Translational lung cancer research最新文献

{"title":"Alectinib impressively enters the adjuvant setting for early-stage <i>ALK</i>-rearranged non-small cell lung cancer and outperforms chemotherapy-let's define who benefits the most.","authors":"Eric Santoni-Rugiu, Jens Benn Sørensen, Edyta Maria Urbanska","doi":"10.21037/tlcr-24-961","DOIUrl":"10.21037/tlcr-24-961","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"310-313"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670807","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}

{"title":"Novel <i>LZTR1</i> germline mutation as a mechanism of resistance to osimertinib in <i>EGFR</i>-mutated lung adenocarcinoma: a case report.","authors":"Wai Park, Jeremy Fricke, Isa Mambetsariev, Giovanny Velasquez, Reza Nadaf-Rahrov, Shaira Therese Dingal, Pauline Kim, Razmig Babikian, Arya Amini, Michelle Afkhami, Ravi Salgia","doi":"10.21037/tlcr-24-723","DOIUrl":"10.21037/tlcr-24-723","url":null,"abstract":"<p><strong>Background: </strong>Tyrosine kinase inhibitors (TKIs) are now the standard of care first-line therapy for epidermal growth factor receptor (<i>EGFR</i>)-mutated advanced non-small cell lung cancer (NSCLC) patients. Despite positive outcomes in most patients, with extended progression-free survival (PFS), a small population of patients respond poorly to these drugs. Complex genetic and non-genetic resistance mechanisms may be the drivers of disease in cancer, but further research is required to identify these mechanisms in the clinic. Germline molecular testing alongside broad-panel somatic next-generation sequencing (NGS) has allowed for detection of resistance mutations in <i>EGFR</i>-mutated NSCLC patients that may be linked with poor response on TKIs.</p><p><strong>Case description: </strong>Here, we present a case of an NSCLC patient harboring an <i>EGFR</i> somatic mutation and a concomitant leucine-zipper-like transcriptional regulator-1 (<i>LZTR1</i>) germline mutation. The patient experienced rapid disease progression on first-line EGFR TKI, osimertinib-chemotherapy, combination therapy with a PFS of only 4 months as compared to the median PFS of 27.9 months in the FLAURA2 study.</p><p><strong>Conclusions: </strong>This case report indicates that identification of germline resistance mutations such as <i>LZTR1</i> may be associated with poor response to EGFR TKIs. Furthermore, further characterization of these resistance mutations beyond somatic mutations can aid in development of future therapeutic options, which currently do not exist. It is recommended that germline testing be performed as part of the initial patient workup, if available.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"625-630"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671098","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}

{"title":"Partial response to lorlatinib in thoracic inflammatory myofibroblastic tumor harboring complex and rare ALK fusions: a case report.","authors":"Li-Bo Tang, Ying-Long Peng, Xiao-Rong Yang, Jia-Ting Li, Chang Lu, Mei-Mei Zheng, Lu Sun, Zheng Yang, Li-Xu Yan, Yu Deng, Zhi-Hong Chen, Si-Di Lv, Qing Zhou, Chong-Rui Xu","doi":"10.21037/tlcr-24-963","DOIUrl":"10.21037/tlcr-24-963","url":null,"abstract":"<p><strong>Background: </strong>Targeted therapy has dramatically altered the treatment paradigm for some patients with inflammatory myofibroblastic tumor (IMT) that possesses specific molecular aberrations. IMT is an exceedingly rare type of sarcoma, with about 50% of cases featuring anaplastic lymphoma kinase (<i>ALK</i>) gene rearrangements. The treatment of IMT with ALK fusions using ALK tyrosine kinase inhibitors (TKIs) has become increasingly common. However, until now, there is a lack of evidence supporting the efficacy of third-generation ALK-TKIs in this disease category.</p><p><strong>Case description: </strong>Here, we report the first case of a patient with advanced IMT harboring the EML4-ALK fusion gene along with two rare ALK fusion genes: PLB1-ALK, which has only been reported in two cases of lung adenocarcinoma and large cell neuroendocrine carcinoma, and unreported ALMS1-ALK. The patient achieved partial response (PR) following first-line treatment with lorlatinib and subsequently underwent successful surgical intervention.</p><p><strong>Conclusions: </strong>This is the inaugural case of a third-generation ALK-TKI achieving therapeutic success in advanced IMT with complex ALK rearrangements, including rare and previously uncharacterized fusion subtypes. Although the biological functions of these two rare ALK fusions still need to be confirmed, this case underscores the dependency of ALK-rearranged IMT on ALK-mediated signaling, suggesting that third-generation ALK-TKIs may offer an optimal targeted therapeutic strategy for ALK-dependent mesenchymal tumor subtypes.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"631-638"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671102","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}

