{"title":"Long-term efficacy and improved overall survival of lorlatinib in anaplastic lymphoma kinase-rearranged lung cancer: is cure a dream or a reality?","authors":"Yoshitsugu Horio, Hiroaki Kuroda, Eiichi Sasaki, Katsuhiro Masago","doi":"10.21037/tlcr-2025-694","DOIUrl":"10.21037/tlcr-2025-694","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2353-2358"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650660","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}
Runzhe Chen, Mingdian Wang, Qi Quan, Dijian Shen, Qiong Li, Xiujiao Shen, Xuan Li, Ming Chen
{"title":"Radiographic ground-glass nodules predict less aggressive features and favorable immune landscapes in early lung adenocarcinoma and its precursors.","authors":"Runzhe Chen, Mingdian Wang, Qi Quan, Dijian Shen, Qiong Li, Xiujiao Shen, Xuan Li, Ming Chen","doi":"10.21037/tlcr-2025-231","DOIUrl":"10.21037/tlcr-2025-231","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) remains the leading cause of cancer-related deaths globally, often due to late-stage diagnosis. Advancements in computed tomography (CT) have revolutionized the detection of indeterminate pulmonary nodules (IPNs), spanning benign lesions to early-stage LUAD. We aimed to understand early lung carcinogenesis and identify clinicopathological and immune features that may influence patient prognosis.</p><p><strong>Methods: </strong>This study retrospectively integrates clinical, radiographic, pathological, and immune data from 174 patients with resected pulmonary nodules, including atypical adenomatous hyperplasia (AAH, n=19), adenocarcinoma in situ (AIS, n=50), minimally invasive adenocarcinoma (MIA, n=40), and stage I invasive adenocarcinoma (ADC, n=65).</p><p><strong>Results: </strong>Among 174 resected nodules, ground-glass nodules (GGNs) were observed in 54.6% of all cases. Early-stage ADCs exhibited the lowest proportion of GGNs compared to AAH, AIS, and MIA, respectively (AAH: 52.6%; AIS: 86.0%; MIA: 72.5%; ADC: 20.0%; P<0.001). Well differentiated ADCs were significantly associated with lower rates of pleural traction (6.7%) and lymphovascular invasion (0%) compared to poorly differentiated ADCs (pleural traction: 36.4%, lymphovascular invasion: 18.2%). Immune profiling showed a progressive decline in CD8<sup>+</sup> T cells and an increased CD4/CD8 ratio from AAH to ADC. GGNs exhibited lower intratumoral CD4<sup>+</sup> and CD8<sup>+</sup> T cell densities than non-GGNs, consistent with their indolent histology and less invasive behavior. Radiographic appearance was strongly correlated with tumor differentiation and aggressiveness.</p><p><strong>Conclusions: </strong>These insights deepen our understanding of early lung carcinogenesis and offer potential pathways for prognostic stratification and personalized care for patients presenting with IPNs during CT screening.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2089-2099"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650672","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":"Utility of serum CYFRA 21-1 as a prognostic biomarker in ALK-positive non-small cell lung cancer treated with ALK-TKIs: a retrospective cohort study.","authors":"Ryo Sawada, Tadaaki Yamada, Yasuhiro Goto, Yoshiki Negi, Akira Nakao, Akihiro Yoshimura, Naoki Furuya, Tomohiro Oba, Makoto Hibino, Haruka Nakatani, Hirokazu Taniguchi, Aya Ohtsubo, Satoshi Watanabe, Takahiro Yamada, Yusuke Chihara, Takashi Kijima, Koichi Takayama","doi":"10.21037/tlcr-2024-1180","DOIUrl":"10.21037/tlcr-2024-1180","url":null,"abstract":"<p><strong>Background: </strong>Anaplastic lymphoma kinase (ALK) fusion gene-positive non-small cell lung cancer (NSCLC) represents 3-7% of all cases and causes oncogene addiction. Although ALK tyrosine kinase inhibitors (ALK-TKIs) are effective for treating ALK-positive NSCLC, some patients still show suboptimal responses and poor outcomes. Clinically simple and detectable biomarkers for this group are limited. Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1 and CYFRA) are widely used tumor markers in NSCLC. Elevated CEA levels are linked to tumor progression and resistance to cell death, while CYFRA is widely expressed in poorly differentiated squamous cell carcinomas. CYFRA has been identified as a prognostic factor in epidermal growth factor receptor (EGFR)-positive NSCLC, but its role in ALK-positive NSCLC remains unclear. Therefore, we retrospectively assessed the value of CEA and CYFRA as predictive biomarkers in patients with ALK-positive NSCLC treated with ALK-TKIs.