Predictive value of the flow cytometric PCNA assay (proliferating cell nuclear antigen) in head and neck tumors after accelerated-hyperfractionated radiochemotherapy.
OBJECTIVE
Proliferation of tumor cells during radiotherapy may limit tumor control, especially in rapidly proliferating tumors such as head and neck carcinomas. We present a flow cytometric method for detection of PCNA in solid head and neck tumors and how these data correlate with outcome.


METHODS
Pretherapeutic biopsies of 20 inoperable patients with Stage IV squamous cell carcinoma were examined. Biparametric 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) were determined. The therapy consisted of an accelerated-hyperfractionated radiochemotherapy (66 Gy/5 weeks, concomitant boost of 1.6 Gy/day in weeks 4+5, Carboplatin 5 x 70 mg/m2 in weeks 1+5). The median follow-up time was 30 months.


RESULTS
Fourteen patients suffered from disease progession and 12 died. Median actuarial, cause-specific survival, and disease-free survival (DFS) times were 17 and 9 months, respectively. PCNA indices ranged from 4 to 70% (median 9%); there were 7 aneuploid and 13 euploid tumors. SPF ranged from 4 to 14.5% (median 10.5%). Neither SPF nor ploidy had a significant influence on outcome. Patients were divided according to PCNA index in higher (n = 10) and lower (n = 10) than the median. Survival and DFS were 13 and 6 months for the group >9% and 20 and 15 months for the group <9%. The difference in DFS was significant (p = 0.03, log rank test).


CONCLUSIONS
These results fall in line with other studies showing the influence of pretherapeutic proliferation on outcome after radiotherapy. Although the moderately accelerated therapy regimen certainly reduces the influence of proliferation on outcome, patients with faster proliferating tumors still have a worse outcome. DFS is the more relevant endpoint in this study because of effective salvage therapies, which influence survival.
Wenz
F
F
Department of Clinical Radiology, University of Heidelberg, Germany.
Lohr
F
F
Flentje
M
M
Rudat
V
V
Dietz
A
A
Wannenmacher
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D011003:Ploidies; D011237:Predictive Value of Tests; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D011879:Radiotherapy Dosage
D000970:Antineoplastic Agents; D015415:Biomarkers; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin