Bio

Clinical Focus


  • Internal Medicine
  • Hematology/Oncology
  • Cancer > Hematology
  • Cancer > Lymphoma

Academic Appointments


Professional Education


  • Board Certification: Medical Oncology, American Board of Internal Medicine
  • Fellowship:Stanford University School of Medicine (2012) CA
  • Residency:Stanford University School of Medicine (2009) CA
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2009)
  • Medical Education:Stanford University School of Medicine (2006) CA

Research & Scholarship

Clinical Trials


  • Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma Not Recruiting

    This phase II trial studies how well combination chemotherapy and pralatrexate works in treating patients with non-Hodgkin lymphoma (NHL). Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

    View full details

  • A Phase 1 Study of Brentuximab Vedotin Given Sequentially and Combined With Multi-Agent Chemotherapy for CD30-Positive Mature T-Cell and NK-Cell Neoplasms Not Recruiting

    The purpose of this study is to assess the safety profile of brentuximab vedotin sequentially and in combination with multi-agent chemotherapy in front-line treatment for CD30-positive mature T-cell and NK-cell neoplasms, including systemic anaplastic large cell lymphoma. It is a phase 1, open-label, dose escalation study in three arms designed to define the MTD, PK, immunogenicity, and anti-tumor activity of brentuximab vedotin in sequence and in combination with multi-agent front-line chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

    View full details

  • A Treatment-Option Study of Brentuximab Vedotin in Patients With Progression of Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma Not Recruiting

    The purpose of this study is to provide the option of brentuximab vedotin treatment to patients randomly allocated to placebo treatment in the Phase 3 study SGN35-005 that experienced disease progression of HL. Additionally in the US only, the purpose of this study is to provide access to brentuximab vedotin for patients with relapsed or refractory HL or patients with relapsed or refractory systemic ALCL who have previously failed frontline chemotherapy.

    Stanford is currently not accepting patients for this trial.

    View full details

  • Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies Recruiting

    This phase I trial studies the side effects and the best dose of donor CD8+ memory T-cells in treating patients with hematolymphoid malignancies. Giving low dose of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-cancer effects). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect

    View full details

  • Immunostimulatory CpG SD-101 + RT in Recurrent/Progressive Lymphoma After Allogeneic Hematopoietic Cell Transplantation (HCT) Recruiting

    Direct intratumoral injection of SD-101 with local radiation is safe in patients with relapsed or refractory lymphoma after allogeneic hematopoietic cell transplant.

    View full details

Publications

Journal Articles


  • Clinical Outcome Prediction by MicroRNAs in Human Cancer: A Systematic Review JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Nair, V. S., Maeda, L. S., Ioannidis, J. P. 2012; 104 (7): 528-540

    Abstract

    MicroRNA (miR) expression may have prognostic value for many types of cancers. However, the miR literature comprises many small studies. We systematically reviewed and synthesized the evidence.Using MEDLINE (last update December 2010), we identified English language studies that examined associations between miRs and cancer prognosis using tumor specimens for more than 10 patients during classifier development. We included studies that assessed a major clinical outcome (nodal disease, disease progression, response to therapy, metastasis, recurrence, or overall survival) in an agnostic fashion using either polymerase chain reaction or hybridized oligonucleotide microarrays.Forty-six articles presenting results on 43 studies pertaining to 20 different types of malignancy were eligible for inclusion in this review. The median study size was 65 patients (interquartile range [IQR] = 34-129), the median number of miRs assayed was 328 (IQR = 250-470), and overall survival or recurrence were the most commonly measured outcomes (30 and 19 studies, respectively). External validation was performed in 21 studies, 20 of which reported at least one nominally statistically significant result for a miR classifier. The median hazard ratio for poor outcome in externally validated studies was 2.52 (IQR = 2.26-5.40). For all classifier miRs in studies that evaluated overall survival across diverse malignancies, the miRs most frequently associated with poor outcome after accounting for differences in miR assessment due to platform type were let-7 (decreased expression in patients with cancer) and miR 21 (increased expression).MiR classifiers show promising prognostic associations with major cancer outcomes and specific miRs are consistently identified across diverse studies and platforms. These types of classifiers require careful external validation in large groups of cancer patients that have adequate protection from bias. -

    View details for DOI 10.1093/jnci/djs027

    View details for Web of Science ID 000302293200008

    View details for PubMedID 22395642

  • STAGE I-IIIA NON-BULKY HODGKIN'S LYMPHOMA. IS FURTHER DISTINCTION BASED ON PROGNOSTIC FACTORS USEFUL? THE STANFORD EXPERIENCE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Advani, R. H., Hoppe, R. T., Maeda, L. S., Baer, D. M., Mason, J., Rosenberg, S. A., Horning, S. J. 2011; 81 (5): 1374-1379

