ABSTRACT
BACKGROUND: Breast cancer 1, early onset (BRCA1) is a tumour-suppressor gene associated with familial epithelial ovarian cancer (EOC). Reduced BRCA1 expression is associated with enhanced sensitivity to platinum-based chemotherapy. We sought to examine the prognostic relevance of BRCA1 expression in EOC patients treated with intraperitoneal platinum/taxane. METHODS: The GOG-172 was a phase III, multi-institutional randomised trial of intravenous paclitaxel and cisplatin (IV therapy) vs intravenous paclitaxel, intraperitoneal cisplatin plus paclitaxel (IP therapy) in patients with optimally resected stage III EOC. The BRCA1 expression was assessed with immunohistochemistry (IHC) staining blinded to clinical outcome in archival tumour specimens. Slides with îº10% staining were defined as aberrant and >10% as normal. Correlations between BRCA1 expression and progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan-Meier method and Cox regression analysis. RESULTS: Of the 393 patients, 189 tumours had aberrant expression, and 204 had normal BRCA1 expression. There was an interaction between BRCA1 expression and route of administration on OS (P=0.014) but not PFS (P=0.054). In tumours with normal BRCA1 expression, the median OS was 58 months for IP group vs 50 months for IV group (P=0.818). In tumours with aberrant BRCA1 expression, the median OS was 84 vs 47 months in the IP vs IV group, respectively (P=0.0002). Aberrant BRCA1 expression was an independent prognostic factor for better survival in women randomised to IP therapy (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.47-0.97, P=0.032). Similar survival was observed in the IV and IP patients with normal BRCA1 expression. Multivariate but not univariate modelling demonstrated that IV patients with aberrant vs normal BRCA1 expression had worse survival. CONCLUSION: Decreased BRCA1 expression is associated with a 36-month survival improvement in patients with EOC treated with IP chemotherapy. Although these results merit validation in future studies, the results suggest that decreased BRCA1 expression predicts for improved response to cisplatin-based IP chemotherapy with cisplatin and paclitaxel.
Subject(s)
Adenocarcinoma, Clear Cell/mortality , Adenocarcinoma, Mucinous/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , BRCA1 Protein/metabolism , Cystadenocarcinoma, Serous/mortality , Endometrial Neoplasms/mortality , Ovarian Neoplasms/mortality , Adenocarcinoma, Clear Cell/drug therapy , Adenocarcinoma, Clear Cell/metabolism , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/metabolism , Adult , Aged , Aged, 80 and over , Cisplatin/administration & dosage , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/metabolism , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/metabolism , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Injections, Intraperitoneal , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Paclitaxel/administration & dosage , Prognosis , Survival RateABSTRACT
BACKGROUND: Intramural ectopic pregnancy is unusual, difficult to diagnose, and associated with a high rate of uterine rupture. CASE: A 35-year-old, gravida 3, para 0-0-2-0 was diagnosed with intramural ectopic pregnancy by ultrasound showing a gestational sac surrounded completely by myometrium. It was confirmed by laparoscopy. With expectant management, the gestation resolved spontaneously. CONCLUSION: Early diagnosis by ultrasound of intramural ectopic pregnancy permits expectant management which, if successful, would aid in maintaining fertility.
Subject(s)
Abortion, Spontaneous , Pregnancy, Ectopic/therapy , Adult , Female , Humans , Pregnancy , Pregnancy, Ectopic/diagnostic imaging , Prenatal Care , Ultrasonography , UterusABSTRACT
PURPOSE: To compare the relative toxicities of bolus versus infusional 5-FU chemotherapy administrated concurrently during external beam irradiation in patients with locally advanced rectal cancer following surgical extirpation. METHODS: A total of 26 eligible patients were retrospectively identified as having been treated for rectal adenocarcinoma at the Stratton VAMC between 1989 and 1997. A comparative analysis of treatment dose intensities, treatment delays and toxicities in these patients was performed. RESULTS: Significantly less WBC toxicity was observed in the patients receiving infusional 5-FU chemotherapy. The other toxicities, with the exception of skin toxicity, were generally less frequent in the 5-FU infusional group. When the toxicities were corrected for 5-FU dose intensity, to yield toxicity per mg of 5-FU, statistically significant differences were found for hematological toxicity (WBC and platelets), and for gastrointestinal toxicity (frequency and severity of diarrhea and weight loss). The majority of patients receiving infusional 5-FU therapy were treated using a circadian pattern of treatment peaking around the time of the radiation therapy. Patients receiving infusional 5-FU were able to tolerate over twice the dose intensity as those receiving bolus administration. Local recurrence rate in all patients was 3.8% comparing favorably to other reported studies. Distant recurrence frequency was also acceptable at 34.6% for the group. CONCLUSION: Infusional 5-FU chemotherapy compared with bolus therapy during pelvic radiation minimizes toxicity to the patient while maximizing the dose of 5-FU that can be delivered. As infusional 5-FU therapy during radiation has previously been shown to increase disease free duration and survival, infusional 5-FU should be considered as an acceptable standard of care to prevent local recurrence of rectal adenocarcinoma following its resection. Shaping this infusional 5-FU chemotherapy within the day so that most of the daily dose is delivered around the time of the radiation therapy may further modify the toxic therapeutic ratio of combined modality therapy.
