Pub Date : 2026-02-01DOI: 10.1016/j.jtocrr.2025.100940
Gustavo Schvartsman MD, PhD , Yasmin M. Amirato MD , Frederico Monfardini MSc , Gustavo Prado dos Santos BSc , Diogo B.D. Gomes MD , Ludmila de O. M. Koch MD , Benoit J. Bibas MD, PhD , Oswaldo Gomes Jr. MD , Paulo V. Campregher MD, PhD , Patrícia Severino PhD , Luciana C. Marti PhD , Vitor R. Paes MD , Laura Leaden PhD , Rodrigo C. Chate MD , Jose M. Ribas MD, PhD , Victor.A.R. Sousa MD , Patrícia Taranto MD , Fernando Moura MD, PhD , Ricardo M. Terra MD, PhD , Ana Carolina Pires de Rezende MD , Marcos N. Samano MD, PhD
Introduction
Stereotactic ablative radiotherapy (SABR) is routinely used in patients with early stage NSCLC who are not candidates for surgery. Despite excellent local tumor control, it is associated with a high rate of regional and distant recurrences. Combining stereotactic radiotherapy with PD-1 inhibitors has demonstrated encouraging results for patients with curative intent, but how it affects the tumor microenvironment and pathologic response remains unclear.
Methods
We designed a phase II, open-label, single-arm study aimed to evaluate the efficacy and safety of neoadjuvant nivolumab combined with SABR in patients with NSCLC measuring up to 4 cm, without positive lymph nodes. Patients were required to be eligible for surgery, with adequate pulmonary and cardiovascular function. Nivolumab was administered at 360 mg every 21 days for three doses, combined with SABR, which was initiated concomitantly with the first cycle. Patients subsequently underwent surgical resection 10 weeks after the last dose of radiation. The primary end point was the pathologic complete response (pCR) rate at surgery. Secondary end points included major pathologic response (MPR) rate, safety, event-free survival, and overall survival at 12 months and a comprehensive biomarker analysis.
Results
A total of 25 patients were enrolled between November 2019 and February 2022. The mean age was 68 years, and 68% were female. The mean tumor size at baseline was 2.47 cm. A total of 24 patients fully completed the experimental therapy and proceeded with surgery. The primary end point of pCR was achieved by 19 of 24 patients (79.2%; 95% confidence interval: 57%–92%, p value 0.0875, in the per-protocol analysis). MPR was observed in 20 cases (83.3%; 95% confidence interval: 61.8%–94%). Four patients have not achieved an MPR, with one of them presenting with 100% residual viable tumor. No patient relapsed to date, with 12-month event-free survival and overall survival of 84%, with median not reached for both. One patient died from alcoholic hepatitis, unrelated to the treatment, and did not undergo resection. Two patients died from surgical complications.
Conclusions
The neoadjuvant combination of three doses of nivolumab and SABR produced a high pCR rate in stage I NSCLC. Further research is warranted to evaluate this treatment modality in patients with medically inoperable NSCLC and whether surgery could be safely omitted for patients who are candidates for resection.
{"title":"Pathologic Responses to Stereotactic Ablative Radiotherapy in Combination With Nivolumab for Early Stage NSCLC: A Phase 2 Study","authors":"Gustavo Schvartsman MD, PhD , Yasmin M. Amirato MD , Frederico Monfardini MSc , Gustavo Prado dos Santos BSc , Diogo B.D. Gomes MD , Ludmila de O. M. Koch MD , Benoit J. Bibas MD, PhD , Oswaldo Gomes Jr. MD , Paulo V. Campregher MD, PhD , Patrícia Severino PhD , Luciana C. Marti PhD , Vitor R. Paes MD , Laura Leaden PhD , Rodrigo C. Chate MD , Jose M. Ribas MD, PhD , Victor.A.R. Sousa MD , Patrícia Taranto MD , Fernando Moura MD, PhD , Ricardo M. Terra MD, PhD , Ana Carolina Pires de Rezende MD , Marcos N. Samano MD, PhD","doi":"10.1016/j.jtocrr.2025.100940","DOIUrl":"10.1016/j.jtocrr.2025.100940","url":null,"abstract":"<div><h3>Introduction</h3><div>Stereotactic ablative radiotherapy (SABR) is routinely used in patients with early stage NSCLC who are not candidates for surgery. Despite excellent local tumor control, it is associated with a high rate of regional and distant recurrences. Combining stereotactic radiotherapy with PD-1 inhibitors has demonstrated encouraging results for patients with curative intent, but how it affects the tumor microenvironment and pathologic response remains unclear.</div></div><div><h3>Methods</h3><div>We designed a phase II, open-label, single-arm study aimed to evaluate the efficacy and safety of neoadjuvant nivolumab combined with SABR in patients with NSCLC measuring up to 4 cm, without positive lymph nodes. Patients were required to be eligible for surgery, with adequate pulmonary and cardiovascular function. Nivolumab was administered at 360 mg every 21 days for three doses, combined with SABR, which was initiated concomitantly with the first cycle. Patients subsequently underwent surgical resection 10 weeks after the last dose of radiation. The primary end point was the pathologic complete response (pCR) rate at surgery. Secondary end points included major pathologic response (MPR) rate, safety, event-free survival, and overall survival at 12 months and a comprehensive biomarker analysis.