</p><p><strong>Methods: </strong>This retrospective study analyzed 197 patients with advanced or recurrent ALK-positive NSCLC, who were diagnosed across 13 institutions in Japan and received their first ALK-TKI between July 1, 2014 and December 31, 2022. Eligible patients had measurable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients were stratified based on normal (≤5.0 and ≤3.5 ng/mL) or high (>5.0 and >3.5 ng/mL) baseline serum CEA and CYFRA levels. Serum CYFRA and CEA levels, which were measured using commercially available immunoassays per standard institutional protocols. The primary endpoint was progression-free survival (PFS) with initial ALK-TKI therapy, and secondary endpoints included overall survival (OS) and objective response rate (ORR). Multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Among 152 patients with available CYFRA data, 91 (59.9%) had normal CYFRA levels and 61 (40.1%) had elevated levels. In this analysis, patients in the high CYFRA group had significantly shorter median PFS and OS (9.27 and 28.8 months, respectively) than those in the normal CYFRA group (42.0 and 143.3 months, respectively). Multivariate analysis confirmed that high CYFRA levels were independent predictors of poor PFS (HR: 2.35, 95% CI: 1.50-3.68, P<0.001) and OS (HR: 3.28, 95% CI: 1.89-5.70, P<0.001). Furthermore, the high CYFRA group had lower ORR and complete response (CR) rates, compared with the normal CYFRA group. In contrast, no significant differences in PFS or OS were observed between patients with normal and elevated CEA levels.</p><p><strong>Conclusions: </strong>Elevated CYFRA levels correlate with reduced PFS and OS in ALK-positive NSCLC, indicating potential as a prognostic biomarker. Given CYFRA's association with tumor heterogeneity, which reduces ALK-TKI efficacy, its assessment could aid in risk strat","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"1986-2000"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650683","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":"Good responses to first-line immunotherapy-included treatment in lung squamous carcinoma with rare driver gene mutations: a report of three cases.","authors":"Li Tu, Yanyang Liu, Xiaoming Qiu, Jiewei Liu","doi":"10.21037/tlcr-2025-469","DOIUrl":"10.21037/tlcr-2025-469","url":null,"abstract":"<p><strong>Background: </strong>In terms of treatment, non-small cell lung cancer (NSCLC) can be classified into driver gene mutation-positive or -negative lung cancer. Compared with adenocarcinoma, lung squamous carcinoma (LUSC) patients with rare driver gene mutations are a small proportion of NSCLC, who experience significantly less benefit from targeted therapies and have limited second-line treatment options and poor prognosis. Immunotherapy is an important treatment strategy for patients with NSCLC. In clinical practice, LUSC patients could receive immunotherapy regardless of the patient's gene mutation status and gene mutation detection is not recommended for LUSC patients for first-line treatment decision. Therefore, there is little data on the efficacy of first-line immunotherapy-included treatments in LUSC with rare driver gene mutations, which deserves to be collected and reported.</p><p><strong>Case description: </strong>In this study, we report three female patients, aged from 28 to 65 years with stage IIIA-IVB LUSC and rare driver gene mutations, including epidermal growth factor receptor (EGFR) exon 18 point mutation G719X/S768I, EGFR exon 20 insertion, and echinoderm microtubule associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion, respectively. All three patients received first-line immunotherapy in combination with chemotherapy and achieved notable treatment outcomes. Case 1 achieved pathologic complete response (CR) after two cycles of immunochemotherapy, followed by a disease-free survival (DFS) of at least 30 months. Case 2 underwent four cycles of immunochemotherapy and rapidly achieved partial response (PR), followed by 2 years of monoimmunotherapy, with a progression-free survival (PFS) of at least 68 months. In case 3, except the primary lesion, there were CR for all metastatic lesions after 2 cycles of immunochemotherapy. These lesions remained absent in the subsequent 8 months until salvage surgery was performed and the DFS was at least 24 months.</p><p><strong>Conclusions: </strong>These findings suggested that first-line immunotherapy-included treatment may provide promising survival benefits for LUSC patients with rare driver gene mutations.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2337-2346"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650655","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":"Needle tract seeding after endobronchial ultrasound-guided intranodal forceps biopsy and cryobiopsy: a case report.","authors":"Kohei Yamamoto, Tatsuya Imabayashi, Yukari Kano, Toshiyuki Tanaka, Kazuki Jinno, Shunya Tanaka, Sayaka Uda, Tatsuya Yuba, Chieko Takumi","doi":"10.21037/tlcr-2025-218","DOIUrl":"10.21037/tlcr-2025-218","url":null,"abstract":"<p><strong>Background: </strong>Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure for diagnosing intrathoracic lymphadenopathy; however, it has limitations in diagnostic yield and sampling adequacy for certain conditions. To address this issue, EBUS-guided intranodal forceps biopsy (EBUS-IFB) and cryobiopsy (EBUS-CRYO) have been performed. Both techniques require the creation of a tract for the insertion of forceps or cryoprobes into the lymph nodes. However, potential adverse events associated with this tract remain unclear. Needle tract seeding (NTS), which is defined as the implantation of tumor cells along the puncture tract, is a rare but clinically significant complication of gastrointestinal procedures. However, its occurrence after bronchoscopy has rarely been reported. This report describes a rare case of NTS following EBUS-IFB and EBUS-CRYO.</p><p><strong>Case description: </strong>An 83-year-old woman with lung adenocarcinoma harboring <i>MET</i> exon 14 skipping mutation presented with right upper lobe nodules and bilateral mediastinal lymphadenopathy. The initial EBUS-TBNA yielded insufficient specimens for molecular testing. Subsequent EBUS-IFB and mediastinal cryobiopsy provided sufficient specimens for definitive diagnosis. Twenty-nine days after the procedure, computed tomography revealed rapid growth of the right upper lobe nodules and a tracheal mass at the biopsy site, consistent with NTS. Despite this complication, the patient demonstrated a marked response to tepotinib therapy, with significant regression of both the lung and tracheal lesions.</p><p><strong>Conclusions: </strong>This case highlights the need for increased awareness of NTS following advanced biopsy techniques. Tumor-related factors such as high malignancy and necrosis, combined with procedural elements, likely contribute to its occurrence. Bronchoscopists should carefully evaluate the procedural approaches and follow-up protocols to mitigate this risk and ensure early detection.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2317-2323"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650669","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}
Tetsuya Sakai, Mami Onishi, Yoshitaka Zenke, Eri Morita Yamamoto, Yuichi Ijiri, Kana Kawasaki, Fumie Kato, Tomoko Sugano, Bishnu Devi Maharjan, Ali Asgar S Bhagat, Tomokazu Yoshida, Shigeki Iwanaga, Masatoshi Yanagida, Koichi Goto
{"title":"Utility of CK8/18 in identifying circulating tumor cells derived from lesions in patients with non-small cell lung cancer.","authors":"Tetsuya Sakai, Mami Onishi, Yoshitaka Zenke, Eri Morita Yamamoto, Yuichi Ijiri, Kana Kawasaki, Fumie Kato, Tomoko Sugano, Bishnu Devi Maharjan, Ali Asgar S Bhagat, Tomokazu Yoshida, Shigeki Iwanaga, Masatoshi Yanagida, Koichi Goto","doi":"10.21037/tlcr-2025-155","DOIUrl":"10.21037/tlcr-2025-155","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumor cells (CTCs) are identified by the absence of pan-leukocyte markers and positive staining for cytokeratin (CK). Anti-panCK antibody (AE1/AE3) is a widely used marker for CK. However, epithelial-mesenchymal transition reduces the expression of panCK markers, leading to low detection rates of CTCs, especially in non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy of a novel CTC detection system using CK8/18 as an epithelial cell marker in patients with NSCLC.</p><p><strong>Methods: </strong>A total of 20 patients with NSCLC (10 <i>EGFR</i> mutant and 10 <i>EGFR</i> wild-type) were included in this study. Blood samples were examined using the novel CTC detection system. Both anti-panCK and anti-CK8/18 antibodies were used to identify CK and detect CTCs. Additionally, CTCs isolated from patients with <i>EGFR</i> mutations underwent single-cell sorting, whole genome amplification, and gene analysis to verify their lung cancer origin.