Departement of Gynecologic Oncology, Norwegian Radium Hospital, Oslo University Hospital, 0424 Oslo, Norway.
Cancer Chemother Pharmacol. 2012 May;69(5):1307-14. doi: 10.1007/s00280-012-1835-9.
We aimed to identify primary platinum resistance in epithelial ovarian cancer (OC) patients with FIGO stage III-IV disease by an in vitro drug-response assay and to correlate the findings with clinical response. We considered whether neoadjuvant chemotherapy or anatomic sample site and tumor heterogeneity would influence the results.
We combined the ATP-based tumor-chemosensitivity and the extreme drug resistance assays for testing of 85 biopsies from 58 patients. Tumors were classified as sensitive or resistant by a resistance index (RI). We did separate analyses of primary tumors and metastases and compared chemo-naïve samples with samples obtained after neoadjuvant chemotherapy. Results were analyzed for association with clinical platinum resistance, progression-free survival (PFS), and overall survival (OS).
RI · 250 predicted primary platinum resistance, without misclassification of sensitive patients. The test sensitivity for primary tumors was 15/15, specificity 3/10, negative predictive value 3/3, and positive predictive value 15/22. Patients with in vitro platinum-resistant samples had shorter PFS compared with patients with sensitive samples (3.4 vs. 10.0 months, p = 0.02). Comparing patient-matched primary and metastatic samples, there was about 1/3 mismatch in resistance. RI for platinum was lower in primary tumors exposed to neoadjuvant chemotherapy than in chemo-naïve tumors (p < 0.01).
This in vitro assay predicted primary platinum resistance, without misclassification of sensitive OC patients, and the results were significantly associated with PFS. We suggest that samples from primary tumor and metastatic samples have different responses to chemotherapy and that exposure to chemotherapy might induce in vitro platinum resistance.
通过体外药物反应测定法，在国际妇产科联盟（FIGO）分期为 III-IV 期的上皮性卵巢癌（OC）患者中确定原发性铂耐药，并将研究结果与临床反应相关联。我们考虑了新辅助化疗或解剖样本部位和肿瘤异质性是否会影响结果。
我们结合基于 ATP 的肿瘤化疗敏感性和极端耐药测定法，对 58 名患者的 85 个活检标本进行了检测。肿瘤通过耐药指数（RI）分为敏感或耐药。我们分别对原发肿瘤和转移瘤进行了分析，并比较了化疗初治样本和新辅助化疗后获得的样本。分析结果与临床铂耐药、无进展生存期（PFS）和总生存期（OS）相关联。
RI·250 预测了原发性铂耐药，没有对敏感患者进行错误分类。该检测对原发肿瘤的敏感性为 15/15，特异性为 3/10，阴性预测值为 3/3，阳性预测值为 15/22。与敏感样本相比，体外铂耐药样本患者的 PFS 更短（3.4 与 10.0 个月，p=0.02）。比较患者匹配的原发和转移样本，耐药性有大约 1/3 的不一致。新辅助化疗暴露的原发肿瘤的 RI 比化疗初治肿瘤的 RI 低（p<0.01）。
该体外检测法预测了原发性铂耐药，没有对敏感 OC 患者进行错误分类，并且结果与 PFS 显著相关。我们建议，原发肿瘤和转移瘤样本的化疗反应不同，化疗暴露可能会导致体外铂耐药。
