Matthew A Powell

Washington University in St. Louis, San Luis, Missouri, United States

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Publications (138)559.57 Total impact

  • Gynecologic Oncology. 11/2014; 135(2).
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    ABSTRACT: This study compares surgical and survival outcomes of women with stage IV uterine serous carcinoma (USC) treated with neoadjuvant chemotherapy (NAC) and interval cytoreduction to women treated with primary cytoreductive surgery (PCS) followed by adjuvant chemotherapy.
    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 10/2014;
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    ABSTRACT: In the United States, 56% of ovarian cancer cases do not receive NCCN guideline care•Delivery of non-guideline care for ovarian cancer is correlated with facility case volume and survival•65% of U.S. cancer centers treat fewer than 8 cases of ovarian cancer annually
    Gynecologic Oncology. 10/2014;
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    ABSTRACT: Sarcopenia or loss of skeletal muscle mass is an objective measure of frailty associated with functional impairment and disability. This study aimed to examine the impact of sarcopenia on surgical complications and survival outcomes in patients with endometrial cancer.
    Annals of Surgical Oncology 09/2014; · 4.12 Impact Factor
  • Sara S Lange, Akiva P Novetsky, Matthew A Powell
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    ABSTRACT: Uterine sarcomas are a heterologous group of rare malignancies accounting for 8-10% of all uterine malignancies, but are significantly more aggressive and have worse prognoses. Management of uterine sarcomas including leiomyosarcoma and endometrial stromal sarcoma are reviewed here, with additional discussions regarding high-grade undifferentiated sarcoma and adenosarcoma. Uterine carcinosarcomas are currently staged and treated similar to high-grade epithelial endometrial carcinomas, thus will not be discussed in this review. Gemcitabine/docetaxel with adriamycin holds promise for the treatment of leiomyosarcoma, but currently, limited advancements have been made in discovering targeted therapies to these tumors. Continued translational research in both medical oncology and gynecologic oncology is necessary to forward the development of novel and targeted therapeutic agents in the treatment of sarcoma. Enrollment of these patients in clinical trials is encouraged, and will allow for the development of safer and more effective therapies.
    Discovery medicine 09/2014; 18(98):133-40. · 2.97 Impact Factor
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    ABSTRACT: Brivanib, an oral, multi-targeted tyrosine kinase inhibitor with activity against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR) was investigated as a single agent in a phase II trial to assess the activity and tolerability in recurrent or persistent endometrial cancer (EMC). Patients and Methods Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and performance status of ≤2. Treatment consisted of brivanib 800mg orally every day until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) at six months and objective tumor response. Expression of multiple angiogenic proteins and FGFR2 mutation status was assessed.
    Gynecologic oncology. 07/2014;
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    ABSTRACT: Obese women have a high incidence of wound separation after gynecologic surgery. We explored the effect of a prospective care pathway on the incidence of wound complications.
    Gynecologic oncology. 06/2014;
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    ABSTRACT: Objective To examine the patterns of care, predictors, and impact of chemotherapy on survival in elderly women diagnosed with early-stage uterine carcinosarcoma. Methods The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify women 65 years or older diagnosed with stage I-II uterine carcinosarcoma from 1991 through 2007. Multivariable logistic regression and Cox-proportional hazards models were used for statistical analysis. Results A total of 462 women met the eligibility criteria; 374 had stage I, and 88 had stage II uterine carcinosarcoma. There were no appreciable differences over time in the percentages of women administered chemotherapy for early stage uterine carcinosarcoma (14.7% in 1991–1995, 14.9% in 1996–2000, and 17.9% in 2001–2007, P = 0.67). On multivariable analysis, the factors positively associated with receipt of chemotherapy were younger age at diagnosis, higher disease stage, residence in the eastern part of the United States, and lack of administration of external beam radiation (P < 0.05). In the adjusted Cox-proportional hazards regression models, administration of three or more cycles of chemotherapy did not reduce the risk of death in stage I patients (HR: 1.45, 95% CI: 0.83-2.39) but was associated with non-significant decreased mortality in stage II patients (HR: 0.83, 95% CI: 0.32-1.95). Conclusions Approximately 15-18% of elderly patients diagnosed with early-stage uterine carcinosarcoma were treated with chemotherapy. This trend remained stable over time, and chemotherapy was not associated with any significant survival benefit in this patient population.
