Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial.

BACKGROUND: CAN-003 was a randomized, open-label, Phase 2 trial evaluating the safety, efficacy and immune outcomes of CVac, a mucin 1 targeted-dendritic cell (DC) treatment as a maintenance therapy to patients with epithelial ovarian cancer (EOC). METHODS: Patients (n = 56) in first (CR1) or second clinical remission (CR2) were randomized (1:1) to standard of care (SOC) observation or CVac maintenance treatment. Ten doses were administered over 56 weeks. Both groups were followed for progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-six patients were randomized: 27 to SOC and 29 to CVac. Therapy was safe with only seven patients with Grade 3-4 treatment-emergent adverse events. A variable but measurable mucin 1 T cell-specific response was induced in all CVac-treated and some standard of care (SOC) patients. Progression free survival (PFS) was not significantly longer in the treated group compared to SOC group (13 vs. 9 months, p = 0.36, hazard ratio [HR] = 0.73). Analysis by remission status showed in the CR1 subgroup a median PFS of 18 months (SOC) vs. 13 months (CVac); p = 0.69 (HR = 1.18; CI 0.52-2.71). However CR2 patients showed a longer median PFS in the CVac-treated group (median PFS not yet reached, >13 vs. 5 months; p = 0.04, HR = 0.32 CI). OS for CR2 patients at 42 months of follow-up showed a difference of 26 months for SOC vs. > 42 months for CVac-treated (as median OS had not been reached; HR = 0.17 (CI 0.02-1.4) with a p = 0.07). CONCLUSIONS: CVac, a mucin 1-dendritic cell maintenance treatment was safe and well tolerated in ovarian cancer patients. A variable but observed CVac-derived, mucin 1-specific T cell response was measured. Notably, CR2 patients showed an improved PFS and lengthened OS. Further studies in CR2 ovarian cancer patients are warranted (NCT01068509). TRIAL REGISTRATION: NCT01068509. Study Initiation Date (first patient screened): 20 July 2010. Study Completion Date (last patient observation): 20 August 2013, the last patient observation for progression-free survival; 29 April 2015, the last patient was documented regarding overall survival.

Laparoscopic surgery in obese women.

OBJECTIVE: To assess the feasibility and complications of operative laparoscopy in women with high body mass indices (BMIs). METHODS: Forty-seven consecutive patients with BMIs exceeding 30 who underwent operative laparoscopy were compared with 160 consecutive patients with BMIs of 30 or less who underwent the same procedure. Patient characteristics, ultrasound features of adnexal masses, and details of operative procedures were compared. Operative and postoperative complications, the percentage of failed laparoscopies, and length of hospital stay were compared between groups. RESULTS: There were no significant differences between groups in terms of age, parity, menopausal status, history of laparotomy, ultrasound features of adnexal masses, complexity of laparoscopic procedures, and the presence and degree of adhesions at the time of laparoscopy. Estimated blood loss, operative times, operative and major postoperative complications, and lengths of hospital stay also did not differ significantly between women with high BMIs and those with low BMIs (180.3 versus 151.4 mL, P = .41; 150.5 versus 146.5 minutes, P = .78; 2.1 versus 1.9%, P = .90; 2.1 versus 1.9%, P = .91; and 2.3 versus 1.9 days, P = .51, respectively). However, women with BMIs exceeding 30 had a significantly higher incidence of procedure conversion to laparotomy (14.9 versus 5.6%, P = .04). CONCLUSION: Operative laparoscopy is safe and feasible in women with high BMIs. Although there is an increased chance of procedure conversion to laparotomy in these women, the morbidity and length of hospitalization associated with the procedure are similar to those among women with low BMIs.

Analysis of failed and complicated laparoscopy on a gynecologic oncology service.

OBJECTIVE: To assess the incidence of and factors that predict failed or complicated operative laparoscopy on a gynecologic oncology service. METHODS: Two hundred four consecutive operative laparoscopies were reviewed. Procedures converted to laparotomy or associated with major operative or postoperative complications were compared with uncomplicated laparoscopies with respect to patient characteristics, details of operative procedure, and length of hospitalization. The influence of patient characteristics, operative findings, and specific procedures on the risk of failed or complicated laparoscopies was estimated. RESULTS: Twenty-five (12. 3%) procedures were either converted to laparotomy or associated with major operative or postoperative complications. Women with failed or complicated laparoscopies had significantly more previous laparotomies and adhesions, greater blood loss, and longer hospital stay than those with uncomplicated laparoscopies (60.0% vs 35.7%, P = 0.03, 68.0% vs 37.4%, P<0.001, 275 ml vs. 132 ml, P = 0.03; and 5. 9 days vs 0.98 days, P< 0.001, respectively). Age, body mass index, parity, menopausal status, preoperative CA-125, appearance of adnexal masses, and complexity of the procedure had no significant influence on failed or complicated laparoscopies. In univariate analysis, history of laparotomy and presence of adhesions and in multivariate analysis only presence of adhesions were predictive of failed or complicated laparoscopies (P = 0.03, <0.001, and 0.006, respectively). CONCLUSIONS: The incidence of failed and complicated laparoscopy is low on a gynecologic oncology service. Presence of adhesions is the only significant independent risk factor predictive of failed or complicated laparoscopy.

Laparoscopic management of women with a family history of ovarian cancer.

BACKGROUND AND OBJECTIVE: The safety of laparoscopic surgery in women with a family history of ovarian cancer predicted to have benign disease has not been established. The objective of this study was to evaluate the feasibility and complications of operative laparoscopy and to describe the pathologic findings in this patient population. METHODS: Sixty-two consecutive women with a family history of ovarian cancer who elected prophylactic oophorectomy or had predicted benign adnexal disease were offered laparoscopic surgery. Patient characteristics, details of laparoscopic surgery, operative and postoperative complications, and histopathologic findings were recorded. RESULTS: Laparoscopy was converted to laparotomy in 2 patients (3.2%); 1 patient (1.6%) had an operative vascular complication, and 1 patient (1.6%) had postoperative bleeding. Median (range) estimated blood loss, operative time, and hospital stay were 50 ml (50-1,500), 120 min (60-290), and 1 day (0-9), respectively. Histopathologic findings included normal ovaries (n = 20), corpus luteum cyst (n = 16), follicular cyst (n = 8), endometriotic cyst (n = 7), serous cystadenoma (n = 5), epithelial hyperplasia (n = 4), dermoid cyst (n = 1), and fibrothecoma (n = 1). CONCLUSIONS: Laparoscopic surgery is feasible and safe in women with a family history of ovarian cancer predicted to have benign disease and is associated with low blood loss and short hospital stay. Most ovaries removed are either normal or have benign disease.

Effective management of pelvic lymphocysts by laparoscopic marsupialization.

BACKGROUND AND OBJECTIVES: To evaluate laparoscopic transperitoneal marsupialization of pelvic lymphocysts at the time of laparoscopically directed assessment of response to first-line therapy in a population of patients treated for International Federation of Gynecologists and Obstetricians (FIGO) stage IC-IIC epithelial ovarian cancer. METHODS: Between March 1995 and March 1998, eight patients with FIGO stage IC-IIC serous epithelial ovarian tumors who developed pelvic lymphocysts after primary surgical staging underwent transperitoneal laparoscopically directed marsupialization of lymphocysts at the time of second-look laparoscopy. RESULTS: The mean age of the patient population was 50 years (range 23-65 years). The mean length of time required for marsupialization was 30 minutes (range 25-35 minutes). No patient required inpatient postoperative care. No intraoperative complications were observed. Computerized axial tomography (CT) scan of the abdomen and pelvis obtained 12 weeks following surgery failed to demonstrate re-accumulation of lymphocysts among any patient in the study population. With a median follow-up of 20 months (range 3-39 months), no patients have demonstrated pelvic lymphocyst recurrence. CONCLUSIONS AND DISCUSSION: Laparoscopically directed marsupialization of pelvic lymphocysts is technically feasible, safe and effective. Further study of this technique appears to be warranted.

Clinical picture, response to therapy, and survival of women with diffuse malignant peritoneal mesothelioma.

