Benjamin E. Greer

Fred Hutchinson Cancer Research Center, Seattle, Washington, United States

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Publications (101)510.77 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage. Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P < .001) for IBD; 2.05 (95% CI, 1.09 to 3.88; P = .026) for LBR; 1.95 (95% CI, 0.894 to 4.25; P = .093) for SBR; and 2.15 for bevacizumab exposure (aggregated 95% CI, 1.05 to 4.40; P = .036). History of treatment for IBD, and bowel resection at primary surgery, increase the odds of GI AEs in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a GI AE, but is not appreciably increased by continuation beyond chemotherapy.
    Journal of Clinical Oncology 03/2014; 32(12). DOI:10.1200/JCO.2013.53.6524 · 17.88 Impact Factor
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    ABSTRACT: Adenocarcinoma of the endometrium (also known as endometrial cancer or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. An estimated 49,560 new uterine cancer cases will occur in 2013, with 8190 deaths resulting from the disease. Uterine sarcomas (stromal/mesenchymal tumors) are uncommon malignancies, accounting for approximately 3% of all uterine cancers. The NCCN Guidelines for Uterine Neoplasms describe malignant epithelial carcinomas and uterine sarcomas; each of these major categories contains specific histologic groups that require different management. This excerpt of these guidelines focuses on early-stage disease.
    Journal of the National Comprehensive Cancer Network: JNCCN 02/2014; 12(2):248-80. · 4.24 Impact Factor
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    ABSTRACT: PURPOSE: To analyze quality of life (QOL) in a randomized, placebo-controlled phase III trial concluding that the addition of concurrent and maintenance bevacizumab (Arm 3) to carboplatin and paclitaxel prolongs progression-free survival in front-line treatment of advanced ovarian cancer compared to chemotherapy alone (Arm 1) or chemotherapy with bevacizumab in cycles 2-6 only (Arm 2). PATIENTS AND METHODS: The Trial Outcome Index of the Functional Assessment of Cancer Therapy-Ovary (FACT-O TOI) was used to assess QOL before cycles 1, 4, 7, 13, and 21; and 6 months after completing study therapy. Differences in QOL scores were assessed using a linear mixed model, adjusting for baseline score, and age. The significance level was set at 0.0167 to account for multiple comparisons. RESULTS: 1693 patients were queried. Arm 2 (p<0.001) and Arm 3 (p<0.001) reported lower QOL scores than those in Arm 1. The treatment differences were observed mainly at cycle 4, when the patients receiving bevacizumab (Arm 2 and Arm 3) reported 2.72 points (98.3% CI: 0.88 ~ 4.57; effect size=0.18) and 2.96 points (98.3% CI: 1.13~4.78; effect size=0.20) lower QOL respectively, than those in Arm 1. The difference in QOL scores between Arm 1 and Arm 3 remained statistically significant up to cycle 7. The percentage of patients who reported abdominal discomfort dropped over time, without significant differences among study arms. CONCLUSION: The small QOL difference observed during chemotherapy did not persist during maintenance bevacizumab.
