G. Larry Maxwell

Prognostic Factors for Stage III Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

PURPOSE Conflicting results on prognostic factors for advanced epithelial ovarian cancer (EOC) have been reported because of small sample size and heterogeneity of study population. The purpose of this study was to identify factors predictive of poor prognosis in a similarly treated population of women with advanced EOC. PATIENTS AND METHODS A retrospective review of demographic, pathologic, treatment, and outcome data from 1,895 patients with International Federation of Gynecology and Obstetrics stage III EOC who had undergone primary surgery followed by six cycles of intravenous platinum/paclitaxel was conducted. A proportional hazards model was used to assess the association of prognostic factors with progression-free survival (PFS) and overall survival (OS). RESULTS Increasing age was associated with increased risks for disease progression (HR = 1.06; 95% CI, 1.02 to 1.11 for an increase every 10 years) and death (HR = 1.12; 95% CI, 1.06 to 1.18). Mucinous or clear-cell histology was associated with a worse PFS and OS compared with serous carcinomas. Patients with performance status (PS) 1 or 2 were at an increased risk for recurrence compared with PS 0 (HR = 1.12; 95% CI, 1.01 to 1.24). Compared with patients with microscopic residual disease, patients with 0.1 to 1.0 cm and > 1.0 cm residual disease had an increased risk of recurrence (HR = 1.96; 95% CI, 1.70 to 2.26; and HR = 2.36; 95% CI, 2.04 to 2.73, respectively) and death (HR = 2.11; 95% CI, 1.78 to 2.49; P < .001; and HR = 2.47; 95% CI, 2.09 to 2.92, respectively). CONCLUSION Age, PS, tumor histology, and residual tumor volume were independent predictors of prognosis in patients with stage III EOC. These data can be used to identify patients with poor prognosis and to design future tailored randomized clinical trials.

Tumor Residual After Surgical Cytoreduction in Prediction of Clinical Outcome in Stage IV Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

PURPOSE To identify factors predictive of poor prognosis in a similarly treated population of women with stage IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS A retrospective review of 360 patients with International Federation of Gynecology and Obstetrics stage IV EOC who underwent primary surgery followed by six cycles of intravenous platinum/paclitaxel was performed. A proportional hazards model was used to assess the association of potential prognostic factors with progression-free survival (PFS) and overall survival (OS). RESULTS The median PFS and OS for this group of stage IV ovarian cancer patients was 12 and 29 months, respectively. Multivariate regression analysis revealed that histology, malignant pleural effusion, intraparenchymal liver metastasis, and residual tumor size were significant prognostic variables. Whereas patients with microscopic residual disease had the best outcome, patients with 0.1 to 1.0 cm residual disease and patients with 1.1 to 5.0 cm residual disease had similar PFS and OS. Patients with a residual size more than 5 cm had a diminished PFS and OS when compared with all other groups. Median OS for microscopic, 0.1 to 5.0 cm, and more than 5.0 cm residual disease was 64, 30, and 19 months, respectively. CONCLUSION Patients with more than 5 cm residual disease have the shortest PFS and OS, whereas patients with 0.1 to 1.0 and 1.1 to 5.0 cm have similar outcome. These findings suggest that ultraradical cytoreductive procedures might be targeted for selected patients in whom microscopic residual disease is achievable. Patients with less than 5.0 cm of disease initially and significant disease and/or comorbidities precluding microscopic cytoreduction may be considered for alternative therapeutic options other than primary cytoreduction.

Surgical staging in patients with ovarian tumors of low malignant potential

OBJECTIVE To compare the outcomes of patients with ovarian tumors of low malignant potential who had complete surgical staging with those who were unstaged to determine whether the rate of recurrence or survival was affected by surgical staging. METHODS A retrospective chart review was performed on 93 consecutive patients who had surgery for histologically confirmed tumors of low malignant potential between 1979 and 1997. Two cohorts of patients were identified: patients who had classic surgical staging (n = 48) versus those who were not staged (n = 45). Outcome data were recorded for patients and compared between the two groups. RESULTS Early stage (I or II) disease was diagnosed in 31 of 48 patients who had surgical staging and 42 of 45 patients who were not staged (P = .001). In 17% of patients their stage was upgraded on the basis of surgical staging, as a result of retroperitoneal involvement in only 6% of those cases (three of 48 staged patients). During the study interval, the frozen section diagnosis of low malignant potential tumor of the ovary was changed to a final diagnosis of invasive cancer in eight other patients. There were three recurrences and two deaths in both the staged and unstaged low malignant potential groups. The average duration of follow‐up was 6.5 ± 4.2 years and was similar in the two groups. Overall 5‐year survival was approximately 93% for all stages. CONCLUSION Survival and recurrence rates were not significantly different between staged and unstaged patients who had surgery for low malignant potential tumors of the ovary.

venous Thromboembolism Prophylaxis: Patients at High Risk to Fail Intermittent Pneumatic Compression

Abstract Objective To identify patients who fail intermittent pneumatic compression and who might be considered for other more intense thromboembolic prophylaxis. Methods We conducted a retrospective review of consecutive gynecologic surgery patients treated with intermittent pneumatic compression. Risk factors associated with thromboemboli and demographic data were reviewed. Clinical suspicion of thromboemboli was confirmed by established diagnostic techniques such as duplex Doppler ultrasound and ventilation perfusion scanning. The association between individual risk factors and the incidence of thromboemboli was identified. To control for confounding of variables, multivariable stepwise logistic regression analysis was performed. Results A total of 1862 patients undergoing gynecologic surgery between 1996 and 1997 were treated perioperatively with intermittent pneumatic compression. The overall incidence of postoperative thromboemboli was 1.3% (15 cases of clinically significant postoperative pulmonary emboli and nine deep venous thrombosis). Risk factors associated with the occurrence of thromboemboli were: cancer (P = .001), history of deep venous thrombosis (P = .03), hypertension (P = .05), use of antihypertensives (P = .04), and age at least 60 years (P = .002). Intraoperative risk factors included duration of anesthesia more than 3 hours (P = .05). The multivariable regression analysis found that the diagnosis of cancer (P = .001), history of deep venous thrombosis (P = .006), and age greater than 60 years (P = .04) were independent prognostic factors. Patients with two or three of these variables had a 3.2% incidence of developing thromboemboli as compared with a 0.6% incidence of thromboemboli if the patient had none or one risk factor. Conclusion Patients most likely to fail intermittent pneumatic compression prophylaxis include those with cancer, a past history of deep venous thrombosis, or who are 60 years or older. This information identifies a “higher-risk” group of patients who should be considered for more intense prophylaxis programs.

Microarray Analysis of Endometrial Carcinomas and Mixed Mullerian Tumors Reveals Distinct Gene Expression Profiles Associated with Different Histologic Types of Uterine Cancer

Previous studies using cDNA microarray have indicated that distinct gene expression profiles characterize endometrioid and papillary serous carcinomas of the endometrium. Molecular studies have observed that mixed mullerian tumors, characterized by both carcinomatous and sarcomatous components, share features that are characteristic of endometrial carcinomas. The objective of this analysis was to more precisely define gene expression patterns that distinguish endometrioid and papillary serous histologies of endometrial carcinoma and mixed mullerian tumors of the uterus. One hundred nineteen pathologically confirmed uterine cancer samples were studied (66 endometrioid, 24 papillary serous, and 29 mixed mullerian tumors). Gene expressions were analyzed using the Affymetrix Human Genome Arrays U133A and U133B Genechip set. Unsupervised analysis revealed distinct global gene expression patterns of endometrioid, papillary serous, mixed mullerian tumors, and normal tissues as grossly separated clusters. Two-sample t tests comparing endometrioid and papillary serous, endometrioid and mixed mullerian tumor, and papillary serous and mixed mullerian tumor pairs identified 1,055, 5,212, and 1,208 differentially expressed genes at P < 0.001, respectively. These data revealed that distinct patterns of gene expression characterize various histologic types of uterine cancer. Gene expression profiles for select genes were confirmed using quantitative PCR. An understanding of the molecular heterogeneity of various histologic types of endometrial cancer has the potential to lead to better individualization of treatment in the future.

Favorable survival associated with microsatellite instability in endometrioid endometrial cancers.

Objective To determine whether microsatellite instability in endometrioid endometrial cancer is associated with favorable survival. Methods Microsatellite instability analysis was performed in 131 patients with endometrioid endometrial cancer using three polymorphic markers in paired cancer and normal DNA. Logistic regression and multivariable analyses calculated the relation between microsatellite instability, clinical features, and survival. Results Microsatellite instability was detected in 29 of 131 (22%) endometrioid endometrial cancers. There was no correlation between microsatellite instability and age, race, grade, stage, or depth of myometrial invasion. Microsatellite instability was associated with better survival in univariate and multivariable analyses after controlling for confounding influences (P = .03). The 5-year survival rate of those with microsatellite instability was 77% (95% confidence interval 55%, 90%) compared with only 48% (95% confidence interval 39%, 57%) in other cases. Microsatellite instability was associated with other molecular features that predict favorable outcome including PTEN mutation (P = .002) and the absence of p53 overexpression (P = .01). Conclusion Microsatellite instability is a molecular alteration associated with favorable outcome in endometrioid endometrial cancers, even when accounting for other prognostic factors. This association might be explained by the finding that the pathway of molecular carcinogenesis characterized by loss of DNA mismatch repair favors alteration of genes that result in a less virulent clinical phenotype.