BACKGROUND AND OBJECTIVE: The clinical picture, response to therapy, and prognosis of women with diffuse malignant peritoneal mesotheliomas (DMPM) are ill defined. The purpose of this study is to report on the clinical picture, response to therapy, and survival of women with DMPM. METHODS: The study is a retrospective review of 15 women with the confirmed pathologic diagnosis of DMPM treated between 1964 and 1996. Survival curves were constructed according to the Kaplan-Meier method. The effect of different factors on survival was studied using the log-rank test. Two-tailed P values < 0.05 were considered significant. RESULTS: Clinical features included abdominal distension (11/15, 73%), abdominal pain (6/15, 40%), ascites (9/15, 60%), abdominal or pelvic masses (14/15, 93%), elevated CA-125 (4/4, 100%), thrombocytosis (4/ 15, 27%), and thrombo-embolic manifestations (3/15, 20%). The response rate to all first-line chemotherapy regimens was 30%. The response rate to paclitaxel/cisplatin was 66.7% and the toxicity was tolerable. The median survival of all patients was 12.5 months. Patients who underwent cytoreductive surgery survived longer than those who underwent biopsy only (median survival 13.5 vs. 6.0 months, P = 0.24). Patients who received chemotherapy survived significantly longer than those who did not receive chemotherapy (29.0 vs. 1.0 months, P = 0.03). Patients who responded to first-line chemotherapy survived significantly longer than those who did not respond (P = 0.04). CONCLUSIONS: Cytoreductive surgery and chemotherapy, especially with paclitaxel and cisplatin, might be of benefit in women with DMPM.

Prolonged disease-free survival by maintenance chemotherapy among patients with recurrent platinum-sensitive ovarian cancer.

OBJECTIVE: The aim of this study was to determine the potential benefit and complications of prolonged salvage and maintenance chemotherapy among patients with recurrent epithelial ovarian cancer who achieve response to salvage chemotherapy. METHODS: Patients with recurrent platinum-sensitive epithelial ovarian cancer who were treated between 1982 and 1996 and achieved complete response to platinum-based salvage chemotherapy were offered prolonged (1 year) monthly salvage followed by maintenance (every 8 weeks) chemotherapy. Patients who accepted such treatment (n = 16) were compared to those who refused and discontinued therapy (n = 11) with regard to overall survival from time of initial diagnosis and overall and disease-free survival from time of recurrence. Chemotherapy-related toxicity in the study group was recorded. Survival curves were constructed according to the Kaplan and Meier method and survival curves were compared using the log-rank test. RESULTS: Patients in the study and control groups were similar with regard to age, stage, histology, grade, performance status, primary cytoreductive surgery, type of primary and salvage chemotherapy, and method of assessment of tumor response. The study group had a significantly longer disease-free interval from date of recurrence than the control group (median: 35.0 versus 6.0 months, respectively, P = 0.001). The study group had longer overall survival from date of recurrence than the control group. However, the difference did not achieve statistical significance (median: 119 versus 90 months, respectively, P = 0.056). There was no significant difference between the study group and the control group as to survival from date of initial diagnosis (median: 157 versus 124 months, respectively, P = 0.28). Chemotherapy-related toxicity was minimal. CONCLUSIONS: Prolonged salvage and maintenance chemotherapy is a safe method of treatment that may extend disease-free interval among patients with platinum-sensitive recurrent epithelial ovarian cancer who achieve response to salvage chemotherapy. These preliminary results need to be confirmed by a larger prospective randomized trial.

Complications related to indwelling caval catheters on a gynecologic oncology service.

OBJECTIVE: To assess the rate of complications of indwelling caval catheter (ICC) use on a gynecologic oncology service and to compare complication rates between subcutaneous ports and external catheters. METHODS: A retrospective analysis of 185 patients who underwent 216 ICC placements between April 1, 1987 and April 1, 1997, was performed. Patient and catheter characteristics were analyzed as they related to the rate of pneumothorax, bacteremia, and deep neck and thoracic vein thrombosis (DNVT). RESULTS: A total of 216 ICCs were placed including 152 implanted ports and 64 external catheters. Pneumothorax occurred in 2% of ICC insertions. Bacteremia complicated 16% of ICCs. Multivariate analysis demonstrated that external catheters (P < 0.01) and neutropenia (P < 0.01) were independent risk factors for bacteremia. DNVT complicated 6% of ICCs and was observed significantly (P < 0.02) more frequently among 11 catheters placed in patients with clear cell malignancies of the female reproductive tract. Unplanned catheter removal occurred significantly (P < 0.01) more frequently among patients with external catheters compared to implanted devices. CONCLUSIONS: Implantable ICCs appear to offer a significant advantage compared to external devices with regard to the development of bacteremia and unplanned catheter removal. Though catheter type, neutropenia, and TPN are associated with an increased incidence of bacteremia, multivariate analysis does not include TPN as an independent risk factor for ICC-related bacteremia. A significant increase in the rate of DNVT among a small number of patients with clear cell gynecologic malignancies warrants further study.

Correlation between extreme drug resistance assay and response to primary paclitaxel and cisplatin in patients with epithelial ovarian cancer.

