Neoadjuvant and adjuvant chemotherapy of cervical cancer: mature results of the phase 2 PBM-PFU protocol.

OBJECTIVE: The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonrandomized, phase 2 Yale University cisplatin, bleomycin, methotrexate, and 5-FU protocol are presented. METHODS: Sixty-seven patients were prospectively accrued with a median follow-up of 5.4 years, and standard parameters of toxicity and efficacy were studied. Both univariate and multivariate analyses were applied. RESULTS: The 5-year disease-free survival of 78% for the 25 patients in the adjuvant group, of which 80% had high-risk features including positive margins, parametria, and lymph nodes and 28% had adenocarcinomas, was comparable to recent relevant literature. Only 64% of patients in this group received consolidation radiation therapy, which did not impact on survival. Only 12% of patients recurred distantly. Notably, those who received 4 months or more of chemotherapy had prolonged survival (P = 0.012). In the neoadjuvant group, chemotherapy response rate among 42 patients (with stages 1B-IIIB cancer) was 79% (50% partial response, 29% complete response), and no patient progressed. In the subgroup of 22 patients who underwent surgery after chemotherapy, 59% had nonsquamous histology. Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy. Ninety-five percent received postoperative radiation therapy. There was a 9% pathologic complete response rate, with positive lymph nodes found in 27%. Notably, those who received 3 months or less of chemotherapy had improved overall survival (P = 0.030). Survival rates of these 22 patients at 3 and 5 years were 73% and 63%, respectively. Although not randomized, these survival rates were similar to those achieved with chemoradiation. CONCLUSIONS: Although there are several logistical/design features of the cisplatin, bleomycin, methotrexate, and 5-FU regimen that are not in line with the current chemotherapy era, our experience with this well-tolerated regimen can serve as a proof of principle. Our data suggests that both neoadjuvant and adjuvant cisplatin-based neoadjuvant chemotherapy may have their place. It also raises the possibility that the optimal duration of chemotherapy in adjuvant cases should be longer than in neoadjuvant cases.

Development of an interdisciplinary women's health training model.

In response to expanded residency training requirements in women's health, faculty from internal medicine, obstetrics/gynecology, and psychiatry at Yale University School of Medicine established an interdisciplinary women's health training and education model, the Interdisciplinary Women's Health Clinic (IWHC). The model was one component of a larger, comprehensive women's health program at Yale funded by the Department of Health and Human Services between 1996 and 2000 under the National Centers of Excellence in Women's Health (CoE) designation. This article describes the structure and function of the model, its value to residents and the institution, and its limitations that led to its closure when Department of Health and Human Services support ended. The IWHC was designed as a consultation service that augmented the primary care provided to low-income, minority-group women in an established outpatient primary care setting. An interdisciplinary team of residents and faculty provided and coordinated a range of services for patients and participated in a weekly core curriculum. The model was an important resource to residents and provided high-level integrated care to patients. The combined educational experience helped refine a core interdisciplinary women's health curriculum. Despite these benefits, the IWHC could not be sustained outside the financial and programmatic structure of the larger CoE program. This experience suggests that longitudinal models where residents from different disciplines train in a shared educational and clinical setting may be more durable. Interdisciplinary models are effective ways to train residents and provide integrated care to women. The model's success depends on highly developed collaborative relationships between faculty, nonclinical sources of support, and long-term institutional commitment.

Vaginal intraepithelial neoplasia: treatment by carbon dioxide laser and risk factors for failure.

OBJECTIVE: To evaluate the effectiveness of CO(2) laser ablation of vaginal intraepithelial neoplasia (VAIN) and to define prognostic factors. STUDY DESIGN: Medical records of 24 patients with VAIN II or III, treated by CO(2) laser ablation from 1990 to 1998 were reviewed. The grade, location, and focality of the lesions, the age, follow-up period and menopausal status of the patients, the power and duration of laser ablation, the presence of concurrent cervical or vulvar neoplasia or previous hysterectomy were evaluated as possible prognostic factors. RESULTS: Ablations of the VAIN were successfully accomplished in all of the patients with a mean period of 25.2+10.2 min, including additional simultaneous ablations of the cervix or vulva in eight (33.3%) patients. There was no early or late major complication. VAIN was completely eliminated in 17 (70.8%) patients after the first and in 19 (79.2%) patients after multiple episodes of ablation with a mean follow-up of 26.7+19.6 months. VAIN progressed to invasive vaginal carcinoma in one woman. None of the evaluated prognostic factors was found to be related to the persistence or recurrence. CONCLUSION: CO(2) laser ablation was a safe and effective method for the treatment of VAIN. However, since no prognostic factor was defined, all patients should be closely evaluated for persistence, recurrence or progression to invasion.

Evolutive peritoneal disease after conservative management and the use of infertility drugs in a patient with stage IIIC borderline micro-papillary serous carcinoma (MPSC) of the ovary: case report.

A young nulliparous woman with stage IIIC bilateral borderline micro-papillary serous carcinoma (MPSC) of the ovary underwent conservative surgery with optimal preservation of future fertility. The left ovary and a substantial portion of the right ovary were removed. The patient became pregnant at the first IVF cycle attempted after conservative management. A Cesarean section was performed in the 37th week of pregnancy and combined with very precise exploration; there were multiple non-invasive implants on the peritoneal surface and liver, and contra-lateral ovarian tissue was of normal appearance. Abdominal hysterectomy and right oophorectomy were done as a definitive treatment 3 months after the Caesarean section. The patient showed a rapid progression to invasive ovarian carcinoma in this period of time. MPSC has the greatest risk of malignant transformation among the advanced stage serous borderline tumours. Fertility-sparing surgery is an option for young, childless women who would like to preserve their fertility. However, the treatment must be taken very cautiously and requires rigorous surveillance.

Procollagen-derived biomarkers in malignant ascites of ovarian cancer. Independent prognosticators for progression-free interval and survival.

OBJECTIVE: Matrix formation is a hallmark of solid tumor biology. Circulating antigens of structural matrix proteins should reflect this fact, yet are subject to systemic variables. We propose that if measured regionally, in a cancer-induced extravascular fluid pool such as malignant ascites of ovarian cancer, the same antigens retain their conceptual advantage as surrogate markers for tumor biology. METHODS: In malignant ascites obtained at staging laparatomy of 35 women with ovarian cancer, the protein-normalized levels of the C-terminal propeptide of procollagen type I (pnPICP) and the N-terminal propeptide of procollagen type III (pnPIIINP) were determined. Using univariate and multivariate analysis, we examined these parameters, their (pnPIIINP/pnPICP) quotient, and clinical criteria (FIGO stage, age, residual tumor, histology, and tumor grade) for impact on progression-free interval and survival. RESULTS: The absolute level of pnPIIINP was the single most powerful independent factor impacting on survival, its P value being distinctly below (P = 0.0005 vs 0.003) and its risk ratio distinctly above (15 vs 2.5) residual tumor after debulking surgery. The relative level of pnPIIINP, i.e. (pnPIIINP / pnPICP), impacted on the likelihood of recurrence even more than residual tumor. By Kaplan-Meier analysis, cutoff values for the absolute or relative pnPIIINP level significantly discriminated patients with shortened survival or progression-free interval, respectively. CONCLUSIONS: Since malignant ovarian epithelium itself forms collagen type III, and since collagen type III is a solid-phase regulator of angiogenesis, we propose that ascitic pnPIIINP is a fluid-phase indicator for angiogenic activity in ovarian cancer and thus represents a tumor virulence index.