    Gynecologic Oncology 12/2012; DOI:10.1016/j.ygyno.2012.11.038 · 3.69 Impact Factor
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    ABSTRACT: Vascular endothelial growth factor is a key promoter of angiogenesis and disease progression in epithelial ovarian cancer. Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, has shown single-agent activity in women with recurrent tumors. Thus, we aimed to evaluate the addition of bevacizumab to standard front-line therapy. In our double-blind, placebo-controlled, phase 3 trial, we randomly assigned eligible patients with newly diagnosed stage III (incompletely resectable) or stage IV epithelial ovarian cancer who had undergone debulking surgery to receive one of three treatments. All three included chemotherapy consisting of intravenous paclitaxel at a dose of 175 mg per square meter of body-surface area, plus carboplatin at an area under the curve of 6, for cycles 1 through 6, plus a study treatment for cycles 2 through 22, each cycle of 3 weeks' duration. The control treatment was chemotherapy with placebo added in cycles 2 through 22; bevacizumab-initiation treatment was chemotherapy with bevacizumab (15 mg per kilogram of body weight) added in cycles 2 through 6 and placebo added in cycles 7 through 22. Bevacizumab-throughout treatment was chemotherapy with bevacizumab added in cycles 2 through 22. The primary end point was progression-free survival. Overall, 1873 women were enrolled. The median progression-free survival was 10.3 months in the control group, 11.2 in the bevacizumab-initiation group, and 14.1 in the bevacizumab-throughout group. Relative to control treatment, the hazard ratio for progression or death was 0.908 (95% confidence interval [CI], 0.795 to 1.040; P=0.16) with bevacizumab initiation and 0.717 (95% CI, 0.625 to 0.824; P<0.001) with bevacizumab throughout. At the time of analysis, 76.3% of patients were alive, with no significant differences in overall survival among the three groups. The rate of hypertension requiring medical therapy was higher in the bevacizumab-initiation group (16.5%) and the bevacizumab-throughout group (22.9%) than in the control group (7.2%). Gastrointestinal-wall disruption requiring medical intervention occurred in 1.2%, 2.8%, and 2.6% of patients in the control group, the bevacizumab-initiation group, and the bevacizumab-throughout group, respectively. The use of bevacizumab during and up to 10 months after carboplatin and paclitaxel chemotherapy prolongs the median progression-free survival by about 4 months in patients with advanced epithelial ovarian cancer. (Funded by the National Cancer Institute and Genentech; number, NCT00262847.).
    New England Journal of Medicine 12/2011; 365(26):2473-83. DOI:10.1056/NEJMoa1104390 · 54.42 Impact Factor
  • European Journal of Cancer 09/2011; 47:12-12. DOI:10.1016/S0959-8049(11)70122-8 · 4.82 Impact Factor
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    ABSTRACT: A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, peritoneal, or fallopian tube cancer (OC). Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m(2) on days 1, 8, and 15 of a 28-day cycle until progressive disease (PD) or excessive toxicity. The primary endpoint was progression-free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity. Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval [CI], 3.0-9.4) and 16.6 months (95% CI, 12.8-22.9), with 22 (55%) patients progression-free for ≥6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P = .03); median PFS, 10.9 versus 2.8 months (P = .08); median OS, 22.9 versus 12.8 months (P = .02). A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.
    Cancer 08/2011; 117(16):3731-40. DOI:10.1002/cncr.25967 · 5.20 Impact Factor
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    ABSTRACT: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor-A (VEGF-A), has clinical activity in multiple tumor types. We conducted a phase II trial to assess the activity and tolerability of single-agent bevacizumab in recurrent or persistent endometrial cancer (EMC). Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status of ≤ 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression or prohibitive toxicity. VEGF-A was assessed by immunohistochemistry in archival tumor and by enzyme-linked immunosorbent assay in pretreatment plasma. Primary end points were progression-free survival (PFS) at 6 months and overall response rate. Fifty-six patients were enrolled. Fifty-two patients were eligible and evaluable. Median age was 62 years, and prior treatment consisted of one or two regimens in 33 (63.5%) and 19 (36.5%) patients, respectively. Twenty-nine patients (55.8%) received prior radiation. Adverse events were consistent with those expected with bevacizumab treatment. No GI perforations or fistulae were seen. Seven patients (13.5%) experienced clinical responses (one complete response and six partial responses; median response duration, 6.0 months), and 21 patients (40.4%) survived progression free for at least 6 months. Median PFS and overall survival times were 4.2 and 10.5 months, respectively. Suggested associations were observed between high VEGF-A and adjusted hazard of death or tumor response when evaluated in tumor/plasma or plasma, respectively. Bevacizumab is well tolerated and active based on PFS at 6 months in recurrent or persistent EMC and warrants further investigation.