    Gynecologic Oncology 06/2014; · 3.93 Impact Factor
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    ABSTRACT: Combination chemotherapy and radiation are used for adjuvant treatment of stage III-IV endometrial cancer. The goal of this study was to review the treatment duration, toxicity, and survival for patients treated with concomitant chemotherapy and radiation. Women with stage III-IV endometrial cancer treated with concurrent chemotherapy and radiation between 2006 and 2013 were included. Toxicities were classified per CTCAE v3.0 and RTOG/EORTC late radiation morbidity scoring. Descriptive statistics were used to quantify treatment and toxicities. Kaplan-Meier method was used to estimate survival. Fifty-one patients met our inclusion criteria. Median age was 60 (range 33-85). Thirty-six patients (70.6%) had endometrioid histology, 13 patients (25.5%) had serous, clear cell, or mixed histology, and two women (3.9%) had carcinosarcoma. Forty-eight patients had stage III disease and three patients were stage IVB. Mean treatment duration was 107±19days. Forty-two patients received all planned chemotherapy, and sixteen patients required a dose reduction. Thirty-four patients (66.7%) experienced grade 3-4 toxicities, the majority of which were hematologic. There were no deaths related to therapy. Eighty-six percent of patients received leukocyte growth factors, and 25% of patients received a blood transfusion. Seven late grade 3-4 complications occured: four gastrointestinal, two genitourinary, and one patient had ongoing neuropathy. Median progression-free survival was 42.8months (range 4.4-81.5months) and median overall survival was 44.9months (range 5.1-82.6months). Three-year overall survival was 80%. Concomitant chemotherapy and radiation is an adequately tolerated treatment modality that allows for shorter treatment duration.
    Gynecologic Oncology 05/2014; · 3.93 Impact Factor
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    ABSTRACT: The objectives of this study are to identify the characteristics of febrile gynecologic oncology patients and to evaluate the utility of common diagnostic procedures used to assess the etiologies of their fevers. Retrospective data were collected for 200 consecutive patients admitted to the gynecologic oncology service at 1 institution between January 2008 and December 2012 for a diagnosis of fever. Data were collected using contingency tables, and the χ test was used as appropriate. Of the patients admitted for evaluation of fever, 142 (71%) of 200 had a documented fever during hospitalization. The most common etiologies of fever in this population were urinary tract infections (28%) and bloodstream infections (27%), whereas 24% of those admitted for fever did not have a source identified. Abdominal/pelvic computed tomography (CT) scans established the etiology of fever in 53 (60%) of the 89 patients tested, whereas chest x-ray and chest CT were diagnostic for 6% and 21%, respectively. Blood and urine cultures were diagnostic in 29% and 32% of cases, respectively. Patients admitted within 30 days of surgery had a higher percentage of wound infections (38% vs 10%, P < 0.001) as compared with those admitted for more than 30 days after surgery. The initial evaluation of the febrile gynecologic oncology patient without obvious source by history and examination should include urinalysis with reflex culture and blood cultures. Abdominopelvic and chest CT may be useful when fever persists and initial assessment is unrevealing. Chest x-ray is commonly done but infrequently diagnostic. Wound exploration may be important in patients with fevers for more than 30 days after surgery.
