Prediction of survival in patients with head and neck cancer using the histoculture drug response assay.
BACKGROUND
Chemoresponse is a significant outcome predictor in patients with head and neck cancer, regardless of the treatment modality used. The histoculture drug response assay (HDRA) has been shown to be a reliable method for in vitro chemoresponse assessment. In this study, we have correlated the HDRA assessment with survival in patients with head and neck squamous cell carcinoma (HNSCC).


METHODS
Tumor specimens from 41 of 42 patients undergoing treatment for HNSCC were successfully evaluated by the HDRA. Tumor tissue was histocultured on Gelfoam sponges gel in 24-well plates, followed by treatment with cisplatin (15 microg/mL) or 5-fluorouracil (40 microg/mL) in triplicate. A control group received no drug treatment. After completion of drug treatment, the relative cell survival in the tumors was determined using the MTT assay. The inhibition rate (IR) for each drug was calculated relative to the control for each case, and sensitivity was defined as a tumor IR of greater than 30%. Treatment was based on established protocols for the location and stage of the tumor and included surgery, radiation, and/or chemotherapy. Survival comparisons were performed using the generalized Wilcoxon test for the comparison of Kaplan-Meier survival curves.


RESULTS
Resistance to 5-fluorouracil was present in 13 cases (32%), to cisplatinum in 13 cases (32%), and to both agents in 11 cases (27%). The 2-year cause-specific survival was significantly greater for patients sensitive to 5-fluorouracil (85% vs 64%; p =.04), cisplatinum (86% vs 64%; p =.05), or both agents (85% vs 63%; p =.01). The association between HDRA assessment of chemoresponse and clinical outcome remained significant even after controlling for the effects of TNM stage and the presence of recurrent cancer at presentation by multivariate analysis.


CONCLUSIONS
Chemosensitivity determined by the HDRA seems to be a strong predictor of survival in patients with advanced HNSCC and should be considered further.
Singh
Bhuvanesh
B
Head and Neck and Medical Oncology Services, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. singhb@mskcc.org
Li
Rongou
R
Xu
Li
L
Poluri
Ashok
A
Patel
Snehal
S
Shaha
Ashok R
AR
Pfister
David
D
Sherman
Eric
E
Goberdhan
Andy
A
Hoffman
Robert M
RM
Shah
Jatin
J
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use; D016903:Drug Monitoring; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D002945:Cisplatin; D005472:Fluorouracil