Abstract
Background: Planar-based measurements of lesions in metastatic melanoma have limitations in estimating tumor
burden of a patient and in predicting response to treatment. Volumetric imaging might add predictive value to
Response criteria in Solid Tumor (RECIST)-measurement. Based on clinical observations, we explored the association
between baseline tumor volume (TV) and duration of treatment with dabrafenib in patients with metastatic
melanoma. We have also explored the prognostic value of TV for overall survival (OS) and progression free survival
(PFS).
Methods: This is a retrospective, chart-review of primary source documents and medical imaging of a cohort of
patients participating in the BRF112680 phase 1 clinical trial at the Prince of Wales Hospital. TV was quantified by
contouring all the measurable baseline target lesions in the standard manner for radiation planning using Voxxar™
software. We used Cox regression models to analyse associations between TV and duration of treatment with
dabrafenib and between TV, PFS and OS.
Results: Among 13 patients of BRAF 112680 trial, 10 were included in the retrospective analysis. Target lesion sum
volume ranged from 0.3 to 1065.5 cm3 (cc), with a median of 27.5 cc. The median PFS and OS were 420 days (range
109–1765) and 1680 days (range 390–2940), respectively. The initial TV was inversely correlated with duration of
treatment with dabrafenib (rho − 0.6; P 0.03). In multivariate analysis, TV was a predictor for OS (HR 2.81 CI 1.06–
6.19) and PFS (8.76 (CI 1.05–43.58). Patients with tumour volume above the median had significantly lower OS of 6-
months compared to 56-months survival for patients with smaller volumes; P = 0.019.
Conclusions: TV is a predictor for treatment duration and is prognostic of OS and PFS in patients with metastatic
melanoma. These findings need to be validated prospectively in clinical trials