Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: an exploratory study of the gynecologic oncology group.

OBJECTIVE: To determine whether chemotherapy-induced neutropenia (C-iN) is associated with improved survival in a population of primary advanced ovarian cancer and peritoneal carcinoma patients treated with a carboplatin plus paclitaxel chemotherapy backbone. METHODS: A post-hoc exploratory analysis of Gynecologic Oncology Group (GOG) protocol 182 was performed. Landmark analysis was conducted on all patients with progression-free survival >18weeks from the time of study entry. Neutropenia was defined as the absolute neutrophil count <1000mm(3). The occurrence of C-iN was analyzed according to demographic, clinicopathologic, and therapeutic intent, including age, body surface area, and treatment arm. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to evaluate independent prognostic factors and to estimate their effects on PFS and OS. RESULTS: Neutropenic data was available for 3447 patients. Neutropenic (n=3196) and non-neutropenic groups (n=251) were similar in demographic and clinicopathologic characteristics. Neutropenic patients experienced significantly improved survival compared to non-neutropenic patients with the adjusted hazard ratio (HR) for death being 0.86 (95% confidence interval 0.74-0.99; p=0.041). There was no survival benefit associated with any of the treatment arms among patients with C-iN. CONCLUSION: These data suggest that C-iN may represent a clinical biomarker associated with a survival advantage for patients with untreated advanced ovarian cancer. The absence of C-iN may indicate under-dosing and ultimately attenuated anti-neoplastic effect in vulnerable populations.

A feasibility study of topotecan with standard-dose cisplatin and concurrent primary radiation therapy in locally advanced cervical cancer.

OBJECTIVES: Topotecan improves response rate (RR), progression-free survival (PFS) and overall survival (OS) when added to cisplatin in treating metastatic and recurrent cervical cancer. The objective of this study was to assess the feasibility of adding weekly topotecan to cisplatin in patients with primary, locally advanced carcinoma of the cervix receiving pelvic irradiation. METHODS: Patients with primary, previously untreated, histologically confirmed invasive squamous cell, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, stages IB2-IVA were treated with external beam pelvic radiotherapy (45 Gy), intracavitary low dose rate brachytherapy (40 Gy) and a parametrial boost (5.4-9 Gy) with overall treatment time not to exceed 8 weeks. Concurrent chemotherapy was IV cisplatin 40 mg/m(2)plus IV topotecan 2 mg/m(2) on days 1, 8, 15, 22, 29 and once during parametrial boost for 6 cycles. Patients were monitored with history, physical examination, tumor measurement and laboratory evaluation before entering the study, before each cycle of chemotherapy, at study termination and every three months thereafter. RESULTS: The study met its accrual goal of 12 patients. With a median follow-up of 22 months, eleven patients completed treatment and ten are in long term follow up without evidence of recurrent disease. The 12th patient developed progressive disease during therapy. All patients completed at least 4 cycles of chemotherapy, with the majority (82%) completing 5 or more. Grade 2 or higher neutropenia delayed treatment in 54% of cycles. The median treatment delay was 1.5 cycles (range: 1 to 5 cycles). Median treatment time was 59 days (range 46 to 81 days). The complete RR was 92% (95% confidence interval, 55%-100%). CONCLUSIONS: The addition of weekly topotecan to cisplatin at this dose and schedule during pelvic irradiation for locally advanced cervical cancer appears to be feasible. Based on this primary treatment data and the activity of cisplatin-topotecan in the recurrent disease setting, phase II and III studies of this combination are warranted.

Tumor board: more than treatment planning--a 1-year prospective survey.

BACKGROUND: The aim of this study was to evaluate the impact of gynecologic oncology tumor boards (TBs) on patient care and graduate education. METHODS: Sequential TBs were prospectively recorded. Case presentations preceded review of diagnostic studies and pathology. Following consultative dialogue, treatment plans were synthesized. Disposition alterations were categorized as major, minor, or none. RESULTS: In 52 weekly TBs, 153 patients were presented. Alterations were made in 53 cases. Major alterations (n = 13) predominantly resulted from pathology reassignments. Minor alterations (n = 40) resulted from pathology, staging, radiology, and surgical team clarifications. CONCLUSIONS: Multidisciplinary TBs provide important information for prospective treatment planning and a significant educational opportunity for postgraduate trainees.

Vaginal hyperpigmentation due to ochronosis.

BACKGROUND: Ochronosis is a manifestation of alkaptonuria, a rare metabolic disorder. It results in the accumulation of pigment in connective tissues. After several years, ochronosis may produce a distinctive form of degenerative arthritis. CASE: Vaginal ochronosis was diagnosed in an asymptomatic elderly woman with vaginal hyperpigmentation and severe degenerative arthritis. CONCLUSION: Vaginal hyperpigmentation is a rare clinical finding that necessitates biopsy.