OBJECTIVE: The extreme drug resistance (EDR) assay has been correlated with failure of response to chemotherapy in greater than 99% of patients. The goal of this study is to correlate the results of the EDR assay to response to first-line paclitaxel/cisplatin among patients with epithelial ovarian cancer. METHODS: Seventy-five of 100 patients with epithelial ovarian cancer for whom EDR assay was performed were treated with weekly induction cisplatin (1 mg/kg body wt) x 4, followed by monthly paclitaxel (135 mg/m2) and cisplatin (75 mg/m2) x 6 and were evaluable for correlation of response to chemotherapy and EDR assay. Specimens for EDR assay were obtained at primary surgery and the EDR assay was performed by Oncotech, Inc. Response to chemotherapy was correlated to EDR assay results regarding paclitaxel and cisplatin. RESULTS: Among 75 evaluable patients, the prevalence of EDR to paclitaxel was 20.0% (n = 15) and to cisplatin it was 2.7% (n = 2). Only 1 patient (1.3%) exhibited EDR to both paclitaxel and cisplatin. Surgical assessment of response was performed in 42 patients; 33 patients were clinically evaluable. The overall response rate was 85.3%. The overall response rate for patients whose tumors demonstrated no EDR to either paclitaxel or cisplatin did not differ significantly from that for patients whose tumors demonstrated EDR to at least one of these two drugs (86.4% versus 81.3%, respectively, P = 0.692). Similarly, the complete surgical response rate for both groups did not differ significantly (25.4% versus 12.5%, respectively, P = 0. 34). A single patient whose tumor exhibited EDR to both paclitaxel and cisplatin had tumor progression. The sensitivity, specificity, positive predictive value, and negative predictive value of the EDR assay were 79.6, 27.0, 86.0, and 19.0%, respectively. CONCLUSIONS: EDR to paclitaxel does not preclude response to the combination of paclitaxel and cisplatin as primary therapy for patients with epithelial ovarian cancer. The role of the EDR assay in the primary management of patients with epithelial ovarian cancer remains to be determined.

Stage I adenocarcinoma of the cervix: does lesion size affect treatment options and prognosis?

A retrospective analysis of 93 patients with International Federation of Gynecology and Obstetrics stage I adenocarcinoma of the cervix was performed to determine the significance of tumor size, patient age, tumor grade, lymph node status, and primary treatment modality as prognostic variables of 5-year survival and 5-year progression-free survival (PFS). Multivariate analysis demonstrated that patient age and tumor grade were significant variables prognostic of survival (p < 0.01 and p = 0.01, respectively). Tumor size was a significant (p < 0.01) prognostic variable of PFS in a multivariate model that included tumor size and patient age. An important advantage in survival and PFS for patients with lesions smaller than 3 cm compared with those patients with lesions 3 cm or more was observed (92% vs. 76% and 89% vs. 67%, respectively). Among surgically treated patients, survival and PFS among patients with lesions smaller than 3 cm were significantly improved compared with patients with tumors 3 cm or more (97% vs. 77% [p = 0.03] and 90% vs. 69% [p = 0.03], respectively). Significant improvement in survival and PFS was observed among patients with lesions smaller than 3 cm who were treated with surgery compared with those who received radiation therapy (97% vs. 77% [p = 0.03] and 90% vs. 77% [p = 0.048], respectively).

Progesterone receptor status is a significant prognostic variable of progression-free survival in advanced epithelial ovarian cancer.

The purpose of this study was to determine if tumor estrogen receptor (ER) or progesterone receptor (PR) status were significant prognostic variables of survival and progression-free survival among patients with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV epithelial ovarian cancer. Tumor steroid receptor status was evaluated among 67 consecutive patients who underwent primary surgery from June 1983 through September 1990. Characteristics of receptor-negative and receptor-positive populations were compared by chi-square analysis. Univariate and multivariate analyses were used to identify variables prognostic of survival and progression-free survival. Fifty-one of 67 patients (76.1%) had ER-positive tumors and 31 (46.3%) patients had PR-positive tumors. Significant differences between receptor-positive and receptor-negative populations were not observed. Neither univariate nor multivariate analysis identified ER or PR status as significant prognostic variables of survival (p = 0.93 and p = 0.06, respectively). Progesterone receptor-positive status was a significant prognostic variable of progression-free survival in both univariate (p = 0.03) and multivariate (p = 0.04) analyses even after adjustment for residual disease and patient age. Estrogen receptor status was not a significant prognostic indicator of progression-free survival in either univariate or multivariate analyses. Progesterone receptor-positive tumor status is shown to be an independent prognostic variable of improved progression-free survival among patients with advanced epithelial ovarian cancer.

