Concurrent stereotactic radiation with antibody-drug conjugates in the treatment of brain metastases is associated with a greater risk of symptomatic radiation necrosis

1. A greater percentage of patients who received concurrent stereotactic radiation therapy with antibody-drug conjugates manifested severe levels of radiation necrosis as compared to those who did not receive concurrent treatment.

2. The severity of symptomatic radiation necrosis was higher in patients who had concurrent stereotactic radiation therapy with antibody-drug conjugates as compared to those who did not.

Evidence Rating Level: 2 (Good)

Study Rundown: Patients with brain metastases are often provided stereotactic radiotherapy (SRT) which has historically been associated with a risk of radiation necrosis (RN). Additionally, some patients receive concurrent treatment with antibody-drug conjugates (ADC) for the management of their brain metastases. This study explored the association between simultaneous SRT and ADC treatment with the risk of developing RN. The primary outcome of this study was the risk of symptomatic RN (SRN). The 2-year overall incidence of RN presenting with symptoms in the entire cohort was 8.5% (6.2-11%). The incidence of severe SRN was greater in patients who received SRT with concurrent ADC as compared to those who did not receive ADC concurrently. Patients who had received radiation for their lesions before the study and who had concurrent ADC with SRT had a 2-year risk greater than patients who did not have simultaneous ADC (42.0% vs. 9.4%). Limitations of this study include that it was difficult to discern between radiation necrosis and a local failure during treatment. An additional limitation of this study includes uncertainty of symptoms particular to brain metastases. Overall, the results from this study suggest that a concurrent SRT and ADC treatment protocol is possibly associated with a greater risk of developing SRN.

Click to read the study in JAMA Oncology

Relevant Reading: Unlocking the potential of antibody-drug conjugates for cancer therapy

In-Depth [retrospective cohort]: This study was a retrospective cohort study that analyzed data from 98 patients: those with brain metastases who had at minimum one round of concurrent therapy including SRT and one dose of an ADC, as well as control cohort patients who had received sequential SRT and ADC. Receiving ADC simultaneously with SRT presented an elevated risk of SRN (subdistribution hazard ratio (SHR), 4.01; 95% confidence interval (CI), 1.79-9.01). For patients who had lesions that received prior radiation, the 2-year risk of RN was 42.0% as compared to 9.4% in patients who did not receive concurrent treatment with ADC. Of patients who received concurrent SRT with ADC 7.1% manifested severe levels of SRN, while only 0.7% of those who did not receive concurrent ADC with SRT experienced severe SRN.

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