    International Journal of Gynecological Cancer 05/2014; · 1.94 Impact Factor
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    ABSTRACT: Intensity-modulated radiation therapy (IMRT) is frequently utilized in the treatment of cervical cancer. Our study compared instances of pelvic fractures, osteonecrosis, and osteomyelitis posttreatment with conventional radiation therapy (RT) versus IMRT in patients with cervical carcinomas. Eighty-three patients primarily treated with IMRT were case matched with 83 historical control subjects treated with conventional RT. Pretreatment and posttreatment computed tomography scans were reviewed. Logistic regression analysis was utilized to examine the effects of treatment type (conventional RT vs IMRT) on the occurrence of posttreatment pelvic bony structure complications while adjusting for confounders. In the IMRT group, 3 (4%) of 83 patients developed posttreatment sacral fractures (median follow-up, 51 months). In the conventional RT group, there were 14 pelvic girdle complications (17%): 9 fractures, 2 cases of osteonecrosis, and 3 cases of osteomyelitis (median follow-up, 43.5 months; odds ratio, 4.49 for conventional vs IMRT groups, P = 0.01; 95% confidence interval, 1.4-14.1). In addition, there were 4 cases of posttreatment osteoporosis in the conventional RT group. All patients with complications in the IMRT group and 11 of 13 in the conventional RT group were symptomatic. Intensity-modulated radiation therapy is associated with a lower risk for pelvic girdle complications than conventional RT.
    International Journal of Gynecological Cancer 03/2014; · 1.94 Impact Factor
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    ABSTRACT: Drug resistance is a significant problem in the treatment of ovarian cancer and can be caused by multiple mechanisms. Inhibition of apoptosis by the inhibitor of apoptosis proteins (IAPs) represents one such mechanism, and can be overcome by a mitochondrial protein called second mitochondria-derived activator of caspases (SMAC). We have previously shown that the ligands of sigma-2 receptors effectively induce tumor cell death. Additionally, because sigma-2 receptors are preferentially expressed in tumor cells, their ligands provide an effective mechanism for selective anti-cancer therapy. In the current work, we have improved upon the previously described sigma-2 ligand SW43 by conjugating it to a pro-apoptotic small molecule SMAC mimetic SW IV-52, thus generating the novel cancer therapeutic SW IV-134. The new cancer drug was tested for receptor selectivity and tumor cell killing activity in vitro and in vivo. We have shown that SW IV-134 retained adequate sigma-2 receptor binding affinity in the context of the conjugate and potently induced cell death in ovarian cancer cells. The cell death induced by SW IV-134 was significantly greater than that observed with either SW43 or SW IV-52 alone and in combination. Furthermore, the intraperitoneal administration of SW IV-134 significantly reduced tumor burden and improved overall survival in a mouse xenograft model of ovarian cancer without causing significant adverse effects to normal tissues. Mechanistically, SW IV-134 induced degradation of cIAP-1 and cIAP-2 leading to NF-[cyrillic small letter ka with descender]B activation and TNFalpha-dependent cell death. Our findings suggest that coupling sigma-2 ligands to SMAC peptidomimetics enhances their effectiveness while maintaining the cancer selectivity. This encouraging proof-of-principle preclinical study supports further development of tumor-targeted small peptide mimetics via ligands to the sigma-2 receptor for future clinical applications.
    Molecular Cancer 03/2014; 13(1):50. · 5.13 Impact Factor
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    ABSTRACT: The targeted delivery of cancer therapeutics represents an ongoing challenge in the field of drug development. TRAIL is a promising cancer drug but its activity profile could benefit from a cancer-selective delivery mechanism, which would reduce potential side effects and increase treatment efficiencies. We recently developed the novel TRAIL-based drug platform TR3, a genetically fused trimer with the capacity for further molecular modifications such as the addition of tumor-directed targeting moieties. MUC16 (CA125) is a well characterized biomarker in several human malignancies including ovarian, pancreatic and breast cancer. Mesothelin is known to interact with MUC16 with high affinity. In order to deliver TR3 selectively to MUC16-expressing cancers, we investigated the possibility of targeted TR3 delivery employing the high affinity mesothelin/MUC16 ligand/receptor interaction. Using genetic engineering, we designed the novel cancer drug Meso-TR3, a fusion protein between native mesothelin and TR3. The recombinant proteins were produced with mammalian HEK293T cells. Meso-TR3 was characterized for binding selectivity and killing efficacy against MUC16-positive cancer cells and controls that lack MUC16 expression. Drug efficacy experiments were performed in vitro and in vivo employing an intraperitoneal xenograft mouse model of ovarian cancer. Similar to soluble mesothelin itself, the strong MUC16 binding property was retained in the Meso-TR3 fusion protein. The high affinity ligand/receptor interaction was associated with a selective accumulation of the cancer drug on MUC16-expressing cancer targets and directly correlated with increased killing activity in vitro and in a xenograft mouse model of ovarian cancer. The relevance of the mesothelin/MUC16 interaction for attaching Meso-TR3 to the cancer cells was verified by competitive blocking experiments using soluble mesothelin. Mechanistic studies using soluble DR5-Fc and caspase blocking assays confirmed engagement of the extrinsic death receptor pathway. Compared to non-targeted TR3, Meso-TR3 displayed a much reduced killing potency on cells that lack MUC16. Soluble Meso-TR3 targets the cancer biomarker MUC16 in vitro and in vivo. Following attachment to the tumor via surface bound MUC16, Meso-TR3 acquires full activation with superior killing profiles compared to non-targeted TR3, while its bioactivity is substantially reduced on cells that lack the tumor marker. This prodrug phenomenon represents a highly desirable property because it has the potential to enhance cancer killing with fewer side-effects than non-targeted TRAIL-based therapeutics. Thus, further exploration of this novel fusion protein is warranted as a possible therapeutic for patients with MUC16-positive malignancies.
