Robbins K T, Connors K M, Storniolo A M, Hanchett C, Hoffman R M
Division of Otolaryngology-Head and Neck Surgery, University of California Medical Center, San Diego.
Arch Otolaryngol Head Neck Surg. 1994 Mar;120(3):288-92. doi: 10.1001/archotol.1994.01880270036007.
Sponge-gel-supported histoculture drug-response assay (SSHDRA) represents a promising method to determine chemosensitivity of solid tumors. To determine whether the assay correlates clinically, we compared the in vivo and in vitro effects of cisplatin in 23 of 26 patients with head and neck cancers.
The criterion for in vitro sensitivity to cisplatin was an 84% or greater inhibition by cisplatin of the number of tritiated thymidine-incorporating cells of the histocultured tumors compared with untreated control culture preparations, as measured by means of histologic autoradiography. Comparisons were made with clinical responses, ie, complete response, partial response, or no response.
The study was carried out in patients with head and neck cancers and comprised 21 patients with squamous-cell carcinoma, three patients with other carcinomas, and two patients with sarcoma.
Ten of 12 patients with in vitro-sensitive tumors had either complete or partial response clinically. The overall accuracy of the SSHDRA was 74% in this correlative clinical trial; the predictive-positive value was 83%, the sensitivity was 71%, and the specificity was 78%. Seven of 11 patients with in vitro-resistant tumors demonstrated no response for a predictive-negative value of 64%.
We conclude that the SSHDRA shows a high correlation for tumors that demonstrate both in vivo drug resistance and sensitivity. The in vitro-like maintenance of three-dimensional tissue architecture of the tumors in histoculture probably contributes to high clinical predictivity of drug response of the SSHDRA. The data support further comparisons to determine the clinical usefulness of the SSHDRA for identifying complete and partial responders to chemotherapy.
海绵凝胶支持的组织培养药物反应测定法(SSHDRA)是一种用于确定实体瘤化学敏感性的有前景的方法。为了确定该测定法与临床是否相关,我们比较了26例头颈癌患者中23例患者顺铂的体内和体外效应。
体外对顺铂敏感性的标准是,通过组织学放射自显影测量,与未处理的对照培养制剂相比,顺铂对组织培养肿瘤中掺入氚化胸腺嘧啶的细胞数量的抑制率达到84%或更高。将其与临床反应进行比较,即完全缓解、部分缓解或无反应。
该研究在头颈癌患者中进行,包括21例鳞状细胞癌患者、3例其他癌症患者和2例肉瘤患者。
12例体外敏感肿瘤患者中有10例临床完全缓解或部分缓解。在这项相关性临床试验中,SSHDRA的总体准确率为74%;预测阳性值为83%,敏感性为71%,特异性为78%。11例体外耐药肿瘤患者中有7例无反应,预测阴性值为64%。
我们得出结论,SSHDRA对于体内显示耐药和敏感的肿瘤具有高度相关性。组织培养中肿瘤三维组织结构的体外样维持可能有助于SSHDRA对药物反应的高临床预测性。这些数据支持进一步比较,以确定SSHDRA在识别化疗完全缓解者和部分缓解者方面的临床实用性。