Dr. Bui is a Clinical Assistant Professor of Medicine at the Stanford Cancer Institute and a specialist in the Sarcoma and Developmental Therapeutics programs. Dr. Bui earned an undergraduate degree in Computer Science at Stanford University and went on to earn his medical degree from the University of Texas Southwestern Medical Center. He completed Internal Medicine residency at Stanford Hospital and Hematology/Oncology fellowship at the University of California San Diego, where he performed extensive research in bioinformatics to analyze tumor sequencing data. His research background and interests are in the field of bioinformatics as applied to large data sets and the study of novel compounds in rare malignancies.
- Internal Medicine
- Medical Oncology
- Phase 1 Trials
Boards, Advisory Committees, Professional Organizations
Member, American Society of Clinical Oncology (ASCO) (2014 - Present)
Associate Member, Stanford Cancer Institute (2018 - Present)
Member, Connective Tissue Oncology Society (CTOS) (2017 - Present)
Residency:Stanford University Internal Medicine Residency (2014) CA
Board Certification: Medical Oncology, American Board of Internal Medicine (2017)
Fellowship:UCSD Hematology and Oncology Training (2017) CA
Board Certification: Hematology, American Board of Internal Medicine (2017)
Medical Education:University of Texas Southwestern Medical School Registrar (2011) TX
Board Certification: Internal Medicine, American Board of Internal Medicine (2014)
B.S., Stanford University, Computer Science (2007)
ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma
The investigators have recently demonstrated that argininosuccinate synthase 1 (ASS1) expression is silenced in 88% of all sarcomas (n=708), and that this loss is associated with a decreased overall survival. Using the extracellular arginine depleting enzyme PEGylated arginine deiminase (ADI-PEG20), an extracellular arginine depleting enzyme, the investigators demonstrated ADI-PEG20 induces a prosurvival metabolic reprogramming in ASS1-deficient sarcomas that redirects glucose into the serine/folate pathway directing the carbons from glucose into pyrimidine biosynthesis, thus sensitizing cells to death by the pyrimidine antimetabolite gemcitabine by using metabolomics. The synthetic lethality was increased by the addition of docetaxel. Therefore a phase II clinical trial of ADI with gemcitabine and docetaxel, a standard second line therapy for soft tissue sarcoma will be conducted to determine if the clinical benefit rate of gemcitabine and docetaxel is improved by the metabolic changes induced by ADI-PEG20
Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations
This phase II trial studies how well olaparib works in treating patients with glioma, cholangiocarcinoma, or solid tumors with IDH1 or IDH2 mutations that have spread to other places in the body (metastatic) and usually cannot be cured or controlled with treatment (refractory). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Olaparib and Temozolomide in Treating Patients With Advanced, Metastatic, or Unresectable Uterine Leiomyosarcoma
This phase II trial studies olaparib and temozolomide in treating patients with uterine leiomyosarcoma (LMS) that has spread to other places in the body (advanced or metastatic) or cannot be removed by surgery (unreserctable). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving olaparib and temozolomide may work better than giving either drug alone in treating patients with LMS.
Stanford is currently not accepting patients for this trial. For more information, please contact Site Public Contact, 650-498-7061.
Increasing Clinical Trial Accrual via Automated Matching of Biomarker Criteria.
Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
2020; 25: 31–42
Successful implementation of precision oncology requires both the deployment of nucleic acid sequencing panels to identify clinically actionable biomarkers, and the efficient screening of patient biomarker eligibility to on-going clinical trials and therapies. This process is typically performed manually by biocurators, geneticists, pathologists, and oncologists; however, this is a time-intensive, and inconsistent process amongst healthcare providers. We present the development of a feature matching algorithmic pipeline that identifies patients who meet eligibility criteria of precision medicine clinical trials via genetic biomarkers and apply it to patients undergoing treatment at the Stanford Cancer Center. This study demonstrates, through our patient eligibility screening algorithm that leverages clinical sequencing derived biomarkers with precision medicine clinical trials, the successful use of an automated algorithmic pipeline as a feasible, accurate and effective alternative to the traditional manual clinical trial curation.
View details for PubMedID 31797584
- Dose escalation of tinostamustine in patients with advanced solid tumors AMER ASSOC CANCER RESEARCH. 2019
Multi-institutional analysis of outcomes in patients with dedifferentiated chondrosarcoma (DDCS).
