A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases.

BACKGROUND: This matched-pair study was initiated to validate the results of a retrospective study of 186 patients published in 2007 that compared whole-brain irradiation (WBI) alone and radiosurgery (RS) alone for up to three brain metastases. METHODS: One-hundred-fifty-two patients receiving WBI alone for up to three brain metastases were matched with 152 patients treated with RS of fractionated stereotactic radiotherapy (FSRT) alone 1:1 for each of eight factors (age, gender, Eastern Oncology Cooperative Group (ECOG)-performance score, nature of tumor, brain metastases number, extra-cerebral spread, period from cancer detection to irradiation of brain metastases, and recursive partitioning analysis (RPA)-class. Groups were analyzed regarding intracerebral control (IC) and overall survival (OS). RESULTS: On univariate analysis of IC, type of irradiation did not significantly affect outcomes (p = 0.84). On Cox regression, brain metastases number (p < 0.001), nature of tumor (p < 0.001) and period from cancer detection to irradiation of brain metastases (p = 0.013) were significantly associated with IC. On univariate analysis of OS, type of irradiation showed no significant association with outcomes (p = 0.63). On multivariate analyses, OS was significantly associated with ECOG performance score (p = 0.011), nature of tumor (p = 0.035), brain metastases number (p = 0.048), extra-cerebral spread (p = 0.002) and RPA-class (p < 0.001). CONCLUSION: In this matched-pair study, RS/FSRT alone was not superior to WBI alone regarding IC and OS. These results can be considered a revision of the findings from our retrospective previous study without matched-pair design, where RS alone resulted in significantly better IC than WBI alone on multivariate analysis.

Whole-brain Radiotherapy With or Without a Simultaneous Integrated Boost for Treatment of Brain Metastases.

BACKGROUND/AIM: Many patients with brain metastases receive whole-brain radiotherapy (WBRT), despite the increasing use of stereotactic radiotherapy alone. A more recent approach includes WBRT combined with simultaneous integrated boost (WBRT+SIB). This study compared WBRT alone and WBRT+SIB for unresected brain metastases. PATIENTS AND METHODS: One-hundred-and-three patients receiving WBRT+SIB were compared to 275 patients receiving WBRT alone for intracerebral control (IC) and overall survival (OS). RESULTS: Both treatment groups (WBRT alone and WBRT+SIB) were balanced with respect to patient characteristics. On multivariate analyses, WBRT+SIB (p=0.041), Karnofsky performance score (KPS) >70 (p<0.001), and 1-3 brain metastases (p=0.016) were significantly associated with IC. KPS >70 (p<0.001), favorable tumor type (p=0.011), 1-3 brain metastases (p=0.011), and absence of extracranial metastases (p<0.001) were significantly associated with OS. CONCLUSION: WBRT+SIB is associated with improved IC but similar OS when directly compared to WBRT for brain metastases. Selected patients with a high risk of intracerebral recurrence may benefit from SIB.

A matched-pair analysis comparing whole-brain radiotherapy with and without a stereotactic boost for intracerebral control and overall survival in patients with one to three cerebral metastases.

BACKGROUND: Twelve years ago, a randomized trial demonstrated that a radiosurgery boost added to whole-brain radiotherapy (WBRT) improved intracerebral control (IC) in patients with one to three cerebral metastases. Overall survival (OS) was improved only in the subgroup of patients with a single metastasis but not in the entire cohort. The present study compared both regimens in a different scenario outside a randomized trial. METHODS: A total of 252 patients with one to three cerebral metastases were included. Eighty-four patients receiving WBRT plus a planned stereotactic boost and 168 patients receiving WBRT alone were individually matched 1:2 for nine factors including fractionation of WBRT, age, gender, performance score, primary tumor, number of cerebral metastases, extracerebral metastases, recursive partitioning analysis class, and time between cancer diagnosis and WBRT. Each group of three patients was required to match for all nine factors. Both groups were compared for IC and OS. RESULTS: IC rates at 6, 12, 18 and 24 months were 88, 71, 45 and 22% after WBRT plus stereotactic boost vs. 75, 48, 38 and 22% after WBRT alone (p = 0.005). OS rates at 6, 12, 18 and 24 months were 76, 53, 32 and 25% after WBRT plus stereotactic boost and 67, 45, 29 and 20% after WBRT alone (p = 0.10). In patients with a single lesion, OS rates were also not significantly different (p = 0.12). CONCLUSIONS: Similar to the previous randomized trial from 2004, this matched-pair study showed that a stereotactic boost in addition to WBRT significantly improved IC but not OS.

Potential Impact of the Overall Treatment Time on Outcomes after Whole-brain Irradiation with 10×3 Gy for Brain Metastases.