Improvements in pelvic exenteration: factors responsible for reducing morbidity and mortality.

BACKGROUND: Since pelvic exenteration for the treatment of recurrent gynecologic malignancy first was described, reported rates of morbidity and mortality have declined steadily. However, the factors responsible for this decline have never been clearly delineated. METHODS: We reviewed the charts of 154 patients who underwent pelvic exenteration for gynecologic malignancy between 1954 and 1994. Charts were abstracted for details of the surgical procedure, pathologic findings, postoperative management, short- and long-term complications, time to recurrence, and overall survival. RESULTS: Seventy-two patients (47%) experienced 95 identifiable postoperative complications, resulting in death in 22 patients (14%). The rate of infectious complications declined to a statistically significant degree between the first two decades and latter two decades of the study (odds ratio [OR] 0.28. 95% CI 0.11-0.69). The use of routine prophylactic antibiotics was associated with this decline in infectious complications (OR 0.25, 95% CI 0.07-0.83). The use of preoperative subcutaneous heparin was associated with a reduction in thrombotic complications from 5 of 100 patients to 0 of 54 patients (P = .11), as well as a significant reduction in overall risk of complications (OR 0.53, 95% CI 0.33-0.85) and risk of postoperative mortality (OR 0.19, 95% CI 0.05-0.80). There was a significant reduction in overall risk of postoperative complications with both intensive care unit monitoring postoperatively (OR 0.65, 95% CI 0.43-0.99) and routine postoperative monitoring with a pulmonary artery catheter (OR 0.61, 95% CI 0.38-0.98). CONCLUSIONS: Routine use of prophylactic antibiotics, prophylactic subcutaneous heparin, and intensive postoperative monitoring appear to have reduced morbidity from pelvic exenteration.

The clinical value of digene hybrid capture HPV DNA testing in a referral-based population with abnormal pap smears.

PURPOSE OF INVESTIGATION: The hybrid capture human papillomavirus (HPV) DNA assay is offered by the manufacturer to assist clinicians with patients with ASCUS pap smear results to assess the risk factor and to potentially direct follow-up of these patients. In our practice, a gynecologic oncology practice that has a referral based population with abnormal pap smears, our purpose was to evaluate the patients referred with all grades of abnormal cervical cytology. METHODS: One hundred consecutive patients who were referred for evaluation of abnormal cervical cytology: atypical squamous cells of undetermined significance (ASCUS); low-grade squamous intraepithelial lesion (LGSIL); high-grade squamous intraepithelial lesion (HGSIL); or squamous cell carcinoma (SCC) were evaluated by repeat pap smear, hybrid capture HPV DNA analysis and colposcopy. Colposcopic findings were recorded, and if appropriate, cervical biopsies were performed. Hybrid capture results were correlated with histologic and cytologic findings. Using histopathologic diagnosis as the reference standard, the sensitivity and positive predictive value of pap smear and high risk HPV were calculated. The Kappa test was used to correlate colposcopic and histopathologic findings. RESULTS: Repeat pap smears at the time of initial consultation demonstrated 25 patients with normal results, 39 with LGSIL, 30 with HGSIL, 1 SCC and 5 ASCUS. Seventy-eight patients underwent cervical biopsy. Colposcopic findings correlated significantly with histopathologic findings (p<0.0001). Forty-four percent of patients tested positive for HPV DNA: 40 patients with high risk HPV, three patients with low risk HPV, and one patient with both high risk and low risk HPV. Sixteen of 39 patients (41%) with LGSIL on pap smear tested positive for high risk HPV; 37% of patients in this group required cervical conization because cervical biopsies demonstrated moderate/severe dysplasia. The diagnosis of moderate/severe dysplasia significantly correlated with the presence of high risk HPV [OR 78.9 (8.31-389.30)]. There was no significant correlation between the HPV DNA signal strengths and the histologic grade of dysplasia. The sensitivity and the positive predictive value of pap smear alone in identifying moderate/severe dysplasia was 62% and 96%, respectively. The combination of HGSIL pap smears and high risk HPV increased the sensitivity but not the positive predictive value for the detection of moderate/severe dysplasia to 77.7% and 95%, respectively (P=NS). CONCLUSIONS: Although in this setting, the use of hybrid capture DNA testing did not significantly improve the sensitivity or positive predictive value of the diagnosis of HGSIL cytology when compared to cytologically indicated plus colposcopically directed cervical biopsies in this population of women at high risk for the presence of disease, the combination of HGSIL pap smears and high-risk HPV did result in a clinically important increase in the diagnosis of moderate/severe dysplasia.

