Memorial Sloan-Kettering Cancer Center Classification Research Articles

Transhepatic hilar approach for Bismuth types III and IV perihilar cholangiocarcinoma with long-term outcomes.

ObjectiveTo compare the outcomes of the transhepatic hilar approach and conventional approach for surgical treatment of Bismuth types III and IV perihilar cholangiocarcinoma.MethodsWe retrospectively reviewed the medical records of 82 patients who underwent surgical resection of Bismuth types III and IV perihilar cholangiocarcinoma from 2008 to 2016. The transhepatic hilar approach and conventional approach was used in 36 (43.9%) and 46 (56.1%) patients, respectively. Postoperative complications and overall survival were compared between the two approaches.ResultsSimilar clinical features were observed between the patients treated by the conventional approach and those treated by the transhepatic hilar approach. The transhepatic hilar approach was associated with less intraoperative bleeding and a lower percentage of Clavien grade 0 to II complications than the conventional approach. However, the transhepatic hilar approach was associated with a higher R0 resection rate and better overall survival. Multivariate analysis showed that using the transhepatic hilar approach, the Memorial Sloan-Kettering Cancer Center classification, and R0 resection were independent risk factors for patient survival.ConclusionThe transhepatic hilar approach might be the better choice for surgical resection of Bismuth types III and IV perihilar cholangiocarcinoma because it is associated with lower mortality and improved survival.

The difference in the survival rate of patients with metastatic renal cell carcinoma in the intermediate-risk group of the Memorial Sloan Kettering Cancer Center criteria.

ObjectivesTo investigate the necessity of stratifying patients in the intermediate-risk group of the Memorial Sloan Kettering Cancer Center (MSKCC) criteria in a real-world population of patients with metastatic renal cell carcinoma.Patients and MethodsWe retrospectively analyzed 234 consecutively treated patients who had received molecular targeted drugs. We examined the difference between progression-free survival and overall survival among patients in the intermediate-risk group of MSKCC criteria. We divided the intermediate group into two subgroups as follows: patients positive for only one risk factor (Int-1) and those positive for two risk factors (Int-2) including performance status, serum hemoglobin level, time from diagnosis to treatment, and corrected calcium and lactate dehydrogenase levels. Next, we evaluated the association between the number of metastatic organs, the presence of pancreatic metastasis, Int-1 or Int-2 grouping, and overall survival.ResultsThe median overall survival was 41.2 months. The median overall survival of the favorable-, intermediate-, and poor-risk groups of the MSKCC criteria were 91.0, 33.6, and 15.2 months, respectively. Patient characteristics were similar between the Int-1 and Int-2 groups. Increased positivity for risk factors of MSKCC classification between the two groups was for performance status and serum hemoglobin level. Progression-free survival and overall survival of the Int-1 group were significantly higher than those of the Int-2 group. In Cox proportional stepwise multivariate analysis, the Int-1 and Int-2 classification was an independent risk factor for overall survival.ConclusionPatients in the intermediate-risk group had different prognoses depending on the number of positive risk factors.

Oncological outcomes classified according to metastatic lesions in the era of molecular targeted drugs for metastatic renal cancer.

Since the introduction of molecular targeted agents for the treatment of metastatic renal cell cancer (mRCC), several treatment outcomes, including those from our facilities, have been reported. However, the outcome of these drugs, classified by the metastatic organs, is not well known. The present study reported the treatment results of molecular-targeted agents as classified by the metastatic organ at Osaka City University Graduate School of Medicine. A total of 180 consecutively treated patients who had received molecular targeted agents for metastatic renal cancer for 3 or more months were retrospectively analyzed. The overall survival was calculated and compared according to the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria, the number of metastatic organs, and metastatic lesions. The median overall survival of patients with mRCC treated by molecular targeted agents was 34 months. A significant difference in survival rate between groups was found according to the MSKCC criteria. Patients with single metastatic organ lived significantly longer compared with those with metastases in multiple organs. Patients with pancreatic metastasis had a good response to molecular targeted drugs. Pancreatic metastasis, the number of metastatic organs, and MSKCC criteria were independent risk factors for overall survival. Treatment of mRCC by molecularly targeted agents did not show any difference by metastatic organs except for the pancreas, although its efficacy depends on the number of metastatic organs and the MSKCC classification.

