Fidel A. Valea

Transcutaneous electrical nerve stimulation as an adjunct for controlling chemotherapy-induced nausea and vomiting in gynecologic oncology patients.

BACKGROUND To evaluate the efficacy of a miniaturized portable transcutaneous electrical nerve stimulation (TENS) unit (ReliefBand) as an adjunct to standard antiemetic therapy for controlling nausea and vomiting induced by cisplatin-based chemotherapy in gynecologic oncology patients. METHODS Forty-two patients were enrolled in a randomized, double-blind, placebo-controlled parallel-subjects trial with a follow-up crossover trial. All patients received a standardized antiemetic protocol, then wore the ReliefBand continuously for 7 days. RESULTS Thirty-two patients were evaluable for the parallel-subjects component, 16 in each group. The percentage of patients with absent or minimal nausea was 59% overall, which was similar to that for both the active (56%) and placebo (62%) groups. The incidence and severity of nausea and vomiting was similar for each group. Eighteen patients completed two consecutive cycles and were evaluable for the crossover component. The average age of the crossover patients and their dose intensity were comparable with those of the overall study population (56.3 versus 58.6 years and 22.7 versus 22.7 mg/m2/week, respectively). The percentage of cycles with absent or minimal nausea was 47% overall, which was similar to that of the active (50%) and placebo (44%) cycles. However, the severity of nausea was significantly lower in the active cycles during days 2 to 4. Patients averaged less than one episode of vomiting daily in each cycle. CONCLUSIONS The ReliefBand is an effective adjunct to standard antiemetic agents for controlling nausea induced by cisplatin-based chemotherapy in gynecologic oncology patients.

Relationship between tamoxifen use and high risk endometrial cancer histologic types

OBJECTIVES We wished to determine whether a pre-existing diagnosis of breast cancer or the use of tamoxifen among patients with pre-existing breast cancer influences the histologic type of subsequently diagnosed endometrial carcinoma, the interval between these diagnoses, or survival. METHODS A single institution retrospective review was performed of all patients who underwent primary surgery for endometrial carcinoma from 1995-2005. We compared the histologic type of endometrial carcinoma among patients with a prior history of breast cancer to those without. Patients with a previous diagnosis of breast cancer were further analyzed by comparing histologic type, progression-free and overall survival between tamoxifen users and non-users. RESULTS Among 732 women with endometrial carcinoma, 59 patients (8%) had a previous diagnosis of breast cancer, of whom 29 (49%) had used tamoxifen. Women with a history of breast cancer were more likely to have a high risk uterine histologic type (grade 3 endometrioid, papillary serous, or clear cell) (18/59; 31%) than those without this prior malignancy (120/670, 18%; p=0.024). Breast cancer survivors whose endometrial carcinoma was of a high risk histologic type had a longer median duration of prior tamoxifen use compared to those with lower risk histologic types (60 versus 46 months, p=0.034). CONCLUSIONS Among women with endometrial carcinoma, those with a history of breast cancer are more likely to harbor a high risk uterine histologic subtype. Tamoxifen use of at least 60 months is associated with high risk uterine histologic subtypes when compared to no tamoxifen use. This study adds to existing data suggesting a relationship between tamoxifen use and development of endometrial carcinoma of more aggressive histologic types.

Multicenter phase II trial of topotecan, cisplatin and bevacizumab for recurrent or persistent cervical cancer

OBJECTIVE We evaluated the activity and safety of the combination of topotecan, cisplatin and bevacizumab in patients with recurrent or persistent carcinoma of the cervix. METHODS Eligible patients had persistent or recurrent cervical cancer not amenable to curative intent treatment. No prior chemotherapy for recurrence was allowed. Treatment consisted of cisplatin 50 mg/m(2) day 1, topotecan 0.75 mg/m(2) days 1, 2 and 3 and bevacizumab 15 mg/kgday 1 every 21 days until disease progression or limiting toxicity. The primary endpoint was progression free survival at 6 months. We explored PET/CT as a potential early indicator of response to therapy. RESULTS Twenty-seven eligible patients received a median of 3 treatment cycles (range, 1-19). Median follow-up was 10 months (range, 1.7-33.4). The 6-month PFS was 59% (80% CI: 46-70%). In 26 evaluable patients, we observed 1 CR (4%; 80% CI: 0.4-14%) and 8 PR (31%; 80% CI: 19-45%) lasting a median of 4.4 months. Ten patients had SD (39%; 80% CI: 25-53%) with median duration of 2.2 months. Median PFS was 7.1 months (80% CI: 4.7-10.1) and median OS was 13.2 months (80% CI: 8.0-15.4). All patients were evaluated for toxicity. Grade 3-4 hematologic toxicity was common (thrombocytopenia 82% leukopenia 74%, anemia 63%, neutropenia 56%). Most patients (78%) required unanticipated hospital admissions for supportive care and/or management of toxicities. CONCLUSION The addition of bevacizumab to topotecan and cisplatin results in an active but highly toxic regimen. Future efforts should focus on identification of predictive biomarkers of prolonged response and regimen modifications to minimize toxicity.