Remarkable response of primary squamous cell carcinoma of the ovary to paclitaxel and cisplatin.

BACKGROUND: The survival rate of patients with advanced stage primary squamous cell carcinoma of the ovary is dismal and the best treatment is unknown. We describe the response of this tumor to systemic chemotherapy employing paclitaxel and cisplatin. CASE: A 31-year-old white woman diagnosed with International Federation of Gynecology and Obstetrics stage IV primary squamous cell carcinoma of the ovary associated with ovarian endometriosis underwent cytoreductive surgery followed by paclitaxel and cisplatin every 4 weeks for 12 courses. The patient tolerated chemotherapy well, demonstrated a dramatic response with disappearance of hepatic metastases, and remains without evidence of disease 2 years after diagnosis. CONCLUSION: Paclitaxel and cisplatin may be effective in treating primary squamous cell carcinoma of the ovary.

Five-year survival after second-line cisplatin-based intraperitoneal chemotherapy for advanced ovarian cancer.

BACKGROUND: To evaluate the 5-year survival rates of second-line intraperitoneal chemotherapy in advanced-staged ovarian cancer. MATERIALS AND METHODS: Between August 1985 and September 1991, 63 patients with advanced epithelial ovarian cancer received intraperitoneal cisplatin and cytarabine chemotherapy as second-line treatment. RESULTS: The median survival from the time of initiation of intraperitoneal chemotherapy (IPC) was 29.1 months. A significant advantage in 5-year survival (40%) and 5-year progression-free survival (37%) was observed among 21 patients who demonstrated a response to first-line and second-line treatment compared to those who demonstrated a response to first-line treatment only (6 and 0%, respectively) (P < 0.0001). No patient (n = 13) who failed to respond to either first-line or second-line treatment survived for 5 years. Among 42 patients with < or = 5 mm residual disease at the time of initiation of IPC, 5-year survival was 36% and 5-year progression-free survival was 31%, while no patient (n = 21) with residual disease measuring > 5 mm at the initiation of IPC survived 5 years (P < 0.0001). CONCLUSION: Given the limitation that this is not a randomized trial, the data appear to indicate that salvage platinum-based intraperitoneal chemotherapy results in significant 5-year survival and progression-free survival in selected patients who initiated therapy with small (< or = 5 mm) tumor burden. These survival rates as second-line therapy approach those achieved by first-line platinum-based intravenous chemotherapy in patients with advanced-stage ovarian cancer with similar small residual disease at the initiation of therapy.

Laparoscopic-assisted application of interstitial brachytherapy for locally advanced cervical carcinoma: results of a pilot study.

PURPOSE: To assess the efficacy of diagnostic laparoscopy at the time of interstitial brachytherapy in patients with FIGO Stages IIB-IVA cervical carcinoma, who were not candidates for conventional brachytherapy after completion of whole pelvic radiation. MATERIALS AND METHODS: Six patients with FIGO Stages IIB-IVA cervical carcinoma completed whole pelvic radiation (WPR) and were assessed for the placement of conventional intracavitary brachytherapy. Three patients (Stage IIB) received 50.40 Gy WPR and three (Stage IIIA-VA) received 61.20 Gy WPR. Because distorted vaginal anatomy precluded the placement of standard intracavitary brachytherapy equipment, interstitial therapy was selected. To minimize the risk of source misplacement, needles were placed with laparoscopic guidance. 192Iridium was utilized as a source of radiation. RESULTS: A total of 98 needles were placed under direct laparoscopic guidance. The median interstitial brachytherapy tumor dose was 20.00 Gy (range 19.00-41.20 Gy). Eleven perforations in the pelvic peritoneum and/or bladder were identified intraoperatively in 5 of the 6 patients, leading to immediate repositioning of needles. No acute or short-term morbidity related to the procedure was appreciated. CONCLUSION: Interstitial brachytherapy offers an alternative for intracavitary radiation therapy for selected patients, in whom adequate placement of intracavitary afterloading equipment is precluded by abnormal pelvic geometry. Historically, the placement of interstitial sources has been a procedure that was performed without visualization of the pelvic cavity. A major concern is direct injury to pelvic viscera and intestine. The use of diagnostic laparoscopy at the time of placement of interstitial brachytherapy may avert potential complications from misapplication of interstitial sources. Longer follow-up is required to substantiate these results.