{"title":"Pathologic complete response following salvage surgery after lazertinib treatment in advanced <i>EGFR</i>-mutated lung adenocarcinoma: case report and literature review.","authors":"Chanmi Kim, Jongsoo Park, Jang Hoon Lee, Seong Yong Jeong, June Hong Ahn","doi":"10.21037/tlcr-24-893","DOIUrl":"10.21037/tlcr-24-893","url":null,"abstract":"<p><strong>Background: </strong>Salvage surgery following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor therapy is a viable treatment option for selected patients with initially unresectable non-small cell lung cancer (NSCLC) harboring <i>EGFR</i> mutations.</p><p><strong>Case description: </strong>We herein describe a 63-year-old man who presented to the emergency department with a 1-week history of speech disturbance and was diagnosed with clinical stage T1cN2M1b, IVA NSCLC with an <i>EGFR</i> exon 21 L858R mutation. The patient underwent brain tumor resection followed by stereotactic radiosurgery and was treated with palliative lazertinib for 6 months. A radiologic complete response was observed in follow-up imaging, and salvage surgery was recommended after multidisciplinary consultation. Right upper lobectomy with mediastinal lymph node dissection revealed a pathologic complete response with no residual tumor cells. The patient remained disease-free for 1 year following lazertinib treatment.</p><p><strong>Conclusions: </strong>This case suggests that salvage surgery after treatment with lazertinib may be a safe and effective approach for NSCLC with common <i>EGFR</i> mutations.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"614-618"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671104","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}

{"title":"Trastuzumab deruxtecan in HER2 overexpressing non-small cell lung cancer (NSCLC).","authors":"Omali Pitiyarachchi, Aaron C Tan","doi":"10.21037/tlcr-24-968","DOIUrl":"10.21037/tlcr-24-968","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"314-322"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670835","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}

{"title":"Unravelling the complexity of <i>EGFR</i>-mutated lung adenocarcinoma: a unique case report with histological transformations and co-alteration acquisition.","authors":"Anissa Boutahir, Véronique Dalstein, Jean Baptiste Oudart, Gaëtan Deslee, Chistine Clavel, Maxime Dewolf, Anne Durlach, Julien Ancel","doi":"10.21037/tlcr-24-707","DOIUrl":"10.21037/tlcr-24-707","url":null,"abstract":"<p><strong>Background: </strong>Osimertinib, a third-generation tyrosine kinase inhibitor that targets epidermal growth factor receptor (EGFR), specifically inhibits both EGFR tyrosine kinase inhibitor-sensitive mutations and T790M resistance mutations. Despite initial positive responses to EGFR tyrosine kinase inhibitors, nearly all patients eventually experience disease progression. Mechanisms of resistance are classically divided into EGFR-dependent and EGFR-independent mechanisms, such as the activation of alternative pathways and histological changes. We report a case of histological transformation into large cell carcinoma associated with the subsequent acquisition of an anaplastic lymphoma kinase (ALK) rearrangement after osimertinib exposure.</p><p><strong>Case description: </strong>A 67-year-old female with no smoking history presented with supraclavicular lymphadenopathy and asthenia, which led to a diagnosis of stage IVB lung adenocarcinoma. Next generation sequencing (NGS) identified an <i>EGFR</i> Ex19del mutation, which suggested the use of afatinib, as it was prescribed prior to osimertinib and was covered by insurance. Initial treatment with afatinib resulted in partial remission, followed by pulmonary progression without the <i>EGFR</i>-T790M mutation. Moreover, ALK and ROS1 were identified through immunohistochemistry (IHC), with ROS1 expression subsequently confirmed by fluorescence in situ hybridization (FISH); this prompted a switch to crizotinib, which was discontinued owing to further disease progression. Osimertinib was then administered, which resulted in a significant positive response; however, after six months pulmonary progression was observed. A subsequent biopsy indicated a transformation to large cell neuroendocrine carcinoma, which led to treatment with platinum-etoposide chemotherapy and, later, paclitaxel and osimertinib, both of which are partially effective. Finally, a new biopsy confirmed ALK positivity in a large cell neuroendocrine carcinoma that was still harbouring an <i>EGFR</i> exon 19 deletion, so alectinib was introduced.</p><p><strong>Conclusions: </strong>To our knowledge, this case is the first reported incidence of transformation into large cell carcinoma coupled with a second acquisition of alterations in ALK. These findings underscore the necessity of monitoring patients with oncogenic addiction through both liquid biopsy for on-target mechanism detection and tissue sampling to detect histological transformations. These mechanisms can occasionally be combined, thereby providing comprehensive panels at each stage of tumour progression.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"639-648"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670837","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}

