Adding immunotherapy to radiotherapy after definitive surgery of the primary cancer site was associated with a significant benefit in overall survival (OS) in a cohort of adult patients with solid tumors characterized by brain metastases. These findings were published in JAMA Network Open.

Brain metastases, typically associated with a poor prognosis, are common in the setting of a variety of solid tumors, including lung cancer, breast cancer, and melanoma. Patients with colorectal cancer, kidney cancer, or some other types of tumors may experience brain metastases as well.

In this retrospective study, the researchers abstracted data on patients aged 19 years or older with a variety of metastatic solid tumor cancers diagnosed between 2010 and 2016 from the National Cancer Database (NCDB). Patients had undergone definitive surgery of the primary cancer site as well as standard treatment with chemotherapy, radiotherapy, or chemoradiation therapy, with or without immunotherapy.

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The primary outcome of the study was OS from diagnosis of brain metastases to death from any cause.

Of the 3112 patients (median age at diagnosis, 61 years) included in the study, 87.72% were White, 8.31% were Black, and 3.98% belonged to other race/ethnicity groups. More than 90% of these patients were residing in urban areas and had health insurance, and approximately three-quarters of them had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0. Primary tumors were breast cancer (23.50%), non-small cell lung cancer (NSCLC; 13.11%), melanoma (30.05%), colorectal cancer (13.11%), or kidney cancer (20.22%).

Patients underwent chemotherapy alone (10.22%), radiotherapy alone (25.32%), chemoradiation alone (44.76%), chemotherapy plus immunotherapy (6.47%), radiotherapy plus immunotherapy (8.37%), or chemoradiation plus immunotherapy (5.17%).

A key study finding was that the median OS of patients treated with immunotherapy was 22.60 months compared with 15.08 months for those not treated with immunotherapy (P <.001).

Furthermore, an analysis of the different treatment groups revealed that median OS in patients who received radiotherapy with immunotherapy was 20.53 months compared with 10.09 months for those treated with radiotherapy alone (P =.006). With respect to chemoradiation, median OS was 28.52 months and 20.21 months with and without immunotherapy, respectively, (P =.04). However, a similar comparison of patients treated with chemotherapy plus immunotherapy vs chemotherapy alone did not reveal a significant difference between the 2 groups.

On multivariable analysis adjusted for multiple factors including age at diagnosis, sex, income, type of hospital, and comorbidity score, as well as treatment with chemotherapy, radiotherapy, or chemoradiation alone, the OS of those treated with immunotherapy was significantly longer compared with the OS of those who did not receive immunotherapy (hazard ratio [HR], 0.62; 95% CI, 0.51-0.76; P <.001).

When multivariable analyses were performed separately for each treatment group, OS was significantly longer for those receiving radiotherapy plus immunotherapy vs radiotherapy alone (HR, 0.59; 95%CI, 0.42-0.84; P =.003). However, the addition of immunotherapy did not significantly improve OS when added to either chemotherapy or chemoradiation.

The researchers hypothesized that the improved OS noted in patients who received radiotherapy with immunotherapy may be associated with the abscopal effect of radiotherapy. “After a tumor is irradiated, injury in the tumor may lead to the release of tumor associated antigens, which can stimulate a tumor-specific immune response, allowing the immune cells (ie, T-cells) to recognize and attack both the primary tumor and metastatic disease in a sort of autovaccination,” explained the researchers.


Amin S, Baine MJ, Meza JL, Lin C. Association of immunotherapy with survival among patients with brain metastases whose cancer was managed with definitive surgery of the primary tumor. JAMA Network Open. Published online September 1, 2020. doi:10.1001/jamanetworkopen.2020.15444