A Markov model to evaluate cost-effectiveness of antiangiogenesis therapy using bevacizumab in advanced cervical cancer.

OBJECTIVE: To evaluate the cost-effectiveness of bevacizumab in recurrent/persistent and metastatic cervical cancer using recently reported updated survival and toxicology data. METHODS: A Markov decision tree based on the Gynecologic Oncology Group 240 randomized trial was created. The 2013 MediCare Services Drug Payment Table and Physician Fee Schedule provided costs. In the 5-year model subjects transitioned through the following states: response, progression, minor complications, severe complications, and death. Patients experiencing a health utility per month according to treatment effectiveness were calculated. Because cervical cancer survival is measured in months rather than years, results were reported in both quality adjusted cervical cancer life months and years (QALmonth, QALY), adjusted from a baseline of having advanced cervical cancer during a month. RESULTS: The estimated total cost of therapy with bevacizumab is approximately 13.2 times that for chemotherapy alone, adding $73,791 per 3.5months (0.29year) of life gained, resulting in an incremental cost-effectiveness ratio (ICER) of $21.083 per month of added life. The ICER increased to $5775 per month of added life and $24,597/QALmonth ($295,164/QALY) due to the smaller difference in QALmonths. With 75% bevacizumab cost reduction, the ICER is $6737/QALmonth ($80,844/QALY), which translates to $23,580 for the 3.5month (0.29year) gain in OS. CONCLUSIONS: Increased costs are primarily related to the cost of drug and not the management of bevacizumab-induced complications. Cost reductions in bevacizumab result in dramatic declines in the ICER, suggesting that cost reconciliation in advanced cervical cancer may be possible through the availability of biosimilars, and/or less expensive, equally efficacious anti-angiogenesis agents.

Physician awareness of enhanced prenatal services for medicaid-insured pregnant women.

CONTEXT: Medicaid enhanced prenatal service (EPS) programs, including care coordination, were developed to improve birth outcomes for low-income pregnant women. In Michigan, less than a third of eligible pregnant women are enrolled in services. Physician or medical clinics provide referrals to community-based EPS. OBJECTIVE: The objective of this study was to examine physician knowledge and perceptions of EPS. DESIGN: A cross-sectional survey of obstetric providers was conducted in 2009. A questionnaire was created to assess understanding of the EPS program. SETTING: The study was conducted in an urban Michigan community. PARTICIPANTS: Participants included a convenience sample (N = 56) of community Obstetrics and Gynecology attending physicians and resident physicians within a single, large health system. MAIN OUTCOME MEASURES: Outcome measures included knowledge of the program and patient participation, referral practices, perceptions of the program, value for patients and providers, appropriateness of physicians to provide program referrals, and barriers to referring. RESULTS: Findings indicated that most physicians (84%) had little familiarity with EPS, 60% did not personally refer to EPS, 54% did not know whether other office staff referred to EPS, and 65% were unaware whether their patients received EPS. Yet, more than 90% of physicians reported that EPS would benefit their patients and believed that it was appropriate for them to refer all their eligible patients. CONCLUSION: Further efforts should be made to better understand how physicians and EPS providers could function together on behalf of patients. Statewide Medicaid-sponsored EPS programs could serve as a valuable patient and physician resource for psychosocial risk screening, care management, education, and referral support if better utilized.

A quality process study of lymph node evaluation in endometrial cancer.

Our objective was to analyze the reported lymph node counts between surgeons, histology prosectors, and pathologists using a cohort of patients enrolled on a national protocol that standardized surgical intent.This is a retrospective review of patients with uterine cancer who underwent a standardized formal staging procedure as dictated by a National Cancer Institute sponsored protocol. Patients were staged using the International Federation of Gynecology and Obstetrics 1988 guidelines. All patients required a hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. Lymphadenectomy specimens were separated by the following regions: external iliac, obturator, common iliac, and periaortic. Lymph node counts were analyzed by region, surgeon, histology prosector, and pathologist.There were 78 patients enrolled in the protocol during the study period. Of them, 72 (92%) patients met the inclusion criteria. A total of 2397 lymph nodes were counted, with an average total number of 33 (SD=9) lymph nodes dissected per patient. Surgeons A, B, and C had an average lymph node count of 32, 33, and 35, respectively, with no significant difference in mean node count (P=0.66). Prosectors 1 to 4 dissected an average of 34, 33, 28, and 35 lymph nodes, respectively (P=0.091). There were 2 pathologists with ≥ 10 cases. Their mean lymph node counts were 35 and 30, respectively, with no significant difference in mean node count (P=0.079).This systematic review did not identify a discrepancy in nodal count among surgeons, prosectors, or pathologists at our institution. The methods used may be helpful in structuring interdepartmental reviews for completeness of nodal dissections in cases where surgical intent has been standardized.

Comprehensive study of the effects of methylation on tautomeric equilibria of nucleic acid bases.

