PREDICTIVE VALUE OF THE FLOW CYTOMETRIC PCNA ASSAY (PROLIFERATING CELL NUCLEAR ANTIGEN) IN HEAD AND NECK TUMORS AFTER ACCELERATED-HYPERFRACTIONATED RADIOCHEMOTHERAPY

Purpose: Proliferation of tumor cells during radiotherapy may limit tu mor control, especially in rapidly proliferating tumors such as head a nd neck carcinomas. We present a flow cytometric method for detection of PCNA in solid head and neck tumors and how these data correlate wit h outcome. Methods and Materials: Pretherapeutic biopsies of 20 inoper able patients with Stage IV squamous cell carcinoma were examined. Bip arametric flow cytometry was done after anti-PCNA (PC10) and propidium iodine staining were performed. PCNA index (percentage PCNA positive cells), DNA index, and S phase fraction (SPF, euploid tumors only) wer e determined. The therapy consisted of an accelerated-hyperfractionate d radiochemotherapy (66 Gy/5 weeks, concomitant boost of 1.6Gy/day in weeks 4 + 5, Carboplatin 5 x 70 mg/m(2) in weeks 1;5). The median foll ow-up time was 30 months. Results: Fourteen patients suffered from dis ease progession and 12 died. Median actuarial, cause-specific survival , and disease-free survival (DFS) times were 17 and 9 months, respecti vely. PCNA indices ranged from 4 to 70% (median 9%); there were 7 aneu ploid and 13 euploid tumors. SPF ranged from 4 to 14.5% (median 10.5%) . Neither SPF nor ploidy had a significant influence on outcome. Patie nts were divided according to PCNA index in higher (n = 10) and lower (it = 10) than the median. Survival and DFS were 13 and 6 months for t he group >9% and 20 and 15 months for the group <9%. The difference in DFS was significant (p = 0.03, log rank test). Conclusion: These resu lts fall in line with other studies showing the influence of pretherap eutic proliferation on outcome after radiotherapy. Although the modera tely accelerated therapy regimen certainly reduces the influence of pr oliferation on outcome, patients with faster proliferating tumors stil l have a worse outcome. DFS is the more relevant endpoint in this stud y because of effective salvage therapies, which influence survival. (C ) 1997 Elsevier Science Inc.