scholarly journals The De Ritis and Neutrophil-to-Lymphocyte Ratios May Aid in the Risk Assessment of Patients with Metastatic Renal Cell Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Sung Han Kim ◽  
Eun Young Park ◽  
Jungnam Joo ◽  
Jinsoo Chung

Purpose. This study aimed to determine whether baseline blood inflammatory markers can predict progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC).Methods. The study included 158 patients with mRCC treated with first-line targeted therapy between 2002 and 2016. A multivariable cox proportional hazards model identified inflammatory factors that predict PFS and OS. Using bootstrap method, new prognostic model compared with Heng and modified MSKCC risk model (mMSKCC). The effect of inflammatory factors were investigated by comparing increased C-index adding significant inflammatory factors to Heng and mMSKCC model.Results. On multivariable analysis, nephrectomy (HR 0.48), NLR (HR 1.04), were significant risk factors for PFS; nephrectomy (HR 0.38), hemoglobin (HR 1.71), alkaline phosphatase (HR 1.73), NLR (HR 1.01) and DRR (HR 1.34), were significant factors for OS (p<0.05). Our new model that incorporated NLR and DRR had higher (though insignificant) predictability (C-index=0.610) than mMSKCC risk model (C-index=0.569) in PFS and significantly better predictability (C-index=0.727) than Heng and mMSKCC risk model (C-index, 0.661, 0.612, respectively) in OS. Adding inflammatory factors to the Heng criteria (C-index, 0.697 for OS) and MSKCC (0.691 for OS) tended to improve their predictive abilities.Conclusions. The NLR and DRR may increase predictive ability compared to the established Heng and mMSKCC risk models in mRCC.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5109-5109 ◽  
Author(s):  
P. Royston ◽  
J. Bacik ◽  
P. Elson ◽  
J. B. Manola ◽  
M. Mazumdar

5109 Background: Numerous well-designed retrospective studies of prognostic factors (pf) for survival (S) in metastatic renal cell carcinoma (mRCC) patients (pts) have been conducted since 1986. However, no single model for describing S in this population has been universally accepted. Methods: Authors of several existing prognostic indices, and others, formed the IKCWG to develop a single validated S model. The IKCWG has established a comprehensive database of previously reported clinical pf from 3748 previously untreated mRCC pts entered on institution review board approved clinical trials conducted by 11 centers in Europe and the United States from 1975–2002. Results: Median age at study entry was 58, 70% of pts were male, 89% had ECOG performance status (PS) 0 or 1; 75% had prior nephrectomy. 72%, 30%, and 19% of pts had lung, bone, and liver metastases (mets), respectively. 72% received interferon-a and/or interleukin-2 based treatments (tx); 25% were txd with chemotherapy/hormones only; 3% received other tx. 88% of pts have died; median S was 11.1 months (m). All examined factors except sex, age, and histology impacted S at p<.001 in univariable analysis. Multivariable analysis using a log-logistic model stratified by center and multivariable fractional polynomials was performed to identify independent predictors of S. Missing data were handled using multiple imputation methods. Using p=.0044 as the criterion for variable selection to avoid overly complex models, a model comprising tx, PS, number of met sites, interval from diagnosis to tx, and pre-tx hemoglobin, WBC, LDH, alkaline phosphatase and calcium was identified. The 25th and 75th percentiles of the prognostic index formed by multiplying each factor by its regression coefficient were used as cutpoints to form three risk (r) groups with median S times (SE) of: favorable r (n=937; 27.8 (0.4) m), intermediate r (n=1874; 11.4 (0.2) m), and poor r (n=937; 4.1 (0.1) m). Conclusions: 9 clinical factors can be used to model S in mRCC and form 3 distinct prognostic groups. Additional model building to determine if model complexity can be reduced further, validation in independent data and comparison to existing prognostic models are underway. No significant financial relationships to disclose.


2019 ◽  
Vol 25 ◽  
pp. 107602961882328 ◽  
Author(s):  
Hyunkyung Park ◽  
Chang Wook Jeong ◽  
Hyeongdong Yuk ◽  
Ja Hyeon Ku ◽  
Hyeon Hoe Kim ◽  
...  

