Jason A. Lachance

Correlation between smoking status and cervical cancer screening: a cross-sectional study.

Objectives. Tobacco use is a risk factor for the development and progression of cervical cancer. The purpose of this study was to determine the correlation between smoking status among women and their compliance with cervical cancer screening guidelines. Materials and Methods. A cross-sectional analysis of the Behavioral Risk Factor Surveillance System was performed using the 2006 survey data. Women with no history of hysterectomy who answered the questions regarding smoking status, age, and last Pap smear were included (n = 150,786). Data were weighted for survey design. Results. The overall prevalence of compliance with cervical cancer screening guidelines was 83.9%. The rate of compliance was highest among former smokers (86.7%) compared with never smokers (83.7%) and current smokers (81.7%; p < .001). Among women aged 21 to 65 years, the odds of current smokers having had a Pap test in the past 3 years was 0.70 compared with women who never smoked (95% confidence interval = 0.63-0.77), when controlled for marital status, income, and access to health care. The odds of former smokers complying with screening guidelines were similar to women who never smoked. Conclusions. Women who smoke are at higher risk for developing cervical cancer but have a lower rate of screening for the disease. Efforts to increase prevalence of Pap test compliance should target current smokers.

Appendiceal Pathology at the Time of Oophorectomy for Ovarian Neoplasms

OBJECTIVE: To investigate the prevalence of appendiceal pathology in women undergoing surgery for a suspected ovarian neoplasm and the predictive value of intraoperative findings to determine the need for appendectomy at the time of surgery. METHODS: Retrospective analysis of patients who underwent oophorectomy and appendectomy during the same surgical procedures at the University of Virginia Health System from 1992 to 2007. Observations were stratified based on the nature (benign, borderline, or malignant) and histology (serous compared with mucinous) of the ovarian neoplasm, frozen compared with final pathological diagnosis, and the gross appearance of the appendix. RESULTS: Among the 191 patients identified, frozen section was consistent with seven mucinous and 35 serous carcinomas, 16 serous and 33 mucinous borderline tumors, 71 mucinous and serous cystadenomas, and 29 cases of suspected metastatic tumor from a gastrointestinal primary. The highest rates of coexisting appendiceal pathology were associated with serous ovarian cancers (94.4% of grossly abnormal and 35.3% of normal appendices) and ovarian tumors suspected to be of primary gastrointestinal origin (83.3% grossly abnormal and 60.0% normal appendices harbored coexisting mucinous neoplasms). Linear regression analysis revealed that appearance of the appendix and frozen section diagnosis of the ovarian pathology were statistically significant predictors of coexisting appendiceal pathology, but the latter was more important. CONCLUSION: The prevalence of coexisting, clinically significant appendiceal pathology is low with a frozen section diagnosis of serous or mucinous cystadenoma. Appendectomy is recommended when frozen section diagnosis is mucinous or serous ovarian carcinoma, borderline tumor or metastatic carcinoma of suspected gastrointestinal origin. LEVEL OF EVIDENCE: III

Biomarkers p16, Human Papillomavirus and p53 Predict Recurrence and Survival in Early Stage Squamous Cell Carcinoma of the Vulva.

Objective Vulvar squamous cell carcinoma (VSCC) develops through 2 distinct molecular pathways, one involving high-risk human papillomavirus (HPV) infection and the other through early p53 suppressor gene mutation. We sought to evaluate the influence of p53 mutation, HPV status, and p16 expression on local recurrence and disease-specific mortality in early stage VSCC. Materials and Methods We performed a retrospective chart review of all patients with stage I VSCC at the Maine Medical Center from 1998 to 2007 (n = 92). Tumor size, depth of invasion, lymphatic/vascular space invasion, and growth pattern were recorded. Paraffin-embedded tissue blocks were stained by immunohistochemistry for p16 and p53; high-risk HPV was detected by polymerase chain reaction assay. Margin distance was determined by a gynecologic pathologist. Survival analyses were conducted to examine predictors of VSCC recurrence and disease-specific mortality. Results Age, depth of invasion, lymphatic/vascular space invasion, growth pattern, and margin status were not significant predictors of recurrence or disease-specific mortality. Tumor size of greater than 4.0 cm indicated a 4-fold increase in disease-specific mortality but did not significantly increase recurrence. p16-Positive patients were less likely to recur and had no VSCC-related deaths. Human papillomavirus–positive patients were less likely to recur and had no VSCC-related deaths. p53-positive patients were 3 times more likely to recur and nearly 7 times more likely to die from vulvar cancer. Conclusions Our findings suggest that HPV and the surrogate biomarker p16 indicate a less aggressive type of vulvar cancer. p53 positivity was associated with poor prognosis and significantly increased both recurrence and disease-specific mortality.