    BMC Cancer 01/2014; 14(1):35. · 3.33 Impact Factor
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    ABSTRACT: Recent reports have suggested that uterine manipulators can induce lymphovascular space involvement (LVSI) by endometrial cancer in laparoscopic hysterectomy specimens. The prognostic significance of this phenomenon known as "vascular pseudo invasion" remains elusive. The authors conducted a retrospective, single institution study of patients who underwent initial surgery for grade 1 and grade 2 endometrioid endometrial cancers with LVSI. Cases were stratified by surgical approach (laparoscopy vs laparotomy). Clinicopathologic and procedure characteristics as well as outcome data were analyzed. Univariate and multivariate analyses were performed. Disease-free survival (DFS) was analyzed using the Kaplan-Meier product limit method. A total of 104 cases (20 laparoscopic, 84 laparotomy) were analyzed. Mean age (65 vs 64 years, respectively), stage distribution, mean number of lymph nodes sampled (18 vs 21, respectively) and use of adjuvant therapy was similar for both groups (p > 0.05). Mean body mass index (BMI) was 30 vs 35 kg/m2, respectively (p = 0.002). Mean follow up was 24 months (range 0.1-102). Univariate analysis demonstrated that LVSI in the laparoscopic setting was associated with worse DFS (p = 0.002). After adjusting for grade the risk of recurrence remained higher for laparoscopic cases (HR: 15.7, 95% CI 1.7-140.0, p = 0.014). Adjusted risk of recurrence associated with LVSI is higher in cases approached laparoscopically arguing against the concept of "vascular pseudo invasion" associated with the use of uterine manipulators and balloons. LVSI should be regarded as a serious risk factor and taken into account for triage to adjuvant therapies, even in laparoscopically treated early-stage endometrial cancer.
    European journal of gynaecological oncology 01/2014; 35(1):7-10. · 0.58 Impact Factor
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    ABSTRACT: This open-label, multi-institutional Phase II trial evaluated activity and safety of rilotumumab (AMG 102), a monoclonal antibody that targets HGF (hepatocyte growth factor), the ligand for the MET receptor, in women with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer. Patients and methods Women were eligible for treatment with rilotumumab if they had measurable disease, a performance status of 0, 1 or 2, previously received platinum-based therapy with a progression-free interval of <12months or a second recurrence, and adequate bone marrow and organ function. Patients received rilotumumab 20mg/kg IV every 14days until evidence of unacceptable toxicity or disease progression. The study utilized co-dual primary endpoints of tumor response and six-month PFS to assess the efficacy of rilotumumab. Secondary endpoints included the frequency and severity of adverse events and the duration of progression-free and overall survival. Thirty-one women enrolled and received rilotumumab. All were eligible for analysis. One patient achieved a complete response (3.2%; 90% CI 0.2 - 14%), and two women had 6-month PFS (6.5%; 90% CI 1.1 - 19%). Most adverse events were grade 1 or 2, with no grade 4 adverse events. Grade 3 adverse events were gastrointestinal (4), metabolic (3) anemia (3), a thromboembolic event(1), ventricular tachycardia(1), hypotension during infusion(1) and fatigue(1). The study was stopped after the first stage of accrual. Rilotumumab was well-tolerated, but had limited activity. The level of activity does not warrant further evaluation of rilotumumab as a single agent in patients with ovarian cancer.