AIM: To investigate the impact of the overall treatment time (OTT) of whole-brain irradiation (WBI) with 10×3 Gy on outcomes in patients with brain metastases. PATIENTS AND METHODS: Seventy-three patients who started WBI on Monday (OTT=12 days, including one weekend without irradiation) were compared to 257 patients who began WBI on Tuesday to Friday (OTT=14 days, including two weekends) for intracerebral control and survival. Seven additional factors were analyzed, including age, gender, Karnofsky performance score (KPS), tumor type, number (N) of brain lesions, extracerebral metastases and interval between cancer diagnosis and WBI. RESULTS: On univariate analysis, age (p=0.039), KPS (p<0.001) and N brain metastases (p=0.006) were associated with intracerebral control; OTT had no significant impact (p=0.20). Age (p<0.001), KPS (p<0.001), N brain metastases (p=0.037) and extracerebral metastases (p<0.001) were associated with survival; OTT had no significant impact (p=0.37). CONCLUSION: OTT (12 vs. 14 days) had no significant impact on outcomes after WBI with 10×3 Gy.

Outcomes After Whole-brain Radiotherapy for Brain Metastases with 5×4 Gy: Importance of Overall Treatment Time.

BACKGROUND/AIM: To investigate the impact of overall treatment time (OTT) of whole-brain radiotherapy (WBRT) with 5×4 Gy on outcomes. PATIENTS AND METHODS: Forty-four patients for whom WBRT was started on a Monday (OTT=5 days) were compared to 136 patients, for whom WBRT was started on another weekday (OTT=7 days; weekend break) regarding intracerebral control and survival. Seven other factors were also analyzed. RESULTS: Intracerebral control at 6 and 12 months was 64% and 36% after OTT of 5 days vs. 57% and 38% after OTT of 7 days (p=0.68). On multivariate analysis, intracerebral control was positively associated with a better Eastern Cooperative Oncology Group performance score (ECOG-PS) (p<0.001). Survival at 6 and 12 months was 36% and 16% after OTT of 5 days vs. 35% and 19% after OTT of 7 days (p=0.81). On multivariate analysis, survival was positively associated with better ECOG-PS (p<0.001) and absence of extracerebral lesions (p=0.004). CONCLUSION: Prolongation of OTT to 7 days had no impact on outcomes after WBRT with 5×4 Gy.

Comparison of 20×2 Gy and 12×3 Gy for Whole-brain Irradiation of Multiple Brain Metastases from Malignant Melanoma.

BACKGROUND/AIM: Most patients with multiple brain metastases from melanoma receive whole-brain irradiation. In a previous study, doses >30 Gy resulted in better outcomes than 10×3 Gy. However, the optimal dose-fractionation regimen has not yet been defined. This study compared 20×2 Gy over four weeks, which was used in the previous study, to 12×3 Gy over two-and-a-half weeks. PATIENTS AND METHODS: Eleven patients treated with 20×2 Gy for multiple brain metastases were compared to 12 patients treated with 12×3 Gy. RESULTS: Intracerebral control rates at 6 and 12 months were 17% and 0% after 20×2 Gy vs. 42% and 11% after 12×3 Gy (p=0.28). Survival rates at 6 and 12 months were 36% and 9% after 20×2 Gy vs. 50% and 25% after 12×3 Gy (p=0.75). CONCLUSION: The less time-consuming regimen 12x3 Gy appeared not inferior to 20×2 Gy and a reasonable treatment option, particularly for patients with a limited life expectancy.

Local Therapies Can Improve Intracerebral Control in Patients with Cerebral Metastasis from Gynecological Cancers.

BACKGROUND/AIM: Patients with gynecological malignancies account for 2% of patients with cerebral metastases. Many patients receive whole-brain irradiation (WBI) alone. Local therapies (resection, stereotactic radiosurgery (SRS)) are becoming more popular. This study compared intracerebral control after local therapy to WBI alone in patients with gynecological malignancies. PATIENTS AND METHODS: Of 56 patients, 45 received WBI alone, 6 SRS alone and 5 resection plus WBI. Treatment type, age, performance score, cancer site, number of cerebral lesions, metastases outside the brain, recursive partitioning analysis (RPA) class and period from gynecological cancer diagnosis to brain metastasis treatment were evaluated. RESULTS: On univariate analyses, local therapy (p=0.003), single cerebral lesion (p<0.001) and RPA class 1/2 (p=0.027) were positively related to intracerebral control. On Cox regression analysis, local therapy (p=0.013) and RPA class 1/2 (p=0.014) were significant. CONCLUSION: Local therapies led to better intracerebral control than WBI alone and should be considered for brain metastasis from gynecological malignancies whenever reasonable.