- Lung Cancer
- Neuroendocrine Tumors
Clinical Assistant Professor, Medicine - Oncology
Honors & Awards
Humanism in Hematology/Oncology Award, Division of Oncology, Stanford Hospital and Clinics (2019)
Methods in Clinical Cancer Research Workshop, ASCO/AACR (2019)
Charles Dorsey Armstrong Award for Excellence in Patient Care by a Senior Resident, Department of Internal Medicine, Stanford Hospital and Clinics (2015)
Board Certification, Hematology, American Board of Internal Medicine (2019)
Board Certification, Oncology, American Board of Internal Medicine (2019)
Board Certification, Internal Medicine, American Board of Internal Medicine (2015)
Fellowship: Stanford University Hematology and Oncology Fellowship (2019) CA
Residency, Stanford University, Internal Medicine Residency, CA (2015)
Medical Education: Stanford University School of Medicine (2012) CA
Brain Metastases in EGFR- and ALK-positive Non-Small Cell Lung Cancer: Outcomes of CNS Penetrant Tyrosine Kinase Inhibitors (TKIs) Alone versus in Combination with Radiation.
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
INTRODUCTION: Management of central nervous system (CNS) metastases in patients with driver-mutated non-small cell lung cancer (NSCLC) has traditionally incorporated both tyrosine kinase inhibitors (TKIs) and intracranial radiation. Whether next-generation, CNS-penetrant TKIs can be used alone without upfront radiation, however, remains unknown. This multi-institutional retrospective analysis aimed to compare outcomes in patients with EGFR- or ALK-positive NSCLC who received CNS-penetrant TKI therapy alone versus in combination with radiation for new or progressing intracranial metastases.METHODS: Data was retrospectively collected from 3 academic institutions. Two treatment groups (CNS-penetrant TKI alone vs TKI+CNS RT) were compared for both EGFR- and ALK-positive cohorts. Outcome variables included time to progression, time to intracranial progression, and time to treatment failure, measured from the date of initiation of CNS-penetrant TKI therapy.RESULTS: A total of 147 patients were included (EGFR n=94, ALK n=52, both n=1). In patients receiving radiation, larger metastases, neurological symptoms, and receipt of steroids were more common. There were no significant differences between TKI vs CNS RT+TKI groups for any of the study outcomes, including time to progression (8.5 vs 6.9 months, p=0.13 [EFGR] and 11.4 vs 13.4 months, p=0.98 [ALK]), time to intracranial progression (14.8 vs 20.5 months, p=0.51 [EGFR] and 18.1 vs 21.8 months, p=0.65 [ALK]), or time to treatment failure (13.8 vs 8.6 months, p=0.26 [EGFR] and 13.5 vs 23.2 months, p=0.95 [ALK]).CONCLUSION: These results provide preliminary evidence that intracranial activity of CNS-penetrant TKIs may enable local radiation to be deferred in appropriately selected patients without negatively impacting progression.
View details for DOI 10.1016/j.jtho.2021.08.009
View details for PubMedID 34455066
Pharmacovigilance analysis of cardiac toxicities associated with targeted therapies for metastatic non-small cell lung carcinoma.
