Circulating DNA microsatellites: Molecular determinants of response to biochemotherapy in patients with metastatic melanoma
Circulating DNA microsatellites: Molecular determinants of response to biochemotherapy in patients with metastatic melanoma
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DOI：
10.1093/jnci/djh011
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发表时间：
2004-01-21
影响因子：
10.3
通讯作者：
Hoon, DSB
中科院分区：
文献类型：
--
作者：
Taback, B;O'Day, SJ;Hoon, DSB
虽然生物化疗似乎是一种有前途的治疗转移性黑色素瘤，其影响仍然是不可预测的。当在原发性肿瘤和癌症患者的血清和/或血浆中鉴定时，杂合性缺失（洛）的微卫星标记似乎具有预后意义。然而，其与全身治疗反应的关系尚待评估。为了确定微卫星标记物是否与治疗反应相关，在生物化疗开始前抽取41例转移性黑色素瘤患者的血清，用9个微卫星标记物分析洛缺失。在13个月的中位随访期间，这41例患者的总体缓解率为56%，包括13例（32%）完全缓解和10例（24%）部分缓解。在41例患者中，12例（29%）血清中检测到洛缺失。这12例患者的缓解率为17%（95%可信区间[CI] = 5%~ 45%），而29例无洛缺失患者的缓解率为72%（95% CI = 54%~ 85%）（P = 0.001）。所有统计检验均为双侧检验。洛缺失的存在具有统计学意义，并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。
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.