Brain Re-Irradiation In Lung Cancer: Not An Exercise In Futility

BACKGROUNDWhole brain radiation therapy (WBRT) is an effective palliative measure and provides durable symptom relief in lung cancer patients with multiple brain metastases (BM). Clinico-radiological progression of BM after WBRT is a common and challenging scenario; treatment is tailored, with various factors like driver mutation status, age, performance status, progression free interval and time since last irradiation influencing the treatment decision. Surgery or focal RT with stereotactic techniques may be an option for patients with oligo-metastases. However, they might not be a feasible option for patients with multiple BM. We aim to study the impact and outcome of patients with BM from lung cancer receiving re-WBRT for clinico-radiological progression. MATERIALS AND METHODSWe retrospectively analyzed patients with BM from lung cancer who were registered at Tata Memorial Hospital, Mumbai, India between January 2016 to January 2019 and had undergone two courses of WBRT. Data of patients were retrieved from electronic medical records. Patients were treated using conventional or conformal technique with either tele-cobalt or Linear accelerator. RESULTSOut of 446 patients with lung cancer, diagnosed and treated with WBRT for BM, 6% patients (n=28) received re-WBRT. There were 16 men and 12 women with a median age of 53 years (range 30 to 70 years). Primary histology was adenocarcinoma in all except two patients who had small cell histology. Eighteen patients had driver mutation positive disease (11 with EGFR and 7 with ALK mutation) and a majority of patients (54%) had BM at presentation. Clinico-radiological progression was the commonest indication of re-WBRT. A majority of these patients had developed new symptoms while about 25% had recurrence of previous symptoms. Mean Karnofsky performance score (KPS) prior to re-WBRT was more than 70 in 13 patients (57%). Mean time interval between the two courses of WBRT were 16 months (range 5-37 months). Most patients received WBRT using a conventional technique (91%) and were treated in a tele-cobalt unit (83%). Re-WBRT fractionation schedule was 25 Gy/10 fractions (n=17, 61%) or 20 Gy/5 fractions (n=10, 36%). Mean biological effective dose (BED2Gy) for the first and second courses of WBRT were 63Gy and 56Gy respectively. The average cumulative BED2Gy was 118.91Gy (range 116.25 - 120Gy). Almost all patients received short acting steroids during the course of re-WBRT. All patients except for one completed the course of treatment. At a median follow up of 2.5 years, median survival of patients after re-WBRT was 5 months. Median survival since re-WBRT was 8 months if pre first course of WBRT ds-GPA was 3.5-4 vs 1 month if it was 0-1 (p= 0.025). CONCLUSIONIn lung cancer patients with symptomatic progression of multiple BM and good prognostic features (driver mutation positive, good performance status and long time interval since last WBRT), re-WBRT is safe and associated with better outcomes.