Anna E. Strohl

Prognosis and treatment of uterine leiomyosarcoma: A National Cancer Database study

OBJECTIVE To determine overall survival and factors associated with survival of women with uterine leiomyosarcoma. METHODS We performed an observational cohort study of women with uterine leiomyosarcoma (n=7455) from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to investigate predictors of survival. Sensitivity and matched cohort analyses were performed to evaluate the roles of oophorectomy, lymphadenectomy, and chemotherapy in early leiomyosarcoma and chemotherapy in metastatic leiomyosarcoma. RESULTS Median (interquartile range) age at diagnosis was 54 (48-63) years. Older age, higher comorbidity, black race, higher stage or grade, larger tumor size, lymph node involvement, metastasis at diagnosis, positive surgical margin, adjuvant chemotherapy, and brachytherapy were independently associated with decreased survival by unmatched cohort analyses. Private insurance was associated with increased survival. By matched cohort analyses, omitting oophorectomy was not associated with survival among women≤51years old at diagnosis (event time ratio (ETR) (95% CI) 1.06 (0.90-1.25), P=0.48). Omitting lymphadenectomy was not associated with survival (ETR (95% CI) 1.02 (0.94-1.10), P=0.60). Among women with stage I leiomyosarcoma, adjuvant chemotherapy was not associated with increased survival (ETR (95% CI) 0.91 (0.78-1.05), P=0.18). Chemotherapy was associated with increased survival of women with metastatic leiomyosarcoma (median survival (95% CI) 19.4 (16.4-23.0) versus 10.9 (7.7-14.3) months, ETR (95% CI) 1.66 (1.46-1.90), P<0.001). CONCLUSION Early and complete resection is the best-evidenced treatment for uterine leiomyosarcoma. Oophorectomy and lymphadenectomy may be safely omitted for clinically uterus-confined leiomyosarcoma. Chemotherapy increases survival of women with metastatic leiomyosarcoma.OBJECTIVE To determine overall survival and factors associated with survival of women with uterine leiomyosarcoma. METHODS We performed an observational cohort study of women with uterine leiomyosarcoma (n=7455) from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to investigate predictors of survival. Sensitivity and matched cohort analyses were performed to evaluate the roles of oophorectomy, lymphadenectomy, and chemotherapy in early leiomyosarcoma and chemotherapy in metastatic leiomyosarcoma. RESULTS Median (interquartile range) age at diagnosis was 54 (48-63) years. Older age, higher comorbidity, black race, higher stage or grade, larger tumor size, lymph node involvement, metastasis at diagnosis, positive surgical margin, adjuvant chemotherapy, and brachytherapy were independently associated with decreased survival by unmatched cohort analyses. Private insurance was associated with increased survival. By matched cohort analyses, omitting oophorectomy was not associated with survival among women≤51years old at diagnosis (event time ratio (ETR) (95% CI) 1.06 (0.90-1.25), P=0.48). Omitting lymphadenectomy was not associated with survival (ETR (95% CI) 1.02 (0.94-1.10), P=0.60). Among women with stage I leiomyosarcoma, adjuvant chemotherapy was not associated with increased survival (ETR (95% CI) 0.91 (0.78-1.05), P=0.18). Chemotherapy was associated with increased survival of women with metastatic leiomyosarcoma (median survival (95% CI) 19.4 (16.4-23.0) versus 10.9 (7.7-14.3) months, ETR (95% CI) 1.66 (1.46-1.90), P<0.001). CONCLUSION Early and complete resection is the best-evidenced treatment for uterine leiomyosarcoma. Oophorectomy and lymphadenectomy may be safely omitted for clinically uterus-confined leiomyosarcoma. Chemotherapy increases survival of women with metastatic leiomyosarcoma.