</div></div><div><h3>Results</h3><div>A total of 25 patients were enrolled between November 2019 and February 2022. The mean age was 68 years, and 68% were female. The mean tumor size at baseline was 2.47 cm. A total of 24 patients fully completed the experimental therapy and proceeded with surgery. The primary end point of pCR was achieved by 19 of 24 patients (79.2%; 95% confidence interval: 57%–92%, <em>p</em> value 0.0875, in the per-protocol analysis). MPR was observed in 20 cases (83.3%; 95% confidence interval: 61.8%–94%). Four patients have not achieved an MPR, with one of them presenting with 100% residual viable tumor. No patient relapsed to date, with 12-month event-free survival and overall survival of 84%, with median not reached for both. One patient died from alcoholic hepatitis, unrelated to the treatment, and did not undergo resection. Two patients died from surgical complications.</div></div><div><h3>Conclusions</h3><div>The neoadjuvant combination of three doses of nivolumab and SABR produced a high pCR rate in stage I NSCLC. Further research is warranted to evaluate this treatment modality in patients with medically inoperable NSCLC and whether surgery could be safely omitted for patients who are candidates for resection.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100940"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-13DOI: 10.1016/j.jtocrr.2025.100942
Matthew Aizpuru MD , Jennifer M. Boland MD , Brendan W. Lunn MD , Sahar A. Saddoughi MD, PhD , K. Robert Shen MD , Stephen D. Cassivi MD , Dennis A. Wigle MD , Janani S. Reisenauer MD , Luis F. Tapias MD
Objectives
Risk stratification of pleuropulmonary solitary fibrous tumors (SFTs) is based on post-resection histopathologic scoring systems. We queried whether preoperative 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) maximum standardized uptake values (SUVmax) had prognostic value for recurrence or metastasis.
Methods
Retrospective review of patients who underwent FDG-PET/CT before resection of SFT between January 2002 and June 2023. Independent review of slides by a pulmonary pathologist and radiologist review of FDG-PET/CT were performed. Statistical analyses included nonparametric tests for correlations, receiver-operating characteristic (ROC) curves, and Kaplan-Meier analysis.
Results
There were 34 patients with a preoperative FDG-PET/CT before SFT resection. Median tumor SUVmax was 2.3 (range: 0.9–38.7). Recurrence occurred in five patients (14.7%) (three local, two metastatic). Tumor SUVmax was associated with tumor size (p < 0.001), parietal pleural origin (p = 0.027), hypercellularity (p = 0.049), mitoses (p < 0.001), and Ki67 (p = 0.015). SUVmax correlated with the modified Demicco score (p < 0.001) and Tapias score (p < 0.001). Prediction of recurrence was excellent with SUVmax (area under ROC curve [AUC] = 0.872, p < 0.001), Tapias score (AUC = 0.914, p < 0.001), and modified Demicco score (AUC = 0.821, p < 0.001). Time-dependent ROC analysis identified SUVmax more than or equal to 2.4 as high risk for recurrence. Recurrence-free survival at 1, 3, 5, and 10 years was 92.9%, 83.6%, 69.6%, and 46.4%, respectively, in patients with SUVmax more than or equal to 2.4, but it was 100% at all time points with SUVmax less than 2.4 (p = 0.002). SUVmax was not associated with overall survival in this small cohort.
Conclusions
Tumor metabolic activity on FDG-PET/CT is predictive of SFT recurrence. Preoperative SUVmax correlates with known histopathologic high-risk features and validated risk scores. Preoperative FDG-PET/CT should be performed before SFT resection to assist in prognostication.
{"title":"FDG-PET/CT SUVmax Predicts Recurrence Risk of Resected Pleuropulmonary Solitary Fibrous Tumors","authors":"Matthew Aizpuru MD , Jennifer M. Boland MD , Brendan W. Lunn MD , Sahar A. Saddoughi MD, PhD , K. Robert Shen MD , Stephen D. Cassivi MD , Dennis A. Wigle MD , Janani S. Reisenauer MD , Luis F. Tapias MD","doi":"10.1016/j.jtocrr.2025.100942","DOIUrl":"10.1016/j.jtocrr.2025.100942","url":null,"abstract":"<div><h3>Objectives</h3><div>Risk stratification of pleuropulmonary solitary fibrous tumors (SFTs) is based on post-resection histopathologic scoring systems. We queried whether preoperative 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) maximum standardized uptake values (SUVmax) had prognostic value for recurrence or metastasis.</div></div><div><h3>Methods</h3><div>Retrospective review of patients who underwent FDG-PET/CT before resection of SFT between January 2002 and June 2023. Independent review of slides by a pulmonary pathologist and radiologist review of FDG-PET/CT were performed. Statistical analyses included nonparametric tests for correlations, receiver-operating characteristic (ROC) curves, and Kaplan-Meier analysis.