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Front. Oncol. | doi: 10.3389/fonc.2019.00922

Abscopal Effect Following Proton Beam Radiotherapy in a Patient with Inoperable Metastatic Retroperitoneal Sarcoma

 Randall J. Brenneman1,  Nima Sharifai2,  Ben Fischer-Valuck3, Comron Hassanzadeh1, Jeffrey Guzelian4,  John S. Chrisinger2, Jeff M. Michalski1,  Peter Oppelt5 and  Brian C. Baumann1*
  • 1Department of Radiation Oncology, Washington University School of Medicine in St. Louis, United States
  • 2Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, United States
  • 3Department of Radiation Oncology, Winship Cancer Institute, Emory University, United States
  • 4Mallinckrodt Institute of Radiology, School of Medicine, Washington University in St. Louis, United States
  • 5Divisions of Hematology & Oncology, School of Medicine, Washington University in St. Louis, United States

Background: Retroperitoneal sarcomas (RPS) are rare and primarily managed with surgery, which improves local recurrence-free and overall survival. Radiation can improve local control or provide palliation for inoperable or metastatic RPS by eliciting tumor cell death via irreparable DNA damage. In extraordinary circumstances radiation-induced cell death promotes immune-mediated regression of non-irradiated lesions in a process termed the abscopal effect. Abscopal effects are rare and incompletely understood, involving a balance of radiation’s immunogenic and immunosuppressive effects. There are currently no methods to predict abscopal responses following radiotherapy. Case reports documenting post-radiotherapy abscopal effects provide additional information to better characterize these responses and to inform ongoing and future clinical trials attempting to harness radiation-induced immune responses to improve outcomes with systemic therapy, such as SARC-032, a cooperative group trial of pre-operative radiation +/- pembrolizumab. We present a case of inoperable metastatic RPS treated with proton radiotherapy with complete responses of un-irradiated metastases.
Case Presentation: A 67 year-old female with inoperable metastatic unclassified round cell RPS was treated with palliative proton radiotherapy only to the primary tumor. Following completion of radiotherapy, the patient demonstrated complete regression of all un-irradiated metastases, and near complete response of the primary lesion without additional therapy.
Conclusions: Metastatic RPS is typically managed with first-line chemotherapy, with objective response rates <50%. We present a case of inoperable metastatic RPS treated with palliative proton radiotherapy for rapidly progressive disease who had complete regression of non-irradiated metastases consistent with the abscopal effect. To our knowledge this is the first case report describing abscopal effects in inoperable metastatic RPS treated with proton radiation and is among the first case reports of an abscopal effect in a patient treated with proton therapy regardless of disease site. Further investigation is warranted regarding the benefit of proton radiation to primary tumors for inoperable metastatic RPS.

Keywords: Retroperitoneal sarcoma, abscopal effects of radiotherapy, Proton therapy, metastasis, SMARCB1 (INI1)

Received: 08 Jul 2019; Accepted: 03 Sep 2019.

Copyright: © 2019 Brenneman, Sharifai, Fischer-Valuck, Hassanzadeh, Guzelian, Chrisinger, Michalski, Oppelt and Baumann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Brian C. Baumann, Department of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, 63110, Missouri, United States, brian.baumann@wustl.edu