Are increased tumor aneuploidy and heightened cell proliferation along with heterogeneity associated with patient outcome for carcinomas of the uterine cervix? A combined analysis of subjects treated in RTOG 9001 and a single-institution trial.
OBJECTIVE
To look for possible associations between measurements of DNA index (DI), S-phase fraction (SPF), and tumor heterogeneity (TH) using flow cytometry and overall survival for patients with invasive cervical carcinoma treated with definitive irradiation.


METHODS
A total of 57 patients with International Federation of Obstetrics and Gynecology Stages IB(2) through IVB cervical carcinomas treated with definitive radiotherapy with or without concurrent chemotherapy were enrolled into this registry study that involved flow cytometric analysis of fresh tissue from each cervical cancer obtained by pretreatment biopsy. These specimens were evaluated for DNA aneuploidy (DI <or=1.5 vs. >1.5), SPF (<or=15% vs. >15%), and TH (uniploid vs. multiploid).


RESULTS
In these analyses 27 of the patients were treated in Radiation Therapy Oncology Group protocol 9001, and an additional 30 were offered chemoradiation at a single institution. Forty-one patients had DI <or=1.5 and 16 DI >1.5. Twenty-nine patients had SPF <or=15%, 26 >15%, and 2 had no determinable SPF. Forty-three patients had uniploid and 14 multiploid tumors. The 4-year estimated overall survival rate for the entire study cohort was 62% (95% confidence interval 48%-74%). With a median follow-up of 3.7 years, there were no observable associations by univariate analysis for DI, SPF, or TH concerning patient survival.


CONCLUSIONS
There were no statistically significant associations among DI, SPF, or TH and patient outcome. Additional studies are indicated to identify tumor biomarkers that could predict patients at risk for disseminated disease.
Wolfson
Aaron H
AH
Department of Radiation Oncology, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, D-31, Miami, FL 33136, USA. awolfson@med.miami.edu
Winter
Kathryn
K
Crook
William
W
Krishan
Awtar
A
Grigsby
Perry W
PW
Markoe
Arnold M
AM
Morris
Mitchell
M
Gaffney
David K
DK
Eifel
Patricia J
PJ
Lucci
Joseph A
JA
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D016196:S Phase; D016019:Survival Analysis; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000532:radiotherapy
D002945:Cisplatin; D005472:Fluorouracil