</div></div><div><h3>Results</h3><div>There were 34 patients with a preoperative FDG-PET/CT before SFT resection. Median tumor SUVmax was 2.3 (range: 0.9–38.7). Recurrence occurred in five patients (14.7%) (three local, two metastatic). Tumor SUVmax was associated with tumor size (<em>p</em> < 0.001), parietal pleural origin (<em>p</em> = 0.027), hypercellularity (<em>p</em> = 0.049), mitoses (<em>p</em> < 0.001), and Ki67 (<em>p</em> = 0.015). SUVmax correlated with the modified Demicco score (<em>p</em> < 0.001) and Tapias score (<em>p</em> < 0.001). Prediction of recurrence was excellent with SUVmax (area under ROC curve [AUC] = 0.872, <em>p</em> < 0.001), Tapias score (AUC = 0.914, <em>p</em> < 0.001), and modified Demicco score (AUC = 0.821, <em>p</em> < 0.001). Time-dependent ROC analysis identified SUVmax more than or equal to 2.4 as high risk for recurrence. Recurrence-free survival at 1, 3, 5, and 10 years was 92.9%, 83.6%, 69.6%, and 46.4%, respectively, in patients with SUVmax more than or equal to 2.4, but it was 100% at all time points with SUVmax less than 2.4 (<em>p</em> = 0.002). SUVmax was not associated with overall survival in this small cohort.</div></div><div><h3>Conclusions</h3><div>Tumor metabolic activity on FDG-PET/CT is predictive of SFT recurrence. Preoperative SUVmax correlates with known histopathologic high-risk features and validated risk scores. Preoperative FDG-PET/CT should be performed before SFT resection to assist in prognostication.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100942"},"PeriodicalIF":3.5,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1016/j.jtocrr.2025.100941
Kaiwen Wang PharmD , Ceylan Altintas Taslic MD , Patricia de Groot MD , Mitchell A. Parma MD , Alvaro Guimaraes Paula MD , Melody Caranto MSN , Komal Shah MD , Mukulika Bose PhD , Cole Ruoff BS , Loukia G. Karacosta PhD , Lauren A. Byers MD , Carl M. Gay MD, PhD , Jianjun Zhang MD, PhD , John V. Heymach MD, PhD , Bingnan Zhang MD, MBA
Small cell transformation has been described as a resistance mechanism to targeted therapy treated in patients with EGFR-mutated NSCLC and less often reported with those with other actionable oncogenic alterations, including ALK-rearranged NSCLC. Given lack of standard-of-care treatments for patients with actionable oncogenic alteration NSCLC transformed to SCLC, this remains a challenge and unmet need for treating these patients.
Here, we present a case of a patient with ALK-rearranged NSCLC with transformation to SCLC, who has progressed on several lines of therapies and successfully treated with tarlatamab to elicit and maintain clinical benefit, including intracranial response.
{"title":"First Report of Response to Tarlatamab in a Patient With Histologic-Transformed SCLC From ALK-Rearranged NSCLC: Case Report","authors":"Kaiwen Wang PharmD , Ceylan Altintas Taslic MD , Patricia de Groot MD , Mitchell A. Parma MD , Alvaro Guimaraes Paula MD , Melody Caranto MSN , Komal Shah MD , Mukulika Bose PhD , Cole Ruoff BS , Loukia G. Karacosta PhD , Lauren A. Byers MD , Carl M. Gay MD, PhD , Jianjun Zhang MD, PhD , John V. Heymach MD, PhD , Bingnan Zhang MD, MBA","doi":"10.1016/j.jtocrr.2025.100941","DOIUrl":"10.1016/j.jtocrr.2025.100941","url":null,"abstract":"<div><div>Small cell transformation has been described as a resistance mechanism to targeted therapy treated in patients with <em>EGFR</em>-mutated NSCLC and less often reported with those with other actionable oncogenic alterations, including <em>ALK</em>-rearranged NSCLC. Given lack of standard-of-care treatments for patients with actionable oncogenic alteration NSCLC transformed to SCLC, this remains a challenge and unmet need for treating these patients.</div><div>Here, we present a case of a patient with <em>ALK</em>-rearranged NSCLC with transformation to SCLC, who has progressed on several lines of therapies and successfully treated with tarlatamab to elicit and maintain clinical benefit, including intracranial response.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100941"},"PeriodicalIF":3.5,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a target of antibody-drug conjugate therapy for NSCLC. High expression of CEACAM5 has been reported in approximately 25% of patients with lung adenocarcinoma. However, CEACAM5 expression has not been systematically examined in a real-world and large patient population with NSCLC. There are also limited data on the prognostic impact of CEACAM5 protein expression.
Methods
We assessed CEACAM5 protein expression by immunohistochemistry in two separate cohorts of patients with NSCLC to include both routine clinical biopsy and resection specimens, using the anti-CEACAM5 clone 769 antibody assay protocol and scoring scheme for the tusamitamab ravtansine clinical trials. Expression levels were categorized as high (≥50% tumor cells at ≥2+ intensity), moderate (1%–49% tumor cells at ≥2+ intensity), and negative (0/1+ intensity) and scored independently by three thoracic pathologists. Interrater reliability was determined by Kendall’s coefficient of concordance and Fleiss’ kappa. Association with PD-L1 and driver mutation was calculated by Fisher exact or chi-square test. Correlation with recurrence-free survival and overall survival was determined by log-rank tests.
Results
The interrater reliability of CEACAM5 assessment was moderate among three pathologists. The overall prevalence of high CEACAM5 expression was 18%. CEACAM5 expression did not significantly correlate with tumor stage, PD-L1 expression, tumor mutation burden, and EGFR or KRAS mutations. There was no prognostic effect of CEACAM5 expression on recurrence-free survival or overall survival.
