Sponge-gel-supported histoculture drug-response assay for head and neck cancer. Correlations with clinical response to cisplatin.
OBJECTIVE
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.


METHODS
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.


METHODS
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.


RESULTS
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%.


CONCLUSIONS
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.
Robbins
K T
KT
Division of Otolaryngology-Head and Neck Surgery, University of California Medical Center, San Diego.
Connors
K M
KM
Storniolo
A M
AM
Hanchett
C
C
Hoffman
R M
RM
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology*; D002945:Cisplatin / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D011237:Predictive Value of Tests; D012074:Remission Induction; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology; D012680:Sensitivity and Specificity
D002945:Cisplatin