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Following the Preclinical Data: Leveraging the Abscopal Effect More Efficaciously.

ABSTRACT: Radiotherapy is employed in the treatment of over 50% of cancer patients. However, this therapy approach is limited to mainly treating localized disease. In 1953, Mole described the remarkable abscopal effect, whereby, localized radiotherapy of a patient's primary tumor might engender regression of cancer at distant sites, which were not irradiated. Current consensus is that if the abscopal effect can be efficaciously leveraged, it would transform the field of radiation oncology, extending the use of radiotherapy to treatment of both localized and metastatic disease. A close examination of the literature on the abscopal effect proffers a disruptive new hypothesis for consideration in future clinical trials. This hypothesis is that generating a subcutaneous human tumor autograft as the primary tumor may be a more efficacious approach to prime the abscopal effect. Following the preclinical data, the merits and demerits of such an approach are examined in this article.

SUBMITTER: Ngwa W

PROVIDER: S-EPMC5388832 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Following the Preclinical Data: Leveraging the Abscopal Effect More Efficaciously.

Ngwa Wilfred W Ouyang Zi Z

Frontiers in oncology 20170407

Radiotherapy is employed in the treatment of over 50% of cancer patients. However, this therapy approach is limited to mainly treating localized disease. In 1953, Mole described the remarkable abscopal effect, whereby, localized radiotherapy of a patient's primary tumor might engender regression of cancer at distant sites, which were not irradiated. Current consensus is that if the abscopal effect can be efficaciously leveraged, it would transform the field of radiation oncology, extending the u ...[more]

PMID: 28447024

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Project description: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.

Dataset Information

Following the Preclinical Data: Leveraging the Abscopal Effect More Efficaciously.

Publications

Following the Preclinical Data: Leveraging the Abscopal Effect More Efficaciously.

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