Taback Bret, O'Day Steven J, Boasberg Peter D, Shu Sherry, Fournier Patricia, Elashoff Robert, Wang He-Jing, Hoon Dave S B
Department of Molecular Oncology, John Wayne Cancer Institute and Saint John's Health Center, Santa Monica, CA 90404, USA.
J Natl Cancer Inst. 2004 Jan 21;96(2):152-6. doi: 10.1093/jnci/djh011.
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.
尽管生物化疗似乎是转移性黑色素瘤一种很有前景的治疗方法，但其效果仍然不可预测。杂合性缺失（LOH）的微卫星标记物在原发性肿瘤以及癌症患者的血清和/或血浆中被发现时似乎具有预后意义。然而，它们与全身治疗反应的关联尚未得到评估。为了确定微卫星标记物是否与治疗反应相关，对41例转移性黑色素瘤患者在开始生物化疗前采集的血清进行了9个微卫星标记物的LOH分析。在中位随访13个月期间，这41例患者的总体反应率为56%，包括13例（32%）完全缓解和10例（24%）部分缓解。在41例患者中的12例（29%）血清中检测到LOH。这12例患者的反应率为17%（95%置信区间[CI]=5%至45%），而29例无LOH患者的反应率为72%（95%CI=54%至85%）（P=.001）。所有统计检验均为双侧检验。LOH的存在具有统计学意义，且与疾病进展独立相关（多变量分析，P=.003）。循环肿瘤DNA标记物可能有助于评估晚期黑色素瘤患者的预后及其对生物化疗的反应。