</p><p><strong>Results: </strong>CTCs were detected in 17 patients (8 <i>EGFR</i> mutant and 9 <i>EGFR</i> wild-type) using CK8/18 and in only 8 patients (5 <i>EGFR</i> mutant and 3 <i>EGFR</i> wild-type) using panCK. The sensitivity of CTC detection based on CK8/18 was significantly higher than that based on panCK (85% <i>vs.</i> 40%, P<0.01). Among the 10 patients with <i>EGFR</i> mutations, <i>EGFR</i> mutations were confirmed in CTCs obtained from six patients in the gene analysis through single-cell sorting, aligning with mutations identified in tissue samples.</p><p><strong>Conclusions: </strong>This study demonstrated the effectiveness of CK8/18 over panCK in detecting CTCs. Adopting CK8/18 in the novel system improved the detection rate of CTCs, highlighting its potential in clinical applications.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2100-2112"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650682","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}
Klara Torok, Bence Ferencz, Kristiina Boettiger, Maria Dorothea Pozonec, Orsolya Pipek, Julianna Bogos, Andras Lantos, Zita Hegedus, Karin Schelch, Peter Radeczky, Krisztina Bogos, Vivien Teglas, Evelyn Megyesfalvi, Anita Ferenczy, Ferenc Renyi-Vamos, Clemens Aigner, Zsolt Megyesfalvi, Balazs Dome, Janos Fillinger
{"title":"Impact of KRAS mutation subtypes on morphological heterogeneity and immune landscape in surgically treated lung adenocarcinoma.","authors":"Klara Torok, Bence Ferencz, Kristiina Boettiger, Maria Dorothea Pozonec, Orsolya Pipek, Julianna Bogos, Andras Lantos, Zita Hegedus, Karin Schelch, Peter Radeczky, Krisztina Bogos, Vivien Teglas, Evelyn Megyesfalvi, Anita Ferenczy, Ferenc Renyi-Vamos, Clemens Aigner, Zsolt Megyesfalvi, Balazs Dome, Janos Fillinger","doi":"10.21037/tlcr-2024-1092","DOIUrl":"10.21037/tlcr-2024-1092","url":null,"abstract":"<p><strong>Background: </strong>Although Kirsten rat sarcoma virus (KRAS) mutations represent the most frequent oncogenic driver alterations in Caucasian lung adenocarcinoma (LADC) patients, their impact on immune phenotype and tumor morphology is largely unexplored. Here, we investigated the associations between KRAS mutation subtypes, immune landscape, and tumor heterogeneity in surgically treated LADC, with a particular focus on specific tumor growth patterns.</p><p><strong>Methods: </strong>This study included 87 surgically treated patients with histologically confirmed early-stage LADC. Three tumorous and one non-tumorous tissue microarray (TMA) cores were collected from each patient. KRAS genotyping was performed using polymerase chain reaction (PCR)-based assays. We assessed the immune landscape by evaluating the NLRP3 inflammasome, CD3, CD163, and PD-L1 expression.</p><p><strong>Results: </strong>The mutational landscape concerning the type of KRAS mutation was mostly homogenous across TMA cores, with KRASG12C being the most frequently detected alteration. Notably, in 19 cases, the dominant mutational subtype differed between the tumor punctures originating from the same tumor. Although KRASG12A mutation was not detected in LADC samples with a lepidic growth pattern and micropapillary LADCs lacked wild-type KRAS gene, no statistically significant association was found between the KRAS mutation subtype and LADC growth pattern. NLRP3 expression significantly correlated with CD3 and CD163 expressions (P<0.001), and elevated NLRP3 levels were characteristic of LADCs with solid growth pattern (P=0.001). Tumor samples with solid morphology expressed significantly higher levels of PD-L1 than acinar- or lepidic-pattern LADCs (P=0.007 and P=0.002, respectively).</p><p><strong>Conclusions: </strong>KRAS mutation subtypes may have a heterogeneous distribution across different tumor regions, contributing to cases with concomitant mutation subtypes that create significant diagnostic challenges. The growth pattern-specificity of NLRP3 and PD-L1 offers additional guidance for the future development of alternative immunotherapeutic approaches.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"1914-1928"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650657","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}
Erika Broström, Johan Isaksson, Panagiotis Xanthoulis, Rebecka Börjesson, Linda Willén, Tomas Hansen, Georg Holgersson, Simon Ekman, Johan Botling, Kristina Lamberg Lundström, Patrick Micke, Magnus Lindskog