    Abstract

    In the United States, early-stage Hodgkin's lymphoma (HL) is defined as asymptomatic stage I/II non-bulky disease. European groups stratify patients to more intense treatment by considering additional unfavorable factors, such as age, number of nodal sites, sedimentation rate, extranodal disease, and elements of the international prognostic score for advanced HL. We sought to determine the prognostic significance of these factors in patients with early-stage disease treated at Stanford University Medical Center.This study was a retrospective analysis of 101 patients treated with abbreviated Stanford V chemotherapy (8 weeks) and 30-Gy (n=84 patients) or 20-Gy (n=17 patients) radiotherapy to involved sites. Outcomes were assessed after applying European risk factors.At a median follow-up of 8.5 years, freedom from progression (FFP) and overall survival (OS) rates were 94% and 97%, respectively. From 33% to 60% of our patients were unfavorable per European criteria (i.e., German Hodgkin Study Group [GHSG], n=55%; European Organization for Research and Treatment of Cancer, n=33%; and Groupe d'Etudes des Lymphomes de l'Adulte, n=61%). Differences in FFP rates between favorable and unfavorable patients were significant only for GHSG criteria (p=0.02) with there were no differences in OS rates for any criteria. Five of 6 patients who relapsed were successfully salvaged.The majority of our patients deemed unfavorable had an excellent outcome despite undergoing a significantly abbreviated regimen. Application of factors used by the GHSG defined a less favorable subset for FFP but with no impact on OS. As therapy for early-stage disease moves to further reductions in therapy, these factors take on added importance in the interpretation of current trial results and design of future studies.

    View details for DOI 10.1016/j.ijrobp.2010.07.041

    View details for Web of Science ID 000297602400024

    View details for PubMedID 20934280

  • Current concepts and controversies in the management of early stage Hodgkin lymphoma LEUKEMIA & LYMPHOMA Maeda, L. S., Lee, M., Advani, R. H. 2011; 52 (6): 962-971

    Abstract

    Over the past three decades, due to the recognition of late effects related to high-dose extended field radiotherapy and heavy alkylator chemotherapy, combined modality therapy with abbreviated chemotherapy and limited field radiotherapy has emerged as the standard of care for early stage Hodgkin lymphoma, with cure rates in excess of 80%. Currently, however, controversy remains over identifying the most appropriate criteria to risk-stratify patients with early stage disease, so that those with a favorable prognosis receive limited treatment without compromising cure rates and those with unfavorable risk receive more intensified therapy. The optimal risk stratification system remains unclear, with variable definitions of favorable and unfavorable disease used by research groups in North America and Europe. Thus, comparison of clinical trial results has been challenging, and additional controversies persist regarding optimal chemotherapy regimens, duration of therapy, and the role of radiotherapy. Investigations are ongoing to assess the potential of functional imaging and biomarkers as tools for risk stratification. The collective goal is to further refine current stratification strategies to allow for an individualized, risk-adapted treatment approach that minimizes long-term late effects without compromising high cure rates.

    View details for DOI 10.3109/10428194.2011.557455

    View details for Web of Science ID 000290869100010

    View details for PubMedID 21463118

  • The emerging role for rituximab in the treatment of nodular lymphocyte predominant Hodgkin lymphoma CURRENT OPINION IN ONCOLOGY Maeda, L. S., Advani, R. H. 2009; 21 (5): 397-400

    Abstract

    Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subset of Hodgkin lymphoma that is distinct from classical Hodgkin lymphoma (cHL). The unique malignant 'popcorn' cells express the B-cell antigen CD20 and lack expression of the cHL markers CD15 and CD30. Traditionally, NLPHL has been included with cHL in clinical trials with excellent prognosis reported in several series. The reliable expression of CD20 has led to the evaluation of the chimeric monoclonal anti-CD20 antibody rituximab in several recent trials.Three series have reported the efficacy of 4 weekly doses of rituximab in all stages of NLPHL, both in the treatment-naive and relapsed settings. Emerging data also suggest that longer courses of antibody therapy may improve the duration of response.Rituximab appears to offer a nonchemotherapy-based effective treatment option, which is well tolerated. Ongoing studies are required to further define the optimal patient population who may benefit from rituximab and evaluate its role in maintenance as well as in combination with radiotherapy and chemotherapy.

