Mmod-11 Radiation Necrosis After Concomitant Egfr-Tki and Radiation: A Case Series and Consideration for Future Patients

Optimal timing of radiation therapy (RT) for brain metastases (BM) and leptomeningeal disease (LMD) from novel targeted systemic therapy is largely unknown, as well as the long-term adverse effects of combination therapy. We describe the clinical course of two patients who developed radiation necrosis (RN) after RT and treatment with EGFR-TKIs. The first patient is a 79-year-old woman with EGFR L858R-mutated metastatic non-small cell lung cancer (NSCLC) who developed progressive BM after being on osimertinib therapy for 3 years. She received stereotactic radiosurgery (SRS) to 5 lesions. Osimertinib was held for 3 days surrounding SRS, and resumed at 80 mg/day. Four months post SRS, the patient developed progressive neurologic symptoms with neuroimaging consistent with RN. She was initiated on dexamethasone however after a 6 week taper, she experienced neurologic decline with repeat neuro-imaging demonstrating worsening RN. She started on therapy with bevacizumab with minimal clinical and radiographic benefit. The second a patient is a 63-year-old man with EGFR L858R-mutated NSCLC with BM. He received concurrent RT and osimertinib at diagnosis and continued osimertinib 80 mg/day for 2 years. Upon progression with LMD he was started on alectinib and received proton craniospinal irradiation. Seven months later he had neurologic decline with neuro-imaging most consistent with RN. He initiated bevacizumab and had clinical and radiographic improvement. The approval and use of novel targeted agents has outpaced the available data surrounding long term risks of combining these therapies with radiation, especially in those patients with BM and LMD. These cases illustrate the challenges of treating patients in the modern era and the need for a multimodal team approach to determine the risk and benefit of combination therapy. Addition of a clinical pharmacist to the decision can help provide expertise in the individual drug pharmacokinetics and dynamics for these complex cases.