A Prognostic Index for Predicting Survival of Patients Undergoing Radiation Therapy for Spine Metastasis Using Recursive Partitioning Analysis.

Background: Physicians' estimate of life expectancy in patients with spine metastasis frequently impacts treatment decisions regarding surgery, radiation techniques, dose, and fractionation. Objective: We aimed to identify predictors of survival and generate a stratification schema that could guide clinical decision making. Materials and Methods: We identified 269 patients who have undergone surgery and/or radiation for spine metastasis from 2002 to 2013 at an academic medical institution in the United States. A univariate survival analysis was carried out using the Kaplan-Meier method. Differences in survival by histology were assessed using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model, then using the same variables, recursive partitioning analysis (RPA) was conducted to determine risk groups associated with survival. Results: The median overall survival was 4.76 months. Twenty percent, 40%, and 57% of patients died within one, three, and six months of radiation treatment, respectively. RPA analysis resulted in three classes; class I included patients with Karnofsky Performance Status (KPS) ≥80. Class II included patients with KPS <80 and radioresistant or favorable histologies. Class III included all other histologies. Median survival in months was 11.4, 6.3, and 2.0, respectively. Conclusion: We developed a stratification schema predictive of survival in patients with spine metastasis. This RPA classification should be validated in independent patient populations from several institutions and may ultimately identify patients who are good candidates for more complex treatment regimens, such as stereotactic body radiotherapy.

Concurrent Radiosurgery and Immune Checkpoint Inhibition: Improving Regional Intracranial Control for Patients With Metastatic Melanoma.

OBJECTIVES: The anti-CTLA-4 and antiprogrammed cell death-1 (PD-1) therapies have significantly improved survival of patients with metastatic melanoma. However, there is limited data regarding the interaction between immunotherapy (IT) and stereotactic radiosurgery (SRS) in patients with brain metastasis, particularly how combination therapy may affect toxicity and intracranial tumor control. METHODS: We retrospectively reviewed 26 patients with metastatic melanoma who received immune check point inhibitors and SRS for brain metastasis from 2011 to 2017. We evaluated lesions receiving SRS concurrently (within 30 days) and sequentially with IT. Overall survival (OS), local control (LC), and regional progression free survival (RPFS) were determined. RESULTS: In total, 26 patients and 90 lesions were treated using pembrolizumab, nivolumab and/or ipilimumab, sequentially, or concurrently with SRS. Median follow-up was 18.9 months (range, 4.9 to 62.3 mo). Median overall survival was 26.1 months. There were 3 local failures, but no significant difference between the 2 groups. Following concurrent SRS and immunotherapy, patients had a significantly longer period of intracranial progression free survival than those treated with nonconcurrent therapy, 19 months versus 3.4 months (P<0.0001). No grade 4-5 toxicities were observed. CONCLUSIONS: Patients with melanoma metastatic to brain treated with SRS and immune checkpoint inhibitors had favorable median survival of 26.1 months compared with historical controls. Patients receiving immunotherapy within 30 days of SRS had significantly improved regional intracranial progression free survival compared with patients receiving sequential therapy. Our findings suggest synergy between checkpoint inhibitor immunotherapy and radiosurgery. Further studies are needed to confirm these findings.

Prognostic significance of the number of positive lymph nodes in women with T1-2N1 breast cancer treated with mastectomy: should patients with 1, 2, and 3 positive lymph nodes be grouped together?

PURPOSE: To determine whether patients with 1, 2, or 3 positive lymph nodes (LNs) have similar survival outcomes. METHODS AND MATERIALS: We analyzed the Surveillance, Epidemiology, and End Results registry of breast cancer patients diagnosed between 1990 and 2003. We identified 10,415 women with T1-2N1M0 breast cancer who were treated with mastectomy with no adjuvant radiation, with at least 10 LNs examined and 6 months of follow-up. The Kaplan-Meier method and log-rank test were used for survival analysis. Multivariate analysis was performed using the Cox proportional hazard model. RESULTS: Median follow-up was 92 months. Ten-year overall survival (OS) and cause-specific survival (CSS) were progressively worse with increasing number of positive LNs. Survival rates were 70%, 64%, and 60% (OS), and 82%, 76%, and 72% (CSS) for 1, 2, and 3 positive LNs, respectively. Pairwise log-rank test P values were <.001 (1 vs 2 positive LNs), <.001 (1 vs 3 positive LNs), and .002 (2 vs 3 positive LNs). Multivariate analysis showed that number of positive LNs was a significant predictor of OS and CSS. Hazard ratios increased with the number of positive LNs. In addition, age, primary tumor size, grade, estrogen receptor and progesterone receptor status, race, and year of diagnosis were significant prognostic factors. CONCLUSIONS: Our study suggests that patients with 1, 2, and 3 positive LNs have distinct survival outcomes, with increasing number of positive LNs associated with worse OS and CSS. The conventional grouping of 1-3 positive LNs needs to be reconsidered.