Barriers to prevention: knowledge of HPV, cervical cancer, and HPV vaccinations among African American women

OBJECTIVE The purpose of this study was to assess knowledge of the human papillomavirus (HPV), cervical cancer, and HPV vaccination in African American women (AAW). STUDY DESIGN This study was a quantitative cross-sectional survey of English-speaking, AAW, 18-70 years old who were recruited from a community fair in Chicago, IL. Surveys were distributed to a convenience sample to assess knowledge of HPV, cervical cancer, and the HPV vaccine. Cumulative knowledge scores were calculated for each participant, and analysis was performed to identify factors that were associated with adequate knowledge scores. RESULTS Three hundred twenty-two surveys were distributed; 242 surveys were collected, and 215 surveys met inclusion criteria. Mean knowledge score was 12.3 ± 4.2 (mean ± SD) of a maximum score of 28 (range, 3-23); 73% of participants scored <65% on the knowledge portion of the survey. Education level (P = .007), household income (P = .010), and having a child who had been offered the HPV vaccine (P = .041) were associated with adequate (≥65% accuracy) knowledge scores. CONCLUSION Knowledge of HPV, cervical cancer, and HPV vaccination was low in this urban African American adult female population. Targeted educational health programs are needed to increase awareness among these women who have the highest rate of cervical cancer mortality in the United States. Such patient educational programs must be developed by physicians and should address the cultural and literacy needs of this particular group of women. In addition, AAW exert influence on the health of their communities and are integral in health-related decision-making; thus, educating them through their health care providers will have far ranging impact.

Survival of women with Mullerian adenosarcoma: A National Cancer Data Base study

OBJECTIVE To determine overall survival (OS) and factors associated with OS of women with Mullerian adenosarcoma. METHODS Women with adenosarcoma of the uterus, cervix or ovary (n=2205) were identified from the 1998-2011 National Cancer Data Base. Kaplan-Meier and multivariate Cox proportional-hazards survival analyses were performed to test for associations of potential explanatory variables with OS. A subset analysis of women with uterine adenosarcoma was also performed. Analyzed confounders included age, insurance status, income, race, surgical margin status, nodal and distant metastasis, surgical procedure type, and treatment with radiation and/or chemotherapy. RESULTS Primary sites were uterus (n=1884), cervix (n=229) and ovary (n=92), representing 0.43% of uterine, 0.16% of cervical, and 0.04% of ovarian cancers in the NCDB. Only 36/1176 (3.1%) and 2.5% (33/1,342) had nodal and/or distant metastasis, respectively, at diagnosis. Distant metastasis, positive surgical margin, increased age, higher composite comorbidity score and adjuvant radiotherapy were independently associated with decreased OS. Primary site, lymph node status, surgical procedure, chemotherapy use, race, insurance status and income quartiles were not significantly associated with OS. Each 1cm increase in tumor size was associated with increased hazard for death (HR (95% CI) 1.06 (1.01-1.12), p=0.018) among women with uterine adenosarcoma. CONCLUSION Complete surgical resection remains the only treatment with well-evidenced OS benefit among women with Mullerian adenosarcoma. Early surgical resection may increase survival of Mullerian adenosarcoma.

Receipt of vaginal brachytherapy is associated with improved survival in women with stage I endometrioid adenocarcinoma of the uterus: A National Cancer Data Base study.

Randomized controlled trials have consistently shown that the use of postoperative radiotherapy (RT) for stage I endometrial cancer leads to a reduction in the incidence of pelvic recurrences without a corresponding reduction in overall mortality. It was hypothesized that a reduction in mortality associated with the receipt of RT could be identified in a large data set with greater statistical power.

Fatal gestational trophoblastic neoplasia: An analysis of treatment failures at the Brewer Trophoblastic Disease Center from 1979-2012 compared to 1962-1978.