Conclusions
Our data revealed that 18% of routinely diagnosed clinical NSCLC samples had high CEACAM5 expression by immunohistochemistry, and its expression was not associated with oncogenic driver mutations or patient prognosis in a predominantly early stage NSCLC cohort.
{"title":"The Landscape of CEACAM5 Expression by Immunohistochemistry in NSCLC","authors":"Ying-Han R. Hsu MD, FRCPC , Amna Almutrafi MD , Katrina Hueniken MSc , Alhareth Azaizeh MD , Likun Hou MD, PhD , Quan Li PhD , Mackenzie Bates BSc , Nhu-An Pham PhD , Ming-Sound Tsao MD, FRCPC","doi":"10.1016/j.jtocrr.2025.100943","DOIUrl":"10.1016/j.jtocrr.2025.100943","url":null,"abstract":"<div><h3>Introduction</h3><div>Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a target of antibody-drug conjugate therapy for NSCLC. High expression of CEACAM5 has been reported in approximately 25% of patients with lung adenocarcinoma. However, CEACAM5 expression has not been systematically examined in a real-world and large patient population with NSCLC. There are also limited data on the prognostic impact of CEACAM5 protein expression.</div></div><div><h3>Methods</h3><div>We assessed CEACAM5 protein expression by immunohistochemistry in two separate cohorts of patients with NSCLC to include both routine clinical biopsy and resection specimens, using the anti-CEACAM5 clone 769 antibody assay protocol and scoring scheme for the tusamitamab ravtansine clinical trials. Expression levels were categorized as high (≥50% tumor cells at ≥2+ intensity), moderate (1%–49% tumor cells at ≥2+ intensity), and negative (0/1+ intensity) and scored independently by three thoracic pathologists. Interrater reliability was determined by Kendall’s coefficient of concordance and Fleiss’ kappa. Association with PD-L1 and driver mutation was calculated by Fisher exact or chi-square test. Correlation with recurrence-free survival and overall survival was determined by log-rank tests.</div></div><div><h3>Results</h3><div>The interrater reliability of CEACAM5 assessment was moderate among three pathologists. The overall prevalence of high CEACAM5 expression was 18%. CEACAM5 expression did not significantly correlate with tumor stage, PD-L1 expression, tumor mutation burden, and <em>EGFR</em> or <em>KRAS</em> mutations. There was no prognostic effect of CEACAM5 expression on recurrence-free survival or overall survival.</div></div><div><h3>Conclusions</h3><div>Our data revealed that 18% of routinely diagnosed clinical NSCLC samples had high CEACAM5 expression by immunohistochemistry, and its expression was not associated with oncogenic driver mutations or patient prognosis in a predominantly early stage NSCLC cohort.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100943"},"PeriodicalIF":3.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.jtocrr.2025.100901
Gowri Swaminathan MD , Jonathan Muratori DO , Faateh Rauf MD , Santino Patrizi DO , Theo Trandafirescu MD , Larry A. Sonna MD, PhD
Solitary fibrous tumors (SFTs) can be either localized or metastatic. We present a rare case of a 69-year-old patient with a metastatic solitary fibrous tumor in uncommon anatomical locations, treated with a short course of pazopanib. While surgical resection remains the primary treatment for localized SFT, chemotherapy has been used for advanced cases. Our unique case highlights the need for more research into treatment options to improve patient outcomes. Since both benign and malignant SFTs can metastasize, mortality is mainly due to thoracic metastases; further studies are needed to understand the prognostic factors that influence disease spread versus local growth.
{"title":"A Rare Metastatic Fibrous Tumor: Review of Literature With a Case Report","authors":"Gowri Swaminathan MD , Jonathan Muratori DO , Faateh Rauf MD , Santino Patrizi DO , Theo Trandafirescu MD , Larry A. Sonna MD, PhD","doi":"10.1016/j.jtocrr.2025.100901","DOIUrl":"10.1016/j.jtocrr.2025.100901","url":null,"abstract":"<div><div>Solitary fibrous tumors (SFTs) can be either localized or metastatic. We present a rare case of a 69-year-old patient with a metastatic solitary fibrous tumor in uncommon anatomical locations, treated with a short course of pazopanib. While surgical resection remains the primary treatment for localized SFT, chemotherapy has been used for advanced cases. Our unique case highlights the need for more research into treatment options to improve patient outcomes. Since both benign and malignant SFTs can metastasize, mortality is mainly due to thoracic metastases; further studies are needed to understand the prognostic factors that influence disease spread versus local growth.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100901"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/j.jtocrr.2025.100936
Qiang Wu MD, Zhenyang Lv MMed, Zhe Fan MMed, Ze Wang MMed, Hao Su MMed, Ting Lei MD
{"title":"Unmasking the Hidden Cardiopulmonary Cost of Lobectomy: A Paradigm Shift Demanded by Exercise Hemodynamics","authors":"Qiang Wu MD, Zhenyang Lv MMed, Zhe Fan MMed, Ze Wang MMed, Hao Su MMed, Ting Lei MD","doi":"10.1016/j.jtocrr.2025.100936","DOIUrl":"10.1016/j.jtocrr.2025.100936","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 1","pages":"Article 100936"},"PeriodicalIF":3.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.1016/j.jtocrr.2025.100935
Erica Pietroluongo MD, PhD , Christine M. Bestvina MD , Rachel Brattin , Pietro De Placido MD, PhD , Anna Di Lello MD , Waqas Haque MD, MPH , Alessandra Esposito PhD , Roberto Bianco MD, PhD , Noura Choudhury MD , Marina Chiara Garassino MD
Introduction
Thymic neuroendocrine tumors (TNENs) are exceptionally rare and a clinically heterogeneous malignancy, often diagnosed at an advanced stage and lacking standardized treatment algorithms. Due to the scarcity of dedicated evidence, most therapeutic strategies are extrapolated from other neuroendocrine neoplasms.
Methods
This narrative review provides an updated overview of current and emerging treatment approaches for TNENs, focusing on histology-driven strategies and the evolving role of targeted and radionuclide therapies. A comprehensive literature search was conducted through PubMed/MEDLINE and Embase from January 1, 2000, up to May 31, 2025, integrating retrospective series, real-world data, and ongoing clinical trials.
Results
Surgical resection remains the cornerstone of treatment whenever feasible. The benefit of adjuvant therapy in well-differentiated tumors is unclear, whereas thymic neuroendocrine carcinomas often require multimodal approaches, including platinum–etoposide chemotherapy and radiotherapy. Retrospective evidence suggests that even well-differentiated, high-grade tumors may respond to cytotoxic agents. Somatostatin analogues are widely used in indolent or peptide receptor-positive tumors, whereas everolimus and, more recently, cabozantinib represent options for progressive disease. Peptide receptor radionuclide therapy has demonstrated encouraging results in somatostatin receptor–positive tumors and is currently under further investigation in prospective trials involving thymic primaries. However, the 5-year overall survival rate varies significantly (approximately 28%–80%), underlining an urgent need for prospective, subtype-specific studies.
Conclusions
The management of TNENs requires a multidisciplinary and individualized approach based on histologic subtype, somatostatin receptor status, and disease aggressiveness. Despite promising therapeutic options, robust prospective data remain limited. The integration of TNENs into basket trials, the molecular refinement of prognostic subgroups (e.g., NET G3), and the conduct of dedicated multicenter prospective studies are urgently needed to define optimal treatment algorithms and improve clinical outcomes in these rare entities.
{"title":"Thymic Neuroendocrine Tumors: Evolving Insights and Innovative Approaches","authors":"Erica Pietroluongo MD, PhD , Christine M. Bestvina MD , Rachel Brattin , Pietro De Placido MD, PhD , Anna Di Lello MD , Waqas Haque MD, MPH , Alessandra Esposito PhD , Roberto Bianco MD, PhD , Noura Choudhury MD , Marina Chiara Garassino MD","doi":"10.1016/j.jtocrr.2025.100935","DOIUrl":"10.1016/j.jtocrr.2025.100935","url":null,"abstract":"<div><h3>Introduction</h3><div>Thymic neuroendocrine tumors (TNENs) are exceptionally rare and a clinically heterogeneous malignancy, often diagnosed at an advanced stage and lacking standardized treatment algorithms. Due to the scarcity of dedicated evidence, most therapeutic strategies are extrapolated from other neuroendocrine neoplasms.</div></div><div><h3>Methods</h3><div>This narrative review provides an updated overview of current and emerging treatment approaches for TNENs, focusing on histology-driven strategies and the evolving role of targeted and radionuclide therapies. A comprehensive literature search was conducted through PubMed/MEDLINE and Embase from January 1, 2000, up to May 31, 2025, integrating retrospective series, real-world data, and ongoing clinical trials.</div></div><div><h3>Results</h3><div>Surgical resection remains the cornerstone of treatment whenever feasible. The benefit of adjuvant therapy in well-differentiated tumors is unclear, whereas thymic neuroendocrine carcinomas often require multimodal approaches, including platinum–etoposide chemotherapy and radiotherapy. Retrospective evidence suggests that even well-differentiated, high-grade tumors may respond to cytotoxic agents. Somatostatin analogues are widely used in indolent or peptide receptor-positive tumors, whereas everolimus and, more recently, cabozantinib represent options for progressive disease. Peptide receptor radionuclide therapy has demonstrated encouraging results in somatostatin receptor–positive tumors and is currently under further investigation in prospective trials involving thymic primaries. However, the 5-year overall survival rate varies significantly (approximately 28%–80%), underlining an urgent need for prospective, subtype-specific studies.</div></div><div><h3>Conclusions</h3><div>The management of TNENs requires a multidisciplinary and individualized approach based on histologic subtype, somatostatin receptor status, and disease aggressiveness. Despite promising therapeutic options, robust prospective data remain limited. The integration of TNENs into basket trials, the molecular refinement of prognostic subgroups (e.g., NET G3), and the conduct of dedicated multicenter prospective studies are urgently needed to define optimal treatment algorithms and improve clinical outcomes in these rare entities.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 2","pages":"Article 100935"},"PeriodicalIF":3.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jtocrr.2025.100876
Kai-Lin Liu BA, BS , Alex Watts MS , Connor B. Grady MPH , Geoffrey Liu MD, MSc , Devalben Patel BSc, MLT , Karmugi Balaratnam MD , Stephen V. Liu MD , Gabriela Bravo Montenegro MD , Yunan Nie MD , Jorge Nieva MD , Amanda Herrmann MD , Kristen Marrone MD , Vincent Lam MD , Fangdi Sun MD , Jonathan Dowell MD , William Schwartzman MD , Vamsidhar Velcheti MD , Olivia Fankuchen MD, MS , Tasfiq Ullah MD , Liza Villaruz MD , Melina E. Marmarelis MD, MSCE
Introduction
The prognostic significance of baseline and on-treatment brain and liver metastasis in ALK+ or ROS1+ metastatic NSCLC (mNSCLC) remains unclear. As we consider intensification strategies, it is critical to identify factors that predict high-risk disease.