AMER SOC CLINICAL ONCOLOGY. 2019
View details for Web of Science ID 000487345804124
A phase II study of ADI-PEG 20 in combination with gemcitabine and docetaxel for the treatment of soft tissue sarcoma.
AMER SOC CLINICAL ONCOLOGY. 2019
View details for Web of Science ID 000487345803233
- Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers NATURE COMMUNICATIONS 2019; 10
- Next-Generation Sequencing of Tissue and Circulating Tumor DNA: The UC San Diego Moores Center for Personalized Cancer Therapy Experience with Breast Malignancies MOLECULAR CANCER THERAPEUTICS 2019; 18 (5): 1001–11
A clinico-genomic analysis of soft tissue sarcoma patients reveals CDKN2A deletion as a biomarker for poor prognosis.
Clinical sarcoma research
2019; 9: 12
Background: Sarcomas are a rare, heterogeneous group of tumors with variable tendencies for aggressive behavior. Molecular markers for prognosis are needed to risk stratify patients and identify those who might benefit from more intensive therapeutic strategies.Patients and methods: We analyzed somatic tumor genomic profiles and clinical outcomes of 152 soft tissue (STS) and bone sarcoma (BS) patients sequenced at Stanford Cancer Institute as well as 206 STS patients from The Cancer Genome Atlas. Genomic profiles of 7733 STS from the Foundation Medicine database were used to assess the frequency of CDKN2A alterations in histological subtypes of sarcoma.Results: Compared to all other tumor types, sarcomas were found to carry the highest relative percentage of gene amplifications/deletions/fusions and the lowest average mutation count. The most commonly altered genes in STS were TP53 (47%), CDKN2A (22%), RB1 (22%), NF1 (11%), and ATRX (11%). When all genomic alterations were tested for prognostic significance in the specific Stanford cohort of localized STS, only CDKN2A alterations correlated significantly with prognosis, with a hazard ratio (HR) of 2.83 for overall survival (p=0.017). These findings were validated in the TCGA dataset where CDKN2A altered patients had significantly worse overall survival with a HR of 2.7 (p=0.002). Analysis of 7733 STS patients from Foundation One showed high prevalence of CDKN2A alterations in malignant peripheral nerve sheath tumors, myxofibrosarcomas, and undifferentiated pleomorphic sarcomas.Conclusion: Our clinico-genomic profiling of STS shows that CDKN2A deletion was the most prevalent DNA copy number aberration and was associated with poor prognosis.
View details for DOI 10.1186/s13569-019-0122-5
View details for PubMedID 31528332
Contemporary management of metastatic soft tissue sarcoma.
Current problems in cancer
Soft tissue sarcoma (STS) is a rare, heterogeneous cancer that can have high rates of distant metastases. Optimal treatment planning requires detailed knowledge of distinct sarcoma histologies as well as the wide array of therapeutic options through surgical, medical, radiation, and interventional oncology. In this review article, we discuss the contemporary management of metastatic STS and the underlying data behind these recommendations. All patients with metastatic STS should be discussed in a multidisciplinary tumor board at an experienced sarcoma center. For patients with oligometastatic disease, there should be strong consideration for definitive local therapy such as surgical resection, stereotactic body radiation therapy, or ablative procedures. In cases with widespread metastases, cytotoxic chemotherapy represents the standard treatment for STS patients with traditional chemotherapies, such as anthracyclines, gemcitabine/docetaxel, ifosfamide, and dacarbazine, still being the most commonly used drugs today. The recent approvals of trabectedin, eribulin, and pazopanib have expanded the therapeutic armamentarium for metastatic STS. Histology-directed treatment is crucial for certain subtypes of STS which are highly sensitive to targeted therapy and relatively insensitive to chemotherapy. Despite the significant progress that has been made in metastatic STS in the past decade, overall prognosis is poor and there is a critical need for novel therapeutics.
View details for DOI 10.1016/j.currproblcancer.2019.06.005
View details for PubMedID 31248634
- Editorial. Current problems in cancer 2019; 43 (4): 249
Reviewing the role of healthy volunteer studies in drug development.
