Zhengjia Chen

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

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Publications (154)841.83 Total impact

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    ABSTRACT: Background: Stereotactic radiosurgery (SRS) is an increasingly common modality used with surgery for resectable brain metastases (BM). Objective: To present a multi-institutional retrospective comparison of outcomes and toxicities of preoperative SRS (Pre-SRS) and postoperative SRS (Post-SRS). Methods: We reviewed the records of patients who underwent resection of BM and either Pre-SRS or Post-SRS alone between 2005 and 2013 at 2 institutions. Pre-SRS used a dose-reduction strategy based on tumor size, with planned resection within 48 hours. Cumulative incidence with competing risks was used to determine estimated rates. Results: A total of 180 patients underwent surgical resection for 189 BM: 66 (36.7%) underwent Pre-SRS and 114 (63.3%) underwent Post-SRS. Baseline patient characteristics were balanced except for higher rates of performance status 0 (62.1% vs 28.9%, P < .001) and primary breast cancer (27.2% vs 10.5%, P = .010) for Pre-SRS. Pre-SRS had lower median planning target volume margin (0 mm vs 2 mm) and peripheral dose (14.5 Gy vs 18 Gy), but similar gross tumor volume (8.3 mL vs 9.2 mL, P = .85). The median imaging follow-up period was 24.6 months for alive patients. Multivariable analyses revealed no difference between groups for overall survival (P = .1), local recurrence (P = .24), and distant brain recurrence (P = .75). Post-SRS was associated with significantly higher rates of leptomeningeal disease (2 years: 16.6% vs 3.2%, P = .010) and symptomatic radiation necrosis (2 years: 16.4% vs 4.9%, P = .010). Conclusion: Pre-SRS and Post-SRS for resected BM provide similarly favorable rates of local recurrence, distant brain recurrence, and overall survival, but with significantly lower rates of symptomatic radiation necrosis and leptomeningeal disease in the Pre-SRS cohort. A prospective clinical trial comparing these treatment approaches is warranted. Abbreviations: BM, brain metastasesCI, confidence intervalCTV, clinical target volumeDBR, distant brain recurrenceGTV, gross tumor volumeLC, local controlLMD, leptomeningeal diseaseLR, local recurrenceMVA, multivariable analysisOS, overall survivalPost-SRS, postoperative stereotactic radiosurgeryPre-SRS, preoperative stereotactic radiosurgeryPTV, planning target volumeRN, radiation necrosisSRN, symptomatic radiation necrosisSRS, stereotactic radiosurgeryWBRT, whole-brain radiation therapy.
    Neurosurgery 11/2015; DOI:10.1227/NEU.0000000000001096 · 3.62 Impact Factor

  • International journal of radiation oncology, biology, physics 11/2015; 93(3):S194. DOI:10.1016/j.ijrobp.2015.07.464 · 4.26 Impact Factor
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    ABSTRACT: Background: The last 3 decades have witnessed limited therapeutic advances in small cell lung cancer (SCLC) management. This study evaluated real-world trends in the use of systemic therapies and the impact on patient outcomes in the United States. Methods: The Surveillance, Epidemiology, and End Results-Medicare database was used to find patients diagnosed with SCLC between 1985 and 2005. The 1985-1990 period served as the baseline for a temporal analysis conducted at 5-year intervals (1985-1990, 1991-1995, 1996-2000, and 2001-2005). Cox proportional models were used to estimate the effect of chemotherapy on survival. Results were validated with a propensity-matched analysis. Results: There were 47,351 eligible patients: 52% were male; the median age was 71 years; and 87% were white, 7% were black, and 1.4% were Asian. The proportion of patients treated with chemotherapy was low but increased over time (38%, 55%, 50%, and 53%; P < .001). Race, diagnosis period, age, stage, and location of residence significantly predicted chemotherapy use. Females (51%), Asians (53%), and rural residents (60%) were more likely to receive chemotherapy. The median overall survival with and without chemotherapy was 9.6 and 3.6 months, respectively. Linear trend analyses showed a modest reduction in the impact of chemotherapy on survival for patients treated with chemotherapy versus untreated patients (hazard ratios [HRs], 0.59, 0.61, 0.64, and 0.62; P < .001) but an overall trend of improved survival for treated (HRs, 1.0, 1.03, 1.00, and 0.96; P = .005) and untreated patients (HRs, 1.0, 0.99, 0.94, and 0.92; P < .001). There was no survival difference between patients treated with carboplatin and patients treated with cisplatin (HR, 0.99; confidence interval [CI], 0.81-1.19; P = .875). Additional therapy beyond platinum-based chemotherapy was associated with a survival benefit (HR, 0.78; CI, 0.75-0.81; P < .001). Conclusions: Chemotherapy use was associated with a survival benefit in Medicare patients with SCLC treated in a real-world setting. Cancer 2015. © 2015 American Cancer Society.
