The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma.
BACKGROUND
The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.


METHODS
Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.


RESULTS
The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.


CONCLUSIONS
An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care.
Melanoma Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.|The Institute of Cancer Research, Division of Radiotherapy and Imaging, 123 Old Brompton Road, London SW7 3RP, UK.|The Institute of Cancer Research, Division of Clinical Studies, 123 Old Brompton Road, London SW7 3RP, UK.
Anna
A
Wilkins
Melanoma Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.|The Institute of Cancer Research, Division of Radiotherapy and Imaging, 123 Old Brompton Road, London SW7 3RP, UK.
Andrew
A
Furness
Department of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK.
Richard W
RW
Corbett
Melanoma Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.
Adam
A
Bloomfield
The Institute of Cancer Research, Division of Clinical Studies, 123 Old Brompton Road, London SW7 3RP, UK.
Nuria
N
Porta
Department of Clinical Oncology, Guy's and St Thomas' NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, UK.
Stephen
S
Morris
Melanoma Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.|The Institute of Cancer Research, Division of Radiotherapy and Imaging, 123 Old Brompton Road, London SW7 3RP, UK.
Zohra
Z
Ali
Melanoma Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.|The Institute of Cancer Research, Division of Clinical Studies, 123 Old Brompton Road, London SW7 3RP, UK.
James
J
Larkin
Melanoma Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.|The Institute of Cancer Research, Division of Radiotherapy and Imaging, 123 Old Brompton Road, London SW7 3RP, UK.
Kevin
K
Harrington
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012878:Skin Neoplasms; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma