High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: Results of a phase II trial

Roshal R Patel; Kewen He; Hampartsoum B Barsoumian; Joe Y Chang; Chad Tang; Vivek Verma; Nathan Comeaux; Stephen G Chun; Saumil Gandhi; Mylene T Truong; Jeremy J Erasmus; David S Hong; Percy P Lee; Matthew S Ning; Quynh-Nhu Nguyen; John V Heymach; Mehmet Altan; George Blumenschein; Frank V Fossella; Duygu Sezen; Dawei Chen; Brett W Carter; Michael A Davies; Isabella C Glitza; Adi Diab; Renata Ferrarotto; Maria E Cabanillas; Ying Yuan; Shalin J Shah; Edwin R Parra; Baohua Sun; Maria Angelica Cortez; James W Welsh

doi:10.1016/j.radonc.2021.06.037

High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: Results of a phase II trial

Radiother Oncol. 2021 Sep:162:60-67. doi: 10.1016/j.radonc.2021.06.037. Epub 2021 Jul 5.

Authors

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

Affiliations

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: [email protected].

PMID: 34237343
DOI: 10.1016/j.radonc.2021.06.037

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.

Keywords: Immunotherapy resistance; Low-dose radiotherapy; Metastatic cancer; Radioimmunotherapy; Salvage radiotherapy.

Publication types

Clinical Trial, Phase II
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Non-Small-Cell Lung*
Combined Modality Therapy
Humans
Immunotherapy
Lung Neoplasms*
Neoplasms, Second Primary*
Treatment Outcome
Tumor Microenvironment

Grants and funding

P30 CA016672/CA/NCI NIH HHS/United States