Journal of translational medicine
2018; 16 (1): 336
BACKGROUND: With the exception of genotoxic oncology drugs, first-in-human, Phase 1 clinical studies of investigational drugs have traditionally been conducted in healthy volunteers (HVs). The primary goal of these studies is to investigate the pharmacokinetics and pharmacodynamics of a novel drug candidate, determine appropriate dosing, and document safety and tolerability.MAIN BODY: When tailored to specific study objectives, HV studies are beneficial to manufacturers and patients alike and can be applied to both non-oncology and oncology drug development. Enrollment of HVs not only increases study accrual rates for dose-escalation studies but also alleviates the ethical concern of enrolling patients with disease in a short-term study at subtherapeutic doses when other studies (e.g. Phase 2 or Phase 3 studies) may be more appropriate for the patient. The use of HVs in non-oncology Phase 1 clinical trials is relatively safe but nonetheless poses ethical challenges because of the potential risks to which HVs are exposed. In general, most adverse events associated with non-oncology drugs are mild in severity, and serious adverse events are rare, but examples of severe toxicity have been reported. The use of HVs in the clinical development of oncology drugs is more limited but is nonetheless useful for evaluating clinical pharmacology and establishing an appropriate starting dose for studies in cancer patients. During the development of oncology drugs, clinical pharmacology studies in HVs have been used to assess pharmacokinetics, drug metabolism, food effects, potential drug-drug interactions, effects of hepatic and renal impairment, and other pharmacologic parameters vital for clinical decision-making in oncology. Studies in HVs are also being used to evaluate biosimilars versus established anticancer biologic agents.CONCLUSION: A thorough assessment of toxicity and pharmacology throughout the drug development process is critical to ensure the safety of HVs. With the appropriate safeguards, HVs will continue to play an important role in future drug development.
View details for PubMedID 30509294
A multicenter phase II study of Q3 week or weekly paclitaxel in combination with bevacizumab for the treatment of metastatic or unresectable angiosarcoma.
2018; 10: 2036361318771771
Paclitaxel (P) and bevacizumab (B) are agents that provide clinical benefit in advanced angiosarcoma (AS). The objective of this study was to assess the efficacy and safety of P-B in two different scheduled regimens. Patients were to receive P 200mg/m2 IV with B 15mg/kg IV every 21 days (Regimen A) or P 90mg/m2 IV weekly D1, 8, 15 with B 15mg/kg IV D1 of a 28 day cycle (Regimen B) x6 cycles. Maintenance B followed at a dose of 15 mg/kg intravenously once every 21 days. The primary end point was 4 month non-progression rate (NPR). A total of 16 patients were enrolled. 4 month NPR was 62.5% with median overall survival 16 months and median progression free survival 5.06 months. 11 patients made it to cycle 3 and were evaluable for response with 1 CR (9%), 4 PR (36%), 2 SD (18%), and 6 PD (36%). There were ten grade 3 toxicities and four grade 4 toxicities. The breakdown between the two regimens revealed comparable efficacy and safety. Paclitaxel and Bevacizumab is an active regimen in angiosarcoma. Q3 week and weekly paclitaxel appear similar in efficacy and safety.
View details for PubMedID 29760870
Disruption of NSD1 in head and neck cancer promotes favorable chemotherapeutic responses linked to hypomethylation.
Molecular cancer therapeutics
Human papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC) represents a distinct classification of cancer with poor expected outcomes. Of the 11 genes recurrently mutated in HNSCC, we identify a singular and substantial survival advantage for mutations in the gene encoding Nuclear Set Domain Containing Protein 1 (NSD1), a histone methyltransferase altered in approximately 10% of patients. This effect, a 55% decrease in risk of death in NSD1-mutated versus non-mutated patients, can be validated in an independent cohort. NSD1 alterations are strongly associated with widespread genome hypomethylation in the same tumors, to a degree not observed for any other mutated gene. To address whether NSD1 plays a causal role in these associations, we use CRISPR-Cas9 to disrupt NSD1 in HNSCC cell lines and find that this leads to substantial CpG hypomethylation and sensitivity to cisplatin, a standard chemotherapy in head and neck cancer, with a 40 - 50% decrease in IC50. Such results are reinforced by a survey of 1,001 cancer cell lines, in which loss-of-function NSD1 mutations have an average 23% decrease in cisplatin IC50 compared to cell lines with wild type NSD1. This study identifies a favorable subtype of head and neck cancer linked to NSD1 mutation, hypomethylation and cisplatin sensitivity.
View details for DOI 10.1158/1535-7163.MCT-17-0937
View details for PubMedID 29636367
Cell-Free DNA from Ascites and Pleural Effusions: Molecular Insights into Genomic Aberrations and Disease Biology
MOLECULAR CANCER THERAPEUTICS
2017; 16 (5): 948-955
Collection of cell-free DNA (cfDNA) from the blood of individuals with cancer has permitted noninvasive tumor genome analysis. Detection and characterization of cfDNA in ascites and pleural effusions have not yet been reported. Herein, we analyzed cfDNA in the ascites and pleural effusions from six individuals with metastatic cancer. In all cases, cfDNA copy number variations (CNV) were discovered within the effusate. One individual had a relevant alteration with a high copy amplification in EGFR in a never smoker with lung cancer, who showed only MDM2 and CDK4 amplification in a prior tissue biopsy. Another subject with metastatic breast cancer had cytology-positive ascites and an activating PIK3CA mutation identified in the tissue, blood, and ascites collectively. This individual had tumor regression after the administration of the mTOR inhibitor everolimus and had evidence of chromotripsis from chromosomal rearrangements noted in the cell-free ascitic fluid. These results indicate that cfDNA from ascites and pleural effusions may provide additional information not detected with tumor and plasma cell-free DNA molecular characterization, and a context for important insights into tumor biology and clonal dynamic change within primary tumor and metastatic deposits. Mol Cancer Ther; 16(5); 948-55. ©2017 AACR.
View details for DOI 10.1158/1535-7163.MCT-16-0436
View details for Web of Science ID 000400713500017
View details for PubMedID 28468865
Strategies to Overcome Bypass Mechanisms Mediating Clinical Resistance to EGFR Tyrosine Kinase Inhibition in Lung Cancer
MOLECULAR CANCER THERAPEUTICS
2017; 16 (2): 265-272
The vast majority of patients with metastatic lung cancers who initially benefit from EGFR-targeted therapies eventually develop resistance. An increasing understanding of the number and complexity of resistance mechanisms highlights the challenge of treating tumors resistant to EGFR inhibitors. Resistance mechanisms include new, second-site mutations within EGFR (e.g., T790M and C797S), upregulation of MET kinase, upregulation of insulin growth factor receptor (IGFR), HER2 amplification, increased expression of AXL, BIM modulation, NF-κB activation, histologic switch to small-cell cancer, epithelial-to-mesenchymal transition, PDL1 expression with subsequent immune tolerance, and release of cytokines such as TGFβ and IL6. Herein, we review the growing body of knowledge regarding EGFR bypass pathways, and the development of new drugs and combination treatment strategies to overcome resistance. Mol Cancer Ther; 16(2); 265-72. ©2017 AACR.
View details for DOI 10.1158/1535-7163.MCT-16-0105
View details for Web of Science ID 000395563700002
View details for PubMedID 28159915
- Molecular insights into desmoid tumors. Oncotarget 2017; 8 (53): 90608–9
- Chart review versus an automated bioinformatic approach to assess real-world crizotinib effectiveness in ALK-positive NSCLC. JCO clinical cancer informatics 2017; 2017
Evolution of early phase clinical trials in oncology.
Journal of molecular medicine (Berlin, Germany)
The therapeutic armamentarium for the treatment of cancer has rapidly evolved with the advent of molecularly targeted and immuno-oncology agents. Dramatic and prolonged responses observed in patients with advanced cancers have created excitement and promise for expedited development of effective new treatments. However, this has also necessitated a rethinking of our early phase clinical trial designs and the process of optimally developing a novel agent. In this review, we discuss the current state and future directions of phase I clinical trials in oncology. Firstly, we cover the statistical methodologies behind rules and model-based dose escalation designs, and what the future holds for optimal dose selection beyond targeting the maximum tolerated dose. Next, we discuss the recent adoption of seamless expansion strategies to expedite drug development timelines, highlighted by the pembrolizumab KEYNOTE-001 trial, and potential pitfalls with this approach. Finally, we delve into the concepts behind genomic matching trials, including early success stories and the challenges that lie ahead.