Minor tautomers of nucleic acid bases can result by intramolecular proton transfer. These rare tautomers could be stabilized through the addition of methyl groups to DNA bases. A comprehensive theoretical study of tautomers of methylated derivatives of guanine, adenine, cytosine, thymine, and uracil was performed. Molecular geometries of all tautomers were obtained at the density functional theory and MP2 levels with the 6-31G(d,p) basis set, and single-point calculations were performed at the CCSD(T)/6-311G(d,p) level. Tautomers obtained by protonation at the preferred protonation site for methylated isolated bases were compared to their nonmethylated counterparts. The effects of methylation on the relative stabilities of nucleic acid base tautomers are also studied and discussed in this work. The results suggest that some sites on the bases may not be mutagenic and may even stabilize the canonical Watson-Crick form. The results also indicate that a number of methylation sites can stabilize the tautomers, suggesting possible mechanisms for mutagenic changes.

Targeted Treatment of a Rare Vaginal Sarcoma With an Anaplastic Lymphoma Kinase Inhibitor.

BACKGROUND: Anaplastic lymphoma kinase is a tyrosine kinase receptor that can become oncogenic. Crizotinib is a tyrosine kinase inhibitor that shows activity in patients with anaplastic lymphoma kinase rearrangements that have failed conventional therapies. CASE: A 34-year-old woman presented with a painful 3-cm left vulvar-vaginal mass, which was excised and determined to be a sarcoma with positive surgical margins. Fluorescence in situ hybridization testing of her tumor was conducted and demonstrated anaplastic lymphoma kinase gene rearrangements. A 3-cm mass recurred 1 month later. Treatment with 250 mg crizotinib orally twice daily resulted in complete regression of all visible or palpable tumor within 3 weeks. CONCLUSION: Molecular evaluation techniques can be used to direct targeted therapy for select malignancies. Future technologic advances will expand the number of malignancies for which these treatment approaches can be used.

Cost-effectiveness of primary debulking surgery when compared to neoadjuvant chemotherapy in the management of stage IIIC and IV epithelial ovarian cancer.

OBJECTIVES: To examine the cost-effectiveness of primary debulking surgery (PDS) when compared to neoadjuvant chemotherapy (NACT) in the management of epithelial ovarian cancer (EOC) using Surveillance, Epidemiology, and End Results data linked to Medicare claims (SEER-Medicare). METHODS: Using a Markov model, the cost-effectiveness of PDS was compared to that of NACT. We modeled cost and survival inputs using data from women in the SEER-Medicare database with ovarian cancer treated by either PDS or NACT between 1992 and 2009. Direct and indirect costs were discounted by an annual rate of 3%. Utility weights were obtained from published data. The incremental cost-effectiveness ratio (ICER) of PDS compared to NACT was calculated. RESULTS: In our model, women with stage IIIC EOC had a higher mean adjusted treatment cost for PDS when compared to NACT ($31,945 vs $30,016) but yielded greater quality-adjusted life-years (QALYs) (1.79 vs 1.69). The ICER was $19,359/QALY gained. Women with stage IV EOC had a higher mean adjusted treatment cost following PDS when compared to NACT ($31,869 vs $27,338) but yielded greater QALYs (1.69 vs 1.66). The ICER was $130,083/QALY gained. A sensitivity analysis showed that for both PDS and NACT the ICER was sensitive to incremental changes in the utility weight. CONCLUSION: PDS is significantly more cost-effective for women with stage IIIC when compared to NACT. In women with stage IV EOC, PDS is also more cost-effective though the QALYs gained are much more costly and exceed a $50,000 willingness to pay.

Bilateral and multinodular signet-ring stromal tumor of the ovary.

BACKGROUND: Signet-ring stromal tumor of the ovary is a rare, benign sex cord stromal tumor that is typically unilateral. Its distinction from malignant signet-ring cell adenocarcinoma metastatic to the ovary (Krukenberg tumor), is critical. CASE: A 69-year-old gravida 5 woman presented with a 1-week history of right lower abdominal pain. Ultrasonography revealed a 4-cm right adnexal mass. Serum CA 125 and carcinoembryonic antigen were within normal limits. An exploratory laparotomy, partial omentectomy, bilateral salpingo-oophorectomy and peritoneal washing were performed. Solid multinodular masses in both ovaries were identified that histologically corresponded to bilateral signet-ring stromal tumors. CONCLUSION: We report a rare example of signet-ring stromal tumor that is bilateral and multinodular mimicking a Krukenberg tumor. Awareness of this unusual presentation can help prevent incorrect diagnosis.

Physical nature of interactions within the active site of cytosine-5-methyltransferase.

The physical nature of interactions within the active site of cytosine-5-methyltransferase (CMT) was studied using a variation-perturbation energy decomposition scheme defining a sequence of approximate intermolecular interaction energy models. These models have been used to analyze the catalytic activity of residues constituting cytosine-5-methyltransferase active site as well their role in the binding group of de novo designed inhibitors. Our results indicate that Glu119, Arg163, and Arg165 appear to play the dominant role in stabilizing the protonated transition state structure and their influence can be qualitatively approximated by electrostatic interactions alone. The stabilization of neutral structures of the alternative reaction pathway is small, which might suggest the protonated pathway as preferred by the enzyme. Exchange and delocalization terms are negligible in most cases, or they cancel each other to some extent. Interactions of inhibitors with the CMT active site are dominated by electrostatic multipole contributions in analogy with previously studied transition state analogue inhibitors of leucyl aminopeptidase.