OBJECTIVE To determine clinical factors that contributed to death from gestational trophoblastic neoplasia (GTN) at the Brewer Trophoblastic Disease Center from 1979-2012 compared to 1962-1978. METHODS Nineteen women who died of GTN from 1979-2012 were retrospectively identified and compared to 45 women previously reported on who died of GTN from 1962-1978. Clinical factors analyzed included demographics, pretreatment human chorionic gonadotropin (hCG) level, duration of disease, antecedent pregnancy, number and sites of metastases, FIGO stage and score, treatment, and cause of death. RESULTS Death from GTN occurred in 19 (4%) of 483 patients treated from 1979-2012 compared to 45 (11%) of 396 patients treated from 1962-1978 (P<0.001). Pretreatment hCG level >100,000 mIU/mL, time from pregnancy event to treatment >4 months, nonmolar antecedent pregnancy and use of surgery to control metastatic disease were similar between the two treatment eras. Patients in the recent series were more likely to have presented with FIGO IV disease or brain metastasis, been initially treated with multiagent chemotherapy, and received treatment before referral to our center compared to the earlier series. The most common causes of death from 1979-2012 and 1962-1978 were hemorrhage from one or more metastatic sites (11% vs. 42%), respiratory failure (37% vs. 31%), and multiorgan failure due to widespread chemoresistant disease (42% vs. 8%), respectively. CONCLUSIONS Our overall survival rate in patients with gestational trophoblastic neoplasia improved from 89% in 1962-1978 to 96% in 1979-2012. More patients treated between 1979-2012 died from widespread chemoresistant disease rather than hemorrhagic complications.

Chemotherapy delay after primary debulking surgery for ovarian cancer

OBJECTIVE To determine the association of chemotherapy delay with overall survival (OS) and investigate predictors of delay among a population-representative American ovarian cancer cohort. METHODS An observational retrospective cohort analysis of women with ovarian cancer who received National Comprehensive Cancer Network guideline-consistent care was performed with the 1998-2011 National Cancer Data Base. Chemotherapy delay was defined as initiation of multiagent chemotherapy >28days from primary debulking surgery. Associations of patient and disease characteristics with chemotherapy delay were tested with multivariate logistic regression. Survival analyses for women diagnosed from 2003 to 2006 approximated a 21-daycycle intravenous platinum-taxane chemotherapy cohort. Overall survival was estimated by Kaplan-Meier analyses and Cox proportional-hazards regressions, with sensitivity analyses using matched cohorts. RESULTS 58.1% (26,149/45,001) of women experienced chemotherapy delay. Race, insurance status, cancer center type, and community median income were significantly associated with chemotherapy delay (P<0.001). Odds for chemotherapy delay were higher for older or sicker women, women with endometrioid or mucinous histology, lower stage or grade disease, and uninsured or low-income women (P<0.05). Chemotherapy delay >35days from surgery was associated with a 7% (95% confidence interval, 2-13%) increased hazard of death (P=0.01). Relative hazard of death was lowest between 25 and 29days after surgery but was not significantly different within the longer two-week interval from 21 to 35days. CONCLUSION A survival benefit may be achieved by consistently starting chemotherapy between 21 and 35days from primary debulking surgery. Women at higher risk for chemotherapy delay may be targeted for close follow-up.

Survival after pelvic exenteration for uterine malignancy: A National Cancer Data Base study

OBJECTIVE To determine overall survival (OS) and factors associated with OS after pelvic exenteration for uterine cancer. METHODS Women with uterine cancer who underwent exenteration (n=1160) were identified from the 1998-2011 National Cancer Data Base. Kaplan-Meier and multivariate Cox proportional-hazards survival analyses were performed to test for associations of potential explanatory variables with OS. Analyzed confounders included age, comorbidity score, insurance status, income, distance from home to treatment center, stage, distant and nodal metastasis, tumor size, surgical margin status, exenteration type, and treatment with radiation and/or chemotherapy. RESULTS Among women with follow-up data (n=652), median (IQR) OS was 63.1 (42.2-107.2) and 17.6 (14.7-23.9) months for women with node-negative versus node-positive disease, respectively. Histology (p=1.5×10-4), grade (p=7.9×10-14), race (p=0.0002), lymph node status (p=1.0×10-14), surgical node evaluation (p=2.8×10-8), surgery for distant metastasis (p=0.004), distant metastasis at diagnosis (p=1.3×10-10), positive surgical margins (p=1.6×10-9), radiotherapy (p=0.004), and insurance status (p=6.5×10-6) were significantly associated with differential, unadjusted Kaplan-Meier OS estimates. Exenteration type was not associated with OS (p=0.357). By multivariate regression, increased age, positive surgical margins, nodal metastasis or unknown nodal status, higher histologic grade, and black race were associated with increased hazards for death. CONCLUSION Exenteration may be curative for well-selected women with uterine cancer, particularly among women with pathologically negative lymph nodes.

