Jung Kwon Kim, Sung Han Kim, Mi Kyung Song, Jungnam Joo, Seong Il Seo, Cheol Kwak, Chang Wook Jeong, Cheryn Song, Eu Chang Hwang, Ill Young Seo, Hakmin Lee, Sung-Hoo Hong, Jae Young Park, Jinsoo Chung, Korean Renal Cell Carcinoma Study Group
Cancer Res Treat. 2019;51(2):758-768. Published online September 7, 2018
Purpose
The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and the Memorial Sloan Kettering Cancer Center (MSKCC) risk models were developed predominantly with clear cell renal cell carcinoma (RCC). Accordingly, whether these two models could be applied to metastatic non-clear cell RCC (mNCCRCC) as well has not been well-known and was investigated herein.
Materials and Methods
From the Korean metastatic RCC registry, a total of 156 patients (8.1%) with mNCCRCC among the entire cohort of 1,922 patients were analyzed. Both models were applied to predict first-line progression-free survival (PFS), total PFS, and cancer-specific survival (CSS).
Results
The median first-line PFS, total PFS, and CSS were 5, 6, and 24 months, respectively. The IMDC risk model reliably discriminated three risk groups to predict survival: the median firstline PFS, total PFS, and CSS for the favorable, intermediate, and poor risk groups were 9, 5, and, 2 months (p=0.001); 14, 7, and 2 months (p < 0.001); and 41, 21, and 8 months (p < 0.001), all respectively. The MSKCC risk model also reliably differentiated three risk groups: 9, 5, and, 2 months (p=0.005); 10, 7, and 3 months (p=0.002); and 50, 21, and 8 months (p < 0.001), also all respectively. The concordance indices were 0.632 with the IMDC model and 0.643 with the MSKCC model for first-line PFS: 0.748 and 0.655 for CSS.
Conclusion
The current IMDC and MSKCC risk models reliably predict first-line PFS, total PFS, and CSS in mNCCRCC.
Citations
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Purpose
The study investigated whether a replacement of neutrophil count and platelet count by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model would improve its prognostic accuracy.
Materials and Methods
This retrospective analysis included consecutive patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. The IMDC and modified-IMDC models were compared using: concordance index (CI), bias-corrected concordance index (BCCI), calibration plots, the Grønnesby and Borgan test, Bayesian Information Criterion (BIC), generalized R2, Integrated Discrimination Improvement (IDI), and continuous Net Reclassification Index (cNRI) for individual risk factors and the three risk groups.
Results
Three hundred and twenty-one patients were eligible for analyses. The modified-IMDC model with NLR value of 3.6 and PLR value of 157 was selected for comparison with the IMDC model. Both models were well calibrated. All other measures favoured the modified-IMDC model over the IMDC model (CI, 0.706 vs. 0.677; BCCI, 0.699 vs. 0.671; BIC, 2,176.2 vs. 2,190.7; generalized R2, 0.238 vs. 0.202; IDI, 0.044; cNRI, 0.279 for individual risk factors; and CI, 0.669 vs. 0.641; BCCI, 0.669 vs. 0.641; BIC, 2,183.2 vs. 2,198.1; generalized R2, 0.163 vs. 0.123; IDI, 0.045; cNRI, 0.165 for the three risk groups).
Conclusion
Incorporation of NLR and PLR in place of neutrophil count and platelet count improved prognostic accuracy of the IMDC model. These findings require external validation before introducing into clinical practice.
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Cancer Res Treat. 2016;48(1):281-287. Published online March 5, 2015
Purpose
Studies suggested the existence of a ‘trial effect', in which for a given treatment, participation in a clinical trial is associated with a better outcome. Sunitinib is a standard treatment for metastatic renal cell carcinoma (mRCC). We aimed to study the effect of clinical trial participation on the outcome of mRCC patients treated with sunitinib, which at present, is poorly defined.
Materials and Methods
The records of mRCC patients treated with sunitinib between 2004-2013 in 7 centers across 2 countries were reviewed. We compared the response rate (RR), progression free survival (PFS), and overall survival (OS), between clinical trial participants (n=49) and a matched cohort of non-participants (n=49) who received standard therapy. Each clinical trial participant was individually matched with a non participant by clinicopathologic factors. PFS and OS were determined by Cox regression.
Results
The groups were matched by age (median 64), gender (male 67%), Heng risk (favorable 25%, intermediate 59%, poor 16%), prior nephrectomy (92%), RCC histology (clear cell 86%), pre-treatment NLR (>3 in 55%, n=27), sunitinib induced hypertension (45%), and sunitinib dose reduction/treatment interruption (41%). In clinical trial participants versus non-participants, RR was partial response/stable disease 80% (n=39) versus 74% (n=36), and progressive disease 20% (n=10) versus 26% (n=13) (p=0.63, OR 1.2). The median PFS was 10 versus 11 months (HR=0.96, p=0.84), and the median OS 23 versus 24 months (HR=0.97, p=0.89).
Conclusions
In mRCC patients treated with sunitinib, the outcome of clinical trial participants was similar to that of non-participants who received standard therapy.
Citations
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Renal cell carcinoma accounts for 85% of all primary renal neoplasm. Its most common sites of distant metastses include lung, 1iver, bone, central nervous system, soft tissue. The treatment of metastatic renal cell carcinoma remain a major problem in clinical medicine. Hormonal therapies, chemotherapies or in combinations, and immunotherapic approaches to this tumor seldom result in objective tumor regression or prolongation of survival and the response are usually temporary. Fewer than 1% of patients with renal cell carcinoma are reported to experience spontaneous regression of metastatic lesions after nephrectomy. We report a case of spontaneous regression of metastatic renal cell carcinoma, which showed bilateral multiple lung metastases, multiple bone involvements, and subcutaneous nodules, with the review of literatures.
The prognosis for metastatic renal cell carcinoma is poor, and also there is no effective treatment for this cancer. Recombinant interferon alpha-2a displays subadditive. additive, and synergic effects when used with a number of cytotoxic agents is vitro and in vivo tumor models. A total of 3l petients with metastatic renal cell carcinoma was recieved recombinant interferon alpha-2a, vinblastine, CCNU and medroxyprogesterone acetate between March 1988 and December 1993. Their mean age was 53.8 years (range; 14 - 78 years).The male to female ratio was 2.1:1. Histologically, clear cell type was dominant (83.8%).Lung metastasis only was in 13 cases(41.9%) and multiple metastasis was in 18cases.Using the deKerion criteria for response, the response rate was 29%(9 cases). The 1,2,5 year survival rates of all the patients were 48%, 18%, 18% respectively, 100%, 60%, 60% for the responder group and 24%, 8%, 0% for the nonresponder (p=0.004).In combination chemothetherapy with recombinant interferon alpha-2a, the Karnofsky performance index was the most significant prognostic factor(p=0.015). Age, sex, metastatic sites, cell type and disease free interval had no significance(p>0.05).The most common side effects were constitutional symptoms(93.5%).Hematologic toxicity(41.9%),G-I toxicity(41.9%) and hepatic toxicity(6%) occured. In conclusions, combination chemotherapy with recombinant interferon alpha-2a raised remssion and survival rates and can be on effective palliative therapy in patients with metastatic renal cell carcinoma.