Sloan-Kettering Cancer Center Risk Classification Research Articles

Prognostic Value of Systemic Inflammatory Biomarkers in Patients with Metastatic Renal Cell Carcinoma.

Metastatic renal cell carcinoma (mRCC) encompasses a heterogeneous group of neoplasms with distinct clinical behavior and prognoses. As a result of the increasing number of therapeutic options in the metastatic setting, it is crucial to improve prognostic stratification ability. We aimed to evaluate the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and combination platelet count and neutrophil lymphocyte ratio (COP-NLR) in patients with mRCC. We evaluated a cohort of mRCC patients treated with first-line pazopanib or sunitinib. Levels of NLR, PLR and COP-NLR were measured prior to systemic treatment and evaluated as prognostic predictors. Primary endpoint was overall survival (OS). Data from 276 patients were included, of which 54.7% received first-line pazopanib and 45.3%, sunitinib. Memorial Sloan-Kettering Cancer Center risk classification was intermediate and poor in 50% and 42.6% of patients, respectively. High NLR (> 3.5) was associated with inferior OS (median 9.6 vs 17.8months, P < 0.001). A high PLR (> 200) was associated with inferior OS (median 10.3 vs 17months, P = 0.002). The median OS in the COP-NLR 1, 2 and 3 groups were 19.0months (95% CI 15.3-26.0), 13.1months (95% CI 9.8-17.0) and 7.4months (95% CI 3.6-11.9), respectively (P < 0.001). In the multivariate analysis, high NLR and high COP-NLR were associated with inferior OS. Both high NLR and high COP-NLR were associated with poorer OS in our cohort of patients with mRCC treated with first-line pazopanib or sunitinib.

A case of renal cell carcinoma metastatic to the ovary: a case report and review of the literature

A 35-year-old woman complained of pain in the left hypochondrium. She was diagnosed as having a left renal carcinoma and treated with retro-approach radical nephrectomy without lymphadenectomy. The histology was renal cell carcinoma (RCC), papillary cell type 2, G3, expansive type, INFα, v(+), pT2N0M0, stage II. The Memorial Sloan-Kettering Cancer Center risk classification was favorable. Then, 18 months later, a multilocular cystic mass (15 × 10 cm) in the pelvis was found on abdominal CT and MRI. Although the ovarian tumor was highly suspicious of malignancy, differentiation between primary and metastatic ovarian tumor was not possible. Examination of the resected right ovarian tumor showed that it consisted of clear cell type (G2) that resembled components of the left RCC. When we resected the right ovarian tumor, we found some nodules on the peritoneum. There seemed to be new suspicious metastases. Immunohistochemistry revealed that only CD10 was positive; 34βE12, CA125, and CK7 were negative. These results indicated renal metastasis. The patient then underwent targeted therapy with sunitinib 50 mg/day for 28 days. One month later, a new metastasis was found in the left ovary and treated surgically. Soon thereafter, a brain metastasis was found and the patient underwent radiation therapy to the brain, but she died 21 months after the nephrectomy. Metastasis to the ovary from RCC is very rare, and only 20 cases have been reported. Its rarity may be related to the difficulty associated with the differential diagnosis of metastatic ovarian tumors from RCC and primary ovarian clear cell carcinoma. Careful histological and immunohistochemical analysis may help differentiate the two.

Efficacy of traditional and alternative sunitinib treatment schedules in Japanese patients with metastatic renal cell carcinoma.

We report the adverse events and efficacy of traditional (4 weeks on 2 weeks off) and alternative sunitinib treatment schedules for Japanese patients with metastatic renal cell carcinoma. We retrospectively investigated 54 patients who received sunitinib for metastatic renal cell carcinoma between May 2006 and June 2012: 32 received a traditional treatment schedule and 22 received an alternative schedule. According to the Memorial Sloan-Kettering Cancer Center risk classification, five patients had favorable prognoses, 42 had intermediate prognoses and seven had poor prognoses. The mean observation periods were 16.3 and 20 months for the traditional and alternative schedule groups, respectively. Adverse events were significantly less common in the alternative schedule group, including most high-grade events. In the traditional and alternative schedule groups, median times to failure were 4.1 and 11.6 months (P = 0.040), median progression-free survival times were 4.1 and 11.3 months (P = 0.031), and median overall survival times were 12.0 and 32.1 months (P = 0.018), respectively. Each of these measures was better in the group of patients who received an alternative treatment schedule, suggesting that individualized changes to the sunitinib administration schedule can be effective.

