Ranjana Advani

Stanford Medicine, Stanford, California, United States

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Publications (105)803.3 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Ibrutinib is an oral Bruton's tyrosine kinase inhibitor, recently approved for the treatment of mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) patients with at least one prior therapy. We developed a population pharmacokinetic (PK) model for ibrutinib in patients.
    Cancer Chemotherapy and Pharmacology 11/2014; · 2.80 Impact Factor
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    ABSTRACT: Belinostat is a pan-histone deacetylase inhibitor with antitumour and anti-angiogenic properties. An open label, multicentre study was conducted in patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who failed ≥1 prior systemic therapy and were treated with belinostat (1000 mg/m2 intravenously ×5 d of a 21-d cycle). The primary endpoint was objective response rate (ORR). Patients with PTCL (n = 24) had received a median of three prior systemic therapies (range 1–9) and 40% had stage IV disease. Patients with CTCL (n = 29) had received a median of one prior skin-directed therapy (range 0–4) and four prior systemic therapies (range 1–9); 55% had stage IV disease. The ORRs were 25% (PTCL) and 14% (CTCL). Treatment-related adverse events occurred in 77% of patients; nausea (43%), vomiting (21%), infusion site pain (13%) and dizziness (11%) had the highest incidence. Treatment-related serious adverse events were Grade 5 ventricular fibrillation; Grade 4 thrombocytopenia; Grade 3 peripheral oedema, apraxia, paralytic ileus and pneumonitis; and Grade 2 jugular vein thrombosis. Belinostat monotherapy was well tolerated and efficacious in patients with recurrent/refractory PTCL and CTCL. This trial was registered at www.clinicaltrials.gov as NCT00274651.
    British Journal of Haematology 11/2014; · 4.94 Impact Factor
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    ABSTRACT: Outcomes have improved for pediatric patients undergoing autologous bone marrow transplantation for refractory or relapsed Hodgkin Lymphoma.•Cyclophosphamide, Carmustine (BCNU), and etoposide (VP-16) is an appropriate therapy for patients <21 years old with relapsed or refractory Hodgkin Lymphoma.•Post-transplantation consolidative radiation therapy may improve outcomes following autologous bone marrow transplantation for relapsed or refractory Hodgkin Lymphoma.•Improved outcomes may be due to factors other than improvements in transplant conditioning regimen.
    Biology of Blood and Marrow Transplantation. 10/2014;
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    ABSTRACT: The main objectives of follow-up studies after completion of treatment for Hodgkin lymphoma are detection of recurrence for salvage therapy and monitoring for sequelae of treatment. The focus of the follow-up shifts, with time after treatment, from detection of recurrence to long-term sequelae. A majority of recurrence is detected by history and physical examination. The yield for routine imaging studies and blood tests is low. Although routine surveillance CT scan can detect recurrence not detected by history and physical examination, its benefit in ultimate survival and cost-effectiveness is not well defined. Although PET scan is a useful tool in assessing response to treatment, its routine use for follow-up is not recommended. Long-term sequelae of treatment include secondary malignancy, cardiovascular disease, pneumonitis, reproductive dysfunction, and hypothyroidism. Follow-up strategies for these sequelae need to be individualized, as their risks in general depend on the dose and volume of radiation to these organs, chemotherapy, age at treatment, and predisposing factors for each sequela. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is either lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
    Journal of the American College of Radiology: JACR 09/2014;
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    ABSTRACT: Front-line treatment of peripheral T-cell lymphomas (PTCL) involves regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and results in a 5-year overall survival (OS) rate of less than 50%. This phase I open-label study evaluated the safety and activity of brentuximab vedotin administered sequentially with CHOP or in combination with CHP (CHOP without vincristine) as front-line treatment in patients with CD30(+) PTCL.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 08/2014;
  • Amin Aalipour, Ranjana H Advani
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    ABSTRACT: Aberrant signaling of the B-cell receptor pathway has been linked to the development and maintenance of B-cell malignancies. Bruton's tyrosine kinase (BTK), a protein early in this pathway, has emerged as a new therapeutic target in a variety of such malignancies. Ibrutinib, the most clinically advanced small molecule inhibitor of BTK, has demonstrated impressive tolerability and activity in a range of B-cell lymphomas which led to its recent approval for relapsed mantle cell lymphoma and chronic lymphocytic leukemia. This review focuses on the preclinical and clinical development of ibrutinib and discusses its therapeutic potential.
    Therapeutic advances in hematology. 08/2014; 5(4):121-33.
