Faculty Publications

BACKGROUND. The purpose was to identify the factors predictive of recurrence and survival in patients with high-risk (stage 1, grade 3; stage IC, stage II, or clear cell) epithelial ovarian cancer after adjuvant therapy. METHODS. Data was extracted from patients who underwent primary surgery followed by adjuvant therapy in 2 randomized trials by the Gynecologic Oncology Group (Protocols 95 and 157). Kaplan-Meier survival estimates and Cox proportional hazards model adjusted for covariates were used for analyses. RESULTS. Of 506 patients (median age = 56.2 years), 347 (68.6%) had stage I and 159 (31.4%) had stage II cancers. The 5-year recurrence-free (RFS) and overall survivals (OS) were 75.5% and 81.7%, respectively. On multivariate analysis, older age, higher stage, higher grade, and malignant cytology were independent prognostic factors predictive for recurrence and poorer survival. The risk of recurrence was higher for those >= 60 versus < 60 years (hazards ratio [HR] = 1.57, 95% confidence interval [CI], 1.12-2.19), stage II (stage II: HR = 2.70, 95% CI, 1.41-5.16) versus stage IA or IB, grade 2 (HR 1.84, 95% CI, 1.04-3.27) and grade 3 (HR = 2.47, 95% CI, 1.39-4.37) versus grade 1, and positive versus negative cytology (HR = 1.72, 95% CI, 1.21-2.45). By using these factors in a prognostic index, those with low-risk (no or I risk factor), intermediate-risk (2 factors), and high-risk (3-4 risk factors) disease had survivals of 88%, 82%, and 75%, respectively (P <.05). CONCLUSIONS. Age, stage, grade, and cytology are important prognostic factors in high-risk early-stage epithelial ovarian cancer. This information may be used in the design of future clinical trials.

Objective. The Gynecologic Oncology Group (GOG) performed a detailed analysis of p53 overexpression in previously-untreated women with invasive early or advanced stage epithelial ovarian cancer (EOC). Methods. Women were eligible for the study if they provided a tumor block for translational research and participated in either GOG-157, a randomized phase III trial of three versus (vs.) six cycles of paclitaxel+carboplatin in high-risk, early stage EOC, or GOG-111, a randomized phase III trial of cyclophosphamide+cisplatin vs. paclitaxel+cisplatin in suboptimally-resected, advanced stage EOC. The N-terminal DO-7 p53 antibody was used to examine the expression of the major normal and Mutant p53-isoforms. p53 overexpression was defined as >= 10%, tumor cells exhibiting nuclear staining. Results. p53 was overexpressed in 51% (73/143) and 66% (90/136) of cases in the GOG-157 and GOG-111 cohorts, respectively. In the GOG-157 cohort, p53 overexpression was not associated with any clinical characteristics or overall survival (OS) but was associated with worse progress ion-free survival (PFS) (logrank test: p=0.013; unadjusted Cox modeling: p=0.015). In the GOG-111 cohort, p53 overexpression was associated with GOG performance status (p=0.018) and grade (p=0.003), but not With age, stage, cell type or with tumor response and disease

Objective. Compared to 3 cycles, to determine if 6 cycles of adjuvant carboplatin (C) and paclitaxel (P) significantly lower the rate of recurrence in surgically staged patients with stage IA grade 3, 113 grade 3, clear cell, IC, and completely resected stage 11 epithelial ovarian cancer (EOC); and to compare toxicities. Methods. Postoperatively, randomization was to either 3 or 6 cycles of chemotherapy consisting of P (175 mg/m(2) over 3 h) and C (7.5 AUC over 30 min) every 21 days. Recurrence was any clinical or radiological evidence of new tumor. Results. Of 457 patients, 427 (93%) were histologically and medically eligible. While thorough surgical staging was required, it was incomplete or inadequately documented in 29% of otherwise eligible patients. Median age was 55.5 years; 69% of patients had stage I disease. Median follow-up is 6.8 years for 344 women alive at last contact. Grade 3 or 4 neurotoxicity occurred in 4/211 (2%) and 24/212 (11%) treated patients on the 3- and 6-cycle regimens, respectively (p < 0.01); 6 cycles also caused significantly more severe anemia and granulocytopenia. The recurrence rate for 6 cycles was 24% lower (hazard ratio [HR]: 0.761; 95% confidence interval [Cl]: 0.51-1.13, p=0.18), and the estimated probability of recurrence within 5 years was 20.1% (6 cycles) versus 25.4% (3 cycles). The overall death rate was similar for these regimens (FIR: 1.02; 95% Cl: 0.662-1.57). Conclusions. Compared to 3 cycles, 6 cycles of C and P do not significantly alter the recurrence rate in high risk early stage EOC but are associated with more toxicity. (c) 2006 Elsevier Inc. All rights reserved.

Although age-adjusted cancer death rates have started to decline in the United States and other developed nations - thanks in large part to widespread screening programs that detect cancers at early, treatable stages - cancer in developing countries is on the rise. Ironically, rising life expectancy in those nations along with the adoption of 'Western' lifestyles will leave many more people vulnerable to cancer. Unfortunately, the early detection tools and treatment technology that have helped control cancer in wealthier lands are often not readily available in many other countries. Much of this increased cancer burden will take the form of cancers that affect women - not only breast, cervical, and other gynecologic cancers but colorectal cancer, lung cancer, and other malignancies related to tobacco. Physicians specializing in cancer care for women need to be alert to every opportunity to improve cancer screening and prevention among the growing, aging populations of less-developed countries. Less precise but less costly and more widely available screening techniques may save thousands more lives than the most sophisticated technology because low-cost programs can be applied widely instead of being reserved for a fortunate few. In addition, education and prevention efforts directed toward tobacco use need to be put in place to help stem an epidemic of tobacco-related cancers that has largely peaked in developed countries but looms ominously in the future of developing nations.