Hand-Foot Skin Reaction is Associated with the Clinical Outcome in Patients with Metastatic Renal Cell Carcinoma Treated with Sorafenib

To elucidate whether Hand-Foot skin reaction could become a biomarker of clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib, we retrospectively examined the association between the Hand-Foot skin reaction and the clinical outcome in metastatic renal cell carcinoma patients treated with sorafenib. Thirty-six Japanese metastatic renal cell carcinoma patients treated with sorafenib were enrolled and divided into the groups with or without Hand-Foot skin reaction. Patient characteristics, best tumor response, progression-free survival and adverse events were investigated and compared between these two groups. A sorafenib-induced Hand-Foot skin reaction in metastatic renal cell carcinoma patients was observed at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification, and with Eastern Cooperative Oncology Group Performance Status of one or less, prior nephrectomy, higher hemoglobin, lower lactate dehydrogenase and lower C-reactive protein. The mean best tumor response was significantly better in the group with Hand-Foot skin reaction (-16.7%) than that in the group without it (17.9%; P < 0.001). The median progression-free survival was significantly longer in the group with Hand-Foot skin reaction (4.6 months) than that in the group without it (1.5 months; P = 0.002). In multivariate analysis, only Hand-Foot skin reaction was shown to be a predictive factor of progression-free survival (hazard ratio 0.312, P = 0.010). A sorafenib-induced Hand-Foot skin reaction in metastatic renal cell carcinoma patients emerged at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification and was significantly associated with best tumor response and progression-free survival, suggesting that Hand-Foot skin reaction might be an independent predictive factor for clinical outcome in metastatic renal cell carcinoma patients treated with sorafenib.

466 EXPRESSION LEVEL OF GLI2 IN RADICAL NEPHRECTOMY SPECIMENS AS A PROGNOSTIC PREDICTOR IN PATINETS WITH METASTATIC RENAL CLEAR CELL CARCINOMA TREATED WITH SUNITINIB

You have accessJournal of UrologyKidney Cancer: Basic Research (III)1 Apr 2013466 EXPRESSION LEVEL OF GLI2 IN RADICAL NEPHRECTOMY SPECIMENS AS A PROGNOSTIC PREDICTOR IN PATINETS WITH METASTATIC RENAL CLEAR CELL CARCINOMA TREATED WITH SUNITINIB Junya Furukawa, Masafumi kumano, Ken-ichi Harada, Mototsugu Muramaki, Hideaki Miyake, and Masato Fujisawa Junya FurukawaJunya Furukawa Kobe, Japan More articles by this author , Masafumi kumanoMasafumi kumano Kobe, Japan More articles by this author , Ken-ichi HaradaKen-ichi Harada Kobe, Japan More articles by this author , Mototsugu MuramakiMototsugu Muramaki Kobe, Japan More articles by this author , Hideaki MiyakeHideaki Miyake Kobe, Japan More articles by this author , and Masato FujisawaMasato Fujisawa Kobe, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1857AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Gli transcription factors mediate hedgehog signaling and especially, Gli2 seems to be the major nuclear effector of hedgehog signaling. Gli2 in carcinogenesis have been shown in several human cancers. The objective of this study is to investigate the expression levels of Gli2 in radical nephrectomy specimens from patients with metastatic renal clear cell carcinoma (RCC) treated with sunitinib in order to identify factors predicting susceptibility to this agent. METHODS This study included a total of 40 consecutive patients undergoing radical nephrectomy, who were diagnosed as having metastatic RCC and subsequently treated with sunitinib. Gli1, Gli2 and major molecular targets of sunitinib such as VEGFR-1, VEGFR-2, PDGF-alpha and PDGF-beta expression level in primary RCC specimens were assessed by immunohistochemical staining. RESULTS The expression level of VEGFR-1, VEGFR-2, and Gli2, Memorial Sloan-Kettering Cancer Center risk classification, pretreatment serum calcium and c-reactive protein level were significantly associated with the progression-free survival (PFS) on univariate analysis. Of these significant factors, only Gli2 expression appeared to be independently related to PFS on multivariate analysis. In fact, PFS in patients with strong expression of Gli2 was significantly poor compared with that in those with weak expression of Gli2. CONCLUSIONS These findings suggest that it would be useful to consider expression levels of potential molecular marker, Gli2, as well as conventional clinical parameters to select metastatic RCC patients likely to benefit from treatment with sunitinib. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e191-e192 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Junya Furukawa Kobe, Japan More articles by this author Masafumi kumano Kobe, Japan More articles by this author Ken-ichi Harada Kobe, Japan More articles by this author Mototsugu Muramaki Kobe, Japan More articles by this author Hideaki Miyake Kobe, Japan More articles by this author Masato Fujisawa Kobe, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1788 EXPRESSION LEVEL OF VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2 IN RADICAL NEPHRECTOMY SPECIMENS AS A PROGNOSTIC PREDICTOR IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA TREATED WITH SUNITINIB