Methods
Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with ALK+ or ROS1+ mNSCLC. Baseline characteristics and the cumulative incidence (CI) of brain and liver metastases were compared (≥2-year survivors versus <2-year; pre-2017 versus post-2017). Multivariable Cox proportional hazard models were used to evaluate the association between factors and overall survival, and multivariable logistic regression models were used for the odds of death within 2 years.
Results
A total of 310 patients with ALK+ mNSCLC were identified (≥2-y: 229, <2-y: 81). There was no difference in cumulative incidence of brain metastases between survival groups (29% at 21 mo). However, the cumulative incidence of liver metastasis was higher in those who survived less than 2 years (20.9% versus 5.4% at 21 mo). The cumulative incidence of brain but not liver metastases has improved post-2017 with the newer generation of ALK tyrosine kinase inhibitors. There were 69 patients with ROS1+ mNSCLC who were identified (≥2-y: 46, < 2-y: 23). There was no significant difference in the cumulative incidence of brain or liver metastases between less-than-2-year and greater-than-or-equal-to-2-year survivor cohorts (p = 0.664, p = 0.201).
Conclusions
Among patients with ALK+ but not ROS1+ mNSCLC, the presence of liver metastases at baseline and on-treatment was associated with worse survival. In the ALK+ population, the cumulative incidence of brain but not liver metastases is improving, highlighting a need for therapies effective at the treatment and prevention of liver metastases.
{"title":"Characteristics of Short-Term Survivors With ALK or ROS1-Altered Metastatic NSCLC","authors":"Kai-Lin Liu BA, BS , Alex Watts MS , Connor B. Grady MPH , Geoffrey Liu MD, MSc , Devalben Patel BSc, MLT , Karmugi Balaratnam MD , Stephen V. Liu MD , Gabriela Bravo Montenegro MD , Yunan Nie MD , Jorge Nieva MD , Amanda Herrmann MD , Kristen Marrone MD , Vincent Lam MD , Fangdi Sun MD , Jonathan Dowell MD , William Schwartzman MD , Vamsidhar Velcheti MD , Olivia Fankuchen MD, MS , Tasfiq Ullah MD , Liza Villaruz MD , Melina E. Marmarelis MD, MSCE","doi":"10.1016/j.jtocrr.2025.100876","DOIUrl":"10.1016/j.jtocrr.2025.100876","url":null,"abstract":"<div><h3>Introduction</h3><div>The prognostic significance of baseline and on-treatment brain and liver metastasis in <em>ALK</em>+ or <em>ROS1</em>+ metastatic NSCLC (mNSCLC) remains unclear. As we consider intensification strategies, it is critical to identify factors that predict high-risk disease.</div></div><div><h3>Methods</h3><div>Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with <em>ALK</em>+ or <em>ROS1</em>+ mNSCLC. Baseline characteristics and the cumulative incidence (CI) of brain and liver metastases were compared (≥2-year survivors versus <2-year; pre-2017 versus post-2017). Multivariable Cox proportional hazard models were used to evaluate the association between factors and overall survival, and multivariable logistic regression models were used for the odds of death within 2 years.</div></div><div><h3>Results</h3><div>A total of 310 patients with <em>ALK</em>+ mNSCLC were identified (≥2-y: 229, <2-y: 81). There was no difference in cumulative incidence of brain metastases between survival groups (29% at 21 mo). However, the cumulative incidence of liver metastasis was higher in those who survived less than 2 years (20.9% versus 5.4% at 21 mo). The cumulative incidence of brain but not liver metastases has improved post-2017 with the newer generation of ALK tyrosine kinase inhibitors. There were 69 patients with <em>ROS1</em>+ mNSCLC who were identified (≥2-y: 46, < 2-y: 23). There was no significant difference in the cumulative incidence of brain or liver metastases between less-than-2-year and greater-than-or-equal-to-2-year survivor cohorts (<em>p</em> = 0.664, <em>p</em> = 0.201).</div></div><div><h3>Conclusions</h3><div>Among patients with <em>ALK</em>+ but not <em>ROS1</em>+ mNSCLC, the presence of liver metastases at baseline and on-treatment was associated with worse survival. In the ALK+ population, the cumulative incidence of brain but not liver metastases is improving, highlighting a need for therapies effective at the treatment and prevention of liver metastases.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100876"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jtocrr.2025.100911
Youling Gong MD , Qingsong Pang MD , Rong Yu MD , Zhengfei Zhu MD , Jiangqiong Huang MD , Yufeng Cheng MD , Diansheng Zhong MD , Hongbo Wu MD , Seung Soo Yoo PhD , Tracy Dobbs MD , Zinan Bao MD , Yunxia Zuo MD , Yujuan Gao PhD , Pu Sun PhD , You Lu MD
Introduction
Patients with limited-stage SCLC (LS-SCLC) have a substantial unmet clinical need for new treatments that delay disease progression and prolong survival.