A phase II study of gemcitabine (gemzar, LY188011) in the treatment of recurrent or persistent endometrial carcinoma: A gynecologic oncology group study

OBJECTIVE The study aims to evaluate the anti-tumor activity and toxicity of gemcitabine in patients with persistent or recurrent endometrial carcinoma. METHODS Patients with advanced or recurrent carcinoma of the endometrium previously treated with one chemotherapy regimen were treated on a phase II trial conducted by the Gynecologic Oncology Group (GOG). Gemcitabine was administered as an intravenous infusion at a dose of 800 mg/m² over 30 min on days 1 and 8 every 21 days. RESULTS Twenty-four patients were entered by 11 GOG member institutions. One patient was ineligible due to wrong primary tumor. A total of ninety 21-day cycles of therapy were administered with 35% of patients receiving four or more cycles. All patients had been previously treated with a platinum-based regimen. One patient had a partial response (4%), nine had stable disease (39%), and twelve had increasing disease (52%). The median progression-free survival was 1.7 months. Treatment was generally well tolerated with only 22% of patients experiencing grade 3 or grade 4 hematologic toxicity. There was one treated-related death due to pulmonary toxicity. CONCLUSION Gemcitabine has minimal activity in the treatment of recurrent or persistent endometrial carcinoma at the dose and schedule tested.

Temozolomide in advanced and recurrent uterine leiomyosarcoma and correlation with O6-methylguanine DNA methyltransferase expression a case series

Introduction: Our objective was to retrospectively review temozolomide in advanced and recurrent uterine leiomyosarcoma and to determine if tumor O6-methylguanine DNA methyltransferase (MGMT) expression correlated with clinical response. Methods: All patients with advanced or recurrent uterine leiomyosarcoma who received temozolomide during treatment were retrospectively identified. Relevant clinical and pathologic data were collected and compared. O6-Methylguanine DNA methyltransferase expression was assessed by immunohistochemistry and scored by a gynecologic pathologist blinded to clinical outcomes. Results: From 1999 to 2008, 9 cases of leiomyosarcoma were diagnosed; 6 patients received temozolomide. Median follow-up was 54 months (range, 4-114 months). There was 1 patient with complete response, 1 durable partial response (27+ months), 3 stable disease (range, 3-10 months), and 1 progressive disease. Overall, 5 out of 6 patients derived clinical benefit. The patient with a complete response recurred 18 months after her last cycle. Median progression free interval was 15.4 months (95% confidence interval, 9.4-21.4). Two patients died of disease. Temozolomide was well tolerated with no dose-limiting toxicities, and no dose adjustments were required in 64 prescribed cycles. The MGMT expression was inversely correlated with response to temozolomide. Patients with tumors negative for MGMT expression had a median progression free interval of 18.5 months compared with 3 months for those whose tumors were positive, although not statistically significant. Conclusions: Temozolomide is an easily administered, well-tolerated chemotherapeutic option in advanced or recurrent uterine leiomyosarcomas with a reasonable response rate. Assessment of MGMT expression may identify a subset of patients that will respond optimally to this therapy.

Intraperitoneal chemotherapy among women in the Medicare population with epithelial ovarian cancer