    Journal of Clinical Oncology 06/2011; 29(16):2259-65. DOI:10.1200/JCO.2010.32.6397 · 17.88 Impact Factor
  • Gynecologic Oncology 03/2011; 120(1). DOI:10.1016/j.ygyno.2010.12.014 · 3.69 Impact Factor
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    ABSTRACT: Primary mucinous adenocarcinomas of the ovary are uncommon, and their biological behavior is uncertain. Retrospective studies have suggested that many mucinous carcinomas initially diagnosed as primary to the ovary have in fact metastasized from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. A phase 3 trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were reclassified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared within the groups and with that of patients with serous carcinomas. Forty-four cases were classified as mucinous adenocarcinoma upon review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high, with unanimity of opinion in 30 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, P < 0.001). Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary.
    Cancer 02/2011; 117(3):554-62. DOI:10.1002/cncr.25460 · 4.90 Impact Factor
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    ABSTRACT: This study aimed to determine the first-cycle maximum tolerated dose (MTD) of intraperitoneal carboplatin in combination with intravenous paclitaxel and then assess the feasibility of this dose over multiple cycles. Beginning at an intraperitoneal (IP) carboplatin dose area under the curve (AUC) of 5 and a fixed intravenous dose of 175mg/m(2) paclitaxel, patients were entered on a dose-escalating phase evaluating first-cycle dose-limiting toxicity (DLT). After estimating the MTD, cohorts of 20 patients were then entered in an expanded phase to evaluate DLT over four cycles. Twenty-one patients were entered on the dose-escalating phase. A first-cycle MTD of carboplatin at AUC 8 was tolerated although thrombocytopenia was dose-limiting over multiple cycles. An additional 69 patients were treated in expanded cohorts. Only 5/90 (5.6%) patients discontinued treatment because of a port problem. Four-cycle DLT required de-escalation to a carboplatin AUC of 6, and even at that dose, there were 14 dose-limiting toxic effects in 40 patients (35%). Seven dose-limiting toxicities were due to neutropenia, and 6 were due to grade 3/4 thrombocytopenia. Six cycles of therapy were completed in 75% of eligible patients, but dose adjustments were required. The first-cycle MTD did not predict the tolerability of this regimen over multiple cycles. Using an IP carboplatin dose of AUC 6 in combination with paclitaxel, the regimen can be administered with a high completion rate over multiple cycles. Because neutropenia is a frequent DLT, the addition of hematopoietic growth factors may permit a high completion rate while maintaining this dose.
    Gynecologic Oncology 02/2011; 121(2):264-8. DOI:10.1016/j.ygyno.2010.12.358 · 3.69 Impact Factor
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    ABSTRACT: Potential predictive/prognostic angiogenic markers were prospectively examined in a phase II trial of bevacizumab in epithelial ovarian cancer (EOC)/primary peritoneal cancer (PPC). Recurrent/persistent EOC/PPC patients were treated with bevacizumab (15 mg/kg IV q21days) until disease progression. Validated-immunohistochemistry (IHC) assays were performed on pre-cycle 1/4 tumor biopsies for CD31-microvessel density (MVD), VEGF-histoscore (HS), p53-HS, and TSP1 image analysis score (IA). Pre-cycle 1/4 serum and plasma VEGF were quantified using a validated-ELISA. CD31-MVD and serum VEGF, evaluated pre-cycle 1 in 41/61 and 51/61 eligible patients, respectively, did not appear to be correlated. High CD31-MVD, categorized at the median, appeared to be associated with tumor response, a 13-month shorter median survival, and an increased risk of death (unadjusted hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.067-4.467). In addition, each standard deviation (SD) increase in CD31-MVD appeared to be associated with worse survival in unadjusted and adjusted analyses. IHC and plasma biomarkers did not change with bevacizumab treatment except for serum VEGF, which appeared to decrease during bevacizumab treatment. This decrease was not associated with response. High pre-cycle 1 serum VEGF, categorized at the median, was associated with 22-month shorter median survival and an increased risk of death (unadjusted HR = 2.7, 95% CI = 1.369-5.191). Categorized p53 appeared to be associated with unadjusted survival and each SD increase in TSP1-IA appeared to be associated with a decreased risk of progression in unadjusted and adjusted analyses. Despite the limitations in sample size and exploratory nature of the study, angiogenic markers in tumor and serum may provide prognostic value in recurrent/persistent EOC/PPC, and are being prospectively evaluated in the GOG phase III trial of carboplatin, paclitaxel and bevacizumab/placebo in previously untreated EOC/PPC.