    Cancer 10/2015; DOI:10.1002/cncr.29674 · 4.89 Impact Factor
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    Journal of Oral Pathology and Medicine 10/2015; DOI:10.1111/jop.12378 · 1.93 Impact Factor
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    ABSTRACT: B43-pokeweed antiviral protein (B43-PAP) is a high-affinity anti-CD19 immunotoxin that is capable of causing apoptotic death in B-lineage leukemic cells with a drug-resistant phenotype. B43-PAP exhibited in vivo antileukemic activity in preclinical studies as well as on a single-agent phase I clinical trial. This pediatric phase I/II study evaluated the toxicity profile and efficacy of B43-PAP immunotoxin in combination with standard induction chemotherapy in children and adolescents with relapsed CD19-positive B-lineage acute lymphoblastic leukemia (B-ALL). Pharmacokinetic profile and immunogenicity of B43-PAP were assessed. B43-PAP in combination with standard 3 and 4-drug induction chemotherapy was administered on days 9-13 and 21-25 of a 28-day treatment course with vincristine, prednisone, L-asparaginase, daunomycin, and intrathecal methotrexate. Thirty patients with relapsed B-ALL were enrolled on study CCG-0957. Grade III/IV nonhematologic dose-limiting toxicities were encountered in 4 patients evaluable for toxicity and included myalgias, motor dysfunction, pulmonary toxicity, and elevated liver transaminase. Dose-limiting toxicities occurred only with the 4-drug regimen. Fourteen patients achieved a complete remission at the end of induction among the 20 patients evaluable for response. B43-PAP in combination with standard induction chemotherapy can be safely administered and exhibits clinical antileukemic activity against relapsed B-ALL.
    Journal of immunotherapy (Hagerstown, Md.: 1997) 09/2015; 38(7):299-305. DOI:10.1097/CJI.0000000000000088 · 4.01 Impact Factor
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    ABSTRACT: The aim of this study is to characterize the changes in the incidence, presentation, surgical treatment, and survival of patients with appendiceal mucinous neoplasm (AMN) over the past 4 decades using nationwide cancer surveillance data. Patients with the diagnosis of AMN were identified in the Surveillance Epidemiology and End Results (SEER) database. Information on demographics, disease characteristics, and surgical treatment was collected. Temporal changes in AMN incidence, characteristics of cases, and survival were analyzed from 1973 to 2011. Determinants of overall survival (OS) were examined using both crude and multivariable Cox proportional hazard models. The overall incidence rate of AMN increased on average 3.1%/1,000,000 persons-years (P<0.001). A significant decline in the age at diagnosis was observed (P=0.014). The proportion of patients presenting with distant disease at diagnosis also significantly increased (P=0.004). Five-year survival of patients with distant stage AMN increased at a rate of 3.5%/y between 1984 and 2006 (P<0.001). Median OS was not reached for localized and regional stage disease. Median OS for distant stage disease was 42 months. There has been an increase in the overall incidence of AMN with an observed increase in the proportion of younger age and distant stage at diagnosis. The OS has improved over time.
