Genetic Alterations Affect Prognosis of Lung Cancer Patients with Spinal Metastases

Patients with metastatic lung cancer typically have a poor prognosis, and it is paramount to identify who might be eligible for surgical treatment. The ability to estimate survival accurately is perhaps the most crucial part of that assessment. Certain gene mutations are known to affect prognosis, but they are not part of the current scoring systems that assist surgeons in making treatment decisions.

Massachusetts General Hospital neurosurgeons, including Bryan D. Choi, MD, PhD, Ganesh M. Shankar, MD, PhD and John H. Shin, MD, director of Metastatic Spine Oncology and Spinal Deformity Surgery, are part of the first team to demonstrate a significant association between certain genetic mutations and overall survival in patients with lung cancer metastatic to the spine. This suggests that models for estimating survival of patients with metastatic lung cancer should incorporate oncogenic molecular markers.

This retrospective study evaluated 26 patients with metastatic lung cancer who underwent surgery or stereotactic radiosurgery for spinal metastases from 2011 to 2017. Published in Spine, this study is the largest series of such patients that includes genetic mutational data.

The genetic markers included in the study were chosen a priori based on genetic data available through SNaPshot Lung Tumor Genotyping Analysis. Mutations in ALK, ROS1, KRAS, MET and EGFR were identified in 3, 2, 6, 2 and 6 patients, respectively. Eight patients had no mutation and one had mutations in both ALK and ROS1.

The median follow-up was 110 days overall and 813 days for the seven patients alive at the time of analysis. Two patients remained free of systemic disease progression over the follow-up period. The median overall survival was 2.7 years from the time of primary malignancy diagnosis and 245 days from the time of intervention.

In univariate analysis, patients who had one or more oncogenic molecular alterations had significantly longer overall survival than patients who had no alteration (hazard ratio, 0.38; 95% confidence interval, 0.12–1.22; P = .03). Analyses of single mutations in isolation did not show significant effects on survival.

Similarly, other factors assessed were not significantly associated with survival, including age, sex, tumor histology, location of extraspinal metastases, radiographic features, surgical approach, clinical scoring or treatment with chemotherapy, radiotherapy or targeted therapy.

The authors note that because the genetic markers in this study were chosen in an unbiased fashion, their data might underestimate the potential predictive capacity of their approach. In larger populations, they say, it would be useful to test whether individual mutations or various combinations could predict prolonged survival even more accurately.

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