J. Michael Straughn

At What Cost Does a Potential Survival Advantage of Bevacizumab Make Sense for the Primary Treatment of Ovarian Cancer? A Cost-Effectiveness Analysis

PURPOSE To determine whether the addition of bevacizumab to paclitaxel and carboplatin for the primary treatment of advanced ovarian cancer can be cost effective. METHODS A cost-effectiveness analysis compared the three arms of the Gynecologic Oncology Group (GOG) 218 study (paclitaxel plus carboplatin [PC], PC plus bevacizumab [PCB], and PCB plus bevacizumab maintenance [PCB+B]). Actual and estimated costs of treatment plus the potential costs of complications were established for each strategy. Progression-free survival (PFS) and bowel perforation rates were taken from recently reported results of GOG 218. Sensitivity analysis was performed for pertinent uncertainties in the model. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were estimated. RESULTS For the 600 patients entered onto each arm of GOG 218 at the baseline estimates of PFS and bowel perforation, the cost of PC was

The Wnt/β-catenin pathway in ovarian cancer: a review.

2.5 million, compared with

Stage IC adenocarcinoma of the endometrium: survival comparisons of surgically staged patients with and without adjuvant radiation therapy.

21.4 million for PCB and

Expression of sperm protein 17 (Sp17) in ovarian cancer

78.3 million for PCB+B. These costs led to an ICER of

Role of chemotherapy for patients with recurrent platinum-resistant advanced epithelial ovarian cancer: A cost-effectiveness analysis.

479,712 per PF-LYS for PCB and

Lynch Syndrome in Women Less Than 50 Years of Age With Endometrial Cancer

401,088 per PF-LYS for PCB+B. When the cost of bevacizumab was reduced to 25% of baseline, the ICER of PCB+B fell below

Lynch Syndrome Screening Strategies Among Newly Diagnosed Endometrial Cancer Patients

100,000 per PF-LYS. ICERs were not substantially reduced when the perforation rate was equal across all arms. CONCLUSION The addition of bevacizumab to standard chemotherapy in patients with advanced ovarian cancer is not cost effective. Treatment with maintenance bevacizumab leads to improved PFS but is associated with both direct and indirect costs. The cost effectiveness of bevacizumab in the adjuvant treatment of ovarian cancer is primarily dependent on drug costs.

The utilization of palliative care in gynecologic oncology patients near the end of life

OBJECTIVE Ovarian cancer is the deadliest gynecologic malignancy and the fifth leading cause of death from cancer in women in the U.S. Since overall survival remains poor, there is a need for new therapeutic paradigms. This paper will review the Wnt/β-catenin pathway as it relates to epithelial ovarian cancer, specifically its role in chemoresistance and its potential role as a target for chemosensitization. METHODS A PubMed search was performed for articles published pertaining to Wnt/β-catenin pathway specific to ovarian cancer. Wnt/β-catenin signaling pathways play an active role in cancer stem cells (CSCs) and carcinogenesis of all ovarian cancer subtypes. Studies also have shown that ovarian CSCs are involved in chemoresistance, metastasis, and tumor recurrence. RESULTS Wnt/β-catenin target genes regulate cell proliferation and apoptosis, thereby mediating cancer initiation and progression. The Wnt/β-catenin pathway is one of the major signaling pathways thought to be involved in epithelial-to-mesenchymal transition (EMT). Alterations affecting Wnt pathway proteins on the cell membrane, in the cytoplasm, and in the nucleus have been shown to play important roles in the tumorigenesis of ovarian cancer. CONCLUSIONS Wnt signaling is activated in epithelial ovarian cancer. Given the role of the Wnt/β-catenin pathway in carcinogenesis, more pre-clinical studies are warranted to further investigate other Wnt inhibitors in ovarian cancer. The Wnt pathway should also be investigated as a potential target in the development of new drugs for ovarian cancer as a single agent and in combination with chemotherapy or other targeted agents.

A review of B7-H3 and B7-H4 immune molecules and their role in ovarian cancer

OBJECTIVE The goal of this study was to determine the outcomes of stage IC endometrial carcinoma patients who are managed with and without adjuvant radiation therapy after comprehensive surgical staging. METHODS Patients with FIGO stage IC adenocarcinoma of the endometrium diagnosed from 1988 to 1999 were identified from tumor registry databases at four institutions. A retrospective chart review identified 220 women who underwent comprehensive surgical staging including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy, and peritoneal cytology. RESULTS Of the 220 stage IC patients, 56 (25%) patients received adjuvant brachytherapy (BT), 19 (9%) received whole-pelvis radiation (WPRT), and 24 (11%) received both WPRT and BT. One hundred twenty-one patients (55%) did not receive adjuvant radiation. There were 6 recurrences (6%) in the radiated group and 14 (12%) in the observation group (P = 0.20). Seven of fourteen recurrences in the observation group were local, and all local recurrences were salvaged with radiation therapy. Two of seven distant recurrences in this group were also salvaged with surgery and chemotherapy. The overall salvage rate for the observation group was 64%. There was a statistical difference in 5-year disease-free survival between the radiated and observation groups (93% vs 75%, P = 0.013). However, the 5-year overall survival was similar in the two groups (92% vs 90%, P = 0.717). CONCLUSION Adjuvant radiation therapy improves disease-free survival in surgical stage IC patients; however, overall survival is not improved with adjuvant radiation therapy since the majority of local recurrences in conservatively managed patients can be salvaged with radiation therapy.

The risk of gastrointestinal perforation and/or fistula in patients with recurrent ovarian cancer receiving bevacizumab compared to standard chemotherapy: A retrospective cohort study ☆

Sperm protein 17 (Sp17) is an antigenic protein highly expressed in spermatozoa. Sp17 expression was demonstrated recently in multiple myeloma, suggesting that it may be a novel cancer‐testis antigen. Expression of Sp17 mRNA and protein was examined in human ovarian tumors. Sp17 mRNA was evaluated by reverse transcription‐polymerase chain reaction (RT‐PCR) and Northern blot analysis of RNA derived from epithelial ovarian tumors and normal tissues. RT‐PCR analysis detected Sp17 transcripts in 15 of 18 (83%) primary ovarian tumors. The transcript was not detected in RNA derived from normal uterus or cervix, whereas weak expression was noted in some normal ovarian tissue samples. Northern blot analysis showed no detectable Sp17 mRNA expression in normal tissues, including normal ovary, but showed Sp17 expression in 17 of 25 ovarian tumors (68%). To evaluate protein expression, mouse monoclonal antibodies were produced against recombinant Sp17 protein and used in Western blot and immunohistochemical analyses of normal reproductive tissue and primary ovarian tumor samples. Sp17 protein was detected by Western blot analysis in normal spermatozoa and in 8 of 19 ovarian tumor samples. Immunohistochemical studies showed Sp17 expression in spermatozoa, ciliated cells of the female reproductive tract, and most ovarian tumors evaluated. Tumors showed a predominately nuclear localization of Sp17 expression, with some cytoplasmic staining. These results demonstrate that Sp17, a protein with restricted expression in somatic tissues, is expressed in ovarian tumors. Because Sp17 is immunogenic, it may represent a novel target for immunotherapeutic interventions for ovarian cancer patients.