    American journal of clinical oncology 08/2015; DOI:10.1097/COC.0000000000000210 · 3.06 Impact Factor
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    Cancer Research 08/2015; 75(15 Supplement):20-20. DOI:10.1158/1538-7445.AM2015-20 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):813-813. DOI:10.1158/1538-7445.AM2015-813 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):CT303-CT303. DOI:10.1158/1538-7445.AM2015-CT303 · 9.33 Impact Factor
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    ABSTRACT: In preclinical studies, the efficacy of the combination of antiangiogenic agents with chemotherapy seems to be dependent on the specific cytotoxic agent. We conducted a systematic review of the efficacy of bevacizumab in combination with taxane or non-taxane containing regimens for untreated, nonsquamous non-small-cell lung cancer patients. An extensive search of published clinical trials was conducted from electronic databases (MEDLINE, EMBASE, and Cochrane) and meeting proceedings using relevant search criteria. Phase 2 and randomized trials reporting on the efficacy of bevacizumab combined with taxane or non-taxane regimens were selected. A systematic analysis of extracted data was performed using Comprehensive Meta-Analysis (Version 2.2) software. Clinical outcome in patients treated with taxane versus non-taxane regimen was compared using point estimates for weighted values of median overall survival, progression-free survival, and response rate. Twenty-nine studies reported between 2005 and 2015 were eligible. A total of 5890 patients (2767 and 3123 in the taxane and non-taxane groups, respectively) were included. The taxane and non-taxane groups were comparable in patient characteristics: median age, 62.8 versus 61.2 years; males, 57% versus 58%; adenocarcinomas, 83% versus 83%; stage IV, 87% versus 82%; performance status 0/1- 45/55% versus 41/59%, respectively. The weighted median overall survival was 14.4 versus 13.7 months (p = 0.5); progression-free survival was 6.93 versus 6.99 months (p = 0.61); response rate was 41% versus 39% (p = 0.65) for taxane and non-taxane groups. The outcomes between taxane and non-taxane regimens when given in combination with bevacizumab for patients with nonsquamous non-small-cell lung cancer are comparable.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2015; 10(8):1142-7. DOI:10.1097/JTO.0000000000000572 · 5.28 Impact Factor
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    ABSTRACT: To evaluate the utility of dynamic, contrast-enhanced magnetic resonance imaging (MRI) in combination with single-shot T2-weighted (ssT2) sequences in the differentiation of lipid-poor adrenal adenomas from non-adenomas. This retrospective study was approved by the institutional review board and is HIPAA compliant. Between January 2007 and December 2010, 46 patients with MRI demonstrating a lipid-poor adrenal lesion who underwent either surgical resection or a minimum of 24 months of imaging follow-up were identified retrospectively. All images were retrospectively reviewed in blinded fashion by two radiologists. Each adrenal lesion was categorized by dynamic enhancement features and qualitative signal on ssT2 images and was categorized as an adenoma if it demonstrated homogenous enhancement in the arterial phase, washout with capsule enhancement in the delayed phase, and T2 signal isointense to normal adrenal tissue. Any lesion that did not fulfill all the criteria was classified as a non-adenoma. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for characterization of adenoma were calculated for each reader with 95% confidence intervals. A κ test assessed level of agreement between readers. Application of our criteria lead to an MRI diagnosis of lipid-poor adrenal adenoma with a sensitivity of 84.2-89.5% (16/19-17/19), specificity of 96.3% (26/27), positive predictive value of 94.1-94.4% (16/17-17/18), negative predictive value of 89.7-92.9% (26/29-26/28), and accuracy of 91.3-93.5% (42/46-43/46). Agreement between the two readers showed substantial κ agreement for the differentiation of adenoma from non-adenoma. Dynamic, contrast-enhanced T1-weighted three-dimensional gradient echo sequences in combination with ssT2 images can accurately differentiate lipid-poor adrenal adenomas from non-adenomas. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    European journal of radiology 07/2015; 84(11). DOI:10.1016/j.ejrad.2015.06.032 · 2.37 Impact Factor