{"title":"Predictors of survival and recurrence patterns following definitive chemoradiotherapy in stage III non-small cell lung cancer-a retrospective cohort study.","authors":"Erika Broström, Johan Isaksson, Panagiotis Xanthoulis, Rebecka Börjesson, Linda Willén, Tomas Hansen, Georg Holgersson, Simon Ekman, Johan Botling, Kristina Lamberg Lundström, Patrick Micke, Magnus Lindskog","doi":"10.21037/tlcr-24-840","DOIUrl":"10.21037/tlcr-24-840","url":null,"abstract":"<p><strong>Background: </strong>Chemoradiotherapy (CRT) is regarded as the treatment of choice for inoperable stage III non-small cell lung cancer (NSCLC) patients. Despite the curative intent, recurrence is frequent, and overall prognosis is poor. Thus, there is a need for clinical biomarkers to better predict outcome and to optimize treatment and follow-up. The aim of this study was to characterize a large cohort of real-world stage III NSCLC patients who received CRT with curative intent and to define parameters that could predict recurrence patterns, overall survival (OS) and survival time from recurrence.</p><p><strong>Methods: </strong>This study is based on a cohort of 193 stage III NSCLC patients receiving CRT with curative intent in mid-Sweden during the years 2009-2018. Data was retrospectively collected from medical records. Clinical parameters, recurrence patterns, salvage treatment, histological and molecular data were analyzed and correlated to outcome.</p><p><strong>Results: </strong>Median follow-up was 52 months, with a median OS of 33 months. Most patients (66%) progressed, commonly within the first 3 years following CRT. Performance status and common blood markers at recurrence were associated with worse survival. The presence of driver mutations [epidermal growth factor receptor (<i>EGFR</i>), Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>)] or metastatic spread to N3 lymph nodes increased the risk of distant recurrence. Immunotherapy as salvage treatment was associated with a significantly better prognosis.</p><p><strong>Conclusions: </strong>Routine diagnostic parameters can be used to predict survival and recurrence patterns in patients receiving curative CRT. Additionally, salvage treatment with immunotherapy was the strongest factor associated with longer survival after disease recurrence.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"1972-1985"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650671","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}
Shunn Theingi, Ashara Mitchell, Elena N Petre, Etay Ziv, Constantinos T Sofocleous, Stephen B Solomon, Erica S Alexander
{"title":"Safety and efficacy of thermal ablation for small cell lung cancer liver metastases.","authors":"Shunn Theingi, Ashara Mitchell, Elena N Petre, Etay Ziv, Constantinos T Sofocleous, Stephen B Solomon, Erica S Alexander","doi":"10.21037/tlcr-2025-112","DOIUrl":"10.21037/tlcr-2025-112","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma associated with early development of distant metastases, which portends a worse prognosis. The median survival of metastatic SCLC with standard treatment is only 9-11 months, with a 5-year survival of 1-2%. Patients with SCLC are often initially responsive to systemic therapies, but once they develop resistance to them, locoregional therapies like thermal ablation should be investigated for possible improvements in morbidity and mortality. This brief retrospective report evaluates six patients with SCLC liver metastases (LMs), treated in 11 thermal ablation sessions (radiofrequency ablation or microwave ablation). Technical success was achieved in all treatments (100%). After the first ablation, 3/7 ablated tumors had residual disease. Survival outcomes were determined using the Kaplan-Meier method. Median local tumor progression-free survival (LTPFS) was 2.9 [95% confidence interval (CI): 0.5-3.9] months. Median assisted LTPFS, defined as tumor control with subsequent retreatment, was 25.9 (95% CI: 8.3-not reported) months. Median overall survival (OS) was 14.3 months. There was one adverse event (1/11) of grade 1, according to the Common Terminology Criteria for Adverse Events version 5.0, fatigue within a month of ablation, which self-resolved. The results suggest that thermal ablation is safe for SCLC LMs. Although LTPFS was very modest, the long duration of assisted LTPFS and OS in this small, retrospective study suggests that thermal ablation may be a promising treatment option.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2309-2316"},"PeriodicalIF":3.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650676","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}