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    ABSTRACT: Waldenström's macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy and treatment strategy have been proposed as part of the consensus panels of International Workshops on WM (IWWM). As part of the IWWM-7 and based on recently published and ongoing clinical trials the panels updated treatment recommendations. Therapeutic strategy in WM should be based on individual patient and disease characteristics (age, comorbidities, need for rapid disease control, candidacy for autologous transplantation, cytopenias, IgM-related complications (hyperviscosity, neuropathy). Mature studies show that rituximab combinations with cyclophosphamide/dexamethasone (DRC), or bendamustine (BR) or bortezomib/dexamethasone (BDR) provided durable responses and are indicated for most patients. New monoclonal antibodies (ofatumumab), second generation proteasome inhibitors (carfilzomib), mTOR inhibitors and BTK inhibitors, are promising and may expand future treatment options. A different regimen is typically recommended for relapsed or refractory disease. In selected patients with relapsed disease after long lasting remission re-use of a prior effective regimen may be appropriate. AutoSCT may be considered in young patients with chemosensitive disease and in newly diagnosed patients with very high-risk features. Active enrollment of patients with WM in clinical trials is encouraged.
    Blood 07/2014; · 9.78 Impact Factor
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    ABSTRACT: Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study.
    Journal of hematology & oncology. 06/2014; 7(1):44.
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    ABSTRACT: Abstract Brentuximab vedotin is an antibody drug conjugate that induces durable objective responses in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Fifteen of 160 patients who participated in 2 pivotal phase 2 studies received a consolidative allogeneic stem cell transplant (allo-SCT) following brentuximab vedotin treatment. This case series describes their experience. The studies were approved by Institutional Review Boards prior to patient enrollment. Patients received 1.8 mg/kg brentuximab vedotin every 3 weeks for up to 16 cycles. The estimated 2-year progression-free survival (PFS) rate was 66% and the median PFS has not yet been reached. Eleven of the 15 patients were alive and the estimated 2-year survival rate was 80%. The safety of brentuximab vedotin treatment in this series was consistent with the known safety profile in this setting. Brentuximab vedotin is a compelling option for reducing tumor burden to facilitate a consolidative allo-SCT.
    Leukemia & lymphoma. 06/2014;
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    ABSTRACT: This phase 2, open-label, multicenter study evaluated the efficacy and safety of brentuximab vedotin, a CD30-directed antibody-drug conjugate, in relapsed/refractory CD30+ non-Hodgkin lymphomas (NCT01421667). The primary endpoint was objective response rate (ORR). Key secondary endpoints included safety, correlation of CD30 expression with response, response duration, and progression-free survival (PFS). Brentuximab vedotin 1.8 mg/kg was administered every 3 weeks until disease progression or unacceptable toxicity. This planned subset analysis included patients enrolled on study with peripheral T-cell lymphomas (PTCLs) (n=35). Diagnoses included angioimmunoblastic T-cell lymphoma (AITL, n=13) and PTCL not otherwise specified (n=22). Median age was 64 years and 63% were refractory to most recent therapy. Of 34 evaluable patients, the ORR was 41% (8 complete remissions [CR], 6 partial remissions [PR]), and the ORR was 54% in AITL (5 CR, 2 PR) with a median PFS of 6.7 months thus far. No correlation between CD30 expression per central review and response was observed. Safety data were generally consistent with the known profile of brentuximab vedotin. The most frequently occurring ≥ Grade 3 events were neutropenia (14%), peripheral sensory neuropathy, and hyperkalemia (9% each). In summary, brentuximab vedotin showed antitumor activity in patients with relapsed PTCL overall, particularly AITL. This study was registered at ClinicalTrials.gov, identifier: NCT01421667.
    Blood 03/2014; · 9.78 Impact Factor
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    ABSTRACT: Brentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study (ClinicalTrials.gov NCT00947856). Twenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment. The objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year.Adverse events (AEs) occurring in >=25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment. With the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials. Retreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL.Trial registration: United States registry and results database ClinicalTrials.gov NCT00947856.
    Journal of Hematology & Oncology 03/2014; 7(1):24. · 4.46 Impact Factor
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    ABSTRACT: The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC. We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs. One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003). BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.
    Annals of Oncology 03/2014; · 7.38 Impact Factor
  • Oncology (Williston Park, N.Y.) 03/2014; 28(3):253-6, 258-60, C3. · 3.19 Impact Factor
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    ABSTRACT: Pediatric Hodgkin lymphoma is a highly curable malignancy and potential long-term effects of therapy need to be considered in optimizing clinical care. An expert panel was convened to reach consensus on the most appropriate approach to evaluation and treatment of pediatric Hodgkin lymphoma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Four clinical variants were developed to assess common clinical scenarios and render recommendations for evaluation and treatment approaches to pediatric Hodgkin lymphoma. We provide a summary of the literature as well as numerical ratings with commentary. By combining available data in published literature and expert medical opinion, we present a consensus to the approach for management of pediatric Hodgkin lymphoma. Pediatr Blood Cancer. © 2014 American College of Radiology.