Objectives: To investigate the expression levels of multiple molecular markers in radical nephrectomy specimens from patients with metastatic renal cell carcinoma (RCC) treated with sunitinib in order to identify factors predicting susceptibility to this agent. Materials and methods: This study included a total of 40 consecutive patients undergoing radical nephrectomy, who were diagnosed as having metastatic RCC and subsequently treated with sunitinib. Expression levels of 10 molecular markers, including Bcl-2, Bcl-xL, Bax, phosphorylated Akt, p44/42 mitogen-activated protein kinase, and signal transducers and activation of transcription 3, vascular endothelial growth factor receptor (VEGFR)-1 and -2, and platelet-derived growth factor receptor- and -, in primary RCC specimens were assessed by immunohistochemical staining. Results: Of several factors examined, tumor grade and the expression level of VEGFR-2 were shown to have significant impacts on response to sunitinib in these 40 patients. Progression-free survival (PFS) was significantly associated with the expression levels of VEGFR-2 in addition to tumor grade, performance status, Memorial Sloan-Kettering Cancer Center risk classification and pretreatment c-reactive protein level on univariate analysis. Of these significant factors, only VEGFR-2 expression appeared to be independently related to PFS on multivariate analysis. In fact, PFS in patients with strong expression of VEGFR-2 was significantly favorable compared with that in those with weak expression of VEGFR-2. Conclusions: Collectively, these findings suggest that it would be useful to consider expression levels of potential molecular markers, particularly VEGFR-2, as well as conventional clinical parameters to select metastatic RCC patients likely to benefit from treatment with sunitinib. © 2013 Elsevier Inc. All rights reserved.

Is Memorial Sloan-Kettering Cancer Center risk classification appropriate for Japanese patients with metastatic renal cell carcinoma in the cytokine era?

ObjectivesWe investigated the prognosis of Japanese patients with metastatic renal cell carcinoma (RCC), and analyzed the validity of Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification. Materials and methodsThe endpoint of the present study was overall survival. Relationships between overall survival and potential prognostic factors were assessed using the Cox proportional hazard model with a step-wise procedure. Prognostic assessment was also performed according to the MSKCC risk classification. The predictive accuracy of the MSKCC risk classification was measured employing the concordance index. ResultsThe median survival for all patients was 22 months (95% CI, 19–28 months). The eight factors were identified as independent prognostic factor; time from initial diagnosis to metastasis, low hemoglobin (Hb), lactate dehydrogenase (LDH), corrected serum calcium (cCa), C-reactive protein (CRP), and the presence or absence of liver metastasis, bone metastasis, and lymph node metastasis. When the MSKCC risk classification was applied to patients, the median overall survival was not reached and 26 and 10 months in the patients classified as favorable, intermediate, and poor risk, respectively. The c-index was 0.73. ConclusionsThe prognosis of Japanese metastatic renal cell carcinoma patients may be better than that of previous studies from North America or Europe. Although there are some differences in the rate of patients in the risk groups and survival time by risk group between these patients, the MSKCC risk classification may be applicable for Japanese patients with metastatic renal cell carcinoma.

Expression level of vascular endothelial growth factor receptor-2 in radical nephrectomy specimens as a prognostic predictor in patients with metastatic renal cell carcinoma treated with sunitinib

ObjectivesTo investigate the expression levels of multiple molecular markers in radical nephrectomy specimens from patients with metastatic renal cell carcinoma (RCC) treated with sunitinib in order to identify factors predicting susceptibility to this agent. Materials and methodsThis study included a total of 40 consecutive patients undergoing radical nephrectomy, who were diagnosed as having metastatic RCC and subsequently treated with sunitinib. Expression levels of 10 molecular markers, including Bcl-2, Bcl-xL, Bax, phosphorylated Akt, p44/42 mitogen-activated protein kinase, and signal transducers and activation of transcription 3, vascular endothelial growth factor receptor (VEGFR)-1 and -2, and platelet-derived growth factor receptor-α and -β, in primary RCC specimens were assessed by immunohistochemical staining. ResultsOf several factors examined, tumor grade and the expression level of VEGFR-2 were shown to have significant impacts on response to sunitinib in these 40 patients. Progression-free survival (PFS) was significantly associated with the expression levels of VEGFR-2 in addition to tumor grade, performance status, Memorial Sloan-Kettering Cancer Center risk classification and pretreatment c-reactive protein level on univariate analysis. Of these significant factors, only VEGFR-2 expression appeared to be independently related to PFS on multivariate analysis. In fact, PFS in patients with strong expression of VEGFR-2 was significantly favorable compared with that in those with weak expression of VEGFR-2. ConclusionsCollectively, these findings suggest that it would be useful to consider expression levels of potential molecular markers, particularly VEGFR-2, as well as conventional clinical parameters to select metastatic RCC patients likely to benefit from treatment with sunitinib.