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    ABSTRACT: BACKGROUND Although heregulin and human epidermal growth factor receptor 3 (HER3) are frequently expressed at high levels in patients with head and neck cancer, their prognostic value remains unclear. The authors explored the prognostic significance of heregulin/HER3 expression in patients with oropharyngeal squamous cell carcinoma (OPSCC), taking into account other HER family members as well as p16 status. METHODS Ninety-six primary tumor specimens from patients with OPSCC were retrospectively collected and analyzed for heregulin messenger RNA (mRNA) using in situ hybridization and for HER3, epidermal growth factor receptor, and human epidermal growth factor receptor 2 (HER2) using quantitative immunohistochemistry. Heregulin and HER3 mRNA levels were also examined among different tumor types using The Cancer Genome Atlas database. RESULTS High heregulin mRNA (> the median) correlated significantly with poor overall survival (OS) (hazard ratio [HR], 8.48; 95% confidence interval [95% CI], 2.17-33.17 [P =.002]) but not disease-free survival (HR, 1.52; 95% CI, 0.64-3.65 [P =.341]) in patients with OPSCC. Heregulin mRNA correlated negatively with OS in both patients with p16-positive (P =.049) and p16-negative (P =.091) OPSCC on univariate analysis. High HER3 (> the median) also correlated with poor OS (HR, 4.68; 95% CI, 1.47-14.90 [P =.009]) on multivariate analysis. Epidermal growth factor receptor levels independently correlated with disease-free survival (P =.025) and inversely correlated with p16 status (P =.012). In addition, The Cancer Genome Atlas data demonstrated that head and neck squamous cell carcinoma exhibits higher heregulin expression compared with other solid tumor types examined. CONCLUSIONS High heregulin mRNA and high HER3 protein levels were found to independently correlate with poor OS in patients with OPSCC. These data support targeting HER3 in patients with heregulin-high OPSCC and warrant further clinical investigation.
    Cancer 07/2015; 121(20). DOI:10.1002/cncr.29549 · 4.89 Impact Factor
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    ABSTRACT: Appendiceal mucinous neoplasms (AMN) are a rare heterogeneous group of diseases. In the absence of randomized trials, AMN management is controversial. The goal of this study was to evaluate the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery on survival in AMN patients. Patient data including demographics, pathology, type of therapy, and outcomes were collected from Emory University, the Ohio State University, and Wayne State University databases. One of the three centers did not use HIPEC. Statistical analysis evaluating overall survival (OS) of AMN patients was performed. Between 1990 and 2010, 163 AMN patients were identified. Histology showed 60 patients had diffuse peritoneal adenomucinosis, 88 had peritoneal mucinous carcinomatosis (PMCA), and 15 had PMCA with indeterminate or discordant features. Complete surgical resection was achieved in 76 patients. HIPEC was used in 79 patients. The median OS was 77 months for patients who received HIPEC compared with 25 months for patients who did not (p < .001). In multivariable analysis, histopathologic subtype (p < .001), complete surgical resection (p < .001), and HIPEC (p < .001) were independent predictors for improved OS. A survival advantage for AMN patients treated at HIPEC-treating centers was observed (p = .0026). After adjusting for HIPEC therapy, no significant survival difference was observed between the non-HIPEC-treating center and the HIPEC-treating centers (p = .094). The addition of HIPEC to cytoreductive surgery likely provides a survival advantage and should be considered in the treatment strategy for AMN. ©AlphaMed Press.
    The Oncologist 06/2015; 20(8). DOI:10.1634/theoncologist.2014-0294 · 4.87 Impact Factor
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    ABSTRACT: Appendiceal tumors are a heterogeneous group of diseases that include typical neuroendocrine tumors (NET, TNET), goblet cell carcinoids (GCC) and atypical GCC. Atypical GCC are classified into signet-ring cell cancers (SRCC) and poorly differentiated appendiceal adenocarcinoids. The prognosis and management of these diseases is unclear because there are no prospective studies. The aim of this study is to assess the characteristics and outcome of appendiceal TNET, GCC and SRCC patients. Appendiceal TNET, GCC and SRCC patients diagnosed between 1973 and 2011 were identified in the Surveillance Epidemiology and End. (SEER) database. Demographics, type of surgery, and clinicopathologic characteristics were collected. Survival functions were estimated by the Kaplan-Meier method, and log-rank test was used to assess the difference in overall survival (OS) among the three histologies. The SEER database yielded 1021 TNET patients, 1582 with GCC, and 534 SRCC patients. TNET presented at a younger age (P<0.001). Patients with SRCC presented with advanced stage disease (P<0.001). The median OS (mOS) for GCC and TNET patients was not reached; mOS for SRCC was 24 months. Multivariate analysis stratified for stage revealed significantly longer survival for TNET and GCC than SRCC (P<0.001). This is the largest report to date for appendiceal NET patients, suggesting a spectrum of diseases with different characteristics and outcomes. In this report, we present a treatment approach for this complex spectrum of disease, based on the experience of Ohio State and Emory University investigators.