Prospective sequential trials of induction weekly cisplatin followed by monthly cisplatin, doxorubicin, cyclophosphamide and paclitaxel and cisplatin in optimal (< or = 1 cm) stage III and IV ovarian cancer.

PURPOSE OF INVESTIGATION: This study was conduced to assess the results of paclitaxel plus cisplatin given over six months as firstline therapy in women with stage III and IV epithelial ovarian cancer with residual disease < 1 cm and compare it to our previous standard of cisplatin, adriamycin, and cyclophosphamide given over ten months in two sequential trials totaling 100 patients. METHODS: We compared induction weekly cisplatin (1 mg/kg x 4) followed by monthly cisplatin (50 mg/m2), doxorubicin (50 mg/m2) and cyclophosphamide (750 mg/m2) x 10 (n = 56) versus induction cisplatin (1 mg/kg x 4) followed by cisplatin (75 mg/m2) and paclitaxel (135 mg/m2) monthly over six months (n = 44). RESULTS: The two groups were similar in age, histologic subtypes, grade, performance status, and substage. The mean dose of cisplatin in the PAC patients was 617.1 (+/-92.7) mg/m2 as compared to 567.1 (+/-89.2) mg/m2 in the TP patients (p < 0.0001). Surgical response was assessed in 83.9% of the PAC and 86.4% of the TP patients. The incidence of nausea and vomiting, myelotoxicity and renal toxicity were similar in the two groups. Peripheral neuropathy occurred more frequently following TP (57% vs 16%; p = 0.001). Cardiac toxicity (grade 1) occurred in 39% of the PAC patients and in 4.5% of the TP patients (p < 0.001). The overall response rate (75% vs 88.7%), surgical response rate (67.9% vs 79.5%), complete surgical responses (37.5% vs 40.9%), estimated two-year survival (80.2% vs 79.6%), progression-free median survival (36 months vs 30.4 months) and two-year progression/recurrence rates (32.3% vs 46.9%), respectively, of PAC and TP patients were not statistically significant (p = NS). CONCLUSIONS: Given the discussed limitations of the study, compared with PAC, TP did not improve overall and surgical response rates, two-year survival, two year disease-free survival, or median time of recurrence in patients with optimal (< 1 cm) stage III and IV ovarian cancer and resulted in higher peripheral neuropathy rates.

Two sequential studies for primary peritoneal carcinoma: induction with weekly cisplatin followed by either cisplatin-doxorubicin-cyclophosphamide or paclitaxel-cisplatin.

OBJECTIVES: The aim of the current study is to evaluate the results of therapy with induction with weekly cisplatin followed by the combination of cisplatin-doxorubicin-cyclophosphamide (PAC) or the combination paclitaxel-cisplatin (TP) as first-line chemotherapy in patients with primary peritoneal adenocarcinoma (PPA). METHODS: Between October 1988 and July 1996, 46 patients with PPA were treated with PAC (n = 25) or TP (n = 21) following cytoreductive surgery in two sequential trials. In trial 1, patients received induction with weekly cisplatin (1 mg/kg) x 4 followed by monthly cisplatin (50 mg/m2), cyclophosphamide (750 mg/m2), and doxorubicin (50 mg/m2) for 10 cycles. In trial 2, patients received induction with weekly cisplatin (1 mg/kg) x 4 followed by monthly cisplatin (75 mg/m2) and paclitaxel (135 mg/m2) over 24 hr for 6 cycles. Surgical assessment of response was performed in 15 (60.0%) and 13 (61.9%) patients in the PAC and TP trials, respectively. Estimated survival and progression-free survival distributions were calculated by the method of Kaplan and Meier. Survival curves were compared using the log rank test. RESULTS: There were no significant differences between patients in either treatment arm with respect to median age, substage, percentage of patients undergoing optimal cytoreductive surgery, median preoperative CA125 values, performance status, proportion of patients who had second-look procedures, or median cumulative doses of cisplatin. The incidence of nausea and vomiting as well as peripheral neuropathy was significantly higher among patients who received TP (P = 0.005 and 0.022, respectively). The overall response, surgical response, and complete surgical response were not statistically different among patients who received PAC and those who received TP (62.5% versus 70.0%, P = 0.75, 73.3% versus 76.9%, P = 0.1, and 13.3% versus 23.1%, P = 0.64, respectively). Patients who underwent optimal cytoreductive surgery demonstrated higher response than patients whose tumors could not be optimally cytoreduced (76.7% versus 42.9%, P = 0.04). There was no statistically significant difference in overall survival or time to progression/recurrence between the PAC and TP groups (median 21.5 versus 24.0 months, P = 0.68, and 17.3 versus 24.0 months, P = 0.59, respectively). In both treatment groups combined, 18 of 32 patients whose tumors were optimally cytoreduced and 3 of 14 patients whose tumors were suboptimally cytoreduced had surgically verified response. Patients who underwent optimal cytoreductive surgery exhibited longer survival than those who underwent suboptimal cytoreductive surgery (median 29.4 versus 18.6 months, P = 0.008). CONCLUSIONS: Both PAC and TP regimens are effective combinations in patients with PPA. The median survival was similar following PAC and TP but the responses and time to recurrence/progression were nonsignificantly better in the paclitaxel combination.

