Comparison of Diagnosis-specific Survival Scores for Patients With Cerebral Metastases from Malignant Melanoma Including the New WBRT-30-MM.

BACKGROUND/AIM: Diagnosis-specific scoring systems developed for predicting survival of patients with cerebral metastases from malignant melanoma (MM) were evaluated. PATIENTS AND METHODS: The new whole-brain radiotherapy (WBRT)-30-MM was created in homogeneously treated patients receiving 10×3 Gy of WBRT for cerebral metastases from MM. It consisted of three groups with significantly different 6-month survival rates of 0% (3-5 points), 30% (7 points) and 52% (9 points) (p=0.001). The WBRT-30-MM was compared to three other scores created for cerebral metastases from MM, including first updated DS-GPA classification, Dziggel-Score and Sehmisch-Score. RESULTS: Positive predictive values (PPVs) for predicting death ≤6 months after WBRT were 100% (WBRT-30-MM), 77% (DS-GPA), 69% (Dziggel-Score) and 73% (Sehmisch-Score). PPVs for predicting survival ≥6 months were 52%, 38%, 63% and 75%, respectively. CONCLUSION: WBRT-30-MM was the most accurate instrument for predicting death ≤6 months. For predicting survival ≥6 months, Sehmisch-Score was most accurate, although all existing scorring systems appeared suboptimal for this purpose.

Development of a Survival Score for Patients with Cerebral Metastases from Melanoma.

BACKGROUND/AIM: To develop a survival score for patients receiving whole-brain irradiation (WBI) alone for cerebral metastases from melanoma. PATIENTS AND METHODS: Forty-five patients who met the required criteria were included. WBI doses had to be >30 Gy. Six variables were analyzed: age, gender, Karnofsky performance score (KPS), number of cerebral metastases, extracranial metastatic spread and interval from diagnosis of melanoma until WBI. In order to estimate patients' survival scores, variables showing at least a trend (p<0.06) on multivariate analysis were considered. One point was assigned to each variable correlating with better survival rates and zero points to those correlating with worse survival rates. RESULTS: By multivariate analysis, age (p=0.002) achieved significance and KPS (p=0.056) showed a trend. Patients' survival scores were obtained by adding zero or one point from each variable and resulted in three groups of 0, 1 or 2 points. The median survival times of these groups were one, four and ten months (p<0.0001). CONCLUSION: A survival score was developed for patients assigned to WBI alone for cerebral metastases from melanoma. This new instrument may facilitate the decision for the appropriate WBI-program.

Prognostic Factors After Whole-brain Radiotherapy Alone for Brain Metastases from Malignant Melanoma.

BACKGROUND/AIM: Many patients with brain metastases from melanoma receive whole-brain radiotherapy (WBRT). WBRT-regimens must consider the patient's prognosis in order to deliver the best therapy. PATIENTS AND METHODS: Seven factors were correlated to intracerebral control and survival after WBRT alone in 92 patients with melanoma: WBRT regimen, age at WBRT, gender, Karnofsky performance score (KPS), number of brain lesions, number of extracranial metastatic sites, and time from melanoma diagnosis to WBRT. RESULTS: On univariate analyses, KPS ≥80 (p=0.075) showed a trend towards improved intracerebral control. Greater WBRT dose (p=0.029), age ≤60 years (p=0.002), KPS ≥80 (p<0.001) and no extracranial site (p=0.008) were positively correlated with survival. On multivariate analyses, KPS (hazard ratio=2.11, 95% confidence interval=1.28-3.47; p=0.003) and number of extracranial metastatic sites (hazard ratio=1.27, 95% confidence interval=1.02-1.56; p=0.030) maintained significance regarding survival. CONCLUSION: The study identified predictors of survival for patients with melanoma receiving WBRT for brain metastases that can contribute to selection of individualized therapies.

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.

Identifying melanoma patients with 1-3 brain metastases who may benefit from whole-brain irradiation in addition to radiosurgery.

BACKGROUND/AIM: To develop a tool for estimating the risk of developing new cerebral lesions in 69 melanoma patients receiving radiosurgery for 1-3 cerebral metastases. PATIENTS AND METHODS: Ten factors were investigated: lactate dehydrogenase (LDH), radiosurgery dose, age, gender, performance status, maximum diameter, location and number of cerebral lesions, extra-cranial spread, time between melanoma diagnosis and radiosurgery. Two factors, number of lesions and extra-cranial spread, were included in the tool. Scoring points were achieved by dividing the 6-month rate of freedom from new cerebral lesions by 10. RESULTS: Sum scores were 9, 11, 12 or 14 points. Six-month rates of freedom from new brain metastases were 28%, 63%, 59% and 92% (p=0.002). Three prognostic groups were designed: A (9 points), B (11-12 points) and C (14 points). Freedom from new cerebral lesion rates were 28%, 60% and 92% (p<0.001). CONCLUSION: Group A and B patients should be considered for additional whole-brain radiotherapy (WBRT).