BACKGROUND Intraperitoneal combined with intravenous chemotherapy (IV/IP) for primary treatment of epithelial ovarian cancer results in a substantial survival advantage for women who are optimally debulked surgically, compared with standard IV only therapy (IV). Little is known about the use of this therapy in the Medicare population. METHODS We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify 4665 women aged 66 and older with epithelial ovarian cancer diagnosed between 2005-2009, with their Medicare claims. We defined receipt of any IV/IP chemotherapy when there was claims evidence of any receipt of such treatment within 12 months of the date of diagnosis. We used descriptive statistics to examine factors associated with treatment and health services use. RESULTS Among 3561 women with Stage III or IV epithelial ovarian cancer who received any chemotherapy, only 124 (3.5%) received IV/IP chemotherapy. The use of IV/IP chemotherapy did not increase over the period of the study. In this cohort, younger women, those with fewer comorbidities, whites, and those living in Census tracts with higher income were more likely to receive IV/IP chemotherapy. Among women who received any IV/IP chemotherapy, we did not find an increase in acute care services (hospitalizations, emergency department visits, or ICU stays). CONCLUSION During the period between 2005 and 2009, few women in the Medicare population living within observed SEER areas received IV/IP chemotherapy, and the use of this therapy did not increase. We observed marked racial and sociodemographic differences in access to this therapy.

Utilization of a uniform grading system for interpreting serous ovarian cancer

OBJECTIVE The purpose of the study was to implement a uniform system for assigning tumor grade in serous ovarian cancer and evaluate its correlation with response to conventional chemotherapy. STUDY DESIGN Serous ovarian cancer tumor samples were retrospectively reviewed by 3 pathologists who were blinded to the original report. Samples were scored for architectural pattern, nuclear pleomorphism, and mitotic activity. Sum scores from these 3 indices were used to classify tumors as low grade or high grade. RESULTS A total of 21 patients were identified as low-grade tumors and 21 were identified as high-grade tumors. Of low-grade tumors, 16 (76%) were found to be platinum resistant, defined as recurrent or persistent disease, 180 days from completion of the final cycle of chemotherapy, Of 21 patients defined as high grade, 9 (43%) were platinum resistant (P = .028). CONCLUSION Utilization of a uniform grading system retrospectively correlates with platinum sensitivity.

A nomogram for estimating the probability of ovarian cancer

OBJECTIVE Accurate preoperative estimates of the probability of malignancy in women with adnexal masses are essential for ensuring optimal care. This study presents a new statistical model for combining predictive information and a graphic decision support tool for calculating risk of malignancy. METHODS The study included 153 women treated with definitive surgery for adnexal mass between 2001 and 2007 with preoperative ultrasound testing and a serum CA125. Multivariable logistic regression was used to develop a statistical model for estimating the probability of ovarian cancer as a function of age, ultrasound score, and CA125 value, with adjustments for nonlinear and interactive relationships. RESULTS A total of 20 cases of pathologically confirmed cancer (13 invasive malignancies, and 7 tumors of low malignant potential) were identified (20/153=13%). The model obtained excellent discrimination (ROC area=0.87), explained nearly half of the observed variation in the risk of malignancy (R²=0.43), and was well calibrated across the full range of malignancy probabilities. The model equation is represented in the form of a nomogram, which can be used to calculate preoperative probability of malignancy. At a 5% risk of malignancy threshold, the model has a sensitivity of 90% and a specificity of 73%. CONCLUSIONS Statistical models for estimating the probability of adnexal mass malignancy are substantially improved by including adjustments for non-linear relationships among key variables. A clinically relevant nomogram provides an objective tool to further aid clinicians in counseling patients and ensuring proper referral to surgical sub-specialists when indicated.

A cost comparison of two strategies for treating stage IB2 cervical cancer

Patients with stage IB2 cervical cancer at our institution are treated primarily with definitive chemoradiation, or chemoradiation followed by adjuvant hysterectomy. We sought to compare the cost differences associated with these two strategies. We identified all patients with stage IB2 cervical cancer who received their entire treatment regimen at our institution between 1995 and 2004. All patients received a combination of chemotherapy, external beam radiation, and one brachytherapy procedure, followed by either a second brachytherapy procedure or a simple hysterectomy. We retrieved cost data associated with hospitalization for the completion of respective treatment, including pharmacy, laboratory and pathology, radiation, and operating room services, as well as the costs of supplies and room and board. We identified 46 patients with stage IB2 cervical cancer, 23 who received a second brachytherapy procedure and 23 who underwent simple hysterectomy. Patients displayed similar demographics and similar disease characteristics including initial tumor diameter and histology. The cost of care for adjuvant hysterectomy group was greater (

Society of Gynecologic Oncology Clinical Outcomes Registry: From small beginnings come great things

8,316.70 vs 5,508.70, P< 0.0001). Specific differences included higher operating room costs (