    View details for DOI 10.1097/CCO.0b013e32832f3ca3

    View details for Web of Science ID 000269172400002

    View details for PubMedID 19606035

  • Impact of positive positron emission tomography on prediction of freedom from progression after Stanford V chemotherapy in Hodgkin's disease JOURNAL OF CLINICAL ONCOLOGY Advani, R., Maeda, L., Lavori, P., Quon, A., Hoppe, R., Breslin, S., Rosenberg, S. A., Horning, S. J. 2007; 25 (25): 3902-3907

    Abstract

    To correlate [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) status after chemotherapy, but before radiation, with outcome in patients treated with the Stanford V regimen.We analyzed retrospectively 81 patients with Hodgkin's disease who had serial [(18)F]FDG-PET scans performed at baseline and again at the completion of Stanford V chemotherapy, before planned radiotherapy. Patients with favorable stage I/II (nonbulky mediastinal disease) and those with bulky mediastinal disease or stage III/IV were scanned after 8 and 12 weeks of chemotherapy, respectively. Radiotherapy fields were determined before starting chemotherapy based on baseline computed tomography scans.After chemotherapy, six of 81 patients had residual [(18)F]FDG-PET-positive sites, all in sites for which radiotherapy was planned. Four of the six patients with positive [(18)F]FDG-PET scans after chemotherapy experienced relapse compared with just three of 75 patients with negative [(18)F]FDG-PET scans. At a median follow-up of 4 years, the freedom from progression (FFP) was 96% in postchemotherapy [(18)F]FDG-PET-negative patients versus 33% in [(18)F]FDG-PET-positive patients (P < .0003). In a bivariate Cox model, [(18)F]FDG-PET positivity after chemotherapy remained a highly significant predictor of progression-free survival even after controlling for bulky disease and International Prognostic Score more than 2.These data indicate that PET status after chemotherapy is strongly predictive of FFP with the Stanford V regimen despite the use of consolidative radiotherapy. These results have implications for the design of clinical trials adapted to functional imaging.

    View details for DOI 10.1200/JCO.2007.11.9867

    View details for Web of Science ID 000249416000019

    View details for PubMedID 17664458

  • Transcription arrest at an abasic site in the transcribed strand of template DNA CHEMICAL RESEARCH IN TOXICOLOGY Tornaletti, S., Maeda, L. S., Hanawalt, P. C. 2006; 19 (9): 1215-1220

    Abstract

    A dedicated excision repair pathway, termed transcription-coupled repair (TCR), targets the removal of DNA lesions from transcribed strands of expressed genes. Transcription arrest at the site of the lesion has been proposed as the first step for initiation of TCR. In support of this model, a strong correlation between arrest of transcription by a lesion in vitro and TCR of that lesion in vivo has been found in most cases analyzed. TCR has been reported for oxidative DNA damage; however, very little is known about how frequently occurring and spontaneous DNA damage, such as depurination and base deamination, affects progression of the transcription complex. We have previously determined that the oxidative lesion, thymine glycol, is a significant block to transcription by T7 RNA polymerase (T7 RNAP) but has no detectable effect on transcription by RNA polymerase II (RNAP II) in a reconstituted system with all of the required factors. Another oxidative lesion, 8-oxoguanine, only slightly blocked T7 RNAP and caused RNAP II to briefly pause at the lesion before bypassing it. Because an abasic site is an intermediate in the repair of oxidative damage, it was of interest to learn whether it arrested transcription. Using in vitro transcription assays and substrates containing a specifically positioned lesion, we found that an abasic site in the transcribed strand is a 60% block to transcription by T7 RNAP but nearly a complete block to transcription by mammalian RNAP II. An abasic site in the nontranscribed strand did not block either polymerase. Our results clearly indicate that an abasic site is a much stronger block to transcription than either a thymine glycol or an 8-oxoguanine. Because the predominant model for TCR postulates that only lesions that block RNAP will be subject to TCR, our findings suggest that the abasic site may be sufficient to initiate TCR in vivo.

    View details for DOI 10.1021/tx060103g

    View details for Web of Science ID 000240543400014

    View details for PubMedID 16978026

  • Transcriptional inhibition by an oxidized abasic site in DNA CHEMICAL RESEARCH IN TOXICOLOGY Wang, Y. L., Sheppard, T. L., Tornaletti, S., Maeda, L. S., Hanawalt, P. C. 2006; 19 (2): 234-241

