Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated Tumors
Introduction: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are a recently defined group of aggressive cancers in which the effectiveness of standard treatments for lung cancer is unknown. Methods: We collected clinical, pathologic, and demographic variables from five institutions...
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Elsevier
2025-01-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364324001292 |
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| author | Alissa J. Cooper, MD Andrea Arfe, PhD Biagio Ricciuti, MD Andréanne Gagné, MD, PhD Lynette M. Sholl, MD Alessandro Di Federico, MD Mark M. Awad, MD, PhD Mihaela Aldea, MD, PhD Maria Rosa Ghigna, MD Miruna Grecea, MD Phoebe Clark, MS Jamie E. Chaft, MD Mark G. Kris, MD Gregory J. Riely, MD Charles M. Rudin, MD, PhD Ibiayi Dagogo-Jack, MD Mari Mino-Kenudson, MD Lingzhi Hong, MD, PhD Neda Kalhor, MD Natalie Vokes, MD Anita Bowman, MS Soo-Ryum Yang, MD Natasha Rekhtman, MD, PhD Adam J. Schoenfeld, MD |
| author_facet | Alissa J. Cooper, MD Andrea Arfe, PhD Biagio Ricciuti, MD Andréanne Gagné, MD, PhD Lynette M. Sholl, MD Alessandro Di Federico, MD Mark M. Awad, MD, PhD Mihaela Aldea, MD, PhD Maria Rosa Ghigna, MD Miruna Grecea, MD Phoebe Clark, MS Jamie E. Chaft, MD Mark G. Kris, MD Gregory J. Riely, MD Charles M. Rudin, MD, PhD Ibiayi Dagogo-Jack, MD Mari Mino-Kenudson, MD Lingzhi Hong, MD, PhD Neda Kalhor, MD Natalie Vokes, MD Anita Bowman, MS Soo-Ryum Yang, MD Natasha Rekhtman, MD, PhD Adam J. Schoenfeld, MD |
| author_sort | Alissa J. Cooper, MD |
| collection | DOAJ |
| description | Introduction: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are a recently defined group of aggressive cancers in which the effectiveness of standard treatments for lung cancer is unknown. Methods: We collected clinical, pathologic, and demographic variables from five institutions for patients whose tumors met criteria for SMARCA4-UTs (undifferentiated phenotype and loss of SMARCA4 (BRG1) by immunohistochemistry). Results: We identified 92 patients with SMARCA4-UTs; 58 (63%) had stage IV disease at diagnosis and 16 (17%) developed recurrent or metastatic disease after initial diagnosis. Median overall survival from metastatic diagnosis was 7.3 (95% confidence interval [CI]: 4.6–12.8) months. Of patients with metastatic disease, 58 (78%) received first-line systemic treatment. Most often, patients received chemo and immunotherapy combination (41%), chemotherapy alone (33%), or immunotherapy alone (16%). Median progression-free survival from start of systemic therapy was 1.9 (95% CI: 1.4–14.5) months for chemo and immunotherapy, 1.6 (95% CI: 1.1–5.8) months for chemotherapy, and 3.3 (95% CI: 1.2–undefined) months for immunotherapy alone. Five patients had durable responses (≥2 y); all received immunotherapy as part of first-line regimens. Nine (16%) of 55 tumor samples tested had programmed death-ligand 1 expression more than or equal to 50%, with 24 (44%) negative samples. Tumor mutational burden was available in 48 cases (52%), and median was 10.5 (range: 2–48) mutations per megabase. Conclusions: This multi-institution retrospective cohort analysis revealed a population of patients with short progression-free survival to standard therapies and poor overall survival. A few patients had remarkable response to regimens including immunotherapy. Prospective clinical studies are urgently needed to identify better therapeutic approaches to treat this aggressive malignancy, and this analysis may serve as a benchmark for future clinical trial design. |
| format | Article |
| id | doaj-art-6b719de6670641c89f91042589fb7cc7 |
| institution | Kabale University |
| issn | 2666-3643 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj-art-6b719de6670641c89f91042589fb7cc72025-01-20T04:17:54ZengElsevierJTO Clinical and Research Reports2666-36432025-01-0161100759Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated TumorsAlissa J. Cooper, MD0Andrea Arfe, PhD1Biagio Ricciuti, MD2Andréanne Gagné, MD, PhD3Lynette M. Sholl, MD4Alessandro Di Federico, MD5Mark M. Awad, MD, PhD6Mihaela Aldea, MD, PhD7Maria Rosa Ghigna, MD8Miruna Grecea, MD9Phoebe Clark, MS10Jamie E. Chaft, MD11Mark G. Kris, MD12Gregory J. Riely, MD13Charles M. Rudin, MD, PhD14Ibiayi Dagogo-Jack, MD15Mari Mino-Kenudson, MD16Lingzhi Hong, MD, PhD17Neda Kalhor, MD18Natalie Vokes, MD19Anita Bowman, MS20Soo-Ryum Yang, MD21Natasha Rekhtman, MD, PhD22Adam J. Schoenfeld, MD23Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Corresponding author. Address for correspondence: Alissa J. Cooper, MD, Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 545 E 73rd Street, New York, New York 10021.Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MassachusettsDepartment of Pathology, Brigham and Women’s Hospital, Boston, MassachusettsDepartment of Pathology, Brigham and Women’s Hospital, Boston, MassachusettsDepartment of Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MassachusettsDepartment of Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MassachusettsDepartment of Medical Oncology, Gustave Roussy, Villejuif, FranceDepartment of Pathology, Gustave Roussy, Villejuif, FranceDepartment of Medical Oncology, Gustave Roussy, Villejuif, FranceDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medical Oncology, Massachusetts General Hospital Cancer Center, Boston, MassachusettsDepartment of Pathology, Massachusetts General Hospital Cancer Center, Boston, MassachusettsDepartment of Thoracic-Head & Neck Medical Oncology, MD Anderson Cancer Center, Houston, TexasDepartment of Pathology, MD Anderson Cancer Center, Houston, TexasDepartment of Thoracic-Head & Neck Medical Oncology, MD Anderson Cancer Center, Houston, TexasDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New YorkIntroduction: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are a recently defined group of aggressive cancers in which the effectiveness of standard treatments for lung cancer is unknown. Methods: We collected clinical, pathologic, and demographic variables from five institutions for patients whose tumors met criteria for SMARCA4-UTs (undifferentiated phenotype and loss of SMARCA4 (BRG1) by immunohistochemistry). Results: We identified 92 patients with SMARCA4-UTs; 58 (63%) had stage IV disease at diagnosis and 16 (17%) developed recurrent or metastatic disease after initial diagnosis. Median overall survival from metastatic diagnosis was 7.3 (95% confidence interval [CI]: 4.6–12.8) months. Of patients with metastatic disease, 58 (78%) received first-line systemic treatment. Most often, patients received chemo and immunotherapy combination (41%), chemotherapy alone (33%), or immunotherapy alone (16%). Median progression-free survival from start of systemic therapy was 1.9 (95% CI: 1.4–14.5) months for chemo and immunotherapy, 1.6 (95% CI: 1.1–5.8) months for chemotherapy, and 3.3 (95% CI: 1.2–undefined) months for immunotherapy alone. Five patients had durable responses (≥2 y); all received immunotherapy as part of first-line regimens. Nine (16%) of 55 tumor samples tested had programmed death-ligand 1 expression more than or equal to 50%, with 24 (44%) negative samples. Tumor mutational burden was available in 48 cases (52%), and median was 10.5 (range: 2–48) mutations per megabase. Conclusions: This multi-institution retrospective cohort analysis revealed a population of patients with short progression-free survival to standard therapies and poor overall survival. A few patients had remarkable response to regimens including immunotherapy. Prospective clinical studies are urgently needed to identify better therapeutic approaches to treat this aggressive malignancy, and this analysis may serve as a benchmark for future clinical trial design.http://www.sciencedirect.com/science/article/pii/S2666364324001292SMARCA4-deficient undifferentiated thoracic tumorsImmunotherapyOutcomesRare tumors |
| spellingShingle | Alissa J. Cooper, MD Andrea Arfe, PhD Biagio Ricciuti, MD Andréanne Gagné, MD, PhD Lynette M. Sholl, MD Alessandro Di Federico, MD Mark M. Awad, MD, PhD Mihaela Aldea, MD, PhD Maria Rosa Ghigna, MD Miruna Grecea, MD Phoebe Clark, MS Jamie E. Chaft, MD Mark G. Kris, MD Gregory J. Riely, MD Charles M. Rudin, MD, PhD Ibiayi Dagogo-Jack, MD Mari Mino-Kenudson, MD Lingzhi Hong, MD, PhD Neda Kalhor, MD Natalie Vokes, MD Anita Bowman, MS Soo-Ryum Yang, MD Natasha Rekhtman, MD, PhD Adam J. Schoenfeld, MD Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated Tumors JTO Clinical and Research Reports SMARCA4-deficient undifferentiated thoracic tumors Immunotherapy Outcomes Rare tumors |
| title | Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated Tumors |
| title_full | Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated Tumors |
| title_fullStr | Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated Tumors |
| title_full_unstemmed | Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated Tumors |
| title_short | Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated Tumors |
| title_sort | brief report clinical characteristics and outcomes of patients with thoracic smarca4 deficient undifferentiated tumors |
| topic | SMARCA4-deficient undifferentiated thoracic tumors Immunotherapy Outcomes Rare tumors |
| url | http://www.sciencedirect.com/science/article/pii/S2666364324001292 |
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