Impact of baseline visceral fat accumulation on prognosis in patients with metastatic renal cell carcinoma treated with systemic therapy.

The aim of this study was to evaluate the clinical significance of visceral fat accumulation as a prognostic factor in patients with metastatic renal cell carcinoma (mRCC) treated with systemic therapies. A total of 114 patients were retrospectively reviewed. All patients received systemic therapy for mRCC at Keio University hospital in Japan. The intra-abdominal visceral fat area was determined by computed tomography at the umbilical level. The visceral fat accumulation was defined as ≥100cm2. The mean visceral fat area was 107.4±62.8cm2. In the whole cohort, the median follow-up was 29months. According to the Memorial Sloan Kettering Cancer Center (MSKCC) classification, 27.2% patients were favorable risk, 53.5% were intermediate risk, and 19.3% were poor risk. Visceral fat accumulation correlated with improved progression-free (P=0.0070) and overall survival (P=0.0001). On multivariate analysis, visceral fat accumulation (P=0.0290) and MSKCC classification (P=0.0085) were independent indices to predict progression-free survival in first-line treatment. In addition, visceral fat accumulation (P=0.0007) and MSKCC classification (P=0.0005) independently predicted overall survival. Prognostic grouping using visceral fat accumulation was identified as an independent prognostic marker in patients with mRCC. The addition of visceral fat accumulation improved the prognostic value of MSKCC classification alone in predicting overall survival in patients treated with systemic therapy for mRCC.

Expression pattern of immune checkpoint–associated molecules in radical nephrectomy specimens as a prognosticator in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors

ObjectiveTo analyze the expression pattern of immune checkpoint–associated molecules in tumor tissues to determine the prognostic significance of these molecules in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). MethodsRadical nephrectomy specimens were obtained from 62 patients treated with TKIs as first-line systemic therapy for mRCC. The proportions of programmed death-1 (PD-1)-positive tumor infiltrating lymphocytes (TILs) as well as those of tumor cells positive for PD-ligand 1 (PD-L1) and PD-L2 were analyzed by immunohistochemical staining. ResultsOverall, 12 patients (19.3%) were revealed to be positive for PD-1-positive TILs, whereas positive expression of PD-L1 and PD-L2 were detected in 12 (19.3%) and 10 (16.1%) patients, respectively. Patients with positivePDL-L1 expression had significantly unfavorable progression-free survival (PFS) compared with those without positive PD-L1 expression, despite the remaining 2 molecules having no significant effect on PFS. Additionally, overall survival in patients positive for PD-1, PD-L1, or PD-L2 expression was significantly poorer than that in those without expression of each immune checkpoint–associated molecule. Multivariate analyses of several parameters identified the following independent prognosticators after the introduction of TKIs: PD-L1 expression status for PFS and lymph node metastasis, Memorial Sloan-Kettering Cancer Center classification and expression statuses of PD-1-positive TILs, and PD-L1 for overall survival. ConclusionsPositive expression of immune checkpoint–associated molecules in tumor tissues could be useful prognosticators in patients with mRCC receiving TKIs as first-line systemic therapy.

1096P - Expression pattern of immune checkpoint-associated molecules in radical nephrectomy specimens as a prognostic predictor in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors

It has not been established whether activation of immune checkpoint pathways is correlated with the clinical course of systemic therapies for metastatic renal cell carcinoma (mRCC), particularly tyrosine kinase inhibitors (TKIs). The objective of this study was to analyze the expression pattern of immune checkpoint-associated molecules in tumor tissues to determine the prognostic significance of these molecules in mRCC patients treated with TKIs. Radical nephrectomy specimens were obtained from 62 patients treated with TKIs as first-line systemic therapy for mRCC. The proportions of programmed death-1 (PD-1)-positive tumor infiltrating lymphocytes (TILs) as well as those of tumor cells positive for PD-ligand 1 (PD-L1) and PD-L2 were analyzed by immunohistochemical staining. Twelve patients (19.3%) were revealed to be positive for PD-1-positive TILs, while positive expression of PD-L1 and PD-L2 were detected in 12 (19.3%) and 10 (16.1%) patients, respectively. Patients with positive PDL-L1 expression had significantly unfavorable progression-free survival (PFS) compared with those without positive PD-L1 expression, despite the remaining two molecules having no significant impact on PFS. Additionally, overall survival (OS) in patients positive for PD-1, PD-L1 or PD-L2 expression was significantly poorer than that in those without expression of each immune checkpoint-associated molecule. Multivariate analyses of several parameters identified the following independent prognostic predictors after the introduction of TKIs: PD-L1 expression status for PFS, and lymph node metastasis, Memorial Sloan-Kettering Cancer Center classification and expression statuses of PD-1-positive TILs and PD-L1 for OS. Positive expression of immune checkpoint-associated molecules in tumor tissues, particularly that of PD-L1, could be useful prognostic indicator in mRCC patients receiving TKIs as first-line systemic therapy.

Assessment of Efficacy, Safety, and Quality of Life of 124 Patients Treated With Axitinib as Second-Line Therapy for Metastatic Renal-Cell Carcinoma: Experience in Real-World Clinical Practice in Japan

PurposeTo comprehensively analyze the efficacy of axitinib for metastatic renal-cell carcinoma (mRCC) patients. Patients and MethodsThis study included 124 consecutive Japanese patients treated with axitinib as second-line systemic therapy for mRCC in a routine clinical setting. ResultsIn addition to 4 indeterminate patients (3.2%), 0 (0%), 21 (16.9%), 87 (70.2%), and 12 (9.7%) were judged to show complete response, partial response, stable disease, and progressive disease, respectively, as the best responses to axitinib. The median progression-free survival (PFS) and overall survival (OS) after initiating treatment with axitinib were 9.3 and 27.0 months, respectively. Multivariate analyses of several parameters identified the following independent predictors of PFS and OS: Memorial Sloan Kettering Cancer Center (MSKCC) classification and C-reactive protein level for PFS; and MSKCC classification, C-reactive protein level, bone metastasis, and liver metastasis for OS. Common grade 3 or higher adverse events associated with axitinib were hypertension in 41 (33.1%), proteinuria in 14 (11.3%), and hand–foot syndrome in 14 (11.3%). Quality-of-life analysis using the Medical Outcomes Study 36-Item Short Form showed that 2 scores were significantly improved 12 weeks after the administration of axitinib, while there were no significant differences in the remaining 6 scores between surveys administered before and 12 weeks after the treatment with axitinib. ConclusionFavorable disease control could be achieved with acceptable tolerability by introducing axitinib as second-line systemic therapy, resulting in improvement of the prognosis and quality of life of Japanese patients with mRCC.

Prognostic Significance of Early Tumor Shrinkage Under Second-Line Targeted Therapy for Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Study in Japan.

The prognostic significance of early tumor shrinkage (ETS) under second-line targeted therapy for metastatic renal cell carcinoma (mRCC) has not been fully documented. The objective of this study was to evaluate the impact of ETS induced by a second-line targeted agent on overall survival (OS) in mRCC patients. This study retrospectively included 271 consecutive Japanese patients with mRCC who received second-line targeted therapy for at least 3months. ETS was defined as the degree of tumor shrinkage at the first post-baseline radiological evaluation conducted 4-8weeks after initiating second-line targeted therapy. Of the 271 patients, 26 had ETS from -100 to -50%, 70 from -49 to -25%, 84 from -24 to 0%, and the remaining 91 failed to achieve a reduction in the tumor size. The median OS following the initiation of second-line targeted therapy stratified according to ETS was 45.8, 30.9, 22.1 and 14.2months, respectively. Univariate analysis identified prior nephrectomy, the Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification, C-reactive protein (CRP) level, number of metastatic organs, sarcomatoid feature, introduced second-line agent and ETS induced by a second-line agent as parameters significantly associated with OS, of which, only the MSKCC classification, CRP level and ETS appeared to have independent impacts on OS on multivariate analysis. These findings suggest that ETS at the first post-baseline assessment under treatment with a second-line targeted agent could serve as a useful parameter with an independent impact on OS in mRCC patients receiving second-line targeted therapy.

