STING pathway synergistically. We further showed that combining low doses of abemaciclib with low-dose RT (LDRT) plus anti-programmed cell death protein-1 (anti-PD-1) antibody substantially potentiated CD8<sup>+</sup> T cell infiltration and significantly inhibited tumor growth and prolonged survival in an Rb-deficient immunocompetent murine SCLC model.</p><p><strong>Conclusions: </strong>Our results define previously uncertain DNA damage-inducing properties of CDK4/6 inhibitor abemaciclib in Rb-deficient SCLCs, and demonstrate that low doses of abemaciclib combined with LDRT inflame the TME and enhance the efficacy of anti-PD-1 immunotherapy in SCLC model, which represents a potential novel therapeutic strategy for SCLC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}