Roshal R Patel1, Kewen He2, Hampartsoum B Barsoumian3, Joe Y Chang3, Chad Tang3, Vivek Verma3, Nathan Comeaux3, Stephen G Chun3, Saumil Gandhi3, Mylene T Truong4, Jeremy J Erasmus4, David S Hong5, Percy P Lee3, Matthew S Ning3, Quynh-Nhu Nguyen3, John V Heymach6, Mehmet Altan6, George Blumenschein6, Frank V Fossella6, Duygu Sezen7, Dawei Chen1, Brett W Carter4, Michael A Davies8, Isabella C Glitza6, Adi Diab8, Renata Ferrarotto6, Maria E Cabanillas9, Ying Yuan10, Shalin J Shah3, Edwin R Parra11, Baohua Sun11, Maria Angelica Cortez3, James W Welsh12. 1. Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Albany Medical College, Albany, USA. 2. Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Departments of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China. 3. Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 4. Departments of Thoracic Imaging, The University of Texas MD Anderson Cancer Center, Houston, USA. 5. Departments of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA. 6. Departments of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 7. Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Radiation Oncology, School of Medicine, Koc University, Istanbul, Turkey. 8. Departments of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 9. Departments of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, USA. 10. Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA. 11. Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. 12. Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: jwelsh@mdanderson.org.
Abstract
AIM: To report early findings from a phase II trial of high-dose radiotherapy (HD-RT) with or without low-dose RT (LD-RT) for metastatic cancer. METHODS: Eligible patients had metastatic disease that progressed on immunotherapy within 6 months. Patients were given either HD-RT (20-70 Gy total; 3-12.5 Gy/f), or HD-RT + LD-RT (0.5-2 Gy/f up to 1-10 Gy total) to separate lesions, with continued immunotherapy. Radiographic response was assessed per RECIST 1.1 and Immune-Related Response Criteria (irRC). Primary endpoints: (1) 4-month disease control (DCR, complete/partial response [CR/PR] or stable disease [SD]) or an overall response (ORR, CR/PR) at any point in ≥10% of patients, per RECIST 1.1; (2) dose-limiting toxicity within 3 months not exceeding 30%. Secondary endpoint was lesion-specific response. RESULTS: Seventy-four patients (NSCLC, n = 38; melanoma n = 21) were analyzed (39 HD-RT and 35 HD-RT + LD-RT). The median follow-up time was 13.6 months. The primary endpoint was met for 72 evaluable patients, with a 4-month DCR of 42% (47% [16/34] vs. 37% [14/38] in HD-RT + LD-RT vs. HD-RT, P = 0.38), and 19% ORR at any time (26% [9/34] vs. 13% [5/38] in HD-RT + LD-RT vs. HD-RT, P = 0.27). Three patients had toxicity ≥grade 3. LD-RT lesion response (53%) was improved compared to nonirradiated lesions in HD-RT + LD-RT (23%, P = 0.002) and HD-RT (11%, P < 0.001). T- and NK cell infiltration was enhanced in lesions treated with LD-RT. CONCLUSIONS: HD-RT plus LD-RT safely improved lesion-specific response in patients with immune resistant solid tumors by promoting infiltration of effector immune cells into the tumor microenvironment.
AIM: To report early findings from a phase II trial of high-dose radiotherapy (HD-RT) with or without low-dose RT (LD-RT) for metastatic cancer. METHODS: Eligible patients had metastatic disease that progressed on immunotherapy within 6 months. Patients were given either HD-RT (20-70 Gy total; 3-12.5 Gy/f), or HD-RT + LD-RT (0.5-2 Gy/f up to 1-10 Gy total) to separate lesions, with continued immunotherapy. Radiographic response was assessed per RECIST 1.1 and Immune-Related Response Criteria (irRC). Primary endpoints: (1) 4-month disease control (DCR, complete/partial response [CR/PR] or stable disease [SD]) or an overall response (ORR, CR/PR) at any point in ≥10% of patients, per RECIST 1.1; (2) dose-limiting toxicity within 3 months not exceeding 30%. Secondary endpoint was lesion-specific response. RESULTS: Seventy-four patients (NSCLC, n = 38; melanoma n = 21) were analyzed (39 HD-RT and 35 HD-RT + LD-RT). The median follow-up time was 13.6 months. The primary endpoint was met for 72 evaluable patients, with a 4-month DCR of 42% (47% [16/34] vs. 37% [14/38] in HD-RT + LD-RT vs. HD-RT, P = 0.38), and 19% ORR at any time (26% [9/34] vs. 13% [5/38] in HD-RT + LD-RT vs. HD-RT, P = 0.27). Three patients had toxicity ≥grade 3. LD-RT lesion response (53%) was improved compared to nonirradiated lesions in HD-RT + LD-RT (23%, P = 0.002) and HD-RT (11%, P < 0.001). T- and NK cell infiltration was enhanced in lesions treated with LD-RT. CONCLUSIONS:HD-RT plus LD-RT safely improved lesion-specific response in patients with immune resistant solid tumors by promoting infiltration of effector immune cells into the tumor microenvironment.
Authors: Hampartsoum B Barsoumian; Duygu Sezen; Hari Menon; Ahmed I Younes; Yun Hu; Kewen He; Nahum Puebla-Osorio; Mark Wasley; Ethan Hsu; Roshal R Patel; Liangpeng Yang; Maria A Cortez; James W Welsh Journal: Cancers (Basel) Date: 2022-01-03 Impact factor: 6.639