    Gynecologic Oncology 12/2013; · 3.93 Impact Factor
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    ABSTRACT: To characterize gynecologic oncology patients' perceptions of the process of disclosure of a cancer diagnosis. We surveyed 100 gynecologic oncology patients between December 2011 and September 2012. An 83-item tool based on three validated assessment tools evaluated patient-centered factors, physician behavior and communication skills, and environmental factors. Associations between patients' satisfaction and these variables were analyzed using Wilcoxon rank-sum, Kruskal-Wallis, and Spearman's rho tests. Poisson regression was used to assess factors associated with patient's satisfaction. Twenty-four percent of patients were notified of their diagnosis by phone, 60% in the physician's office, and 16% in the hospital. Disclosure was performed by an obstetrician-gynecologist (58%), gynecologic oncologist (26%), primary care physician (8%), or other (8%). Fifty-two percent of all patients were accompanied by a support person. Higher patient satisfaction scores were associated with face-to-face disclosure (mean score 91% compared with over the phone 72%, P=.02), a private setting (mean score 92% compared with impersonal setting 72%, P=.004), and duration of the encounter of greater than 10 minutes (mean score 94% compared with less than 10 minutes 79%, P<.001). Multivariate analysis confirmed that both physician communication skills (P<.001) and patient-centered factors (eg, perception of physician sensitivity and empathy, opportunities to ask questions and express emotion, and set the pace of conversation; P=.013) were associated with higher patient satisfaction. Effective physician communication skills and patient-centered factors resulted in higher patient satisfaction with the gynecologic cancer diagnosis disclosure experience. LEVEL OF EVIDENCE:: II.
    Obstetrics and Gynecology 10/2013; · 4.80 Impact Factor
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    ABSTRACT: To evaluate the efficacy and safety of combination bevacizumab/pemetrexed for the treatment of recurrent epithelial ovarian cancer (EOC). Platinum-sensitive or -resistant patients with recurrent or persistent EOC were eligible if they had received up to 2 prior chemotherapy regimens, including a platinum/taxane regimen without prior bevacizumab. Pemetrexed 500mg/m(2) IV and bevacizumab 15mg/kg IV were administered every 3weeks. The primary endpoint was 6-month progression-free survival (PFS); other endpoints included toxicities, PFS and overall survival (OS). Thirty-four patients received a median of 7 treatment cycles (range, 2-26). Median follow-up was 25.7months (range, 3.0-47.2). Six month progression-free survival (PFS) was 56% (95%CI: 38-71). The following response rates were documented (%; 95%CI): 0 complete response, 14 partial responses (41%; 25-59), 18 stable disease (53%; 35-70) and 2 progressive disease (6%; 1-20). Median PFS was 7.9months (95%CI, 4.6-10.9), with a median OS of 25.7months (95% CI, 15.4-29.8). Twenty-two patients (64.7%) had a platinum-free interval (PFI) of >6months prior to enrollment. Grade 3-4 hematologic toxicities included neutropenia (50%), leukopenia (26%), thrombocytopenia (12%) and anemia (9%). Non-hematologic grade 3-4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). Two patients developed hematologic malignancies within one year of treatment. Combination bevacizumab/pemetrexed is an active option for both platinum-sensitive and -resistant recurrent EOC. Further investigation of cost and novel toxicities associated with this regimen may be warranted.
    Gynecologic Oncology 10/2013; · 3.93 Impact Factor
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    ABSTRACT: These NCCN Guidelines Insights focus on the major updates to the 2013 NCCN Guidelines for Ovarian Cancer. Four updates were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials. The topics include 1) intraperitoneal chemotherapy, 2) CA-125 monitoring for ovarian cancer recurrence, 3) surveillance recommendations for less common ovarian histopathologies, and 4) recent changes in therapy for recurrent epithelial ovarian cancer. These NCCN Guidelines Insights also discuss why some recommendations were not made.