The inferior gluteal flap in the difficult vulvar and perineal reconstruction.

OBJECTIVE: The objective was to study the feasibility and complications of the use of the inferior gluteal flap in the difficult vaginal, perineal, and vulvar reconstruction among women treated for gynecologic cancers. METHODS: A prospective pilot study is reported. Between October 1994 and May 1996, seven patients underwent either unilateral (n = 3) or bilateral (n = 4) inferior gluteal flaps for primary reconstruction of extensive vulvar, perineal, and vaginal defects. RESULTS: The median age of the patients was 59 years (range, 40-70). The indications for the construction of the flaps were radical resection of recurrent vulvar cancer (n = 2), radical resection of stage IV vulvar cancer (n = 2), resection of recurrent Paget's disease of the vulva (n = 1), resection of perineal recurrence of cancer of the cervix (n = 1), and resection of enteroperineal fistula following total pelvic exenteration (n = 1). The median surface area of the vulvar and perineal defect was 113 cm2 (range, 10.5-448 cm2). The median operative time for both the extirpative and the reconstructive procedures was 270 min (95-685 min) and the median estimated blood loss was 200 mL (50-950 mL). The median postoperative hospital stay was 15 days (9-29). None of the patients experienced complete graft loss. Two patients suffered necrosis of the tip of the flap that resulted in minimal wound dehiscence which healed by secondary intention, and one patient suffered graft separation which required graft revision and reconstruction. The patients were followed for a median of 11 months (3-26 months). No late complications of the reconstructive surgery were recorded. CONCLUSIONS: The inferior gluteal flap can be safely used for the reconstruction of the difficult and extensive vulvar, perineal, and vaginal defects with excellent results.

Estrogen replacement therapy following oophorectomy in women with a family history of ovarian cancer.

Compliance with estrogen replacement therapy (ERT) following surgical menopause is poor. In women who have a family history of ovarian cancer, fear of the oncogenic potential of estrogen might affect compliance with ERT following oophorectomy. Compliance with ERT in such a select group of women has not been previously reported. The aim of the present study was to report on compliance with and side effects of ERT in women with a family history of ovarian cancer who underwent oophorectomy either prophylactically or for benign disease. Eighty women with a family history of ovarian cancer who underwent oophorectomy at Roswell Park Cancer Institute were followed for a median duration of 4.2 years (range, 5 months to 14 years). Of the 76 women who were given prescriptions for ERT, the rates of commencement and maintenance of ERT at 1, 2, and 5 years were calculated. Side effects related to the different modalities of ERT were recorded. Seventy-one of 76 women (93.4%) who were given prescriptions for ERT initiated treatment. The rate of commencement of ERT was higher in premenopausal than in postmenopausal women (98.3% versus 75%, respectively, P = 0.003). Except for one patient who developed breast cancer after the oophorectomy and was advised to stop estrogen, all patients said they continued to use ERT. The maintenance rates at 1, 2, and 5 years were 100% as per patients' history. The pharmacy records for ERT prescription refills were reviewed for 52 patients who were on ERT for more than 1 year. ERT compliance was confirmed in 42 patients (80.7%). Seven of 30 patients (23.3%) who retained their uterus developed irregular uterine bleeding and 4 underwent endometrial biopsies. The incidence of irregular uterine bleeding was significantly higher after continuous compared to cyclic estrogen and progestogen (37.6 and 7% respectively, P = 0.049). Four patients (5.6%) complained of hot flashes and were managed by changing the dose or formula of estrogen. Compliance with ERT among patients with a family history of ovarian cancer who underwent oophorectomy either prophylactically or for benign disease was excellent. The presence of the uterus and the incidence of irregular uterine bleeding did not affect patients' compliance with ERT.