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
INTRODUCTION: Targeted therapies have transformed treatment of driver-mutated metastatic non-small cell lung carcinoma (NSCLC). We compared cardiovascular adverse events between and within targeted therapy classes.METHODS: We used WHO pharmacovigilance database VigiBase to compare odds of heart failure, conduction disease, QT prolongation, supraventricular tachycardia (SVT), and ventricular arrhythmias between inhibitors of EGFR (erlotinib, gefitinib, afatinib, osimertinib), BRAF (dabrafenib), MEK (trametinib), and ALK ± ROS1 (alectinib, brigatinib, ceritinib, crizotinib, lorlatinib).RESULTS: Of 98,765 adverse reactions reported with NSCLC targeted therapies, 1,783 (1.8%) were arrhythmias and 1,146 (1.2%) were heart failure. ALK/ROS1 inhibitors were associated with increased odds of conduction disease (reporting odds ratio [ROR] 12.95, 99% CI: 10.14-16.55) and QT prolongation (ROR 5.16, 99% CI: 3.92-6.81) relative to BRAF and EGFR inhibitors. Among ALK/ROS1 inhibitors, crizotinib had highest odds of conduction disease (ROR 1.75, 99% CI: 1.30-2.36) and QT prolongation (ROR 1.91, 99% CI: 1.22-3.00). Dabrafenib (ROR 2.24, 99% CI: 1.86-2.70) and trametinib (ROR 2.44, 99% CI: 2.03-2.92) had higher odds of heart failure than other targeted therapies. Osimertinib was strongly associated with QT prolongation (ROR 6.13, 99% CI: 4.43-8.48), heart failure (ROR 3.64, 99% CI: 2.94-4.50), and SVT (ROR 1.90, 99% CI: 1.26-2.86) relative to other targeted therapies.CONCLUSIONS: ALK/ROS1 inhibitors are associated with higher odds of conduction disease and QT prolongation than other targeted therapies. Osimertinib is strongly associated with QT prolongation, SVT, and heart failure relative to other EGFR inhibitors and targeted therapies. Monitoring for heart failure and arrhythmias should be considered with NSCLC targeted therapies, especially osimertinib.
View details for DOI 10.1016/j.jtho.2021.07.030
View details for PubMedID 34418561
Safety of lorlatinib following alectinib-induced pneumonitis in two patients with ALK-rearranged non-small cell lung cancer: a case series.
Translational lung cancer research
2021; 10 (1): 487–95
Drug-induced interstitial lung disease (DI-ILD) is a rare adverse event associated with targeted therapies that inhibit the anaplastic lymphoma kinase (ALK) protein. Although newer-generation ALK inhibitors such as alectinib significantly improve survival in metastatic ALK-rearranged non-small cell lung cancer (NSCLC), the risk of DI-ILD is similar to that of earlier-generation therapies. Lorlatinib is a third-generation ALK inhibitor that is active in patients with metastatic NSCLC whose tumors have developed secondary resistance to alectinib. While it is associated with low rates of DI-ILD in initial phase 1/2 clinical trials, the safety of lorlatinib in patients with a history of DI-ILD has not been well-described. In this case series, we therefore report two patients with metastatic ALK-rearranged NSCLC who each tolerated lorlatinib following recovery from alectinib-related DI-ILD. Both cases were notable for the acute onset of dyspnea, hypoxia, and diffuse ground-glass opacities within one month of initiating alectinib. With no alternative etiology of pneumonitis identified, both patients were treated empirically for grade 3 DI-ILD with corticosteroids and discontinuation of alectinib. Following rapid clinical recovery and eventual radiographic resolution of opacities, each patient was started on lorlatinib at the time of cancer progression, with neither person developing symptoms or radiographic findings consistent with recurrent DI-ILD. In the following series, we describe these two cases in greater detail and discuss their significance within the context of the prior literature. While further descriptions are needed, our experience suggests that lorlatinib may be a safe therapeutic option in some patients who have recovered from DI-ILD.
View details for DOI 10.21037/tlcr-20-564
View details for PubMedID 33569330
Advances in the Treatment of Stage III Non-Small Cell Lung Cancer.
Clinics in chest medicine
2020; 41 (2): 211–22
Treatment of stage III non-small cell lung cancer (NSCLC) traditionally has involved combinations of chemotherapy, radiation, and surgical resection. Although the multimodality approach remains standard, only a fraction of patients with stage III lung cancer can undergo complete resection, and long-term prognosis remains poor. The PACIFIC trial generated significant enthusiasm when it demonstrated that the programmed death ligand-1 inhibitor, durvalumab, improved survival in patients with unresectable stage III NSCLC after completion of definitive concurrent chemoradiation. This article reviews the indications for traditional therapies in stage III NSCLC and highlights ongoing advances that have led to the incorporation of novel therapeutic agents.
View details for DOI 10.1016/j.ccm.2020.02.008
View details for PubMedID 32402357
- Real-world treatment patterns and survival of patients with BRAF V600-mutated metastatic non-small cell lung cancer LUNG CANCER 2019; 128: 74–90
Natural Disease History, Outcomes, and Co-mutations in a Series of Patients With BRAF-Mutated Non-small-cell Lung Cancer.