    Pediatric Blood & Cancer 02/2014; · 2.35 Impact Factor
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    ABSTRACT: Universal expression of CD20 by malignant cells in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) led us to evaluate rituximab (R) as a therapeutic option. Patients with previously treated or newly diagnosed NLPHL were treated with R (375 mg/m(2) once per week for 4 weeks) or, after a protocol amendment, with R plus R maintenance (MR; administered once every 6 months for 2 years). Primary and secondary outcome measures were progression-free survival (PFS) and overall response rate (ORR), respectively. A total of 39 patients were enrolled (R, n = 23; R + MR, n = 16). After four once-per-week treatments, ORR was 100% (complete response, 67%; partial response, 33%). At median follow-ups of 9.8 years for R and 5 years for R + MR, median PFS were 3 and 5.6 years (P = .26), respectively; median overall survival (OS) was not reached. Estimated 5-year PFS and OS for patients treated with R versus R + MR were 39.1% (95% CI, 23.5 to 65.1) and 95.7% (95% CI, 87.7 to 100) versus 58.9% (95% CI, 38.0 to 91.2) and 85.7% (95% CI, 69.2 to 100), respectively. Nine of 23 patients experiencing relapse had evidence of transformation to aggressive B-cell lymphoma; six of these patients had infradiaphragmatic involvement at study entry. R is an active agent in NLPHL. Although responses are not durable in most patients, a significant minority experience remissions lasting > 5 years. R + MR results in a nonsignificant increase in PFS compared with R. R may be considered in the relapsed setting for NLPHL. The potential for transformation of NLPHL to aggressive B-cell lymphoma underscores the importance of rebiopsy and long-term follow-up.
    Journal of Clinical Oncology 02/2014; · 18.04 Impact Factor
  • Catherine Diefenbach, Ranjana Advani
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    ABSTRACT: Although most patients with Hodgkin lymphoma (HL) are cured with primary therapy, patients with primary refractory disease or relapse after initial treatment have poor outcomes and represent an unmet medical need. Recent advances in unraveling the biology of HL have yielded a plethora of novel targeted therapies. This review provides an overview of the data behind the hype generated by these advances and addresses the question of whether or not clinically these targeted therapies offer hope for patients with HL.
    Hematology/oncology clinics of North America 02/2014; 28(1):105-22. · 2.05 Impact Factor
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    ABSTRACT: Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited data on pathology and outcome. A multicentre retrospective study was undertaken to determine prognostic factors and the incidence of central nervous system (CNS) relapses. Data was retrospectively collected on patients from 8 US academic centres. Only patients with stage I/II disease (involvement of breast and localized lymph nodes) were included. Histologies apart from primary DLBCL were excluded. Between 1992 and 2012, 76 patients met the eligibility criteria. Most patients (86%) received chemotherapy, and 69% received immunochemotherapy with rituximab; 65% received radiation therapy and 9% received prophylactic CNS chemotherapy. After a median follow-up of 4·5 years (range 0·6-20·6 years), the Kaplan-Meier estimated median progression-free survival was 10·4 years (95% confidence interval [CI] 5·8-14·9 years), and the median overall survival was 14·6 years (95% CI 10·2-19 years). Twelve patients (16%) had CNS relapse. A low stage-modified International Prognostic Index (IPI) was associated with longer overall survival. Rituximab use was not associated with a survival advantage. Primary breast DLBCL has a high rate of CNS relapse. The stage-modified IPI score is associated with survival.
    British Journal of Haematology 01/2014; · 4.94 Impact Factor
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    ABSTRACT: VcR-CVAD (rituximab, bortezomib, modified hyper-CVAD) induction chemoimmunotherapy and maintenance rituximab (MR) was evaluated for efficacy and safety in ECOG protocol E1405. Patients with previously untreated mantle cell lymphoma (MCL) received VcR-CVAD chemotherapy every 21 days for 6 cycles, followed by MR for 2 years. Transplant eligible patients had the option of autologous stem cell transplantation (ASCT) consolidation instead of MR. The primary end point was the complete response (CR) rate to VcR-CVAD. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities. Seventy-five eligible patients with a median age of 62 (range 40-76) were enrolled. The ORR was 95% and a CR was achieved in 68% of patients. After a median follow-up of 4.5 years, 3-year PFS and OS were 72% and 88%, respectively. No substantial difference in PFS or OS was observed between patients treated with MR (n=44) versus ASCT (n=22). There were no unexpected toxicities. VcR-CVAD produced high ORR and CR rates in MCL. MR after VcR-CVAD induction performed similarly to ASCT and may improve response duration. Randomized clinical trials (RCTs) comparing MR against ASCT should be considered and RCTs evaluating bortezomib's contribution to conventional therapy are underway. This study was registered with clinicaltrials.gov (identifier NCT00433537).
