Clinical outcomes of patients with multiple courses of radiosurgery for brain metastases from non-small cell lung cancer

Abstract

We investigated the long-term clinical outcomes of patients who underwent multiple courses (≥ 5) of gamma knife radiosurgery (GKRS) due to recurrent brain metastases (BM) from non-small cell lung cancer (NSCLC). Between December 2001 and July 2019, consecutive 2571 patients underwent GKRS for BM from NSCLC. Clinical and radiological outcomes were investigated in 76 patients who underwent GKRS ≥ 5 times. The median follow-up period after the diagnosis of NSCLC was 54.6 months (range 14.5-159.1 months). The median number of GKRS procedures per patient was six (range 5-15). Actuarial post-GKRS survival rates at 1, 2, 3, 4, and 5 years following initial GKRS were 88.1%, 79.5%, 65.3%, 51.4%, and 37.3%, respectively. No significant difference in overall survival was observed between patients (n = 22) with whole-brain radiotherapy (WBRT) and patients (n = 54) without WBRT (p = 0.076). The incidence of radiation-induced leukoencephalopathy was 64% and 18% in patients with and without WBRT, respectively (p < 0.0001). Multiple courses of SRS are a tolerable and effective treatment option for recurrent BM from NSCLC. Repeat SRS may be an alternative treatment option to avoid or delay WBRT.

Figure 1

Flowchart showing the numbers of included and excluded patients.

Figure 2

The clinical course of the a 36-year-old woman experiencing 15 GKRS procedures for BM from lung cancer. The patient was diagnosed with synchronous BM with adenocarcinoma of the lung. (a) Contrast-enhanced T1-weighted MR images for GKRS treatment. Target volume (red solid line) and prescription isodose volume (PIV) (yellow solid line) have appeared on each treatment planning image. PIVs of previously irradiated BM by gamma knife is marked with blue solid lines. The numerous lesions are indicated with white arrowheads resulting in an additional WBRT after the fifth GKRS. An Ommaya reservoir is inserted into a large cystic BM at the sixth GKRS. The newly developed hemorrhagic BM is shown in the cerebellum of the patient, resulting in metastasectomy and ventriculo-peritoneal shunt surgery after the 14th GKRS. (b) The chest X-rays showing lung cancer (black arrowhead) without systemic progression until the 15th GKRS (114 months after the first GKRS). Chest X-ray showing a large amount of pulmonary effusion on the left side after her death, following acute respiratory failure due to septic shock subsequent to 8 months of the last GKRS. *Data from the 9th GKRS session are lost.

Figure 3

Fluid attenuation inversion recovery (FLAIR) images showing the white matter signal change. Radiation-induced leukoenchepalopathy (RIL) is classified into four grades using the grading system. Tumor-related edema is not regarded as the RIL (white arrowheads).

Figure 4

Kaplan–Meier survival curves. (a) A survival curve from the diagnosis of NSCLC. The median OS is 65.6 months (95% CI 53.42–77.78 months). (b) A survival curve from the first GKRS procedure. The median OS is 52.3 months (95% CI 41.47–63.13 months). (c) The median OS from the first GKRS procedure in patients with WBRT and the patients without WBRT is 35.9 months (95% CI 31.09–40.71 months) and 56.0 months (95% CI 42.34–69.66 months), respectively (p = 0.076). (d) The survival curves from the second GKRS in 64 patients without WBRT before the first GKRS. The median OS after the second GKRS in the 10 patients with salvage WBRT and the 54 patients without salvage WBRT was 27.0 months (95% CI 2.83–51.17) and 42.9 months (95% CI 28.97–56.83), respectively (p = 0.32). *The median OS is marked using a black dotted line in each figure. OS overall survival, NSCLC non-small cell lung cancer, GKRS gamma knife radiosurgery, WBRT whole-brain radiotherapy.

Figure 5

Timeline of the 14 patients who underwent salvage WBRT due to distant failure after the first GKRS. The diamond symbols indicate the repeat GKRS. The black arrow heads indicate the salvage WBRT. The cross “X” indicates the time of death. GKRS gamma knife radiosurgery, WBRT whole-brain radiotherapy.