Clinical lung cancer
BACKGROUND: BRAF mutations occur in 1% to 4% of non-small-cell lung cancer (NSCLC) cases. Previous retrospective studies have reported similar outcomes for BRAF-mutated NSCLC as compared with wild-type tumors without a known driver mutation or tumors harboring other mutations. However, select cases of prolonged survival have also been described, and thus, the natural history of BRAF-mutated NSCLC remains an area of ongoing study. The aim of this series was to describe the natural history, clinical outcomes, and occurrence of co-mutations in patients with BRAF-mutated NSCLC.PATIENTS AND METHODS: Patients with BRAF-mutated NSCLC seen at Stanford University Medical Center from January 1, 2006 through July 31, 2015 were reviewed. The Kaplan-Meier method was used to calculate median overall survival, and the generalized Wilcoxon test was used to compare median survivals across subgroups of patients.RESULTS: Within a cohort of 18 patients with BRAF-mutated NSCLC, V600E mutations were most common (72%; 13/18). Clinicopathologic features were similar between patients with V600E versus non-V600E mutations, although there was a trend toward more patients with non-V600E mutations being heavy smokers (80% vs. 31%; P= .12). Co-occurring mutations in TP53 were identified most commonly (28%; 5/18). The median overall survival for the entire cohort was 40.1 months, and the median survival from the onset of metastases (n= 16) was 28.1 months. Survival rates at 2 and 5 years from the onset of metastases were 56% and 13%, respectively.CONCLUSION: The clinical behavior of BRAF-mutated NSCLC is variable, but favorable outcomes can be seen in a subset of patients.
View details for PubMedID 30442523
-Mutant Non-Small Cell Lung Cancer: From Molecular Profiling to Rationally Designed Therapy.
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths globally. However, the identification of oncogenic driver alterations involved in the initiation and maintenance of NSCLC, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocation, has led to the development of novel therapies that directly target mutant proteins and associated signaling pathways, resulting in improved clinical outcomes. As sequencing techniques have improved, the molecular heterogeneity of NSCLC has become apparent, leading to the identification of a number of potentially actionable oncogenic driver mutations. Of these, one of the most promising therapeutic targets is B-Raf proto-oncogene, serine/threonine kinase (BRAF). Mutations in BRAF, observed in 2%-4% of NSCLCs, typically lead to constitutive activation of the protein and, as a consequence, lead to activation of the mitogen-activated protein kinase signaling pathway. Direct inhibition of mutant BRAF and/or the downstream mitogen-activated protein kinase kinase (MEK) has led to prolonged survival in patients with BRAF-mutant metastatic melanoma. This comprehensive review will discuss the clinical characteristics and prognostic implications of BRAF-mutant NSCLC, the clinical development of BRAF and MEK inhibitors from melanoma to NSCLC, and practical considerations for clinicians involving BRAF mutation screening and the choice of targeted therapy. The Oncologist 2017;22:1-11 IMPLICATIONS FOR PRACTICE: Personalized medicine has begun to provide substantial benefit to patients with oncogene-driven non-small cell lung cancer (NSCLC). However, treatment options for patients with oncogenic driver mutations lacking targeted treatment strategies remain limited. Direct inhibition of mutant B-Raf proto-oncogene, serine/threonine kinase (BRAF) and/or downstream mitogen-activated protein kinase kinase has the potential to change the course of the disease for patients with BRAF-mutant NSCLC, as it has in BRAF-mutant melanoma. Optimization of screening strategies for rare mutations and the choice of appropriate agents on an individual basis will be key to providing timely and successful intervention.