{"title":"Risk factors for postoperative pulmonary complications in non-adenocarcinoma non-small cell lung cancer patients undergoing surgery after neoadjuvant therapy.","authors":"Hu Zhang, Xiaowei Mao, Jingwei Xu, Lijiang Song, Zhengwei Huang, Yao Li, Jiajing Sun, Jiali Qian, Shan Xu, Fabrizio Minervini, Kentaro Inamura, Zhengfu He","doi":"10.21037/tlcr-2025-25","DOIUrl":"10.21037/tlcr-2025-25","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant therapy followed by surgery is the recommended treatment for patients with locally advanced lung cancer. No studies have examined the risk factors of postoperative pulmonary complications (PPCs) in this group of patients. The addition of immune checkpoint inhibitors (ICIs) can improve the efficacy of neoadjuvant therapy; however, it is unknown whether ICIs will also increase the PPC incidence. Thus, we conducted this study to identify the predictors of PPCs.</p><p><strong>Methods: </strong>We reviewed the database of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University. Patients with non-adenocarcinoma non-small cell lung cancer (non-ADC NSCLC) who underwent surgery after neoadjuvant therapy were included. The clinical information was collected, the PPCs and mortality were evaluated.</p><p><strong>Results: </strong>The cohort in this study consisted of 108 patients. Among them, 36 had PPCs, and the incidence of PPCs was 33.3% (36/108). The majority of PPCs were prolonged time to chest tube removal and pneumonia. One patient died within 30 days due to serious postoperative complications. The mortality within 30 days was 0.9%. The addition of ICIs to neoadjuvant therapy did not increase the incidence of PPCs, but the operation time was longer in the ICI group. Multivariate analysis indicated that age, blood urea nitrogen (BUN) level and N2 stage may be superior predictors of PPCs.</p><p><strong>Conclusions: </strong>The addition of ICIs did not increase the incidence of PPCs but did prolong the operation time. Age, BUN level, and N2 stage were excellent predictors of PPCs in non-ADC NSCLC patients treated with surgery after neoadjuvant therapy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"552-562"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670823","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}

{"title":"Rapid detection of non-small cell lung cancer driver mutations using droplet digital polymerase chain reaction analysis of bronchial washings: a prospective multicenter study.","authors":"Kohei Somekawa, Nobuaki Kobayashi, Satoshi Nagaoka, Kenichi Seki, Yukihito Kajita, Suguru Muraoka, Ami Izawa, Ayami Kaneko, Yukiko Otsu, Momo Hirata, Sousuke Kubo, Ryo Nagasawa, Kota Murohashi, Hiroaki Fuji, Shuhei Teranishi, Ken Tashiro, Keisuke Watanabe, Nobuyuki Horita, Yu Hara, Makoto Kudo, Takeshi Kaneko","doi":"10.21037/tlcr-24-772","DOIUrl":"10.21037/tlcr-24-772","url":null,"abstract":"<p><strong>Background: </strong>Molecular profiling of non-small cell lung cancer (NSCLC) is crucial for personalized treatment, but obtaining adequate tumor tissue can be challenging. This study evaluated the utility of droplet digital polymerase chain reaction (ddPCR) analysis of bronchial washings (BWs) and serum for detecting driver oncogene mutations in NSCLC patients, comparing its performance to standard tissue genotyping methods.</p><p><strong>Methods: </strong>In this prospective, multicenter study conducted at two university hospitals in Yokohama, Japan, 73 treatment-naïve NSCLC patients underwent bronchoscopy with BW collection and blood sampling between October 2022 and April 2024. ddPCR was performed on BW and serum samples to detect epidermal growth factor receptor (EGFR; L858R, exon 19 deletions, G719X), KRAS (G12/13), and BRAF (V600E) mutations. Results were compared with standard tissue genotyping methods, including AmoyDx and Oncomine Dx Target Test (DxTT) assays. Turnaround time (TAT) for results was also assessed. The study protocol was approved by the institutional review boards, and all participants provided informed consent.</p><p><strong>Results: </strong>ddPCR analysis of BW samples showed high concordance with tissue genotyping, detecting EGFR mutations in 31.5% of cases (identical to tissue). For common EGFR mutations (L858R and exon 19 deletions), BW genotyping demonstrated 100% sensitivity and 98.0% specificity compared to tissue. TAT was significantly shorter for BW ddPCR compared to tissue genotyping (4.4±1.8 <i>vs.</i> 20.4±7.7 days, P<0.001). Serum ddPCR showed lower sensitivity (7.8% <i>vs.</i> 33.3% for EGFR mutations) compared to tissue genotyping, with detection associated with the presence of bone metastases. KRAS and BRAF mutations were detected at similar rates in BW and tissue samples, but at lower rates in serum.</p><p><strong>Conclusions: </strong>ddPCR analysis of BWs demonstrates high accuracy and rapid TAT for detecting common driver mutations in NSCLC. This approach represents a promising alternative to tissue biopsy for molecular profiling, potentially expediting treatment decisions. While serum ddPCR showed limited utility, it may complement tissue genotyping in specific clinical scenarios.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"353-362"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670089","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}

{"title":"Novel immune checkpoint inhibitor strategies in advanced non-small cell lung cancer: towards biomarker-driven therapies?","authors":"M Benthe Muntinghe-Wagenaar, T Jeroen N Hiltermann","doi":"10.21037/tlcr-24-966","DOIUrl":"10.21037/tlcr-24-966","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"328-333"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671100","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}

{"title":"Ion robotic bronchoscopy laser ablation and Da Vinci robotic segmentectomy for bilateral pulmonary nodules: a case report.","authors":"Teng Sun, Yong Ge, Zhiqiao Chen, Tianyue Ma, Shoujie Feng, Hao Zhang","doi":"10.21037/tlcr-24-922","DOIUrl":"10.21037/tlcr-24-922","url":null,"abstract":"<p><strong>Background: </strong>The treatment strategy of multiple pulmonary nodules presents significant challenges in thoracic surgery, particularly regarding precise diagnosis and treatment. The integration of emerging technologies for concurrent hybrid diagnostic and therapeutic approaches represents a potential breakthrough. The purpose of this study is to provide a new paradigm for the synchronous mixed treatment of multiple pulmonary nodules.</p><p><strong>Case description: </strong>A 34-year-old female patient was initially diagnosed with multiple pulmonary nodules in August 2023 and has been undergoing regular follow-up since then. A computed tomography (CT) in September 2024 showed a mixed ground-glass nodule (mGGN) in the dorsal segment (S6) of the left lower lobe of the lung, measuring approximately 11 mm × 7 mm, indicating a high risk of malignancy; and a ground-glass opacity (GGO) measuring 5 mm × 4 mm between the dorsal segment and anterior basal segment (S6 and S8) of the right lower lobe, with both nodules showing enlargement compared to a year ago. A simultaneous bilateral lung surgery is planned. The Ion robotic system was utilized to navigate precisely to the lesion along the B6b bronchus of the right lower lobe, where the lung nodule was ablated with a laser. Subsequently, the Da Vinci robotic system used to assist in the precise resection of the S6. Pathology on the left showed adenocarcinoma; a CT one week postoperatively showed a 1 cm patchy shadow with a cavity on the right.</p><p><strong>Conclusions: </strong>This report presents the first surgical technique for ion robotic-assisted laser ablation and dual-robot collaborative surgery, offering a novel strategy for the integration of airway diagnostic and therapeutic interventions.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 2","pages":"619-624"},"PeriodicalIF":4.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671017","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}