Dr. Thong is a urologist specializing in urologic oncology and general urology. He has experience in all aspects of adult urology care, including endoscopic, robotic, and open surgery, and has a special interest in the treatment of prostate, kidney and bladder cancer. He has won numerous awards including the NIH Ruth L. Kirschstein National Research Service Award, and has authored and co-authored publications on the treatment of urologic cancers.
- Urologic oncology
Clinical Assistant Professor, Urology
Boards, Advisory Committees, Professional Organizations
Associate member, Society of Urologic Oncology (2015 - Present)
Member, American Society of Clinical Oncology (2015 - Present)
Associate member, American Urological Association (2010 - Present)
Associate fellow, American College of Surgeons (2008 - Present)
Member, American Medical Association (2008 - Present)
Residency:Stanford Medicine Dept of Urology (2014) CA
AB, Princeton University (2004)
MD, University of Chicago, Pritzker School of Medicine (2008)
Residency, Stanford University (2014)
Fellowship, Memorial Sloan Kettering Cancer Center (2016)
MPH, Harvard University (2016)
Development of a realistic in vivo bone metastasis model of human renal cell carcinoma
CLINICAL & EXPERIMENTAL METASTASIS
2014; 31 (5): 573-584
About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastases. The incidence of RCC is increasing and bone metastatic RCC merits greater focus. Realistic preclinical bone metastasis models of RCC are lacking, hampering the development of effective therapies. We developed a realistic in vivo bone metastasis model of human RCC by implanting precision-cut tissue slices under the renal capsule of immunodeficient mice. The presence of disseminated cells in bone marrow of tissue slice graft (TSG)-bearing mice was screened by human-specific polymerase chain reaction and confirmed by immunohistology using human-specific antibody. Disseminated tumor cells in bone marrow of TSG-bearing mice derived from three of seven RCC patients were detected as early as 1 month after tissue implantation at a high frequency with close resemblance to parent tumors (e.g., CAIX expression and high vascularity). The metastatic patterns of TSGs correlated with disease progression in patients. In addition, TSGs retained capacity to metastasize to bone at high frequency after serial passaging and cryopreservation. Moreover, bone metastases in mice responded to Temsirolimus treatment. Intratibial injections of single cells generated from TSGs showed 100 % engraftment and produced X-ray-visible tumors as early as 3 weeks after cancer cell inoculation. Micro-computed tomography (μCT) and histological analysis revealed osteolytic characteristics of these lesions. Our results demonstrated that orthotopic RCC TSGs have potential to develop bone metastases that respond to standard therapy. This first reported primary RCC bone metastasis model provides a realistic setting to test therapeutics to prevent or treat bone metastases in RCC.
View details for DOI 10.1007/s10585-014-9651-8
View details for Web of Science ID 000337082400008
View details for PubMedID 24715498
Preclinical trial of a new dual mTOR inhibitor, MLN0128, using renal cell carcinoma tumorgrafts
INTERNATIONAL JOURNAL OF CANCER
2014; 134 (10): 2322-2329
mTOR is a rational target in renal cell carcinoma (RCC) because of its role in disease progression. However, the effects of temsirolimus, the only first-generation mTOR inhibitor approved by the FDA for first-line treatment of metastatic RCC, on tumor reduction and progression-free survival are minimal. Second-generation mTOR inhibitors have not been evaluated on RCC. We compared the effects of temsirolimus and MLN0128, a potent second-generation mTOR inhibitor, on RCC growth and metastasis using a realistic patient-derived tissue slice graft (TSG) model. TSGs were derived from three fresh primary RCC specimens by subrenal implantation of precision-cut tissue slices into immunodeficient mice that were randomized and treated with MLN0128, temsirolimus, or placebo. MLN0128 consistently suppressed primary RCC growth, monitored by magnetic resonance imaging (MRI), in three TSG cohorts for up to 2 months. Temsirolimus, in contrast, only transiently inhibited the growth of TSGs in one of two cohorts before resistance developed. In addition, MLN0128 reduced liver metastases, determined by human-specific quantitative polymerase chain reaction, in two TSG cohorts, whereas temsirolimus failed to have any significant impact. Moreover, MLN0128 decreased levels of key components of the two mTOR subpathways including TORC1 targets 4EBP1, p-S6K1, HIF1α and MTA1 and the TORC2 target c-Myc, consistent with dual inhibition. Our results demonstrated that MLN0128 is superior to temsirolimus in inhibiting primary RCC growth as well as metastases, lending strong support for further clinical development of dual mTOR inhibitors for RCC treatment.
View details for DOI 10.1002/ijc.28579
View details for Web of Science ID 000332309700007
View details for PubMedID 24243565
Relating prognosis in chromophobe renal cell carcinoma to the chromophobe tumor grading system.
Korean journal of urology
2014; 55 (4): 239-244
The chromophobe subtype of renal cell carcinoma (chRCC) has generally been associated with a better prognosis than the clear cell type; however, debate continues as to absolute prognosis as well as the significance of certain prognostic variables. We investigated the significance of pathologic stage and a recently proposed chromophobe tumor grading (CTG) scheme in predicting chRCC outcomes.All available chRCCs were identified from our surgical pathology archives from 1987-2010. Original slides were reviewed to verify diagnoses and stage, and each case was graded following a novel chromophobe tumor grade system criteria. Disease status was obtained from a clinical outcome database, and cancer specific deaths and recurrences were recorded.Eighty-one cases of chRCC were identified, and 73 had adequate follow-up information available. There were only 3 instances of cancer related recurrence or mortality, which included 1 disease specific mortality and 2 disease recurrences. Pathologic stage and CTG 3 were found to be significantly associated with the recurrences or death from chRCC, but there was no association with CTG 1 and CTG 2.chRCC is associated with a very low rate of cancer specific events (4.1%) even at a tertiary referral center. In our study, pathologic stage and CTG 3, but not CTG 1 or 2, were significantly associated with the development of these events.
View details for DOI 10.4111/kju.2014.55.4.239
View details for PubMedID 24741411
- Tissue slice grafts of human renal cell carcinoma: An authentic preclinical model with high engraftment rate and metastatic potential UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS 2014; 32 (1)
Estimating the risk of chronic kidney disease after nephrectomy
CANADIAN JOURNAL OF UROLOGY
2013; 20 (6): 7035-7041
To identify factors associated with the development of chronic kidney disease (CKD) after nephrectomy and to create a clinical model to predict CKD after nephrectomy for kidney cancer for clinical use.We identified 144 patients who had normal renal function (eGFR > 60) prior to undergoing nephrectomy for kidney cancer. Selected cases occurred between 2007 and 2010 and had at least 30 days follow up. Sixty-six percent (n = 95) underwent radical nephrectomy and 62.5% (n = 90) developed CKD (stage 3 or higher) postoperatively. We used univariable analysis to screen for predictors of CKD and multivariable logistic regression to identify independent predictors of CKD and their corresponding odds ratios. Interaction terms were introduced to test for effect modification. To protect against over-fitting, we used 10-fold cross-validation technique to evaluate model performance in multiple training and testing datasets. Validation against an independent external cohort was also performed.Of the variables associated with CKD in univariable analysis, the only independent predictors in multivariable logistic regression were patient age (OR = 1.27 per 5 years, 95% CI: 1.07-1.51), preoperative glomerular filtration rate (GFR), (OR = 0.70 per 10 mL/min, 95% CI: 0.56-0.89), and receipt of radical nephrectomy (OR = 4.78, 95% CI: 2.08-10.99). There were no significant interaction terms. The resulting model had an area under the curve (AUC) of 0.798. A 10-fold cross-validation slightly attenuated the AUC to 0.774 and external validation yielded an AUC of 0.930, confirming excellent model discrimination.Patient age, preoperative GFR, and receipt of a radical nephrectomy independently predicted the development of CKD in patients undergoing nephrectomy for kidney cancer in a validated predictive model.
View details for Web of Science ID 000328717300007
View details for PubMedID 24331345
Stage I Testicular Seminoma: A SEER Analysis of Contemporary Adjuvant Radiotherapy Trends.
journal of urology
2013; 190 (4): 1240-1244
PURPOSE: Patients with clinical stage I testicular seminoma have historically been treated with adjuvant radiotherapy (RT) in the United States. However, nearly 80% of patients on surveillance will not relapse and even with relapse, salvage rates approach 100%. It remains unclear how practice patterns have changed with recently accumulating evidence and changes in guidelines. We evaluated, in a population-based setting, contemporary trends and factors that may affect utilization of adjuvant RT. MATERIALS AND METHODS: A total of 8,151 men from 2000 to 2009 diagnosed with stage I testicular seminoma were identified in the national Surveillance, Epidemiology, and End Results (SEER) registry. A multivariate regression model was constructed to analyze the association of year, age, race, socioeconomic status, SEER region, pathologic stage, and tumor size with administration of adjuvant RT. RESULTS: Utilization of adjuvant RT significantly decreased from 2000 to 2009. In 2000, 74.7% of patients received radiation, compared with only 37.7% of patients in 2009 (p<0.0001). Later year of diagnosis was significantly associated with decreased odds of receiving adjuvant RT (p<0.0001, 2000-2005 vs. 2006-2009, Odds ratio (OR) 0.40, 95% CI 0.36-0.44). Men older than 35 years (p<0.0002, OR 1.20, 95% CI 1.09-1.32) and men in the highest socioeconomic index quartile (p<0.0001, OR 1.34, 95% CI 1.16-1.54) were more likely to receive adjuvant RT. CONCLUSIONS: Utilization of adjuvant RT for clinical stage I testicular seminoma has decreased significantly in the last decade. Older age and higher socioeconomic status were associated with higher rates of adjuvant RT.
View details for DOI 10.1016/j.juro.2013.03.114
View details for PubMedID 23567749
Patient-derived tissue slice grafts accurately depict response of high-risk primary prostate cancer to androgen deprivation therapy
JOURNAL OF TRANSLATIONAL MEDICINE
Effective eradication of high-risk primary prostate cancer (HRPCa) could significantly decrease mortality from prostate cancer. However, the discovery of curative therapies for HRPCa is hampered by the lack of authentic preclinical models.We improved upon tumorgraft models that have been shown to predict drug response in other cancer types by implanting thin, precision-cut slices of HRPCa under the renal capsule of immunodeficient mice. Tissue slice grafts (TSGs) from 6 cases of HRPCa were established in mice. Following androgen deprivation by castration, TSGs were recovered and the presence and phenotype of cancer cells were evaluated.High-grade cancer in TSGs generated from HRPCa displayed characteristic Gleason patterns and biomarker expression. Response to androgen deprivation therapy (ADT) was as in humans, with some cases exhibiting complete pathologic regression and others showing resistance to castration. As in humans, ADT decreased cell proliferation and prostate-specific antigen expression in TSGs. Adverse pathological features of parent HRPCa were associated with lack of regression of cancer in corresponding TSGs after ADT. Castration-resistant cancer cells remaining in TSGs showed upregulated expression of androgen receptor target genes, as occurs in castration-resistant prostate cancer (CRPC) in humans. Finally, a rare subset of castration-resistant cancer cells in TSGs underwent epithelial-mesenchymal transition, a process also observed in CRPC in humans.Our study demonstrates the feasibility of generating TSGs from multiple patients and of generating a relatively large number of TSGs from the same HRPCa specimen with similar cell composition and histology among control and experimental samples in an in vivo setting. The authentic response of TSGs to ADT, which has been extensively characterized in humans, suggests that TSGs can serve as a surrogate model for clinical trials to achieve rapid and less expensive screening of therapeutics for HRPCa and primary CRPC.
View details for DOI 10.1186/1479-5876-11-199
View details for Web of Science ID 000323850900001
View details for PubMedID 23985008