Race Disparities Between Black and White Women in the Incidence, Treatment, and Prognosis of Endometrial Cancer

BACKGROUND Uterine cancer is the most common gynecologic malignancy in the United States, with an estimated 40,100 new cases and 7,470 deaths occurring in 2008. Although the incidence of endometrial cancer is lower among black women compared with white women, the proportion of cancer-related deaths among blacks is higher and has continued to rise over the past two decades. METHODS The authors conducted a survey of recent literature published in the English language and have used these articles as the basis for this review. RESULTS The etiology for the racial disparity among black women with endometrial cancer is multifactorial and may be the result of barriers that impede access to care, an increased incidence of comorbidities among black women, inequalities in surgical care, adjuvant chemotherapy and radiation treatment, and underlying biological differences associated with more aggressive tumors that often develop in black women. CONCLUSIONS Black women with endometrial cancer have a poorer prognosis compared with white women. Factors that contribute to this racial disparity include later diagnosis, treatment disparities, comorbid conditions, and genetic differences in tumors. An improved understanding of the causative factors associated with racial disparities in endometrial cancer outcome is needed to facilitate efforts aimed at correcting this important health care problem and providing individualized care to those at highest risk for poor outcome.

Racial disparity in survival among patients with advanced/recurrent endometrial adenocarcinoma: a Gynecologic Oncology Group study.

Previous studies have reported shorter survival of black women compared with white women who had advanced/recurrent endometrial cancer. It has been suggested that this may reflect racially based differences in treatment.

Does Aggressive Surgery Improve Outcomes? Interaction Between Preoperative Disease Burden and Complex Surgery in Patients With Advanced-Stage Ovarian Cancer: An Analysis of GOG 182

PURPOSE To examine the effects of disease burden, complex surgery, and residual disease (RD) status on progression-free (PFS) and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and complete surgical resection (R0) or < 1 cm of RD (MR) after surgical cytoreduction. PATIENTS AND METHODS Demographic, pathologic, surgical, and outcome data were collected from 2,655 patients with EOC or PPC enrolled onto the Gynecologic Oncology Group 182 study. The effects of disease distribution (disease score [DS]) and complexity of surgery (complexity score [CS]) on PFS and OS were assessed using the Kaplan-Meier method and multivariable regression analysis. RESULTS Consistent with existing literature, patients with MR had worse prognosis than R0 patients (PFS, 15 v 29 months; P < .01; OS, 41 v 77 months; P < .01). Patients with the highest preoperative disease burden (DS high) had shorter PFS (15 v 23 or 34 months; P < .01) and OS (40 v 71 or 86 months; P < .01) compared with those with DS moderate or low, respectively. This relationship was maintained in the subset of R0 patients with PFS (18.3 v 33.2 months; DS moderate or low: P < .001) and OS (50.1 v 82.8 months; DS moderate or low: P < .001). After controlling for DS, RD, an interaction term for DS/CS, performance status, age, and cell type, CS was not an independent predictor of either PFS or OS. CONCLUSION In this large multi-institutional sample, initial disease burden remained a significant prognostic indicator despite R0. Complex surgery does not seem to affect survival when accounting for other confounding influences, particularly RD.

Intraperitoneal bevacizumab for the palliation of malignant ascites in refractory ovarian cancer

BACKGROUND Malignant ascites often has a profound impact on the quality of life of patients with refractory ovarian cancer. Current treatments, including dietary, medical, and procedural are often temporary and unsatisfactory options in patients approaching the end of life. CASE We present a case of an 88 year-old receiving home hospice care with refractory ovarian cancer and severe symptomatic ascites. We performed a paracentesis and treated her with intraperitoneal bevacizumab with dramatic improvement in her ascites and the quality of her final weeks of life. CONCLUSION Intraperitoneal bevacizumab may be a useful tool in the palliation of malignant ascites and is worthy of further study.