Bio

Clinical Focus


  • Intensive Care of the Medical Patient
  • Lung Cancer
  • Solitary Pulmonary Nodule
  • Pulmonary Disease

Academic Appointments


Administrative Appointments


  • Affiliate, Canary Center at Stanford for Cancer Early Detection (2013 - Present)
  • Instructor of medicine, Stanford University, Div of PCCM (2012 - Present)
  • Post-doctoral reseach fellow and clinical instructor, Stanford University, Division of Pulmonary & Critical Care (2010 - 2012)

Honors & Awards


  • Loan Repayment Program "In vivo and In vitro diagnostics to improve lung cancer care", NIH NCI (10/13-10/15)
  • In vivo and in vitro diagnostics for assessing the lung nodule, LUNGevity Foundation Career Development Award (07/12-07/15)
  • An analysis of early-stage NSCLC transcriptomics across varying FDG uptake levels on PET imaging, Lung Cancer Research Foundation (11/10-11/11)
  • PET-FDG uptake, gene expression and outcome in stage I resected lung adenocarcinoma, The CHEST Foundation, Clinical Research Award (07/09-07/10)

Professional Education


  • Board Certification: Critical Care Medicine, American Board of Internal Medicine (2010)
  • Bachelor of Arts, University of Pennsylvania, Chemistry (1998)
  • Medical Education:Ohio State University (6/2004) OH
  • Residency:Santa Clara Valley Medical Center (6/2007) CA
  • Fellowship:Stanford University Division of PCCM (6/2010) CA
  • Masters of Science, Stanford University, Clinical Epidemiology (2011)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2007)
  • Board Certification: Pulmonary Disease, American Board of Internal Medicine (2009)
  • Board Certification, Critical Care Medicine, American Board of Internal Medicine (2010)

Research & Scholarship

Current Research and Scholarly Interests


I am interested in better translating new non-invasive technologies and integrating existing ones to improve care for the early-stage lung cancer patient by applying the principles of epidemiology and computational biology. Specifically, my research focuses on integrating imaging and blood biomarker (in vivo and in vitro) diagnostics to improve clinical practice. Additionally, I am interested in understanding the current limitations of ?omics? and biomarker studies in clinical practice, thereby facilitating improved diagnostic and prognostic tests for the lung cancer patient.

Publications

Journal Articles


  • NF-?B protein expression associates with (18)F-FDG PET tumor uptake in non-small cell lung cancer: A radiogenomics validation study to understand tumor metabolism. Lung cancer Nair, V. S., Gevaert, O., Davidzon, G., Plevritis, S. K., West, R. 2014; 83 (2): 189-196

    Abstract

    We previously demonstrated that NF-?B may be associated with (18)F-FDG PET uptake and patient prognosis using radiogenomics in patients with non-small cell lung cancer (NSCLC). To validate these results, we assessed NF-?B protein expression in an extended cohort of NSCLC patients.We examined NF-?Bp65 by immunohistochemistry (IHC) using a Tissue Microarray. Staining intensity was assessed by qualitative ordinal scoring and compared to tumor FDG uptake (SUVmax and SUVmean), lactate dehydrogenase A (LDHA) expression (as a positive control) and outcome using ANOVA, Kaplan Meier (KM), and Cox-proportional hazards (CPH) analysis.365 tumors from 355 patients with long-term follow-up were analyzed. The average age for patients was 67±11 years, 46% were male and 67% were ever smokers. Stage I and II patients comprised 83% of the cohort and the majority had adenocarcinoma (73%). From 88 FDG PET scans available, average SUVmax and SUVmean were 8.3±6.6, and 3.7±2.4 respectively. Increasing NF-?Bp65 expression, but not LDHA expression, was associated with higher SUVmax and SUVmean (p=0.03 and 0.02 respectively). Both NF-?Bp65 and positive FDG uptake were significantly associated with more advanced stage, tumor histology and invasion. Higher NF-?Bp65 expression was associated with death by KM analysis (p=0.06) while LDHA was strongly associated with recurrence (p=0.04). Increased levels of combined NF-?Bp65 and LDHA expression were synergistic and associated with both recurrence (p=0.04) and death (p=0.03).NF-?B IHC was a modest biomarker of prognosis that associated with tumor glucose metabolism on FDG PET when compared to existing molecular correlates like LDHA, which was synergistic with NF-?B for outcome. These findings recapitulate radiogenomics profiles previously reported by our group and provide a methodology for studying tumor biology using computational approaches.

    View details for DOI 10.1016/j.lungcan.2013.11.001

    View details for PubMedID 24355259

  • A Dominant Adenocarcinoma With Multifocal Ground Glass Lesions Does Not Behave as Advanced Disease ANNALS OF THORACIC SURGERY Gu, B., Burt, B. M., Merritt, R. E., Stephanie, S., Nair, V., Hoang, C. D., Shrager, J. B. 2013; 96 (2): 411-418

    Abstract

    Invasive lung adenocarcinomas increasingly present with synchronous, multifocal, in situ lesions that appear as ground glass opacities (GGOs). The optimal approach in this circumstance (often nonsmokers) remains unclear. We evaluated a general strategy of anatomic resection of the dominant tumor (DT) and wedge resection of accessible ipsilateral GGOs.This is a retrospective review of 39 patients with suspected multifocal in situ adenocarcinomas and 1 DT in a predominantly Caucasian population. Mean follow-up is 30.7 months.Forty-nine percent of patients had no or minimal smoking history; 21% were Asian. The resected DT was pathologically "bronchioloalveolar carcinoma" (26%), minimally invasive adenocarcinoma (5%), adenocarcinoma with bronchioloalveolar features (41%), or moderate well-differentiated adenocarcinoma (28%). The p stage of the DT was IA in 20, IB in 15, and IIA in 4, with mean diameter of 2.6 cm. Thirty-two patients (82%) underwent anatomic resection of the DT; 7 (18%) underwent wedge resection. The mean number of GGOs present initially was 2.7 (range, 1 to 7) with a 5.2-mm mean diameter. An unresected nodule increased in size during follow-up in only 9 patients (23%). The mean diameter growth among these was 3.2 mm, with mean doubling time of 49 months. New GGOs (range, 1 to 8) developed in 16 patients (41%), all of which remained at 7 mm or less. Distant metastasis developed in 2 patients (5.2%); only 1 patient has required intervention for progression of a GGO. The overall survival is 100%.Patients with limited, multifocal, in situ adenocarcinomas and a clinical N0 DT enjoy prolonged survival with generally anatomic resection of the DT and wedge resection of accessible GGOs. These patients should not be considered to harbor T4 or M1a disease.

    View details for DOI 10.1016/j.athoracsur.2013.04.048

    View details for Web of Science ID 000323177800015

    View details for PubMedID 23806231

  • An Observational Study of Circulating Tumor Cells and F-18-FDG PET Uptake in Patients with Treatment-Naive Non-Small Cell Lung Cancer PLOS ONE Nair, V. S., Keu, K. V., Luttgen, M. S., Kolatkar, A., Vasanawala, M., Kuschner, W., Bethel, K., Iagaru, A. H., Hoh, C., Shrager, J. B., Loo, B. W., Bazhenova, L., Nieva, J., Gambhir, S. S., Kuhn, P. 2013; 8 (7)

    Abstract

    We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by (18)F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis.We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs"). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6) and median maximum standardized uptake value (SUVmax) was 7.2 (IQR 3.7-15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r?=?0.27, p-value?=?0.03) and not correlated with tumor diameter (r?=?0.07; p-value?=?0.60). For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.

    View details for DOI 10.1371/journal.pone.0067733

    View details for Web of Science ID 000321425300025

    View details for PubMedID 23861795

  • Circulating tumour cells in early breast cancer LANCET ONCOLOGY Nair, V. S., Keu, K. V., Kuhn, P., Gambhir, S. S. 2012; 13 (9): E370-E371

    View details for Web of Science ID 000308425600024

    View details for PubMedID 22935234

  • Prognostic PET F-18-FDG Uptake Imaging Features Are Associated with Major Oncogenomic Alterations in Patients with Resected Non-Small Cell Lung Cancer CANCER RESEARCH Nair, V. S., Gevaert, O., Davidzon, G., Napel, S., Graves, E. E., Hoang, C. D., Shrager, J. B., Quon, A., Rubin, D. L., Plevritis, S. K. 2012; 72 (15): 3725-3734

    Abstract

    Although 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake during positron emission tomography (PET) predicts post-surgical outcome in patients with non-small cell lung cancer (NSCLC), the biologic basis for this observation is not fully understood. Here, we analyzed 25 tumors from patients with NSCLCs to identify tumor PET-FDG uptake features associated with gene expression signatures and survival. Fourteen quantitative PET imaging features describing FDG uptake were correlated with gene expression for single genes and coexpressed gene clusters (metagenes). For each FDG uptake feature, an associated metagene signature was derived, and a prognostic model was identified in an external cohort and then tested in a validation cohort of patients with NSCLC. Four of eight single genes associated with FDG uptake (LY6E, RNF149, MCM6, and FAP) were also associated with survival. The most prognostic metagene signature was associated with a multivariate FDG uptake feature [maximum standard uptake value (SUV(max)), SUV(variance), and SUV(PCA2)], each highly associated with survival in the external [HR, 5.87; confidence interval (CI), 2.49-13.8] and validation (HR, 6.12; CI, 1.08-34.8) cohorts, respectively. Cell-cycle, proliferation, death, and self-recognition pathways were altered in this radiogenomic profile. Together, our findings suggest that leveraging tumor genomics with an expanded collection of PET-FDG imaging features may enhance our understanding of FDG uptake as an imaging biomarker beyond its association with glycolysis.

    View details for DOI 10.1158/0008-5472.CAN-11-3943

    View details for Web of Science ID 000307354100004

    View details for PubMedID 22710433

  • 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

  • Fluorodeoxyglucose-PET Scanning in the Diagnosis of Pleural Disease CHEST Nair, V. S. 2011; 139 (4): 966-967

    View details for DOI 10.1378/chest.10-2754

    View details for Web of Science ID 000289538500037

    View details for PubMedID 21467067

  • PET Scan F-18-Fluorodeoxyglucose Uptake and Prognosis in Patients With Resected Clinical Stage IA Non-small Cell Lung Cancer CHEST Nair, V. S., Barnett, P. G., Ananth, L., Gould, M. K. 2010; 137 (5): 1150-1156

    Abstract

    Our objective was to examine the association between (18)F-fluorodeoxyglucose (FDG) uptake on PET scan and prognosis in patients with surgically treated, clinical stage IA non-small cell lung cancer (NSCLC).We reviewed data collection forms and Veterans Affairs administrative records of 75 patients with surgically treated, stage IA NSCLC who were enrolled in a prospective study of PET imaging from 1999 to 2001. We used Cox proportional hazards analysis to examine the association between FDG uptake and survival 4 years following enrollment.Most patients were men (97%), and the mean age was 68 +/- 9 years. Almost half of the patients (44%) had adenocarcinoma, and 35% underwent a sublobar resection. The mean maximum standardized uptake value (SUVmax) was 4.9 +/- 2.5 in survivors and 7.1 +/- 3.9 in nonsurvivors (P = .045). Before and after adjustment for age, tumor size, histology, and type of resection, the hazard of death was significantly higher in patients with squamous cell histology (adjusted hazard ratio [HR], 4.54; 95% CI, 1.09-18.9) and those with higher degrees of FDG uptake (adjusted HR, 1.21 per 1 unit increment; 95% CI, 1.01-1.45). At a threshold value of 5 for SUVmax, 34 of 39 patients (87%) with low FDG uptake survived, compared with only 24 of 36 patients (67%) with high FDG uptake (P = .04). Visual assessment of FDG uptake was not associated with an increased hazard of death (HR 0.66; 95% CI, 0.19-2.29).High FDG uptake as measured by SUVmax identifies individuals with clinical stage IA NSCLC who are at increased risk of death following surgery. Such high-risk patients may be good candidates for participation in future trials of adjuvant therapy.

    View details for DOI 10.1378/chest.09-2356

    View details for Web of Science ID 000277542300023

    View details for PubMedID 20038738

  • Management of Lung Nodules Detected by Volume CT Scanning NEW ENGLAND JOURNAL OF MEDICINE Nair, V. S. 2010; 362 (8): 757-757

    View details for Web of Science ID 000274845600018

    View details for PubMedID 20181979

  • Positron Emission Tomography F-18-Fluorodeoxyglucose Uptake and Prognosis in Patients with Surgically Treated, Stage I Non-small Cell Lung Cancer: A Systematic Review JOURNAL OF THORACIC ONCOLOGY Nair, V. S., Krupitskaya, Y., Gould, M. K. 2009; 4 (12): 1473-1479

    Abstract

    18F-fluorodeoxyglucose (FDG) uptake holds potential as a noninvasive biomarker in patients with non-small cell lung cancer (NSCLC). We aimed to investigate the association between tumor FDG uptake and survival in patients with surgically resected, stage I NSCLC.We used systematic methods to identify studies for inclusion, assess methodological quality, and abstract relevant data about study design and results.Our literature search identified 1578 citations, of which nine retrospective, cross-sectional studies met eligibility criteria. In all studies, higher degrees of FDG uptake in the primary tumor were associated with worse overall or disease free survival after 2 to 5 years of follow-up, but these differences were statistically significant in only five studies. Across studies, the median overall or disease free survival was 70% for patients with higher FDG uptake compared with 88% for patients with lower FDG uptake. In three studies that performed multivariable analysis, the adjusted hazard of death or recurrence was 1.9 to 8.6 times greater in patients with higher FDG uptake.Current evidence suggests that increasing tumor FDG uptake is associated with worse survival in patients with stage I NSCLC. FDG uptake has the potential to be used as a biomarker for identifying stage I patients who are at increased risk of death or recurrence and therefore could identify candidates for participation in future trials of adjuvant therapy.

    View details for Web of Science ID 000272095500005

    View details for PubMedID 19887967

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