    Blood 01/2014; · 9.78 Impact Factor
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    ABSTRACT: Women treated with mantle irradiation for Hodgkin lymphoma (HL) are at an increased risk of developing breast cancer (BC). Current guidelines recommend screening breast magnetic resonance imaging (MRI) as an adjunct to mammography (M) in these patients. There are limited data, however, as to the impact of breast MRI on cancer detection rates. The aim of the current study is to evaluate the use of breast MRI in survivors of HL treated and followed at a single institution. We retrospectively reviewed 980 female patients treated with mantle irradiation for HL between 1961 and 2008. Records were reviewed to determine age at radiotherapy treatment, radiotherapy dose, breast imaging (including M and breast MRI), biopsy results if applicable, and incidence of BC. A total of 118 patients had breast imaging performed at our institution. Median age at HL diagnosis was 28 years (range, 10 to 69 y). Median radiotherapy dose was 36 Gy (range, 20 to 45 Gy). Seventy-nine patients (67%) underwent M screening only, 1 (1%) breast MRI only, and 38 (32%) both M and breast MRI. Of these 38, 19 (50%) underwent 54 screening MRI studies (range per patient=1 to 8), 13 (34%) underwent preoperative MRI for workup of BC, and 6 (16%) initiated screening MRI of the contralateral breast only after diagnosed with BC. Fifty-nine biopsies were performed: 47 were prompted by suspicious M findings only, 10 by palpable findings on physical examination (PE), and 2 by suspicious breast MRI findings. Of the 47 biopsies prompted by M, 24 revealed malignant disease, whereas 23 proved to be benign. All 10 biopsies performed by palpation were malignant. Both biopsies prompted by MRI findings were benign. With M, there were 34 true-positive findings in 32 patients, 23 false-positive findings, and 1 false-negative finding. With screening MRI, there were 2 false-positive findings, 1 false-negative finding, and no true-positive findings. The role of screening breast MRI in women previously irradiated for HL is evolving. Further education of patients and physicians is important to increase awareness of more sensitive BC screening modalities in this high-risk population. Future studies are necessary to determine the appropriate integration of screening breast MRI into the ongoing follow-up of these women.
    American journal of clinical oncology 01/2014; · 2.21 Impact Factor
  • Ranjana H Advani, Richard T Hoppe
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    ABSTRACT: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon entity that, in contrast to classical HL (cHL), universally expresses CD20, a hallmark of the disease. Majority of patients present with early stage disease and treatment with local radiation provides excellent disease control and overall survival (OS). For locally extensive or advanced stages, paradigms used for cHL have been employed with similar outcomes. Unlike cHL, late relapses may occur, as well as a propensity to transform to an aggressive B cell non-Hodgkin lymphoma that underscores the importance of long- term follow-up as well as re-biopsy at the time of relapse. Deaths due to NLPHL are uncommon and in older series secondary malignancies and other treatment related toxicities contributed appreciably to overall mortality. Expression of CD20 in NLPHL has led to the evaluation of rituximab as a therapeutic option. While results with single agent rituximab in the front line setting are inferior to conventional therapy, rituximab is a reasonable choice for relapsed disease due to the high overall response rate and excellent tolerability. Most patients have a long OS, therefore overall goals of therapy should be to minimize the risk of relapse, and long-term toxicity.
    Blood 11/2013; · 9.78 Impact Factor

Publication Stats

2k Citations
803.30 Total Impact Points

Institutions

  • 2005–2014
    • Stanford Medicine
      • • Stanford Cancer Center
      • • Department of Medicine
      • • Division of Oncology
      Stanford, California, United States
  • 2013
    • University of Florida Proton Therapy Institute
      Jacksonville, Florida, United States
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
  • 2003–2013
    • Stanford University
      • • Division of Oncology
      • • Division of Hematology
      Palo Alto, California, United States
  • 2008–2011
    • University of Miami
      • Department of Medicine
      Coral Gables, FL, United States