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Published on: June 7, 2015
The Effect of Concurrent Stereotactic Body Radiation and Anti-PD-1 Therapy for Recurrent Metastatic Sarcoma
Cameron M Callaghan1, Steven N Seyedin1, Imran H Mohiuddin1
1Department of Radiation Oncology.
Abstract:
Patients diagnosed with metastatic sarcoma have limited options for achieving both local and distant tumor control. While SBRT can achieve local control, distant response rates remain low. There is limited evidence demonstrating the safety and efficacy for combining SBRT with concurrent PD-1 checkpoint blockade in metastatic sarcoma. In this prospective case-series, we examined five patients with metastatic sarcoma on pembrolizumab treated concurrently with SBRT from July 1, 2016-October 30, 2018. Acute and chronic toxicity were recorded using Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). SBRT-treated tumor control was assessed using Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). With median follow-up of 14.9 months, three patients with undifferentiated pleomorphic sarcoma, one with intimal, and one with chondroblastic osteosarcoma received SBRT with concurrent pembrolizumab to 10 sites of metastatic disease. No grade 5 toxicities were observed. There was a single incidence of transient grade 4 lymphopenia which resolved without intervention. Grade 3 toxicities included anemia, thrombocytopenia, lymphopenia and colitis. One tumor demonstrated local progression after SBRT, and all others remained stable or with response. In conclusion, combining SBRT with PD-1 inhibition appeared to be safe in this patient population. Expected high rates of treated-tumor local control after SBRT were observed. Two of five patients demonstrated either enhanced local tumor regression, or possible abscopal effect.
Insights
Combining SBRT with PD-1 inhibition (pembrolizumab) showed promising safety and local tumor control in metastatic sarcoma patients. Some patients experienced enhanced regression or abscopal effects, suggesting potential benefits beyond local treatment.
Area of Science:
- Oncology
- Radiation Oncology
- Immunotherapy
Background:
- Metastatic sarcoma presents challenges for local and distant tumor control.
- Stereotactic Body Radiation Therapy (SBRT) offers local control, but distant response rates are low.
- Limited data exists on combining SBRT with PD-1 checkpoint inhibitors for metastatic sarcoma.
Purpose of the Study:
- To evaluate the safety and efficacy of concurrent SBRT and PD-1 inhibition (pembrolizumab) in patients with metastatic sarcoma.
- To assess toxicity profiles and tumor response in this combination therapy setting.
Main Methods:
- Prospective case-series of five metastatic sarcoma patients treated with SBRT and concurrent pembrolizumab.
- Toxicity assessed using Common Terminology Criteria for Adverse Events (CTCAE v5.0).
- Tumor response evaluated by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Main Results:
- No Grade 5 toxicities observed; one transient Grade 4 lymphopenia.
- Grade 3 toxicities included anemia, thrombocytopenia, lymphopenia, and colitis.
- High rates of local tumor control achieved with SBRT; two patients showed enhanced regression or abscopal effect.
Conclusions:
- Concurrent SBRT and PD-1 inhibition appears safe for metastatic sarcoma.
- SBRT achieved expected local tumor control.
- The combination may enhance local tumor regression and potentially induce abscopal effects.