Motor function and survival following radiotherapy alone for metastatic epidural spinal cord compression in melanoma patients.

The major goal of this study was the identification of predictors for motor function and survival after irradiation alone for metastatic epidural spinal cord compression (MESCC) from melanoma. Ten variables (age, gender, performance status, number of involved vertebrae, pre-radiotherapy ambulatory status, further bone metastases, visceral metastases, interval from melanoma diagnosis to MESCC, time developing motor deficits before radiotherapy, fractionation regimen) were investigated for post-radiotherapy motor function, ambulatory status and survival in 27 patients. On multivariate analysis, motor function was significantly associated with time developing motor deficits (P = 0.006). On univariate analysis, post-radiotherapy ambulatory rates were associated with pre-radiotherapy ambulatory status (P < 0.001) and performance status (P = 0.046). Variables having a significant impact on survival in the univariate analysis were performance status (P < 0.001), number of involved vertebrae (P = 0.007), pre-radiotherapy ambulatory status (P = 0.020), further bone metastases (P = 0.023), visceral metastases (P < 0.001), and time developing motor deficits (P = 0.038). On multivariate analysis of survival, the Eastern Cooperative Oncology Group (ECOG) performance status (risk ratio [RR] = 4.35; 95% confidence interval [CI] = 1.04-16.67; P = 0.044) and visceral metastases (RR = 3.70; 95% CI = 1.10-12.50; P = 0.034) remained significant and were included in a survival score. Scoring points were obtained from 6-month survival rates divided by 10. Total scores represented the sum scores of both variables and were 3, 9 or 15 points. Six-month survival rates were 7%, 29% and 100% (P = 0.004). Thus, three predictors for functional outcomes were identified. The newly developed survival score included three prognostic groups. Patients with 3 points may receive 1 × 8 Gy, patients with 9 points 5 × 4 Gy and patients achieving 15 points longer-course radiotherapy. In the latter two groups, upfront decompressive surgery may be considered.

Radiosurgery alone for 1-3 newly-diagnosed brain metastases from melanoma: impact of dose on treatment outcomes.

BACKGROUND/AIM: To compare different doses of stereotactic radiosurgery (SRS) for 1-3 newly-diagnosed cerebral metastases from melanoma. PATIENTS AND METHODS: Fifty-four patients were assigned to dose groups of 20 Gy (N=36) and 21-22.5 Gy (N=18). Variables additionally analyzed were age, gender, Karnofsky Performance Score (KPS), lactate dehydrogenase (LDH) before SRS, number of cerebral lesions, extracranial lesions, time from melanoma diagnosis to SRS. RESULTS: The 12-month local control was 72% after 20 Gy and 100% after 21-22.5 Gy (p=0.020). Freedom from new cerebral metastases (p=0.13) and survival (p=0.13) showed no association with SRS dose. On multivariate analyses, improved local control showed significant associations with SRS doses of 21-22.5 Gy (p=0.007) and normal lactate dehydrogenase levels (p=0.018). Improved survival was associated with normal LDH levels (p=0.006) and KPS 90-100 (p=0.046). CONCLUSION: SRS doses of 21-22.5 Gy resulted in better local control than 20 Gy. Freedom from new brain metastases and survival were not significantly different.

Estimating survival of patients receiving radiosurgery alone for cerebral metastasis from melanoma.

This study aimed to identify clinical factors associated with survival and to develop a prognostic tool in patients receiving radiosurgery alone for very few cerebral metastases from melanoma. Ten characteristics of 69 patients treated with radiosurgery alone for 1-3 cerebral metastases from melanoma were retrospectively analyzed for survival. Serum lactate dehydrogenase levels before radiosurgery, Karnofsky performance score, maximum diameter of all irradiated cerebral lesions, and extracranial lesions were significantly associated with survival and included in the tool. Twelve-month survival rate (in %) divided by 10 was calculated for each of these four factors. The four scores were summed resulting in total scores ranging 9-22 points. Based on the 12-month survival rates, three groups were formed: less than 15 points (group I, n = 25); 15-20 points (group II, n = 34); and more than 20 points (group III, n = 10). Corresponding 12-month survival rates were 10 ± 6%, 51 ± 9% and 90 ± 9%, respectively (P < 0.001). In group I, death within 12 months following radiosurgery occurred mostly due to extracranial progression, whereas cerebral progression was the major cause of death in group II. In group III, only one of 10 patients died within 1 year. This new prognostic tool helps predict the survival time following radiosurgery of very few cerebral metastases from melanoma. An individual treatment approach should consider a patient's survival time and the most likely cause of death (cerebral or extracranial progression).