Tumor thrombus is a unique characteristic of renal cell carcinoma (RCC). However, only a few studies have reported its clinical influence on the occurrence of venous thromboembolism (VTE). This study aimed to clarify the influence of tumor thrombus and other risk factors for VTE and to elucidate the impact of tumor thrombus on survival outcomes. We retrospectively reviewed data from patients with RCC who underwent radical or partial nephrectomy from September 1999 to August 2015 at Seoul National University Hospital. A total of 2762 patients were enrolled. The 1- and 5-year cumulative incidences of VTE were 0.5% ± 0.1% and 1.5% ± 0.3%, respectively. During a median follow-up of 39.0 months (95% confidence interval [CI], 37.1-41.0 months), deep vein thrombosis occurred in 13 patients and pulmonary embolism in 15 patients. Patients with tumor thrombus (diagnosed by surgical pathology findings) had a significantly higher incidence of VTE than those without thrombus (odds radio 8.160, 95% CI, 1.480-45.004). Older age (≥60 years) and higher preoperative C-reactive protein (>0.5 mg/dL) were also significant risk factors for VTE. Additionally, tumor thrombus was independently associated with worse progression-free survival (PFS) but not with overall survival (OS) in multivariable analysis (hazard ratio [HR] 1.916, 95% CI, 1.295-2.834 for PFS; HR 1.164, 95% CI, 0.755-1.793 for OS). In conclusion, the incidence of VTE was relatively low in patients who underwent surgery for RCC. Nevertheless, patients with tumor thrombus had an increased risk of VTE and should be closely monitored for VTE.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 491-491
Author(s):  
Inkeun Park ◽  
Yong Mee Cho ◽  
Jae-Lyun Lee ◽  
Jin-Hee Ahn ◽  
Dae Ho Lee ◽  
...  

491 Background: To verify the prognostic importance of selected tumor tissue biomarkers in metastatic renal cell carcinoma (mRCC) patients (pts), we performed immunohistochemical (IHC) staining in tumor sample and statistical analyses. Methods: The clinicopathological features, treatment, and outcome of mRCC pts treated with vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI) between July 2006 and March 2011 at our center were reviewed. IHC staining for FGF base, FGFR1, 2, 3, and 4, HGF, PTEN, CAIX, pS6, HIF-1a, HIF-2a, IL-8, mTOR was done, and each specimen was scored based on the staining intensity and the percentage of positive cells. We performed univariate and multivariable analyses to verify prognostic factors for overall survival (OS). Results: We found 123 pts who met inclusion criteria. Most pts had clear cell carcinoma (107 pts, 87.0%). Fuhrman’s nuclear grade (NG) was 2 in 21 (17.1%), 3 in 49 (39.8%), and 4 in 52 (42.3%), respectively. Sarcomatoid change and coagulative necrosis were found in 51 pts and 58 pts. Using Heng’s criteria, 20 pts (16.3%), 87 (70.7%), and 16 (13.0%) belonged to favorable, intermediate, and poor risk group, respectively. First-line VEGFR TKIs prescribed were sunitinib (97 pts, 78.9%), sorafenib (23 pts, 18.7%), and pazopanib (3 pts, 2.4%). In univariate analysis, CAIX (less than 47.5% vs 47.5% or more, p=0.001), mTOR (20% or less vs more than 20%, p=0.0032), Heng risk group (good vs intermediate vs poor, p<0.001), sarcomatoid change (40% or less vs more than 40%, p<0.001), coagulative necrosis (20% or less vs more than 20%, p<0.001), Furhman NG (2 vs 3 vs 4, p=0.037) were statistically significant. In multivariable analysis, CAIX, Heng risk group, sarcomatoid change, and hyaline necrosis were identified as independent prognostic factors (Table). Conclusions: All investigated biomarkers but CAIX did not show prognostic importance for mRCC pts receiving VEGFR TKI. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4578-4578
Author(s):  
Bimal Bhindi ◽  
Jeffrey Graham ◽  
Connor Wells ◽  
Frede Donskov ◽  
Felice Pasini ◽  
...  

