Prognostic stratification of patients with advanced renal cell carcinoma treated with sunitinib: comparison with the Memorial Sloan-Kettering prognostic factors model

Bamias, Aristotelis; Karadimou, Alexandra; Lampaki, Sofia; Lainakis, G.; Malettou, Lia; Timotheadou, Eleni; Papazisis, Kostas; Andreadis, Charalambos; Kontovinis, Loukas; Anastasiou, Ioannis; Stravodimos, Konstantinos; Xanthakis, Ioannis; Skolarikos, Andreas; Syrigos, K.; Papandreou, Christos N.; Razi, Evangelia; Dafni, Urania; Fountzilas, George; Dimopoulos, Meletios Α.

doi:10.1186/1471-2407-10-45

Cited by 30 publications

(26 citation statements)

References 28 publications

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“…In this study, although MSKCC scores had been previously identified as prognostic in patients treated with cytokines, these factors were significantly or marginally associated with poor OS (Table 2). This is similar to recent reports that have identified patients who are more likely to benefit from the tyrosine kinase inhibitors [12][13][14]. Their results suggest that MSKCC scores are associated with the behavior of the disease rather than with a specific form of therapy.…”

Section: Discussionsupporting

confidence: 90%

Treatment outcome and prognostic factors in renal cell cancer patients with bone metastasis

Yuasa

Urakami

Yamamoto

et al. 2011

Clin Exp Metastasis

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We retrospectively analyzed treatment outcomes and factors for poor prognosis for patients with renal cell cancer (RCC) bone metastases. Patients with bone metastases at initial diagnosis of metastasis secondary from RCC, treated at our hospital between 1984 and 2009, were retrospectively reviewed and statistically analyzed. Among 214 RCC patients with metastasis, 71 patients (33%) were found to have bone metastases at initial diagnosis of metastasis. The median follow-up was 21.1 months (intra-quartile range: IQR, 9.1-47.4 months). The estimated median overall survival time from the diagnosis of bone metastasis was 27.7 months. The probability of patients surviving at 1, 2, and 5 years was 63.7, 52.2, and 19.3%, respectively. When they were stratified by MSKCC scores, the probability of the median overall survival of the populations classified as favorable, intermediate, and poor was not reached, 32.9, and 10.5 months, respectively (P = 0.002). In addition, poor performance status (PS) (hazard ratio [HR]: 1.938, P = 0.035) and no prior nephrectomy (HR: 3.008, P = 0.004) were extracted as independent poor prognostic factors by multivariate analysis. All treatment modalities-including radical en bloc surgery, radiation therapy, cytokine therapy, molecular targeted therapy, and administration of zoledronic acid-seemed to contribute to favorable survival. More than half of the patients with bone metastases secondary from RCC were predicted to survive more than 24 months. In this population, MSKCC scores were valid predictors of survival. With increased treatment options, RCC patients with bone metastasis may benefit further from subsequent modalities and/or agents.

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Section: Discussionsupporting

confidence: 90%

Treatment outcome and prognostic factors in renal cell cancer patients with bone metastasis

Yuasa

Urakami

Yamamoto

et al. 2011

Clin Exp Metastasis

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“…In an initial analysis of 109 patients, we identified PS, time from diagnosis and number of metastatic sites as independent predictors of survival (Bamias et al , 2010). The combination of these factors led to the development of a prognostic model with similar performance with that of the more complex MSKCC model.…”

mentioning

confidence: 99%

Development and validation of a prognostic model in patients with metastatic renal cell carcinoma treated with sunitinib: a European collaboration

Bamias¹,

Tzannis²,

Beuselinck³

et al. 2013

Br J Cancer

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Background:Accurate prediction of outcome for metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy is essential. Most of the available models have been developed in patients treated with cytokines, while most of them are fairly complex, including at least five factors. We developed and externally validated a simple model for overall survival (OS) in mRCC. We also studied the recently validated International Database Consortium (IDC) model in our data sets.Methods:The development cohort included 170 mRCC patients treated with sunitinib. The final prognostic model was selected by uni- and multivariate Cox regression analyses. Risk groups were defined by the number of risk factors and by the 25th and 75th percentiles of the model's prognostic index distribution. The model was validated using an independent data set of 266 mRCC patients (validation cohort) treated with the same agent.Results:Eastern Co-operative Oncology Group (ECOG) performance status (PS), time from diagnosis of RCC and number of metastatic sites were included in the final model. Median OS of patients with 1, 2 and 3 risk factors were: 24.7, 12.8 and 5.9 months, respectively, whereas median OS was not reached for patients with 0 risk factors. Concordance (C) index for internal validation was 0.712, whereas C-index for external validation was 0.634, due to differences in survival especially in poor-risk populations between the two cohorts. Predictive performance of the model was improved after recalibration. Application of the mRCC International Database Consortium (IDC) model resulted in a C-index of 0.574 in the development and 0.576 in the validation cohorts (lower than those recently reported for this model). Predictive ability was also improved after recalibration in this analysis. Risk stratification according to IDC model showed more similar outcomes across the development and validation cohorts compared with our model.Conclusion:Our model provides a simple prognostic tool in mRCC patients treated with a targeted agent. It had similar performance with the IDC model, which, however, produced more consistent survival results across the development and validation cohorts. The predictive ability of both models was lower than that suggested by internal validation (our model) or recent published data (IDC model), due to differences between observed and predicted survival among intermediate and poor-risk patients. Our results highlight the importance of external validation and the need for further refinement of existing prognostic models.

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“…( 28 ) The time from diagnosis to the start of sunitinib of <1 year, multiple metastatic sites ( P = 0.003), and poor PS were independently correlated with OS (Table 1). ( 28 )…”

Section: Biomarkers To Predict the Response To Sunitinib Therapymentioning

confidence: 98%

Biomarkers to predict response to sunitinib therapy and prognosis in metastatic renal cell cancer

et al. 2011

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Sunitinib is an orally‐administered, multitargeted tyrosine kinase inhibitor. The main targets are vascular endothelial growth factor receptor (VEGFR)‐1, VEGFR‐2, VEGFR‐3, platelet‐derived growth factor receptor (PDGFR)‐α, and PDGFR‐β. Among therapeutic targeting agents, it is the best available in the USA for patients with metastatic renal cell cancer (RCC). Well‐constructed clinical trials have led to the worldwide approval of various agents for RCC. However, in clinical practice, it remains difficult to determine the best treatment strategy with these agents. Therefore, the identification of biomarkers to predict response and side‐effects and to select optimal dosages is urgently needed. Potential mechanisms of action and resistance need to be understood in order to make accurate predictions. This article briefly reviews candidate biomarkers of sunitinib therapy in terms of clinical variables, genetic factors, and circulating proteins and endothelial cells. Although further validation and implementation is necessary, if validated, biomarkers will help measure the therapeutic response in individual patients and establish treatment strategies for metastatic RCC. (Cancer Sci, 102: 1949–1957)

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Prognostic stratification of patients with advanced renal cell carcinoma treated with sunitinib: comparison with the Memorial Sloan-Kettering prognostic factors model

Cited by 30 publications

References 28 publications

Treatment outcome and prognostic factors in renal cell cancer patients with bone metastasis

Treatment outcome and prognostic factors in renal cell cancer patients with bone metastasis

Development and validation of a prognostic model in patients with metastatic renal cell carcinoma treated with sunitinib: a European collaboration

Biomarkers to predict response to sunitinib therapy and prognosis in metastatic renal cell cancer

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