    Cancer Research and Treatment 06/2015; DOI:10.4143/crt.2015.029 · 3.32 Impact Factor
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    ABSTRACT: To save valuable time and resources in new drug development, Phase I/II clinical trials with toxicity control and drug efficacy as dual primary endpoints have become increasingly popular. Escalation with over-dose control (the EWOC) is a Bayesian adaptive Phase I clinical trial design that can accurately estimate the maximum tolerated dose (MTD) level and control the probability of overdosing patients during the dose allocation phase. In this paper, we extend EWOC to Phase I/II clinical trials by controlling for under-dosing with a Gumbel Copula model to provide patients with at least minimum drug efficacy. We propose a utility function to measure the composite effect of toxicity and efficacy and select the optimal dose. To deal with the common issue that the efficacy endpoint often cannot be quickly ascertained, we employ Bayesian data augmentation to handle delayed efficacy and allow for flexible patient accrual without a waiting period. Extensive simulations demonstrate that the proposed new design not only provides better therapeutic effect by reducing the probability of treating patients at under-dose levels while protecting patients from being overdosed, but also improves trial efficiency and increases the accuracy of dose recommendation for subsequent clinical trials. We apply the proposed design to a Phase I/II solid tumor trial. Copyright © 2015. Published by Elsevier Inc.
    Contemporary clinical trials 05/2015; 43. DOI:10.1016/j.cct.2015.05.014 · 1.94 Impact Factor
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    ABSTRACT: Diffuse large B cell lymphoma (DLBCL) is the most common form of lymphoma in the United States. DLBCL comprises biologically distinct subtypes including germinal center-like (GCB) and activated-B-cell-like DLBCL (ABC). The most aggressive type, ABC-DLBCL, displays dysregulation of both canonical and noncanonical NF-κB pathway as well as genomic instability. Although, much is known about the tumorigenic roles of the canonical NF-kB pathway, the precise role of the noncanonical NF-kB pathway remains unknown. Here we show that activation of the noncanonical NF-κB pathway regulates chromosome stability, DNA damage response and centrosome duplication in DLBCL. Analysis of 92 DLBCL samples revealed that activation of the noncanonical NF-κB pathway is associated with low levels of DNA damage and centrosome amplification. Inhibiting the noncanonical pathway in lymphoma cells uncovered baseline DNA damage and prevented doxorubicin-induced DNA damage repair. In addition, it triggered centrosome amplification and chromosome instability, indicated by anaphase bridges, multipolar spindles and chromosome missegregation. We determined that the noncanonical NF-κB pathway execute these functions through the regulation of GADD45α and REDD1 in a p53-independent manner, while it collaborates with p53 to regulate cyclin G2 expression. Furthermore, this pathway regulates GADD45α, REDD1 and cyclin G2 through direct binding of NF-κB sites to their promoter region. Overall, these results indicate that the noncanonical NF-κB pathway plays a central role in maintaining genome integrity in DLBCL. Our data suggests that inhibition of the noncanonical NF-kB pathway should be considered as an important component in DLBCL therapeutic approach. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 05/2015; 136(10). DOI:10.1002/ijc.29301 · 5.09 Impact Factor

  • Gastrointestinal Endoscopy 05/2015; 81(5):AB518. DOI:10.1016/j.gie.2015.03.1771 · 5.37 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-391. DOI:10.1016/S0016-5085(15)31315-9 · 16.72 Impact Factor
