Nam Bui

All Publications

• A multicenter phase II study of Q3 week or weekly paclitaxel in combination with bevacizumab for the treatment of metastatic or unresectable angiosarcoma. Rare tumors Bui, N., Kamat, N., Ravi, V., Chawla, S., Lohman, M., Ganjoo, K. N. 2018; 10: 2036361318771771

  Abstract

  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 DOI 10.1177/2036361318771771

  View details for PubMedID 29760870

  View details for PubMedCentralID PMC5946584

• Disruption of NSD1 in head and neck cancer promotes favorable chemotherapeutic responses linked to hypomethylation. Molecular cancer therapeutics Bui, N., Huang, J. K., Bojorquez-Gomez, A., Licon, K., Sanchez, K. S., Tang, S. N., Beckett, A. N., Wang, T., Zhang, W., Shen, J. P., Kreisberg, J. F., Ideker, T. 2018

  Abstract

  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 Husain, H., Nykin, D., Nam Bui, N., Quan, D., Gomez, G., Woodward, B., Venkatapathy, S., Duttagupta, R., Fung, E., Lippman, S. M., Kurzrock, R. 2017; 16 (5): 948-955

  Abstract

  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 Husain, H., Scur, M., Murtuza, A., Bui, N., Woodward, B., Kurzrock, R. 2017; 16 (2): 265-272

  Abstract

  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 Bui, N., Kummar, S. 2017; 8 (53): 90608–9

  View details for DOI 10.18632/oncotarget.21293

  View details for PubMedID 29207578

  View details for PubMedCentralID PMC5710859

• Chart review versus an automated bioinformatic approach to assess real-world crizotinib effectiveness in ALK-positive NSCLC. JCO clinical cancer informatics Bui, N., Henry, S., Wood, D., Wakelee, H. A., Neal, J. W. 2017; 2017

  View details for DOI 10.1200/CCI.16.00055

  View details for PubMedID 28868517

• Evolution of early phase clinical trials in oncology. Journal of molecular medicine (Berlin, Germany) Bui, N. Q., Kummar, S. 2017

  Abstract

  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 DOI 10.1007/s00109-017-1612-7

  View details for PubMedID 29177698

• Novel Treatment Strategies for Brain Metastases in Non-small-cell Lung Cancer CURRENT TREATMENT OPTIONS IN ONCOLOGY Bui, N., Woodward, B., Johnson, A., Husain, H. 2016; 17 (5)

  Abstract

  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 CURRENT ONCOLOGY Bui, N., Wong-Sefidan, I. 2015; 22 (6): 430-432

  Abstract

  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 Mojallal, A., Ouyang, D., Saint-Cyr, M., Bui, N., Brown, S. A., Rohrich, R. J. 2011; 128 (1): 280-288

  Abstract

  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