Methods
In this phase 2, multicenter, randomized, multiarm, open-label trial, patients with untreated LS-SCLC received ociperlimab and tislelizumab plus concurrent chemoradiotherapy (cCRT) (arm A), tislelizumab plus cCRT (arm B), or cCRT (arm C). The primary objective was to compare progression-free survival (PFS) per investigator for arms A and B versus C (NCT04952597). The contribution of ociperlimab was explored by comparison of arms A versus B. Statistical analyses were descriptive, with no formal hypothesis testing.
Results
A total of 126 patients were randomized to arms A (N = 41), B (N = 42), and C (N = 43). The median PFS [95% confidence interval] exhibited a trend for improvement in arms A (12.6 [8.7–not estimable] months) and B (13.2 [8.5–not estimable]) compared with C (9.5 [8.3–14.4]); the PFS benefit was comparable between Arms A and B.
The objective response rate, complete response rate, and median duration of response were numerically higher in arms A and B than in C. The median overall survival was not reached in all three arms, and the median distant metastasis–free survival revealed no trend for improvement for arms A and B compared with C. All patients experienced at least one treatment-related treatment-emergent adverse event.
Conclusions
Ociperlimab and tislelizumab plus cCRT and tislelizumab plus cCRT exhibited a trend for improvement in PFS and numerically higher objective response rate compared with cCRT, with no new safety signals beyond the known profiles of immune checkpoint inhibitors and cCRT. Adding ociperlimab to tislelizumab plus cCRT was not associated with additional improvement in efficacy.
{"title":"AdvanTIG-204: A Phase 2, Randomized, Open-Label Study of Ociperlimab Plus Tislelizumab and Concurrent Chemoradiotherapy Versus Tislelizumab and Concurrent Chemotherapy Versus Concurrent Chemoradiotherapy in First-Line Limited-Stage SCLC","authors":"Youling Gong MD , Qingsong Pang MD , Rong Yu MD , Zhengfei Zhu MD , Jiangqiong Huang MD , Yufeng Cheng MD , Diansheng Zhong MD , Hongbo Wu MD , Seung Soo Yoo PhD , Tracy Dobbs MD , Zinan Bao MD , Yunxia Zuo MD , Yujuan Gao PhD , Pu Sun PhD , You Lu MD","doi":"10.1016/j.jtocrr.2025.100911","DOIUrl":"10.1016/j.jtocrr.2025.100911","url":null,"abstract":"<div><h3>Introduction</h3><div>Patients with limited-stage SCLC (LS-SCLC) have a substantial unmet clinical need for new treatments that delay disease progression and prolong survival.</div></div><div><h3>Methods</h3><div>In this phase 2, multicenter, randomized, multiarm, open-label trial, patients with untreated LS-SCLC received ociperlimab and tislelizumab plus concurrent chemoradiotherapy (cCRT) (arm A), tislelizumab plus cCRT (arm B), or cCRT (arm C). The primary objective was to compare progression-free survival (PFS) per investigator for arms A and B versus C (NCT04952597). The contribution of ociperlimab was explored by comparison of arms A versus B. Statistical analyses were descriptive, with no formal hypothesis testing.</div></div><div><h3>Results</h3><div>A total of 126 patients were randomized to arms A (N = 41), B (N = 42), and C (N = 43). The median PFS [95% confidence interval] exhibited a trend for improvement in arms A (12.6 [8.7–not estimable] months) and B (13.2 [8.5–not estimable]) compared with C (9.5 [8.3–14.4]); the PFS benefit was comparable between Arms A and B.</div><div>The objective response rate, complete response rate, and median duration of response were numerically higher in arms A and B than in C. The median overall survival was not reached in all three arms, and the median distant metastasis–free survival revealed no trend for improvement for arms A and B compared with C. All patients experienced at least one treatment-related treatment-emergent adverse event.</div></div><div><h3>Conclusions</h3><div>Ociperlimab and tislelizumab plus cCRT and tislelizumab plus cCRT exhibited a trend for improvement in PFS and numerically higher objective response rate compared with cCRT, with no new safety signals beyond the known profiles of immune checkpoint inhibitors and cCRT. Adding ociperlimab to tislelizumab plus cCRT was not associated with additional improvement in efficacy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100911"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jtocrr.2025.100875
Sanjana Mullangi MD , Manidhar Reddy Lekkala MD , Sarah Blocker PharmD , Diana Kim PharmD , Jun Zhang MD , Chao Huang MD , Prakash Neupane MD , Haoran Li MD , Timothy Schieber PharmD
Introduction
SCLC remains the most aggressive lung cancer with a poor prognosis. Tarlatamab, a bispecific T-cell engager, is approved for use in extensive-stage SCLC after progression on a platinum-based chemotherapy on the basis of the DeLLphi-301 trial. Because of the restrictive inclusion criteria of this trial, substantial gaps remain in our understanding of treatment for many patients.