Postmolar choriocarcinoma: An independent risk factor for chemotherapy resistance in low-risk gestational trophoblastic neoplasia

OBJECTIVE To evaluate the effect of a clinicopathologic diagnosis of choriocarcinoma (CCA) on clinical characteristics, extent of disease, and response to chemotherapy in low-risk gestational trophoblastic neoplasia (GTN). METHODS We reviewed the records of 678 patients with low-risk GTN (FIGO stage I and stages IIIII, score<7) treated from 1962 to 2009. Patient and disease characteristics, treatment course, as well as clinical response and survival were analyzed retrospectively. Patients with a clinicopathologic diagnosis of CCA were compared to those with a clinical diagnosis of postmolar GTN. RESULTS Of 678 women with low-risk GTN, 129 (19.0%) had a clinicopathologic diagnosis of CCA. Patients with CCA had higher parity (median 1 vs. 0, p=0.003), more pretreatment human chorionic gonadotropin (hCG) levels at >100,000mIU/mL (12.7% vs. 5.9%, p=0.009), longer duration of disease (19.6 vs. 9.9weeks, p<0.001), and higher FIGO scores (median 2 vs. 1, p<0.001) compared with those with other histology; however, patients with CCA and postmolar GTN presented with similar stage of disease (stage I, 83.1% vs 88.2%, p=0.126). Although there was no difference in survival between groups, increased resistance to first-line methotrexate chemotherapy was significantly associated with a diagnosis of postmolar CCA (OR 2.67, p=0.007)), pretreatment hCG level at >10,000mIU/mL (OR 2.62, p=0.002), and higher FIGO score (3-4: OR 2.02, p=0.027; 5-6: OR 5.56, p<0.001) on multivariate analysis. CONCLUSIONS Clinicopathologic diagnosis of postmolar CCA in patients with low-risk GTN is associated with higher pretreatment hCG levels, higher FIGO scores, and increased resistance to first-line single-agent methotrexate chemotherapy.

Survival after Pelvic Exenteration for Cervical Cancer: A National Cancer Database Study

Objective To determine overall survival (OS) and factors associated with OS after pelvic exenteration for cervical cancer. Methods Women with cervical cancer who underwent exenteration (n = 517) were identified from the 1998 to 2011 National Cancer Database. Kaplan-Meier and multivariate Cox proportional-hazards survival analyses were performed to test for associations of potential explanatory variables with OS. Analyzed confounders included age, insurance status, income, distance from home to treatment center, stage, exenteration type, surgical margin status, and treatment with adjuvant radiation and/or chemotherapy. Results Among the entire cohort with clinical follow-up (n = 313), median OS was 24 months. Stage (P = 2.5 × 10−12), lymph node status (P = 1.3 × 10−7), insurance status (P = 1.5 × 10−5), and histologic type (P = 0.04) were significantly associated with OS by the log-rank test. Unadjusted median OS was 24.2 and 61.8 months for women with squamous and adenocarcinoma histologies, respectively. By multivariate Cox regression, age, insurance status, stage, margin status, and adjuvant radiation were associated with OS. Histology was not independently associated with OS on multivariate regression. Among women with node-negative disease, median OS was 73.2 months. Conclusions Exenteration may be curative for more than half of women with node-negative cervical cancer. Stage, insurance status, lymph node status, and surgical margin are independently associated with differential OS after exenteration.

Clinical Epidemiology of Gestational Trophoblastic Disease

The epidemiology of gestational trophoblastic disease (GTD) is not well defined. The rarity of the disease and challenges in data collection limit interpretation of incidence data. Incidence of GTD appears to be influenced by geographic region, with the highest rates occurring in Southeast Asia and Japan. Risk factors for molar pregnancy include extremes of maternal age, reproductive history, and dietary deficiencies. Risk factors for choriocarcinoma include age, ethnicity, history of complete molar pregnancy, and ABO blood group status. With improvements in socioeconomic conditions and diet as well as diagnosis and management of GTD, the incidence of trophoblastic disease is declining worldwide. Future studies should focus on mechanisms by which risk factors influence development and progression of GTD.