Early tumor shrinkage under first-line tyrosine kinase inhibitor as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma.

523 Background: The objective of this study was to assess the prognostic impact of early tumor shrinkage induced by first-line tyrosine kinase inhibitors (TKIs) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Methods: This study included a total of 185 consecutive Japanese patients with mRCC, consisting of 120 and 65 who were treated with sunitinib and sorafenib, respectively, for at least 3 months as first-line therapy. Prognostic outcomes in these 185 patients were retrospectively assessed focusing on the significance of tumor shrinkage at 12 weeks after the introduction of TKIs as a predictive factor of OS. Results: As the best responses to TKIs, 3, 40, 105 and 37 were judged to show a complete response, partial response, stable disease and progressive disease, respectively. The median progression-free survival (PFS) and OS in the 185 patients was 7.3 and 33.6 months, respectively. At 12 weeks after the introduction of TKIs, 9 patients reached a tumor shrinkage from -100 to -50%, 42 patients from -49 to -25%, 59 patients from -24 to 0%, and the remaining 70 patients had a gain of tumor size or new metastatic lesions. The median OS stratified according to tumor shrinkage at 12 weeks after the introduction of TKIs as shown above was 59.2, 39.1, 27.8 and 19.1 months, respectively. Univariate analysis identified the Memorial Sloan-Kettering Cancer Center (MSKCC) classification, Heng risk classification, C-reactive protein (CRP) level, lymph node metastasis, bone metastasis, liver metastasis, number of metastatic organs, histological subtype, sarcomatoid feature, PS and tumor shrinkage as significant predictors of OS. Of these significant factors, only the MSKCC classification, CRP level, liver metastasis and tumor shrinkage were shown to be independently associated with OS by multivariate analysis. Conclusions: These findings suggest that tumor shrinkage at 12 weeks after the introduction of TKIs was shown to have a significant impact on the OS in mRCC patients; therefore, early tumor shrinkage could be used as a reliable surrogate endpoint of OS in patients with mRCC receiving TKI as first-line agent.

Impact of precise quantitative assessment of visceral obesity on outcomes of patients with metastatic renal cell carcinoma treated with systemic therapy.

597 Background: With its excellent resolution of adipose tissue, CT presents precise quantitative assessment of visceral obesity. We assessed the impact of visceral obesity on progression free and overall survival in patients treated with systemic therapy for metastatic renal cell carcinoma. Methods: This retrospective cohort study included 114 patients treated with systemic therapy for metastatic renal cell carcinoma between 2007 and 2015 at Keio university hospital in Japan. The visceral fat area was measured at the level of umbilicus using CT. A visceral fat area ≥100cm2 was used as the definition of visceral obesity. Progression free and overall survival was compared according to visceral obesity. Results: In the whole cohort, the median progression free survival in first line treatment was 12.0 month. The median overall survival was 42.5 month. According to Memorial Sloan-Kettering Cancer Center classification, 31 patients were favorable risk, 61 were intermediate risk, and 22 were poor risk; median overall survival for these groups were 76.9, 40.8, and 23.7 months, respectively (P<0.0001). Visceral obesity correlated with improved progression free (P=0.0095) and overall survival (P=0.0002). On multivariate analysis, visceral obesity (HR 0.64, P=0.0393) and Memorial Sloan-Kettering Cancer Center classification (P=0.0037) were independent indices to predict progression free survival in first line treatment. In addition, visceral obesity (HR 0.42, P=0.0016) and Memorial Sloan-Kettering Cancer Center classification (P=0.0006) independently predicted overall survival. Conclusions: The precision of CT imaging for measuring visceral fat tissue provides useful clinical venue to predict prognosis for metastatic renal cell carcinoma. Visceral obesity may be a useful and independent indicator for a better prognosis in patients treated with systemic therapy for metastatic renal cell carcinoma.