    Abstract

    2-Deoxyribonolactone (dL) is an oxidized abasic site in DNA that can be induced by gamma-radiolysis, ultraviolet irradiation, and numerous antitumor drugs. Although this lesion is incised by AP endonucleases, suggesting a base-excision repair mechanism for dL removal, subsequent excision and repair synthesis by DNA polymerase beta is inhibited due to accumulation of a protein-DNA cross-link. This raises the possibility that additional repair pathways might be required to eliminate dL from the genome. Transcription-coupled repair (TCR) is a pathway of excision repair specific to DNA lesions present in transcribed strands of expressed genes. A current model proposes that transcription arrest at the site of DNA damage is required to initiate TCR. In support of this model, a strong correlation between transcription arrest by a lesion in vitro and TCR of the lesion in vivo has been found in most cases analyzed. To assess whether dL might be subject to TCR, we have studied the behavior of bacteriophage T3 and T7 RNA polymerases (T3RNAP, T7RNAP) and of mammalian RNA polymerase II (RNAPII) when they encounter a dL lesion or its "caged" precursor located either in the transcribed or in the nontranscribed strand of template DNA. DNA plasmids containing a specifically located dL downstream of the T3, T7 promoter or the Adenovirus major late promoter were constructed and used for in vitro transcription with purified proteins. We found that both dL and its caged precursor located in the transcribed strand represented a complete block to transcription by T3- and T7RNAP. Similarly, they caused more than 90% arrest when transcription was carried out with mammalian RNAPII. Furthermore, RNAPII complexes arrested at dL were subject to the transcript cleavage reaction mediated by elongation factor TFIIS, indicating that these complexes were stable. A dL in the nontranscribed strand did not block either polymerase.

    View details for DOI 10.1021/tx050292n

    View details for Web of Science ID 000235584800006

    View details for PubMedID 16485899

  • Effect of 8-oxoguanine on transcription elongation by T7 RNA polymerase and mammalian RNA polymerase II DNA REPAIR Silvia, T. A., Maeda, L. S., Kolodner, R. D., Hanawalt, P. C. 2004; 3 (5): 483-494

    Abstract

    8-Oxoguanine (8-oxoG) is a major oxidative lesion produced in DNA by normal cellular metabolism or after exposure to exogenous sources such as ionizing radiation. Persistence of this lesion in DNA causes G to T transversions, with deleterious consequences for the cell. As a result, several repair processes have evolved to remove this lesion from the genome. It has been reported that 8-oxoG is subject to transcription-coupled repair (TCR), a process dedicated to removal of lesions from transcribed strands of expressed genes. A current model assumes that RNA polymerase arrest at the site of the lesion is required for initiation of TCR. As a first step to understand how TCR of 8-oxoG occurs, we have studied the effect of 8-oxoG on transcription elongation by T7 RNA polymerase (T7 RNAP) and rat liver RNA polymerase II (RNAPII). We have utilized an in vitro transcription system with purified RNA polymerase and initiation factors, and substrates containing a single 8-oxoG in the transcribed or in the non-transcribed strand downstream of the T7 promoter or the Adenovirus major late promoter. We found that 8-oxoG only slightly inhibited T7 RNAP transcription, with a readthrough frequency of up to 95%. Similarly, this lesion only transiently blocked transcription by RNAPII. However, changes in nucleotide concentration affected the extent of RNAPII blockage at the 8-oxoG. When this lesion was positioned in the non-transcribed strand, complete lesion bypass was observed with either polymerase. Binding of the Saccharomyces cerevisiae MSH2-MSH6 complex to 8-oxoG containing substrates did not increase the frequency of RNAPII arrest at the site of the lesion, suggesting that this complex was displaced by the elongating polymerase. These results are discussed in the context of possible models for TCR.

    View details for DOI 10.1016/j.dnarep.2004.01.003

    View details for Web of Science ID 000221156400005

    View details for PubMedID 15084310

  • Effect of thymine glycol on transcription elongation by T7 RNA polymerase and mammalian RNA polymerase II JOURNAL OF BIOLOGICAL CHEMISTRY Tornaletti, S., Maeda, L. S., Lloyd, D. R., Reines, D., Hanawalt, P. C. 2001; 276 (48): 45367-45371

    Abstract

    Thymine glycols are formed in DNA by exposure to ionizing radiation or oxidative stress. Although these lesions are repaired by the base excision repair pathway, they have been shown also to be subject to transcription-coupled repair. A current model for transcription-coupled repair proposes that RNA polymerase II arrested at a DNA lesion provides a signal for recruitment of the repair enzymes to the lesion site. Here we report the effect of thymine glycol on transcription elongation by T7 RNA polymerase and RNA polymerase II from rat liver. DNA substrates containing a single thymine glycol located either in the transcribed or nontranscribed strand were used to carry out in vitro transcription. We found that thymine glycol in the transcribed strand blocked transcription elongation by T7 RNA polymerase approximately 50% of the time but did not block RNA polymerase II. Thymine glycol in the nontranscribed strand did not affect transcription by either polymerase. These results suggest that arrest of RNA polymerase elongation by thymine glycol is not necessary for transcription-coupled repair of this lesion. Additional factors that recognize and bind thymine glycol in DNA may be required to ensure RNA polymerase arrest and the initiation of transcription-coupled repair in vivo.

    View details for Web of Science ID 000172406700132

    View details for PubMedID 11571287

Stanford Medicine Resources: