Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis.

BACKGROUND: This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the radiation dose was investigated. METHODS: Data from 220 patients were retrospectively analyzed for overall survival and local control. Nine potential prognostic factors were evaluated: tumor type, WBI schedule, age, gender, Karnofsky performance score, number of brain metastases, extracerebral metastases, interval from diagnosis of cancer to WBI, and recursive partitioning analysis (RPA) class. RESULTS: Survival rates at 6 and 12 months were 32% and 19%, respectively. In the multivariate analysis, WBI doses >30 Gy (p = 0.038), KPS ≥70 (p < 0.001), only 1-3 brain metastases (p = 0.007), no extracerebral metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved survival. Local control rates at 6 and 12 months were 37% and 15%, respectively. In the multivariate analyses, KPS ≥70 (p < 0.001), only 1-3 brain metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved local control. In RPA class 3 patients, survival rates at 6 months were 10% (35 of 39 patients) after 10 × 3 Gy and 9% (2 of 23 patients) after greater doses, respectively (p = 0.98). CONCLUSIONS: Improved outcomes were associated with WBI doses >30 Gy, better performance status, fewer brain metastases, lack of extracerebral metastases, and lower RPA class. Patients receiving WBI alone appear to benefit from WBI doses >30 Gy. However, such a benefit is limited to RPA class 1 or 2 patients.

Do patients receiving whole-brain radiotherapy for brain metastases from renal cell carcinoma benefit from escalation of the radiation dose?

PURPOSE: Whole-brain radiotherapy (WBRT) is the most common treatment for brain metastases from renal cell carcinoma (RCC). Most patients cannot receive more aggressive therapies including surgery or radiosurgery. The standard WBRT regimen, 30 Gy/10 fractions (10 × 3 Gy), has resulted in poor survival (OS). This study investigates whether escalation of the WBRT dose improves treatment outcomes. METHODS AND MATERIALS: Data from 60 patients receiving WBRT for brain metastases from RCC were retrospectively analyzed. A dose of 10 × 3 Gy (n = 31) was compared with higher doses (40 Gy/20 fractions or 45 Gy/15 fractions; n = 29) for OS and local control (LC). Additional factors evaluated were patient age, sex, performance status, number of metastases, interval from diagnosis of RCC to WBRT, extracerebral metastases, recursive partitioning analysis (RPA) class, and year of WBRT. RESULTS: The OS at 6 months was 29% after 10 × 3 Gy and 52% after higher doses (p = 0.003). The OS at 12 months was 13% and 47%, respectively. On multivariate analysis, higher WBRT doses (p = 0.022), Karnofsky performance status score ≥70 (p = 0.017), fewer than four brain metastases (p = 0.035), and RPA Class 1 (p = 0.003) resulted in better OS. The LC at 6 months was 21% after 10 × 3 Gy and 57% after higher doses (p = 0.013). The LC at 12 months was 7% and 35%, respectively. On multivariate analysis, fewer than four brain metastases (p < 0.001) were associated with LC. A trend was found for WBRT regimen (p = 0.06) and RPA class (p = 0.06). CONCLUSIONS: The findings suggest that escalation of the WBRT dose beyond 10 × 3 Gy improves outcomes in patients with brain metastases from RCC. The results should be confirmed in a randomized trial stratifying for significant prognostic factors.

Dose escalation in patients receiving whole-brain radiotherapy for brain metastases from colorectal cancer.

BACKGROUND AND PURPOSE: Whole-brain radiotherapy (WBRT) alone is the most common treatment for brain metastases from colorectal cancer, as most patients are not candidates for more aggressive therapies such as resection or radiosurgery. The standard WBRT regimen, 30 Gy in ten fractions (10 x 3 Gy), has generally resulted in poor outcomes. This study investigated whether an escalation of the WBRT dose improves these results. PATIENTS AND METHODS: Data from 53 patients receiving WBRT alone for brain metastases from colorectal cancer were retrospectively analyzed. 10 x 3 Gy (n = 35) was compared to higher doses (40 Gy/20 fractions or 45 Gy/15 fractions; n = 18) for overall survival (OS) and local control (LC). Additional factors evaluated for prognostic importance included age, gender, performance status, number of metastases, and extracerebral metastases. RESULTS: The OS rates at 6 months were 17% after 10 x 3 Gy and 50% after 20 x 2 Gy/15 x 3 Gy (p = 0.014). On multivariate analysis, improved OS was significantly associated with higher WBRT dose (p = 0.047), Karnofsky Performance Score (KPS) > or = 70 (p = 0.034), less than four brain metastases (p = 0.036), and lack of extracerebral metastases (p = 0.010). The LC rates at 6 months were 17% after 10 x 3 Gy and 50% after higher doses (p = 0.018). On multivariate analysis of LC, higher WBRT dose was significant (p = 0.028). A trend was observed for KPS > or = 70 (p = 0.08) and less than four brain metastases (p = 0.06). CONCLUSION: These data suggest that patients with brain metastases from colorectal cancer treated with WBRT alone appeared to benefit from escalation of the radiation dose beyond 10 x 3 Gy in terms of improved OS and LC.

Dose escalation of whole-brain radiotherapy for brain metastases from melanoma.

PURPOSE: The majority of patients with brain metastases from melanoma receive whole-brain radiotherapy (WBRT). However, the results are poor. Hypofractionation regimens failed to improve the outcome of these patients. This study investigates a potential benefit from escalation of the WBRT dose beyond the "standard" regimen 30 Gy in 10 fractions (10x3 Gy). METHODS AND MATERIALS: Data from 51 melanoma patients receiving WBRT alone were retrospectively analyzed. A dosage of 10x3 Gy (n = 33) was compared with higher doses including 40 Gy/20 fractions (n = 11) and 45 Gy/15 fractions (n = 7) for survival (OS) and local (intracerebral) control (LC). Additional potential prognostic factors were evaluated: age, gender, performance status, number of metastases, extracerebral metastases, and recursive partitioning analysis (RPA) class. RESULTS: At 6 months, OS rates were 27% after 10x3 Gy and 50% after higher doses (p = 0.009). The OS rates at 12 months were 4% and 20%. On multivariate analysis, higher WBRT doses (p = 0.010), fewer than four brain metastases (p = 0.012), no extracerebral metastases (p = 0.006), and RPA class 1 (p = 0.005) were associated with improved OS. The LC rates at 6 months were 23% after 10x3 Gy and 50% after higher doses (p = 0.021). The LC rates at 12 months were 0% and 13%. On multivariate analysis, higher WBRT doses (p = 0.020) and fewer than brain metastases (p = 0.002) were associated with better LC. CONCLUSIONS: Given the limitations of a retrospective study, the findings suggest that patients with brain metastases from melanoma receiving WBRT alone may benefit from dose escalation beyond 10x3 Gy. The hypothesis generated by this study must be confirmed in a randomized trial stratifying for significant prognostic factors.