    Journal of the National Comprehensive Cancer Network: JNCCN 10/2013; 11(10):1199-209. · 5.11 Impact Factor
  • Akiva P Novetsky, Matthew A Powell
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    ABSTRACT: Uterine sarcomas are rare malignancies accounting for 8-10% of all uterine malignancies, but are significantly more aggressive and have worse prognosis. Management of uterine sarcomas including leiomyosarcoma (LMS), endometrial stromal sarcoma, high-grade undifferentiated sarcoma and adenosarcoma is reviewed. Uterine carcinosarcomas are staged and treated similarly to high-grade epithelial endometrial carcinomas and are no longer considered uterine sarcomas. Gemcitabine/docetaxel with doxorubicin holds promise for the treatment of LMS. A recently developed nomogram was demonstrated to predict disease recurrence in patients with LMS which may allow us to identify a subset of patients who are likely to recur and target this population for adjuvant systemic therapy. Cytogenetic abnormalities have been identified that allow differentiation of endometrial stromal sarcomas from high-grade undifferentiated uterine sarcomas which may be useful in pathologically difficult cases. Uterine sarcomas are a heterogeneous group of tumors. To date, limited advancements have been made in discovering targeted therapies to these tumors. Chemotherapy with gemcitabine/docetaxel followed by doxorubicin holds promise in the treatment of LMS. Given the rarity of these tumors and the lack of clinical trials to guide management, patients with uterine sarcomas should be encouraged to enroll on clinical trials.
    Current opinion in oncology 09/2013; 25(5):546-52. · 4.09 Impact Factor
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    ABSTRACT: OBJECTIVE: The objective of this study was to assess patients' preferences of the timing of referral for genetic counseling and testing in relation to the diagnosis, treatment, and recurrence of ovarian, tubal, or primary peritoneal cancers. METHODS: Ninety-two patients who underwent counseling and testing by 1 certified genetic counselor were identified. An introductory letter, consent form, and questionnaire were mailed to gather information regarding factors influencing the decision to undergo genetic counseling and testing and opinions regarding optimal timing. Medical records were reviewed for demographic and clinical data. RESULTS: Of 47 consenting women, 45 underwent testing. Eight (18%) were found to have a genetic mutation. Women lacked consensus about the optimal time for referral for and to undergo genetic testing, although women with stage I disease preferred testing after completion of chemotherapy. Most women were comfortable receiving the results by phone, but one third preferred an office visit. CONCLUSIONS: Patients' views regarding the best time to be referred for and undergo counseling and testing varied greatly. Because of the high mortality of this disease, clinicians should discuss referral early and personalize the timing to each patient. The subset of patients who prefer results disclosure during an office visit should be identified at the time of their initial counseling.
    International Journal of Gynecological Cancer 06/2013; · 1.94 Impact Factor

Publication Stats

2k Citations
559.57 Total Impact Points

Institutions

  • 2002–2014
    • Washington University in St. Louis
      • Department of Obstetrics and Gynecology
      San Luis, Missouri, United States
  • 2013
    • Temple University
      Philadelphia, Pennsylvania, United States
  • 2008–2012
    • Translational Genomics Research Institute
      Phoenix, Arizona, United States
  • 2002–2010
    • University of Washington Seattle
      • • Department of Radiation Oncology
      • • Department of Obstetrics and Gynecology
      Seattle, WA, United States
  • 2005–2009
    • Barnes Jewish Hospital
      • Department of Obstetrics and Gynecology
      Saint Louis, MO, United States
  • 2007–2008
    • Columbia University
      • Department of Obstetrics and Gynecology
      New York City, New York, United States
    • National Institutes of Health
      • Branch of Radiation Oncology
      Bethesda, MD, United States
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 2006
    • University of Alabama at Birmingham
      • Department of Obstetrics and Gynecology
      Birmingham, Alabama, United States
    • Northwestern University
      • Department of Obstetrics and Gynecology
      Evanston, IL, United States