Andreas Herz, Maja Guberina, Christoph Pöttgen, Thomas Gauler, That Truong Mike Ton, Gerrit Fischedick, Lars Oliver Kiwitt, Wolfgang Lübcke, Christian Hoffmann, Martin Schuler, Martin Metzenmacher, Benedikt M Schaarschmidt, Denise Bos, Marcel Opitz, Hubertus Hautzel, Kaid Darwiche, Servet Bölükbas, Konstantinos Grapatsas, Verena Jendrossek, Lena Gockeln, Florian Wirsdörfer, Mario Hetzel, Emil Mladenov, Martin Stuschke, Nika Guberina
{"title":"The effect of durvalumab consolidation after definitive radiochemotherapy for non-operable stage III non-small cell lung cancer on the dose effect relation for therapy related pulmonary infiltrates as a risk factor for pneumonitis.","authors":"Andreas Herz, Maja Guberina, Christoph Pöttgen, Thomas Gauler, That Truong Mike Ton, Gerrit Fischedick, Lars Oliver Kiwitt, Wolfgang Lübcke, Christian Hoffmann, Martin Schuler, Martin Metzenmacher, Benedikt M Schaarschmidt, Denise Bos, Marcel Opitz, Hubertus Hautzel, Kaid Darwiche, Servet Bölükbas, Konstantinos Grapatsas, Verena Jendrossek, Lena Gockeln, Florian Wirsdörfer, Mario Hetzel, Emil Mladenov, Martin Stuschke, Nika Guberina","doi":"10.21037/tlcr-2024-1284","DOIUrl":"10.21037/tlcr-2024-1284","url":null,"abstract":"<p><strong>Background: </strong>Consolidation therapy with the anti-programmed death-ligand 1 (PD-L1) antibody durvalumab, or other immune checkpoint inhibitors, has been associated with improved progression-free and overall survival in patients with stage III non-small cell lung cancer (NSCLC) as demonstrated in randomized clinical trials. The purpose of the present study is to evaluate the dose-response relationship for partial lung infiltrate volumes per dose bin after definitive radiochemotherapy as a sensitive end point to detect a durvalumab effect on the lung parenchyma in patients with subclinical or grade ≤2 pneumonitis.</p><p><strong>Methods: </strong>Consecutive patients from a prospective registry with inoperable NSCLC stage III who developed no or pneumonitis grade ≤2 after definitive radiochemotherapy with or without durvalumab consolidation were included. Pulmonary infiltrates outside the planning target volumes were contoured in the follow-up computed tomography (CT) at the time of maximum infiltrate expression. Partial lung infiltrate volumes per dose bin were determined over the entire dose range. A mixed random and fixed effect model was used to fit dose response curves stepwise in dose bins of 5 Gy. The Akaike information criterion (AIC) was used for model comparison.</p><p><strong>Results: </strong>Sixty patients with and 44 without durvalumab consolidation were analysed. The step model showed a significant dose response relationship for the pulmonary infiltrates (P<0.001, <i>F</i>-test) that was modified by the durvalumab effect (P<0.001, <i>F</i>-test). There was a significant dependence of the durvalumab effect on radiation dose (P=0.003). The durvalumab effect increased with dose from 0% in the lowest dose bin as reference to 5.2%±1.2% partial lung infiltrate volume in the highest dose bin. There was significant inter-individual heterogeneity of partial lung infiltrate volumes at each dose bin (P<0.001, <i>F</i>-test). The percentage of lung volume receiving at least 5 Gy (V5) was the most significant characteristic increasing risk of pulmonary infiltrates (P<0.001, <i>F</i>-test). Multivariable proportional hazards Cox-model showed that pulmonary infiltrates at 5-10 and 35-40 Gy dose bins were dominant factors determining the risk of pneumonitis grade 2.</p><p><strong>Conclusions: </strong>The relationship between radiation dose and lung infiltrates observed by follow-up CT scans after radiochemotherapy is sensitive enough to detect factors that systematically increase the radiation dose response. In this case, the focus is on durvalumab consolidation and radiation dose to the lung. The dose-response relationship may help in the prediction of grade 2 pneumonitis. However, further research is needed to understand the biological factors that contribute to the large differences in response to radiation dose between individuals.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2074-2088"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650679","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}