ICIs Increase Risk for Brain Injury From Cranial Radiotherapy

M. Alexander Otto, PA, MMS

December 01, 2022

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key Takeaway

  • Immune checkpoint inhibitors increase the risk for brain injury among patients with lung cancer who receive cranial radiotherapy to treat brain metastases, especially when immunotherapy is used within 3 months of radiotherapy.

Why This Matters

  • Cranial radiotherapy is the chief treatment for brain metastases.

  • Many studies have shown that combining cranial radiotherapy with immune checkpoint inhibitors (ICIs) improves outcomes.

  • However, it's unclear whether the combination increases the risk for radiation-induced brain injury; data are lacking in lung cancer, in particular. 

  • The findings may help clinicians better weigh the risks and benefits of dual therapy.    

Study Design

  • The team reviewed the medical records of 210 patients with lung cancer who had cranial radiotherapy for brain metastases at their institution.

  • The authors then compared outcomes between the 56 patients who received ICIs within 6 months before or after cranial radiotherapy with those from 154 patients treated with other systemic therapies, including tyrosine kinase inhibitors and chemotherapy.

  • Brain radiation-induced necrosis and white matter lesions were assessed by brain-enhanced MRIs evaluated by three imaging experts.

Key Results

  • Overall, 17 patients (8.1%) developed radiation-induced necrosis and 142 (67.6%) patients developed white matter lesions.

  • The incidence of radiation-induced necrosis in the ICI group was 14.3% vs 5.8% among patients who did not receive ICIs (P = .09).

  • When ICIs were used within 3 months of cranial radiotherapy, the incidence of radiation-induced necrosis was 18.5% in the ICI group vs 5.4% in the non-ICI group (P = .045).

  • On multivariate analysis, a maximum diameter of brain metastasis greater than 3.3 cm and a total cumulative radiation dose greater than 75.7 Gy were risk factors for radiation-induced necrosis (P = .018). There was also a trend for increased risk with secondary radiotherapy. 

  • Whole brain radiotherapy and a higher dose per fraction or cumulative dose of whole brain radiotherapy was associated with a higher incidence of white matter lesions.


  • It was a retrospective study with a relatively small sample size.

  • Cognitive function evaluations were limited.  


  • The work was funded by the National Natural Science Foundation of China and the Natural Science Foundation of Shandong Province.

  • The investigators didn't report any disclosures.

This is a summary of a preprint research study, "Brain injury after cranial radiotherapy combined with immunotherapy for brain metastases in lung cancer: a retrospective study," led by Jiatong Li of the Shandong Academy of Medical Sciences, Shandong, China, provided to you by Medscape. The study has not been peer reviewed. The full text can be found at researchsquare.com.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who has worked for several major news outlets before joining Medscape and also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.

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