Circulating DNA microsatellites: molecular determinants of response to biochemotherapy in patients with metastatic melanoma.
Although biochemotherapy appears to be a promising treatment for metastatic melanoma, its impact remains unpredictable. Microsatellite markers for loss of heterozygosity (LOH) appear to have prognostic significance when identified in primary tumors and serum and/or plasma from cancer patients. However, their association with response to systemic therapy has yet to be assessed. To determine whether microsatellite markers are associated with response to therapy, serum from 41 patients with metastatic melanoma, drawn before the initiation of biochemotherapy, was analyzed for LOH with nine microsatellite markers. During a median follow-up of 13 months, the overall response rate for these 41 patients was 56%, including 13 (32%) complete responses and 10 (24%) partial responses. LOH was detected in sera from 12 (29%) of the 41 patients. The response rate of these 12 patients was 17% (95% confidence interval [CI] = 5% to 45%), whereas that of the 29 patients without LOH was 72% (95% CI = 54% to 85%) (P =.001). All statistical tests were two-sided. The presence of LOH was statistically significant and independently associated with disease progression (multivariable analysis, P =.003). Circulating tumor DNA markers may be useful in assessing prognosis for advanced melanoma patients and their response to biochemotherapy.
Taback
Bret
B
Department of Molecular Oncology, John Wayne Cancer Institute and Saint John's Health Center, Santa Monica, CA 90404, USA.
O'Day
Steven J
SJ
Boasberg
Peter D
PD
Shu
Sherry
S
Fournier
Patricia
P
Elashoff
Robert
R
Wang
He-Jing
HJ
Hoon
Dave S B
DS
D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary*; D018895:Microsatellite Repeats; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm