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Tan M.-H.,National Cancer Center Singapore | Tan M.-H.,National University of Singapore | Tan M.-H.,NCCS VARI Laboratory of Translational Cancer Research | Li H.,Singapore General Hospital | And 8 more authors.
Cancer | Year: 2011

Background: Outcomes after surgical removal of localized renal cell carcinoma (RCC) are variable. There have been multiple prognostic nomograms and risk groups developed for estimation of survival outcomes, with different models in use for evaluating patient eligibility in ongoing trials of adjuvant therapy. The authors aimed to establish the most useful prognostic model for patients with localized RCC to guide trial design, biomarker research, and clinical counseling. METHODS: A total of 390 consecutive patients who underwent nephrectomy for sporadic localized RCC in a tertiary institution (1990-2006) with 65 months median follow-up were retrospectively evaluated. The Karakiewicz nomogram, the Kattan nomogram, the Sorbellini nomogram, and the Leibovich model were compared in predicting survival outcomes (overall survival, cancer-specific survival, and freedom from recurrence) using likelihood analysis, adequacy indices, decision curve analysis, calibration, and concordance indices. RESULTS: Overall, the Karakiewicz nomogram outperformed the Kattan nomogram, the Sorbellini nomogram, and the Leibovich model. Highly improved accuracy was seen using the Karakiewicz nomogram in survival prediction, using likelihood ratio analysis in bivariate models including the competing prognostic models. The Karakiewicz nomogram showed higher adequacy and concordance indices and improved clinical benefit relative to all other nomograms. All 4 models were reasonably calibrated. Exploratory comparisons of prespecified discretized Karakiewicz nomograms and the SORCE trial recruitment criteria (a discretized Leibovich model) of high-risk patients favored the discretized Karakiewicz nomograms. CONCLUSIONS: The Karakiewicz nomogram was shown to be superior to the other tested nomograms and risk groups in predicting survival outcomes in localized RCC. Routine integration of this model into trial design and biomarker research should be considered. © 2011 American Cancer Society. Source


Poon E.,National Cancer Center | Ong S.J.,National Cancer Center | Chuang X.E.,National Cancer Center | Lim W.T.,National Cancer Center | And 6 more authors.
Journal of Medical Case Reports | Year: 2011

Introduction. Although metastatic carcinoma in the presence of an occult primary tumor is well recognized, underlying reasons for the failure of the primary tumor to manifest are uncertain. Explanations for this phenomenon have ranged from spontaneous regression of the primary tumor to early metastasis of the primary tumor before manifestation of a less aggressive primary tumor. We report a case of 'prechronous' metastasis arising from clear cell renal cell carcinoma, where metastatic disease initially manifested in the absence of a primary renal tumor, followed by aggressive growth of the primary renal lesion. Case presentation. A 43-year-old Malay man initially presented to our facility with fever and cough. He subsequently underwent surgical resection of a 9 cm right-sided lung mass found on radiological examination. Histology showed a high-grade clear cell tumor with sarcomatoid differentiation, suggestive of a metastasis from clear cell renal cell carcinoma. However, no concurrent renal lesions were noted on computed tomographic evaluation at that time. Then, four months after lung resection, he presented with a subcutaneous mass in the left loin, as well as right loin discomfort. Computed tomography scanning revealed a 10 cm right renal mass, with renal vein and inferior vena cava invasion, as well as recurrent disease in the right thorax. Histological examination of the excised subcutaneous mass revealed a high-grade carcinoma consistent with clear cell renal cell carcinoma. Conclusions: This is the first reported case of prechronous metastasis of renal cell carcinoma, with metastatic disease manifesting prior to the development of the primary lesion. The underlying mechanism is uncertain, but our patient's case provides anecdotal support for the early dissemination model of metastasis. © 2011 Poon et al; licensee BioMed Central Ltd. Source


Tan M.-H.,National Cancer Center Singapore | Tan M.-H.,NCCS VARI Laboratory of Translational Cancer Research | Yang J.,National Cancer Center Singapore | Tan H.L.,NCCS VARI Laboratory of Translational Cancer Research | And 9 more authors.
Annals of the Academy of Medicine Singapore | Year: 2010

Introduction: Genetic predisposition to clear cell renal cell carcinoma (ccRCC) has been linked to disorders such as von Hippel-Lindau (VHL) syndrome. While twin research is a classic approach for elucidating genetic and environmental contributions to disease, no monozygotic twin-pair concordant for ccRCC in the absence of VHL syndrome has been previously reported in the literature or in major twin registries. Clinical Picture: We describe a unique monozygotic twin-pair concordant for ccRCC, with discordant but early ages of onset of 25 and 38 respectively. Cytogenetic studies and direct sequencing for VHL gene mutations in the second twin proved unremarkable. Conclusions: This is the first reported case of monozygotic twins concordant for ccRCC in the absence of VHL gene mutation. The early yet discordant, age of onset of disease in both twins suggests both genetic and environmental contributions to ccRCC. Source


Tan M.-H.,National Cancer Center Singapore | Tan M.-H.,NCCS VARI Laboratory of Translational Cancer Research | Tan M.-H.,National University of Singapore | Kanesvaran R.,National Cancer Center Singapore | And 9 more authors.
Urology | Year: 2010

Objectives: To directly compare the models-the UCLA-Integrated Scoring System (UISS) and the Leibovich models-using various survival endpoints. Several Phase III trials of adjuvant therapy in renal cell carcinoma (RCC) have been initiated after advances in targeted therapy. To select patients at high risk of relapse and mortality, 2 aforementioned prognostic models have been incorporated into these trials. These models have not been compared previously. Methods: A retrospective study of 355 patients with unilateral nonmetastatic clear cell RCC undergoing nephrectomy between 1990 and 2006 at the Singapore General Hospital was undertaken. Performance of the UISS and the Leibovich models, as well as corresponding trial inclusion criteria, was directly compared using log-likelihood statistics. Adequacy and concordance indices were also calculated. Study endpoints tested were overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Results: Likelihood ratio testing demonstrated a significant benefit in prediction when adding the Leibovich model to the UISS model in all outcomes tested, with no benefit using the converse approach (OS: P = .002 vs P = .27; CSS: P = .0001 vs P = .57; DFS: P = <0.0001 vs P = .30). Benefit was seen primarily in disease-free survival when adding the Leibovich trial criteria to UISS trial criteria, with no benefit using the converse approach (OS: P = .16 vs P = .27; CSS: P = .17 vs P = .11; DFS: P = .01 vs P = .26). Conclusions: Both the Leibovich model and trial criteria are superior to the UISS model and trial criteria, respectively, in estimating survival outcomes in patients with nonmetastatic clear cell RCC after nephrectomy. © 2010 Elsevier Inc. All rights reserved. Source

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