A prognostic index that predicts outcome following palliative whole brain radiotherapy for patients with metastatic malignant melanoma

Abstract

To determine the outcome of patients with metastatic malignant melanoma (MMM) treated with palliative whole brain radiotherapy (WBRT) and to identify factors that predict treatment outcome to assist future trial design, a retrospective study was performed on patients with MMM who received WBRT at the Royal Marsden Hospital between 1998 and 2003. Data regarding patient factors, tumour factors and survival were collected. A total of 112 patients were identified and full data were available for 102 patients. The median age was 53 years (range 25 -81 years), 66.7% were male and 33.3% female. The median dose prescribed was 20 Gy in five fractions as a mid-plane dose. The median survival after WBRT for the whole group was 51 days (range 3 -1386). In an attempt to define prognostic groups, we used the validated RTOG recursive partitioning analysis (RPA) classification for brain metastasis (class 1: Karnofsky Performance Score (KPS) X70%, age o65 years with no extracranial metastasis; class 3: KPS o70%; class 2: all others). The median survivals were 151, 71 and 21 days for RPA class 1, 2 and 3, respectively (Po0.001). Multivariate analysis showed that RPA class, leptomeningeal involvement, presence and number of extracranial metastatic sites and progressive disease in the brain on imaging before WBRT are important independent predictive factors. A prognostic index was derived from these factors that allowed identification of patients unlikely to benefit from WBRT. In conclusion, the RTOG RPA classification is valid when applied to patients with MMM. Patients in RPA class 1 and good prognosis class 2 are likely to benefit from palliative WBRT and should be considered for entry into trials that aim to improve duration of response. We identified that patients with RPA class 3, leptomeningeal involvement or RPA class 2 with poor prognostic index are unlikely to benefit from palliative WBRT.

Temozolomide in advanced malignant melanoma with small brain metastases

“…Intracranial hemorrhagic complica- 15 Patients with brain metastases from melanoma who received WBRT had a median survival of 2.3 months for RPA class 2 and 0.7 months for RPA class 3. 16 The reported objective response rates of symptomatic brain metastases from melanoma to WBRT range from 11% to 14%. 2,[7][8][9][10]16 These data indicate that WBRT is of little benefit in the majority of patients who have symptomatic brain metastases from melanoma.…”

“…16 The reported objective response rates of symptomatic brain metastases from melanoma to WBRT range from 11% to 14%. 2,[7][8][9][10]16 These data indicate that WBRT is of little benefit in the majority of patients who have symptomatic brain metastases from melanoma. In addition, the duration of such treatment will take a substantial part of the rest of these patients lives, and its side effects, like fatigue, nausea, and hair loss, signify an additional burden for these patients.…”

The effectiveness of brain metastases radiotherapy in patients with melanoma

“…The prognosis of patients with MBM is poor with a mean survival of 3-6 months; in patients treated solely with corticosteroids, the mean survival is 2 months, whilst after the whole brain radiotherapy (WBRT) -it is about 3-4 months [6,8,10,[12][13][14][15][16]. Numerous publication data suggests that some patients may benefit from surgical treatment or radio-surgery (with the application of stereotactic methods of radiotherapy -SBRT), where the survival period varies between a few months and more than one year (12 months).…”

“…Melanoma gives rise to 7-13% of all brain metastases (MBM -melanoma brain metastases) and is ranked as third leading cause of brain metastases, after lung cancer (30-60%) and breast cancer (15-25%) [1][2][3][4][5][6][7][8]. The prevalence of melanoma brain metastases in patients with locoregional advancement melanoma is about 10%, whereas in patients with a generalised stage of the disease, it exceeds 15-46% [1,2,4,6,8].…”

“…The prevalence of melanoma brain metastases in patients with locoregional advancement melanoma is about 10%, whereas in patients with a generalised stage of the disease, it exceeds 15-46% [1,2,4,6,8]. In almost half of the patients with melanoma, MBM is the cause of death, whilst autopsies shows the presence of MBM in 50-75% of such melanoma cases [1,2,4,5,[8][9][10][11].…”