    Gynecologic Oncology 12/2010; 119(3):484-90. DOI:10.1016/j.ygyno.2010.08.016 · 3.69 Impact Factor
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    ABSTRACT: Overview An estimated 12,200 new cases of cervical cancer will be diagnosed in the United States in 2010, and 4200 people will die of the disease.(1) Cervical cancer rates are decreasing among women in the United States, although incidence remains high among Hispanic/Latino, black, and Asian women.(2-5) However, cervical cancer is a major world health problem for women. The global yearly incidence of cervical cancer for 2002 was 493,200; the annual death rate was 273,500. It is the third most common cancer in women worldwide,(6,7) with 78% of cases occurring in developing countries, where cervical cancer is the second most frequent cause of cancer death in women. Persistent human papillomavirus (HPV) infection is regarded as the most important factor contributing to the development of cervical cancer. A relationship seems to exist between the incidence of cervical cancer and the prevalence of HPV in the population. The prevalence of chronic HPV in countries with a high incidence of cervical cancer is 10% to 20%, whereas its prevalence in low-incidence countries is 5% to 10%.(6) Immunization against HPV prevents infection with certain types of HPV and, thus, is expected to prevent specific HPV cancer in women (see NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines] for Cervical Cancer Screening, in this issue; to view the most recent version of these guidelines, visit the NCCN Web site at Other epidemiologic risk factors associated with cervical cancer are a history of smoking, parity, contraceptive use, early age at onset of coitus, larger number...
    Journal of the National Comprehensive Cancer Network: JNCCN 12/2010; 8(12):1388-416. · 4.24 Impact Factor
  • Journal of the National Comprehensive Cancer Network: JNCCN 06/2009; 7(5):498-531. · 4.24 Impact Factor
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    ABSTRACT: The Gynecologic Oncology Group (GOG) examined the association between ERBB2 amplification and clinical covariates, tumor response, disease status post-chemotherapy, progression-free survival (PFS), and overall survival (OS) in epithelial ovarian cancer (EOC). Women with suboptimally-resected, advanced stage EOC who participated in GOG-111, a multi-center randomized phase III trial of cyclophosphamide+cisplatin versus paclitaxel+cisplatin, and provided a tumor block through the companion protocol GOG-9404 were eligible. ERBB2 amplification was examined using fluorescence in situ hybridization (FISH) with probes for ERBB2 and the centromere of chromosome 17 (CEP17). ERBB2 amplification, defined as >2 copies of ERBB2/CEP17, was a rare event in EOC with 7% (9/133) of women exhibiting between 2.2 and 33.7 copies of ERBB2/CEP17, and was not associated with patient age, race, GOG performance status, stage, cell type, grade, measurable disease status, volume of ascites, tumor response or disease status post-chemotherapy. Women with >2 verses < or =2 copies of ERBB2/CEP17 did not have a reduced risk of disease progression (hazard ratio [HR]=0.56; 95% confidence interval [CI]=0.27-1.16; p=0.120) or death (HR=0.57; 95% CI=0.26-1.23; p=0.152), and ERBB2 amplification was not an independent prognostic factor for PFS or OS. ERBB2 amplification, defined as >4 copies of ERBB2/nuclei, was observed in 9% (12/133) of women with levels ranging from 4.2 to 49.2 copies of ERBB2/nuclei, and was associated with older age and volume of ascites, but not with the other clinical covariates or outcome. ERBB2 amplification is a rare event and has no predictive or prognostic value in suboptimally-resected, advanced stage EOC treated with platinum-based combination chemotherapy.
    Gynecologic Oncology 03/2009; 113(3):341-7. DOI:10.1016/j.ygyno.2009.02.009 · 3.69 Impact Factor
  • Gynecologic Oncology 12/2008; 111(2):375-6. DOI:10.1016/j.ygyno.2008.07.065 · 3.69 Impact Factor
  • Journal of the National Comprehensive Cancer Network: JNCCN 10/2008; 6(8):766-94. · 4.24 Impact Factor
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    ABSTRACT: Treatment of early-stage cervical and endometrial cancer has been associated with significant sexual difficulties in at least half of women following hysterectomy. Despite the fact that women report such sexual side effects to be the most distressing aspect of their cancer treatment, evidence-based treatments for Female Sexual Arousal Disorder (FSAD), the most common sexual symptom in this group, do not exist. We developed and pilot tested a brief, three session psychoeducational intervention (PED) targeting FSAD in 22 women with early-stage gynecologic cancer. The PED consisted of three, 1-h sessions that combined elements of cognitive and behavioral therapy with education and mindfulness training. Women completed questionnaires and had a physiological measurement of genital arousal at pre- and post-PED (sessions 1 and 4) and participated in a semi-structured interview (session 4) during which their feedback on the PED was elicited. There was a significant positive effect of the PED on sexual desire, arousal, orgasm, satisfaction, sexual distress, depression, and overall well-being, and a trend towards significantly improved physiological genital arousal and perceived genital arousal. Qualitative feedback indicated that the PED materials were very user-friendly, clear, and helpful. In particular, women reported the mindfulness component to be most helpful. These findings suggest that a brief 3-session PED can significantly improve aspects of sexual response, mood, and quality of life in gynecologic cancer patients, and has implications for establishing the components of a psychological treatment program for FSAD.
    Archives of Sexual Behavior 05/2008; 37(2):317-29. DOI:10.1007/s10508-007-9196-x · 3.53 Impact Factor
  • Journal of the National Comprehensive Cancer Network: JNCCN 02/2008; 6(1):58-82. · 4.24 Impact Factor
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    Journal of the National Comprehensive Cancer Network: JNCCN 02/2008; 6(1):14-36. · 4.24 Impact Factor
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    ABSTRACT: Vascular endothelial growth factor (VEGF) seems to be a promoter of tumor progression for epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC). We conducted a phase II trial to assess the efficacy and tolerability of single-agent bevacizumab, an anti-VEGF monoclonal antibody. Eligible patients had persistent or recurrent EOC/PPC after one to two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status of at least 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 21 days until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and clinical response. The study consisted of 62 eligible and assessable patients, median age 57 years, 41 (66.1%) having received two prior regimens and 26 (41.9%) considered platinum resistant. Grade 3 adverse events at least possibly related to bevacizumab were hematologic (1), GI (3), hypertension (6), thromboembolism (1), allergy (2), hepatic (1), pain (3), coagulation (1), constitutional (1), and dyspnea (1). Grade 4 adverse events included pulmonary embolus (1), vomiting and constipation (1), and proteinuria (1). Thirteen patients (21.0%) experienced clinical responses (two complete, 11 partial; median response duration, 10 months), and 25 (40.3%) survived progression free for at least 6 months. Median PFS and overall survival were 4.7 and 17 months, respectively. There was no significant association of prior platinum sensitivity, age, number of prior chemotherapeutic regimens, or performance status with the hazard of progression or death. Bevacizumab seems to be well tolerated and active in the second- and third-line treatment of patients with EOC/PPC and merits phase III investigation.
    Journal of Clinical Oncology 12/2007; 25(33):5165-71. DOI:10.1200/JCO.2007.11.5345 · 17.88 Impact Factor

Publication Stats

4k Citations
510.77 Total Impact Points


  • 1997–2012
    • Fred Hutchinson Cancer Research Center
      Seattle, Washington, United States
  • 1983–2011
    • University of Washington Seattle
      • • Department of Obstetrics and Gynecology
      • • Department of Radiation Oncology
      Seattle, Washington, United States
  • 2008
    • University of Alabama at Birmingham
      • Comprehensive Cancer Center
      Birmingham, AL, United States
  • 1999
    • Washington Hospital Center
      Washington, Washington, D.C., United States
  • 1992
    • West Georgia Obstetrics and Gynecology
      Georgetown, Georgia, United States