Early Tumor Shrinkage Under Treatment with First-line Tyrosine Kinase Inhibitors as a Predictor of Overall Survival in Patients with Metastatic Renal Cell Carcinoma: a Retrospective Multi-Institutional Study in Japan.

Prognostic significance of early tumor shrinkage following treatment with tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) has not been fully elucidated. The aim of this study was to assess the impact of early tumor shrinkage induced by first-line TKIs on overall survival (OS) in mRCC patients. This study retrospectively included 185 consecutive Japanese patients with mRCC treated with either sunitinib or sorafenib for at least 3months as first-line molecular-targeted therapy between April 2011 and December 2014 at Kobe University Hospital and its affiliated institutions. Median OS in the 185 patients was 33.6months. At 12weeks after the introduction of TKIs, 9 patients had achieved tumor shrinkage from -100 to -50%, 43 from -49 to -25%, 61 from -24 to 0%, and the remaining 72 patients showed an increase in tumor size. The median OS stratified according to tumor shrinkage as shown above was 59.2, 39.1, 31.4, and 16.1months, respectively. Univariate analysis identified prior nephrectomy, Memorial Sloan Kettering Cancer Center (MSKCC) risk classification, C-reactive protein (CRP) level, liver metastasis, number of metastatic organs, histological subtype, sarcomatoid feature, and early tumor shrinkage as significant predictors of OS. Of these significant factors, only the MSKCC classification, CRP level, liver metastasis, and early tumor shrinkage were shown to be independently associated with OS on multivariate analysis. Early tumor shrinkage could be a useful predictor of OS in mRCC patients receiving TKIs as a first-line molecular-targeted agent.

MP69-10 ASSESSMENT OF EFFICACY, SAFETY AND QUALITY OF LIFE OF 110 PATIENTS TREATED WITH SUNITINIB AS FIRST-LINE THERAPY FOR METASTATIC RENAL CELL CARCINOMA: EXPERIENCE IN REAL WORLD CLINICAL PRACTICE IN JAPAN

You have accessJournal of UrologyKidney Cancer: Advanced II1 Apr 2015MP69-10 ASSESSMENT OF EFFICACY, SAFETY AND QUALITY OF LIFE OF 110 PATIENTS TREATED WITH SUNITINIB AS FIRST-LINE THERAPY FOR METASTATIC RENAL CELL CARCINOMA: EXPERIENCE IN REAL WORLD CLINICAL PRACTICE IN JAPAN Ken-ichi Harada, Hideaki Miyake, and Masato Fujisawa Ken-ichi HaradaKen-ichi Harada More articles by this author , Hideaki MiyakeHideaki Miyake More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2514AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Sunitinib, an orally available inhibitor of multiple tyrosine kinases, is regarded as having one of the strongest antitumor activities against metastatic renal cell carcinoma (mRCC); however, there have been no studies including a comparatively large number of Japanese patients treated with sunitinib as first-line therapy for mRCC. The objective of this study was to comprehensively evaluate the clinical outcomes of 110 consecutive Japanese patients who received at least two cycles of sunitinib as first-line therapy for mRCC in a routine clinical setting. METHODS This was conducted as a retrospective study reviewing clinicopathological data from a total of 110 consecutive Japanese patients with mRCC who were treated with sunitinib as first-line therapy between September 2008 and October 2013 in a routine clinical setting at our institution. RESULTS Initially, 50 mg of sunitinib was administered once daily on a 4-weeks-on, followed by 2-weeks-off dosing schedule; however, dose modification was required in 102 patients, and the relative dose-intensity was 62.6% throughout this series. As the best responses to sunitinib, 2, 28, 65 and 15 were judged to show a complete response, partial response, stable disease and progressive disease, respectively. The median progression-free survival (PFS) and overall survival (OS) following the treatment with sunitinib was 7.8 and 33.2 months, respectively. Multivariate analyses of several factors identified the following independent predictors of PFS and OS: Memorial Sloan-Kettering Cancer Center (MSKCC) classification and C-reactive protein (CRP) level for PFS and liver metastasis, MSKCC classification and CRP level for OS. The common adverse events related to sunitinib corresponding to grade 3 ≤ were thrombocytopenia in 59, leukopenia in 23, fatigue in 22, hand-foot syndrome in 15 and hypertension in 12. Quality of life (QOL) analysis using SF-36 revealed no significant differences in any scale scores between surveys performed before and 3 months after the treatment with sunitinib. CONCLUSIONS Collectively, these findings suggest that the introduction of sunitinib as a first-line agent can lead to favorable disease control with acceptable tolerability, resulting in improved prognosis of Japanese mRCC patients without the impairment of QOL. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e870 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ken-ichi Harada More articles by this author Hideaki Miyake More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prognostic outcome in patients treated with tyrosine kinase inhibitors as first-line molecular-targeted therapy for metastatic renal cell carcinoma: Experience in real-world clinical practice in Japan