View details for PubMedID 29177698
Novel Treatment Strategies for Brain Metastases in Non-small-cell Lung Cancer
CURRENT TREATMENT OPTIONS IN ONCOLOGY
2016; 17 (5)
Brain metastases are common in patients with non-small cell lung cancer (NSCLC), and due to associated poor prognosis, this field is an important area of need for the development of innovative medical therapies. Therapies including local approaches through surgical intervention and/or radiation and evolving systemic therapies have led to improvements in the treatment of brain metastases in patients with lung cancer. Strategies that consider applying advanced radiation techniques to minimize toxicity, intervening early with effective systemic therapies to spare radiation/surgery, testing radiosensitization combinations, and developing drug penetrant molecules have and will continue to define new practice patterns. We believe that in carefully considered asymptomatic patients, first-line systemic therapy may be considered before radiation therapy and small-molecule targeted therapy may provide an opportunity to defer radiation therapy for recurrence or progression of disease. The next several years in oncology drug development will see the reporting on of brain penetrant molecules in oncogene-defined non-small cell lung cancer. Ongoing studies will evaluate immunotherapies in patients with brain metastases with associated endpoints. We hope that continued drug development and carefully designed clinical trials may afford an opportunity to improve the lives of patients with brain metastases.
View details for DOI 10.1007/s11864-016-0400-x
View details for Web of Science ID 000374565200002
View details for PubMedID 27085533
Reactivation of hepatitis B virus after withdrawal of erlotinib
2015; 22 (6): 430-432
Reactivation of hepatitis B virus (hbv) is a reported complication for patients undergoing chemotherapy, particularly immunochemotherapy with anti-CD20 agents such as rituximab. However, as the use of molecularly targeted agents increases, the risk of viral reactivation is less clearly defined. Here, we present the case of a 62-year-old woman with newly diagnosed EGFR mutation-positive metastatic non-small-cell lung cancer (nsclc). Per interview, our patient had a remote history of hbv infection. She was started on erlotinib and developed profound diarrhea leading to renal failure that required hospital admission and temporary discontinuation of erlotinib. At 8 days after erlotinib cessation, she had a marked spike in her liver function tests, with viral serologies that were consistent with hbv reactivation. Although erlotinib and other tyrosine kinase inhibitors (tkis) are not classically associated with hbv reactivation, hbv reactivation can occur even in the setting of tki withdrawal. Before tki initiation, careful patient screening in those at risk for hbv should be performed to attenuate preventable hepatotoxicity and to differentiate between other causes of hepatotoxicity (for example, drug-induced toxicity).
View details for DOI 10.3747/co.22.2665
View details for Web of Science ID 000366983500022
View details for PubMedID 26715877
View details for PubMedCentralID PMC4687665
Dorsal aesthetic lines in rhinoplasty: a quantitative outcome-based assessment of the component dorsal reduction technique.
Plastic and reconstructive surgery
2011; 128 (1): 280-288
Preservation or reconstruction of the middle nasal vault structure and internal nasal valve after dorsal reduction is challenging. The purpose of this study was to retrospectively analyze a series of 100 consecutive rhinoplasty cases with respect to preservation or restoration of the dorsal nasal lines following component dorsal reduction. A new quantitative mathematical application for subject digital images was performed.Medical information and digital images were obtained from 100 consecutive primary rhinoplasty patients from one author (R.J.R.) with University of Texas Southwestern Medical Center Institutional Review Board consent. All postoperative subject digital images were taken at more than 1-year follow-up. Preoperative and postoperative digital images of the dorsal nasal aesthetic lines were analyzed using a software application that quantitated various facial anatomical features compared with landmark measurements unique for each subject (pupil-to-pupil distance). Dorsal line symmetry, nose width, and variation of deformities on each side of the face were determined.Mean subject dorsal line symmetry was 68 percent preoperatively and 94 percent postoperatively. Only 32.5 percent of dorsal lines were harmonious preoperatively, whereas 97 percent of dorsal lines were harmonious postoperatively. Identification of dorsal lines postoperatively versus preoperatively was similar in 74.6 percent, improved in 15.7 percent, and decreased in 9.7 percent. Nasal width lines were similar in 36 subjects, 21 subjects had wider nasal width lines, and 43 subjects had narrower width lines after surgery.Component dorsal hump reduction procedures result in reliable and reproducible clinical outcomes. Quantitative assessments provide evidence that improved and harmonious curves of dorsal aesthetic lines are achievable.Therapeutic, IV.(Figure is included in full-text article.).
View details for DOI 10.1097/PRS.0b013e318218fc2d
View details for PubMedID 21701345