Methods
We performed a retrospective chart review of patients who were treated with tarlatamab at the University of Kansas Cancer Center from May 2024 through December 2024 for SCLC (cohort 1) or extrapulmonary small cell carcinoma (EPSCC) (cohort 2). Patients were included if they received at least one dose of tarlatamab regardless of baseline characteristics.
Results
A total of 21 patients were included in cohort 1, and three patients were included in cohort 2. In the SCLC cohort, 14 patients (66.6%) had central nervous system (CNS) involvement, five patients (23.8%) required baseline oxygen, and five patients (23.8%) had an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or greater. There were 13 patients (61.9%) who developed cytokine release syndrome (CRS), with grade 3 or higher CRS noted in two patients (15.3%). There were 10 patients (47.6%) who developed immune effector cell–associated neurotoxicity syndrome (ICANS), with three patients (14.2%) developing grade 3 or higher ICANS. In the three patients with extrapulmonary small cell carcinoma, any-grade CRS occurred in two patients (66.7%), and grade 1 ICANS occurred in one patient (33.3%). Characteristics such as ECOG of 2 or higher, baseline oxygen use, and untreated CNS metastases are associated with high rates of CRS and ICANS. In 17 patients evaluable for best response in cohort 1, partial response was seen in six (35.2%) patients. No patients in cohort 2 had disease assessment performed at the time of data cutoff. Alternative CNS disease control using tarlatamab alone or with concurrent radiation provided clinical benefit to three patients.
Conclusions
Baseline risk factors such as oxygen dependence, poor ECOG performance status, bulky disease, and untreated CNS involvement may increase CRS and ICANS rates after tarlatamab. However, subsequent doses exhibited a more favorable safety profile, supporting outpatient administration and reduced observation time. CNS management strategies, including concurrent radiation or monotherapy with tarlatamab, exhibited promising efficacy. These findings highlight the need for further research into CRS and ICANS risk stratification, optimal CNS management, and efficacy in extrapulmonary small cell carcinoma through larger studies.
{"title":"Safety, Efficacy, and Central Nervous System Control in Patients with High Baseline Risk Factors Treated with Tarlatamab for SCLC or Extrapulmonary Small Cell Carcinoma","authors":"Sanjana Mullangi MD , Manidhar Reddy Lekkala MD , Sarah Blocker PharmD , Diana Kim PharmD , Jun Zhang MD , Chao Huang MD , Prakash Neupane MD , Haoran Li MD , Timothy Schieber PharmD","doi":"10.1016/j.jtocrr.2025.100875","DOIUrl":"10.1016/j.jtocrr.2025.100875","url":null,"abstract":"<div><h3>Introduction</h3><div>SCLC remains the most aggressive lung cancer with a poor prognosis. Tarlatamab, a bispecific T-cell engager, is approved for use in extensive-stage SCLC after progression on a platinum-based chemotherapy on the basis of the DeLLphi-301 trial. Because of the restrictive inclusion criteria of this trial, substantial gaps remain in our understanding of treatment for many patients.</div></div><div><h3>Methods</h3><div>We performed a retrospective chart review of patients who were treated with tarlatamab at the University of Kansas Cancer Center from May 2024 through December 2024 for SCLC (cohort 1) or extrapulmonary small cell carcinoma (EPSCC) (cohort 2). Patients were included if they received at least one dose of tarlatamab regardless of baseline characteristics.</div></div><div><h3>Results</h3><div>A total of 21 patients were included in cohort 1, and three patients were included in cohort 2. In the SCLC cohort, 14 patients (66.6%) had central nervous system (CNS) involvement, five patients (23.8%) required baseline oxygen, and five patients (23.8%) had an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or greater. There were 13 patients (61.9%) who developed cytokine release syndrome (CRS), with grade 3 or higher CRS noted in two patients (15.3%). There were 10 patients (47.6%) who developed immune effector cell–associated neurotoxicity syndrome (ICANS), with three patients (14.2%) developing grade 3 or higher ICANS. In the three patients with extrapulmonary small cell carcinoma, any-grade CRS occurred in two patients (66.7%), and grade 1 ICANS occurred in one patient (33.3%). Characteristics such as ECOG of 2 or higher, baseline oxygen use, and untreated CNS metastases are associated with high rates of CRS and ICANS. In 17 patients evaluable for best response in cohort 1, partial response was seen in six (35.2%) patients. No patients in cohort 2 had disease assessment performed at the time of data cutoff. Alternative CNS disease control using tarlatamab alone or with concurrent radiation provided clinical benefit to three patients.</div></div><div><h3>Conclusions</h3><div>Baseline risk factors such as oxygen dependence, poor ECOG performance status, bulky disease, and untreated CNS involvement may increase CRS and ICANS rates after tarlatamab. However, subsequent doses exhibited a more favorable safety profile, supporting outpatient administration and reduced observation time. CNS management strategies, including concurrent radiation or monotherapy with tarlatamab, exhibited promising efficacy. These findings highlight the need for further research into CRS and ICANS risk stratification, optimal CNS management, and efficacy in extrapulmonary small cell carcinoma through larger studies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 11","pages":"Article 100875"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号