The aim of this study was to evaluate the oncological efficacy of tyrosine kinase inhibitors (TKIs) as first-line molecular-targeted therapy for Japanese patients with metastatic renal cell carcinoma (mRCC) in a routine clinical setting. This study included a total of 271 consecutive Japanese patients with TKI-naive mRCC, including 172 patients who received sorafenib and 99 who received sunitinib for ≥2 months as a first-line molecular-targeted agent. The prognostic outcomes of these patients were retrospectively assessed. During the observation period (median, 19 months), 126 patients (46.5%) succumbed to the disease and the median overall survival (OS) for the entire cohort was 33.1 months. The univariate analysis identified the Memorial Sloan-Kettering Cancer Center (MSKCC) classification, C-reactive protein (CRP) level, lymph node metastasis, bone metastasis, liver metastasis, histological subtype and sarcomatoid characteristics as significant predictors of OS. Of these factors, only the MSKCC classification, CRP level and liver metastasis were found to be independently associated with OS in the multivariate analysis. Furthermore, there were significant differences in OS according to the positivity for these 3 independent risk factors (i.e., negative for all factors vs. positive for a single factor vs. positive for 2 or 3 factors). These findings suggest that the introduction of TKIs as first-line molecular-targeted agents resulted in favorable cancer control outcomes in Japanese mRCC patients and that the prognosis of these patients may be stratified by 3 potential parameters, including the MSKCC classification, CRP level and liver metastasis.

Assessment of efficacy, safety and quality of life of 110 patients treated with sunitinib as first-line therapy for metastatic renal cell carcinoma: experience in real-world clinical practice in Japan

The objective of this study was to comprehensively evaluate the clinical outcomes of 110 consecutive Japanese patients who received at least two cycles of sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC) in a routine clinical setting. Initially, 50 mg of sunitinib was administered once daily on a 4 weeks on, followed by 2 weeks off dosing schedule; however, dose modification was required in 102 patients, and the relative dose intensity was 62.6 % throughout this series. As the best responses to sunitinib, 2, 28, 65 and 15 were judged to show a complete response, partial response, stable disease and progressive disease, respectively. The median progression-free survival (PFS) and overall survival (OS) following the treatment with sunitinib were 7.8 and 33.2 months, respectively. Multivariate analyses of several factors identified the following independent predictors of PFS and OS: Memorial Sloan Kettering Cancer Center (MSKCC) classification and C-reactive protein (CRP) level for PFS and liver metastasis, MSKCC classification and CRP level for OS. The common adverse events related to sunitinib corresponding to ≥grade 3 were thrombocytopenia in 59, leukopenia in 23, fatigue in 22, hand-foot syndrome in 15 and hypertension in 12. Quality of life (QOL) analysis using 36-Item Short Form revealed no significant differences in any scale scores between surveys performed before and 3 months after the treatment with sunitinib. Collectively, these findings suggest that the introduction of sunitinib as a first-line agent can lead to favorable disease control with acceptable tolerability, resulting in improvement in the prognosis and QOL of Japanese patients with mRCC.

