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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Clin Cancer Res. Author manuscript; available in PMC 2018 January 1.
Published in final edited form as:
PMCID: PMC5215783

Reply to Hiniker et al. (Phase I trial: SABR and ipilimumab – letter)

We thank Dr. Hiniker and colleagues for their interest in our work(1). We are delighted to hear that their patient continues to maintain a prolonged disease free interval for now >5 years(2). We have also read with great interest their recent manuscript reporting on the combination of ipilimumab and radiation to treat melanoma(3). We would like to highlight the observed activation of peripheral CD8+ T-cells observed both by Hiniker et al. and others(4, 5) as a marker of systemic disease response. These data are in alignment with the data reported in our study, where greater CD8+ peripheral T-cell activation and numbers were associated with achievement of clinical benefit(1).

Given the increasing number and variety of immunotherapy agents, greater and more effective salvage systemic options are becoming available. These options coupled with the utilization of more traditional modalities including salvage radiation (as demonstrated by Hiniker et al.(2)) may allow for the conversion of immunotherapy refractory patients to long-term responders. We are currently conducting a phase II clinical trial investigating this phenomenon further (NCT02710253). In this trial, patients who progress on immunotherapy agents including standard of care or experimental immunotherapy agents are treated with salvage radiation at the time of progression.

We therefore believe that it is important to identify biomarkers that facilitate early detection of patients unlikely to mount an effective systemic response. We hope that utilization of such biomarkers with effective salvage options can help to create more cases like your patient with >5 year disease free survival(2).


Chad Tang

James Welsh

David Hong

Departments of radiation oncology and investigational cancer therapeutics, MD Anderson Cancer Center, 77030 Houston, TX


1. Tang C, Welsh JW, de Groot P, Massarelli E, Chang JY, Hess KR, et al. Ipilimumab with stereotactic ablative radiation therapy: Phase I results and immunologic correlates from peripheral T-cells. Clinical cancer research: an official journal of the American Association for Cancer Research. 2016 [PubMed]
2. Hiniker SM, Chen DS, Knox SJ. Abscopal effect in a patient with melanoma. The New England journal of medicine. 2012;366:2035. author reply -6. [PubMed]
3. Hiniker SM, Reddy SA, Maecker HT, Subrahmanyam PB, Rosenberg-Hasson Y, Swetter SM, et al. A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma. International journal of radiation oncology, biology, physics. 2016;96:578–88. [PMC free article] [PubMed]
4. Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520:373–7. [PMC free article] [PubMed]
5. Dovedi SJ, Lipowska-Bhalla G, Beers SA, Cheadle EJ, Mu L, Glennie MJ, et al. Antitumor Efficacy of Radiation plus Immunotherapy Depends upon Dendritic Cell Activation of Effector CD8+ T Cells. Cancer immunology research. 2016;4:621–30. [PMC free article] [PubMed]