Dose-escalation of whole-brain radiotherapy for brain metastasis in patients with a favorable survival prognosis.

BACKGROUND: Patients with brain metastases who have a favorable survival prognosis may benefit from intensive treatments, including neurosurgery and radiosurgery. However, many patients cannot receive such treatments, and whole-brain radiotherapy (WBRT) alone is their only option. The most common WBRT schedule is 30 grays (Gy) in 10 fractions. In this retrospective study, the authors investigated whether these patients benefit from a dose escalation beyond 30 Gy. METHODS: Data from 109 patients who received 30 Gy in 10 fractions were compared with 75 patients who received 40 Gy in 20 fractions. All patients had a favorable survival prognosis. Both groups were compared for local control (LC) and overall survival (OS). Subgroup analyses were performed for patients who had less radiosensitive tumors (N = 27) and for other patients (N = 157). RESULTS: The LC rate at 1 year was 28% after 30 Gy and 44% after 40 Gy (P = .064). On multivariate analysis, the 40 Gy dose was associated with improved LC (P = .047). The survival rate at 1 year was 50% after 30 Gy and 61% after 40 Gy (P = .007). On multivariate analysis, the 40 Gy dose was associated with improved OS (P = .008). On subgroup analysis of patients who had less radiosensitive tumors, the 1-year LC rate was 7% after 30 Gy and 38% after 40 Gy (P = .031); and the 1-year OS rate was 40% and 73%, respectively (P = .008). On subgroup analysis of patients who had other tumor types, the 1-year LC rate was 31% after 30 Gy and 45% after 40 Gy (P = .26); and the 1-year OS rate was 52% and 59%, respectively (P = .08). CONCLUSIONS: Escalation of the WBRT dose beyond 30 Gy resulted in better outcomes, particularly for patients who had less radiosensitive tumors.

Scoring systems to estimate intracerebral control and survival rates of patients irradiated for brain metastases.

PURPOSE: To create and validate scoring systems for intracerebral control (IC) and overall survival (OS) of patients irradiated for brain metastases. METHODS AND MATERIALS: In this study, 1,797 patients were randomly assigned to the test (n = 1,198) or the validation group (n = 599). Two scoring systems were developed, one for IC and another for OS. The scores included prognostic factors found significant on multivariate analyses. Age, performance status, extracerebral metastases, interval tumor diagnosis to RT, and number of brain metastases were associated with OS. Tumor type, performance status, interval, and number of brain metastases were associated with IC. The score for each factor was determined by dividing the 6-month IC or OS rate (given in percent) by 10. The total score represented the sum of the scores for each factor. The score groups of the test group were compared with the corresponding score groups of the validation group. RESULTS: In the test group, 6-month IC rates were 17% for 14-18 points, 49% for 19-23 points, and 77% for 24-27 points (p < 0.0001). IC rates in the validation group were 19%, 52%, and 77%, respectively (p < 0.0001). In the test group, 6-month OS rates were 9% for 15-19 points, 41% for 20-25 points, and 78% for 26-30 points (p < 0.0001). OS rates in the validation group were 7%, 39%, and 79%, respectively (p < 0.0001). CONCLUSIONS: Patients irradiated for brain metastases can be given scores to estimate OS and IC. IC and OS rates of the validation group were similar to the test group demonstrating the validity and reproducibility of both scores.

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.

Surgical resection followed by whole brain radiotherapy versus whole brain radiotherapy alone for single brain metastasis.

PURPOSE: To compare the outcome of surgical resection followed by whole brain radiotherapy (WBRT) with WBRT alone in patients treated for single brain metastasis. METHODS AND MATERIALS: The data from 195 patients with single brain metastases were retrospectively evaluated. Of the 195 patients, 99 underwent resection of the metastasis followed by WBRT and 96 underwent WBRT alone. Seven additional potential prognostic factors were investigated: age, gender, Eastern Cooperative Oncology Group performance score, tumor type, interval between initial tumor diagnosis and WBRT, extracranial metastases, and recursive partitioning analysis class. Both treatment groups were well balanced for these factors. RESULTS: On multivariate analysis, improved survival was associated with resection (relative risk [RR], 1.20; 95% confidence interval [CI], 1.11-1.31; p < 0.001), lower recursive partitioning analysis class (RR, 1.58; 95% CI, 1.22-2.06; p < 0.001), age < or = 61 years (RR, 1.79; 95% CI, 1.23-2.61; p = 0.002), Eastern Cooperative Oncology Group performance score of 0-1 (RR, 2.47; 95% CI, 1.70-3.59; p < 0.001), and the absence of extracranial metastases (RR, 1.99; 95% CI, 1.41-2.79; p < 0.001). Improved local control was associated with resection (RR, 1.25; 95% CI, 1.11-1.41; p < 0.001) and age < or = 61 years (RR, 1.77; 95% CI, 1.09-2.88; p = 0.020). Improved brain control distant from the original site was associated with lower recursive partitioning analysis class (RR, 1.65; 95% CI, 1.03-2.69; p < 0.035), age < or = 61 years (RR, 1.81; 95% CI, 1.12-2.96; p = 0.016), and the absence of extracranial metastases (RR, 2.42; 95% CI, 1.52-3.88; p < 0.001). Improved control within the entire brain was associated with surgery (RR, 1.24; 95% CI, 1.12-1.38; p < 0.001) and age < or = 61 years (RR, 1.83; 95% CI, 1.21-2.77; p = 0.004). CONCLUSION: In patients with a single brain metastasis, the addition of resection to WBRT improved survival, local control at the original metastatic site, and control within the entire brain, but did not prevent the development of new brain metastases distant to the original site.

Dose escalation beyond 30 grays in 10 fractions for patients with multiple brain metastases.

BACKGROUND: Whole-brain radiotherapy (WBRT) to 30 grays (Gy) in 10 fractions is the standard treatment in patients with multiple brain metastases in the majority of treatment centers worldwide. The current study investigated the potential benefit of dose escalation beyond 30 Gy. METHODS: Data regarding 416 patients who were treated with WBRT for multiple brain metastases were evaluated retrospectively. Survival and freedom from recurrent brain metastasis (local control) of 257 patients who were treated with 10 fractions of 3 Gy each for 2 weeks were compared with those of 159 patients treated with 45 Gy in 15 fractions for 3 weeks or 40 Gy in 20 fractions for 4 weeks. Eight additional potential prognostic factors were investigated including age, gender, Karnofsky performance score (KPS), tumor type, interval between tumor diagnosis and RT, number of metastases, extracranial metastases, and Recursive Partitioning Analysis (RPA) class. RESULTS: On multivariate analysis, improved survival was found to be associated with lower RPA class (P < .001), age <60 years (P = .026), KPS >or=70 (P < .001), and absence of extracranial metastases (P = .003). A trend was observed for number of metastases (2-3 vs >or=4; P = .07). Improved local control was associated with a KPS >or=70 (P < .001) and breast cancer (P < .001). A trend was observed for number of metastases (P = .059). The RT schedule did not appear to have any significant impact on survival (P = .86) or local control (P = .61). The subgroup analyses, performed for each of the 3 RPA classes, did not demonstrate a significantly better outcome with dose escalation. CONCLUSIONS: Dose escalation beyond 30 Gy in 10 fractions does not appear to improve survival or local control in patients with multiple brain metastases but does increase the treatment time and cost of therapy.