Significance of circulating matrix metalloproteinase-9 to tissue inhibitor of metalloproteinases-2 ratio as a predictor of disease progression in patients with metastatic renal cell carcinoma receiving sunitinib

ObjectivesTo assess the significance of circulating matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as predictors of disease progression in patients with metastatic renal cell carcinoma (mRCC) receiving sunitinib. Materials and methodsCirculating levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 in sera from 52 patients with mRCC treated with sunitinib were measured at the baseline and on the first day of each treatment cycle until progression using enzyme-linked immunosorbent assays. ResultsThe baseline level of MMP-9 in nonresponders to sunitinib was significantly higher than that in responders, whereas the baseline level of TIMP-2 in nonresponders was significantly lower than that in responders. However, there were no significant differences in the serum levels of MMP-2 and TIMP-1 between responders and nonresponders. The serum MMP-9/TIMP-2 ratio at the baseline in nonresponders was also significantly higher than that in responders. Univariate analysis showed that the MMP-9/TIMP-2 ratio, but not MMP-9 and TIMP-2 levels, was significantly correlated with progression-free survival, and the MMP-9/TIMP-2 ratio, in addition to the Memorial Sloan-Kettering Cancer Center classification and C-reactive protein level, appeared to be independently associated with progression-free survival on multivariate analysis. Furthermore, despite the lack of significant differences in the serum levels of MMP-9 and TIMP-2 between the baseline and the time of progression, the MMP-9/TIMP-2 ratio at the time of progression was significantly elevated compared with the baseline ratio. ConclusionsAn imbalance between the serum MMP-9 and TIMP-2 levels could be a novel biomarker to predict disease progression in patients with mRCC under treatment with sunitinib.

Can enough lymph nodes be taken out through lateral neck dissection in patients with larynx cancer?

This study aims to evaluate whether the number of lymph nodes which are dissected by lateral neck dissection (LND) is enough and to compare the number of lymph nodes which are dissected from the same lymph node regions by radical and type 1 modified radical neck dissection (RND). Between January 2000 and June 2004, data of 98 neck dissection materials which were performed to 63 patients (52 males, 11 females; mean age 61.9 years; range 48 to 75 years) with larynx cancer were retrospectively analyzed. The number of lymph nodes taken from the second, third and fourth regions of radical and type 1 modified RND and LND were individually and totally compared. The American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) classification system was used for primary tumor and neck metastasis classification, while the Memorial Sloan-Kettering Cancer Center classification system was used for the classification of cervical lymphatic chain. Two patients (3.17%) had subglottic, 19 (30.15%) had glottic, and 42 (66.66%) had supraglottic lesions. A total of 732 lymph nodes were removed from three regions in RND group, while 1042 lymph nodes were removed in LND group. Our study results showed that the number of lymph nodes removed by LND was sufficient and RBD was not superior in terms of the number of lymph nodes removed.

Impact of maximum standardized uptake value (SUVmax) evaluated by 18-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG PET/CT) on survival for patients with advanced renal cell carcinoma.

4626 Background: In this era of molecular targeting therapy when various systematic treatments can be selected, prognostic biomarkers are required for the purpose of risk-directed therapy selection. Numerous reports of various malignancies have revealed that 18-Fluoro-2-deoxy-D-glucose (18F-FDG) accumulation, as evaluated by positron emission tomography, can be used to predict the prognosis of patients. The purpose of this study was to evaluate the impact of the maximum standardized uptake value (SUVmax) from 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET/CT) on survival for patients with advanced renal cell carcinoma (RCC). Methods: A total of 67 patients with advanced or metastatic RCC were enrolled in this study. The FDG uptake of all RCC lesions diagnosed by conventional CT was evaluated by FDG PET/CT. The impact of SUVmax on patient survival was analyzed prospectively. Results: The mean duration of observation was 461 days (range, 7-1229 days). The SUVmax before treatment of 67 patients ranged between undetectable level and 16.6 (mean 7.6±3.6). The patients with RCC tumors showing high SUVmax before treatment demonstrated poor prognosis (p<0.001 hazard ratio 1.289, 95% CI 1.161-1.430). The median survival time of 36 patients with RCC showing SUVmax less or 7.0 was 1229±991 days, that of 21 patients with RCC showing SUVmax between 7.0 and 12.0 was 446±202 days, and that of 10 patients RCC showing SUVmax higher than 12.0 was 95±43 days (≤7.0 vs. 7.0< ≤12.0 p=0.0052, 7.0< ≤12.0 vs. 12.0<:p=0.0169, log-rank test). SUVmax demonstrated a tendency to predict the survival compared with the Memorial Sloan-Kettering Cancer Center classification (p =0.015 vs 0.315, multivariate Cox analyses). Conclusions: The survival of patients with advanced RCC can be predicted by evaluating their SUVmax using FDG PET/CT. FDG PET/CT has potency as an “imaging biomarker” to provide helpful information for the clinical decision-making.

Prognostic Factors for Renal Cell Carcinoma With Bone Metastasis: Who Are the Long-Term Survivors?

Renal cell carcinoma is sometimes associated with bone metastasis. Several risk factors have been reported but some are still controversial. Also, the significance of laboratory tests has not been fully examined for such cases. We collected data on 94 renal cell carcinoma cases with bone metastasis treated at 3 tertiary referral centers. Clinicopathological parameters and outcome data were analyzed to search for predictors of overall survival retrospectively. The log rank test and the Cox proportional hazard model were used for univariate and multivariate analyses, respectively. There were 64 males with a median age of 63.9 years. Histological diagnosis showed clear cell renal cell carcinoma in 63 patients, nonclear cell renal cell carcinoma in 7 and unclassified cancer in 6. Sarcomatoid differentiation was found in 17 cases. Metastasis was detected synchronously in 37 patients or metachronously at a median interval of 33.1 months. Multivariate analysis identified sarcomatoid differentiation (p = 0.001), vertebral bone involvement (p = 0.003), extraosseous metastasis (p = 0.021), alkaline phosphatase increased to 1.5 times the upper limit of normal (p = 0.0003) and C-reactive protein increased to greater than 0.3 mg/dl (p = 0.018) as significant risk factors. Cases were classified into 3 groups based on the number of risk factors, including low risk-28 with 0 or 1 risk factor, intermediate risk-26 with 2 risk factors and high risk-40 with 3 to 5 risk factors. This grouping clearly separated survival among these groups (each p <0.001). It also confirmed the usefulness of the Memorial-Sloan Kettering Cancer Center classification system. Our risk classification incorporating 5 risk factors enables accurate prediction of survival, which can be helpful to make clinical decisions in cases of renal cell carcinoma with bone metastasis.

Frequency of metastases at the area of the supraretrospinal (level IIB) lymph node in laryngeal cancer

Neck dissection is the surgical gold standard for the treatment of patients with cervical lymphatic spread. The purpose of this study was to determine the presence of metastases in the supraretrospinal (level IIB) nodal group and the necessity of routine dissection of level IIB during neck dissection, in patients with squamous cell carcinoma of the larynx. Over a 4-year period (between January 2000 and June 2004), the records of patients undergoing laryngectomy and neck dissection were retrospectively evaluated. The numbers of the lymph node and carcinoma metastases at level IIB were recorded. The American Joint Committee on Cancer tumor-node-metastasis classification system was used to classify the primary tumor and neck, and the Memorial Sloan-Kettering Cancer Center classification was used to classify the cervical lymphatic chain. Sixty-three patients with 98 neck dissections were included in the study. Two patients (3.17%) had subglottic lesions, 19 patients (30.15%) had glottic lesions, and 42 patients (66.66%) had supraglottic lesions. In total, 673 lymph nodes were dissected from level II, and 340 were dissected from level IIB. The 11 supraretrospinal lymph nodes of the 340 dissected nodes demonstrated histologic evidence of metastases (3.23%). Six patients (9.52%; 6/63) had metastases at level IIB, and 2 of them also had synchronous metastases at the contralateral level IIB. The patients without palpable lymph nodes at the neck had no metastases at level IIB. Our results showed that, if the level IIA shows positive metastatic changes, perioperative pathologic examination by frozen section that includes level IIb could be an alternative approach. This area may not be routinely dissected during the surgical management of laryngeal carcinoma with no palpable lymph nodes.