View details for DOI 10.1634/theoncologist.2016-0458
View details for PubMedID 28487464
- Adding to the targeted therapy toolbox: BRAF and MEK inhibition in the treatment of BRAF V600E metastatic non-small cell lung cancer TRANSLATIONAL CANCER RESEARCH 2016; 5: S1233-S1240
- Long-Term Survival of a Patient With Non-Small-Cell Lung Cancer Harboring a V600E Mutation in the BRAF Oncogene. Clinical lung cancer 2016; 17 (2): e17-21
Variations in the neurobiology of reading in children and adolescents born full term and preterm
2016; 11: 555-565
Diffusion properties of white matter tracts have been associated with individual differences in reading. Individuals born preterm are at risk of injury to white matter. In this study we compared the associations between diffusion properties of white matter and reading skills in children and adolescents born full term and preterm. 45 participants, aged 9-17 years, included 26 preterms (born < 36 weeks' gestation) and 19 full-terms. Tract fractional anisotropy (FA) profiles were generated for five bilateral white matter tracts previously associated with reading: anterior superior longitudinal fasciculus (aSLF), arcuate fasciculus (Arc), corticospinal tract (CST), uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF). Mean scores on reading for the two groups were in the normal range and were not statistically different. In both groups, FA was associated with measures of single word reading and comprehension in the aSLF, AF, CST, and UF. However, correlations were negative in the full term group and positive in the preterm group. These results demonstrate variations in the neurobiology of reading in children born full term and preterm despite comparable reading skills. Findings suggest that efficient information exchange required for strong reading abilities may be accomplished via a different balance of neurobiological mechanisms in different groups of readers.
View details for DOI 10.1016/j.nicl.2016.04.003
View details for PubMedID 27158588
Developmental Changes within White Matter Tracts of Healthy Children Age 9 to 16 Years Old
LIPPINCOTT WILLIAMS & WILKINS. 2013: S5
View details for Web of Science ID 000330358800018
- Case series: fractional anisotropy along the trajectory of selected white matter tracts in adolescents born preterm with ventricular dilation. Journal of child neurology 2013; 28 (6): 771-777
Tract Profiles of White Matter Properties: Automating Fiber-Tract Quantification
2012; 7 (11)
Tractography based on diffusion weighted imaging (DWI) data is a method for identifying the major white matter fascicles (tracts) in the living human brain. The health of these tracts is an important factor underlying many cognitive and neurological disorders. In vivo, tissue properties may vary systematically along each tract for several reasons: different populations of axons enter and exit the tract, and disease can strike at local positions within the tract. Hence quantifying and understanding diffusion measures along each fiber tract (Tract Profile) may reveal new insights into white matter development, function, and disease that are not obvious from mean measures of that tract. We demonstrate several novel findings related to Tract Profiles in the brains of typically developing children and children at risk for white matter injury secondary to preterm birth. First, fractional anisotropy (FA) values vary substantially within a tract but the Tract FA Profile is consistent across subjects. Thus, Tract Profiles contain far more information than mean diffusion measures. Second, developmental changes in FA occur at specific positions within the Tract Profile, rather than along the entire tract. Third, Tract Profiles can be used to compare white matter properties of individual patients to standardized Tract Profiles of a healthy population to elucidate unique features of that patient's clinical condition. Fourth, Tract Profiles can be used to evaluate the association between white matter properties and behavioral outcomes. Specifically, in the preterm group reading ability is positively correlated with FA measured at specific locations on the left arcuate and left superior longitudinal fasciculus and the magnitude of the correlation varies significantly along the Tract Profiles. We introduce open source software for automated fiber-tract quantification (AFQ) that measures Tract Profiles of MRI parameters for 18 white matter tracts. With further validation, AFQ Tract Profiles have potential for informing clinical management and decision-making.
View details for DOI 10.1371/journal.pone.0049790
View details for PubMedID 23166771
G328E and G409E sialin missense mutations similarly impair transport activity, but differentially affect trafficking
MOLECULAR GENETICS AND METABOLISM
2007; 92 (4): 371-374
Two disease-associated missense mutations in the sialin gene (G328E and G409E) have recently been identified in patients with lysosomal free sialic acid storage disease. We have assessed the effect of these mutations and find complete loss of measurable transport activity with both and impaired trafficking of the G409E protein. These results suggest that the two residues are important for proper function of sialin and confirm the association of loss of transport with disease causative mutations.
View details for DOI 10.1016/j.ymgme.2007.08.121
View details for Web of Science ID 000252054000012
View details for PubMedID 17933575
View details for PubMedCentralID PMC2171360