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    ABSTRACT: Background: The categories of the International Myeloma Working Group (IMWG) response criteria for multiple myeloma are based on the magnitude of the change in paraprotein and the normalization of the free light chain ratio (rFLC). However, the relationship between the response by these biomarkers and clinical outcomes has not been validated with novel compounds in the phase 1 setting. Early response predictors may have prognostic value and speed development plans for new agents. Methods: The relationship between biomarkers of response and clinical outcomes was examined in 87 relapsed or refractory multiple myeloma patients enrolled in nontransplant phase I clinical trials from January 2004 through November 2011 at 4 time landmarks. Progression-free survival (PFS) was the primary outcome, and overall survival (OS) was also assessed. Results: The normalization of rFLC within 4 months predicted improvement in PFS (11.3 vs 2.8 months, P = .038), whereas the normalization of rFLC within 12 months predicted improvement in PFS (6.1 vs 2.8 months, P = .015) and OS (45 vs 17.4 months, P = .002). The magnitude of response in paraprotein predicted and correlated linearly with PFS at all time landmarks (R(2) = 0.703-0.943) when it was assessed with 2 different boundaries. Conclusions: These findings suggest that the normalization of rFLC and the magnitude of response are viable biomarkers for surrogate endpoints in early-phase clinical trials, validate the use of current IMWG response criteria in the phase 1 setting, and support the use of these biomarkers for drug development endpoints.
    Blood 03/2015; 122(6-21):1958. DOI:10.1002/cncr.29136 · 10.45 Impact Factor
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    ABSTRACT: BACKGROUND Malignant bowel obstruction affects an estimated 3% to 15% of patients with cancer, with a mean survival of <4 weeks reported in patients with inoperable malignant bowel obstruction. In the current study, the authors assessed predictors of survival and the influence of treatment modality in US patients with cancer who were hospitalized for malignant bowel obstruction.METHODS All the US cancer patients hospitalized with malignant bowel obstruction in 2006 and 2010 were included. Data were obtained from the Nationwide Inpatient Sample provided by the Agency for Healthcare Research and Quality. Malignant bowel obstruction diagnoses and treatment variables were identified using Clinical Classifications Software codes based on International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Univariate and multivariate analyses were performed with a logistic model, weighted chi-square test, and a generalized linear model.RESULTSThe authors identified 942,014 and 1,103,528 hospitalizations for malignant bowel obstruction in 2006 and 2010, respectively. Medical management, upper gastrointestinal obstruction, health insurance coverage, and obesity were found to be significantly associated with better hospital survival. Multivariate analysis also demonstrated significantly increased odds of death with male sex, advanced age, AJCC stage IV disease, multiple comorbid conditions (except acquired immunodeficiency syndrome), and weight loss. There were no significant differences with stratification based on the location and etiology of the obstruction (primary tumor vs metastatic).CONCLUSIONS Malignant bowel obstruction is a common cause of death in hospitalized patients with advanced cancer in the United States. The odds of death are especially high in older patients and those with concurrent medical illnesses. Lack of insurance coverage, significant weight loss, and surgical management also appear to be associated with higher mortality in this population. Cancer 2015. © 2015 American Cancer Society.
    Cancer 03/2015; 121(11). DOI:10.1002/cncr.29297 · 4.89 Impact Factor

Publication Stats

2k Citations
841.83 Total Impact Points


  • 2015
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
  • 2008-2015
    • Emory University
      • • Department of Biostatistics and Bioinformatics
      • • Department of Pediatrics
      Atlanta, Georgia, United States
  • 2014
    • Georgia Department of Public Health
      Marietta, Georgia, United States
  • 2011
    • Moffitt Cancer Center
      • Department of Cancer Epidemiology
      Tampa, Florida, United States
  • 2010
    • St. Jude Children's Research Hospital
      Memphis, Tennessee, United States
  • 2005-2010
    • Children's Oncology Group
      Monrovia, California, United States
  • 2007-2009
    • University of Southern California
      • • Keck School of Medicine
      • • Department of Preventive Medicine
      Los Angeles, California, United States
  • 2006
    • Massachusetts General Hospital
      • Department of Radiation Oncology
      Boston, Massachusetts, United States