Role of p53 alteration in primary peritoneal carcinoma

SummaryAlthough the clinicopathologic features of primary peritoneal carcinoma (PPC) in women are relatively well defined, the molecular pathogenesis of the disease has not been examined. The object of this study was to assess the biological significance of p53 alterations in PPC. Twenty-nine PPCs studied for p53 protein accumulation with monoclonal antibody DO-7 consisted of 26 serous carcinomas, one clear cell carcinoma, one tumor with endometrioid features, and one malignant mixed müllerian tumor. P53 was overexpressed in 83% of all PPCs and in 81% of the serous PPCs. Among eight immunopositive tumors with at least two distinct anatomic sites sampled, six tumors showed concordance, whereas two tumors showed discordance for p53 immunopositivity. The latter two tumors support the concept of a multifocal origin of PPC. This is the first report to suggest that loss of p53 function plays an important role in the development of PPC and might contribute to the poor prognosis of this disease. Parallels to serous papillary carcinomas of the uterus and ovary are discussed.

Projecting the need for gynecologic oncologists for the next 40 years.

OBJECTIVE: To estimate the ratio of gynecologic cancer cases to practicing gynecologic oncologists in the United States over the next 40 years. METHODS: Using population projections from the U.S. Census Bureau and incidence and mortality rates from Surveillance, Epidemiology and End Results surveys, we estimated the annual number of new gynecologic cancer cases through 2050; the effects of human papillomavirus (HPV) vaccination was included in cervical cancer estimates. The number of practicing gynecologic oncologists was projected through 2050 using data from the 2005 Society of Gynecologic Oncologists Practice Survey, current Society of Gynecologic Oncologists membership information, American Board of Obstetrics and Gynecology and Gynecologic Oncology oral examination results, and mortality estimates from U.S. life tables. Projected time in practice was sex-dependent based on Society of Gynecologic Oncologists Practice Survey. For sensitivity analyses, we varied annual number and sex distribution of fellowship graduates, HPV vaccination coverage rates, and future incidence of overweight and obesity. RESULTS: At constant training rates, the annual number of new cancer cases per practicing gynecologic oncologist will rise from 112 in 2010 to 133 in 2050, a 19% increase. If the annual number of fellowship graduates increases by 25%, the ratio of cancer cases per gynecologic oncologist will decrease to 106, a 5% decrease. Projections are more sensitive to changes in physician demographics than to changes in HPV vaccination coverage rates. CONCLUSION: The gynecologic cancer caseload of practicing gynecologic oncologists will increase by almost 20% over the next 40 years at constant training rates. Changes in the projected sex distribution of fellowship graduates and their time in practice affect these projections.

Cost of care using prophylactic negative pressure wound vacuum on closed laparotomy incisions

OBJECTIVE We wished to determine the reduction in the rate of wound complications that would render the use of prophylactic negative pressure wound vacuum therapy (NPWT) cost saving compared to routine incision care (RC) following laparotomy for gynecologic malignancy. METHODS A decision tree was designed from a payer perspective to compare strategies for incision management following laparotomy for gynecologic malignancy: (1) RC; (2) prophylactic NPWT. Rates of wound complication, antibiotic use, re-hospitalization, re-operation, and home health use were obtained from a published cohort of 431 women who underwent laparotomy for endometrial cancer 2002-2007. Costs were estimated using Medicare reimbursements; cost of NPWT (

Utility Scores and Treatment Preferences for Clinical Early-Stage Cervical Cancer

200) was obtained from hospital financial department. A 50% reduction in wound complications using NPWT was assigned initially and varied for sensitivity analysis. RESULTS The mean BMI was 36. The wound complication rate was 31% (37% for BMI>30, 41% for BMI>40). The overall cost of incision care was

Adverse events associated with laparoscopy vs laparotomy in the treatment of endometrial cancer.

104 lower for NPWT than for RC. At the lowest cost of NPWT (

Patient preferences in advanced or recurrent ovarian cancer

200), the risk of wound complication must be reduced by 33% (relative risk=0.67) for NPWT to achieve cost savings in this cohort. Modeling obese and morbidly obese cohorts, the NPWT resulted in overall cost savings of

Robotic-Assisted Laparoscopic Gynecologic Procedures in a Fellowship Training Program

163 and