4578 Background: While the CARMENA trial prompts more caution with upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC), 17% of patients in the sunitinib alone arm underwent deferred CN (dCN). Upfront systemic therapy has been proposed as a potential litmus test to identify patients suitable for CN, but data on outcomes are limited. We sought to characterize outcomes of dCN after upfront sunitinib relative to sunitinib alone. Methods: Patients with newly diagnosed mRCC receiving upfront sunitinib were identified from the International mRCC Database Consortium (IMDC) from 2006-2018. All CNs done after initial sunitinib were included, excluding CNs performed after sunitinib failure. The outcomes were overall survival (OS) and time to treatment failure (TTF). Kaplan Meier and multivariable Cox regression analyses were performed; dCN was analyzed as a time-varying covariate to account for immortal time bias. Results: The cohort included 708 patients of whom 53 (7.5%) underwent dCN at a median of 6.5 months (IQR 3.5,10.5) from diagnosis. Patients in the dCN group were more likely to have better Karnofsky performance status (KPS), intermediate IMDC risk, fewer metastatic sites, and response to upfront sunitinib (Table). There were 604 deaths during a median follow-up of 63 months. Median OS and TTF with dCN were 43.5 and 19.8 months vs. 9.4 and 4.3 months without, respectively. Upon multivariable analysis, dCN remained significantly associated with OS (HR 0.45, 95%CI 0.31-0.65; p < 0.001) but not TTF (HR 0.73, 95%CI 0.52-1.01; p = 0.056). Conclusions: Patients who received dCN were carefully selected and achieved long OS. With these benchmark outcomes, optimal selection criteria need to be identified and confirmation of the role of dCN in a clinical trial is warranted. [Table: see text]


Kidney Cancer ◽  
2021 ◽  
pp. 1-9
Author(s):  
Hanbo Zhang ◽  
Naveen S. Basappa ◽  
Sunita Ghosh ◽  
Isaiah Joy ◽  
Aly-Khan A. Lalani ◽  
...  

Background: Cabozantinib is an oral multitargeted tyrosine kinase inhibitor (TKI) that has demonstrated efficacy in metastatic renal-cell carcinoma (mRCC) randomized trials. Objective: To explore the real-world effectiveness of cabozantinib in pretreated patients with mRCC, including patients who progressed on immune-oncology checkpoint inhibitor (ICI) therapy. Methods: Using the Canadian Kidney Cancer information system (CKCis), patients with mRCC treated with cabozantinib monotherapy as second-line or later from January 1, 2011 to September 1, 2019 were identified. Patients were stratified based on line of cabozantinib received. We reported overall survival (OS), time to treatment failure (TTF) and disease control rate (DCR). Prognostic variables were analyzed using multivariable analysis. Results: 157 patients received cabozantinib (median TTF 8.0 months; median OS 15.8 months): 37 (24%) in the second line (median TTF 10.4 months; median OS 18.9 months) 66 (42%) in third line (median TTF 5.9 months; median OS 13.3 months) and 54 (34%) in either 4th or 5th line (median TTF 9.4 months; median OS 16.8 months). One hundred sixteen patients (74%) received cabozantinib after prior ICI therapy (median TTF of 7.6 months; median OS of 15.8 months). DCR in all patients was 63% with 46%, 65% and 72% in 2nd line, 3rd line and 4th/5th line patients respectively. DCR in patients who received cabozantinib after prior ICI therapy was 64%. Conclusions: Cabozantinib is effective in a real-world, unselected population of mRCC patients, including in those who have progressed on prior ICI therapy, and in those exposed to multiple lines of therapy.


2020 ◽  
Vol 14 (11) ◽  
Author(s):  
Jun Teishima ◽  
Shogo Inoue ◽  
Tetsutaro Hayashi ◽  
Akio Matsubara ◽  
Koji Mita ◽  
...  

Introduction: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria are the most representative risk model for patients with metastatic renal cell carcinoma (mRCC). However, the intermediate-risk group of IMDC criteria is thought to include patients with different prognoses because the majority of the patients are classified into the intermediate-risk group. In this study, we investigated the impact of systemic immune-inflammation index (SII), which is calculated based on neutrophil count, platelet count, and lymphocyte count, on predicting the prognosis in patients with mRCC and its usefulness for re-classification of patients with a more sophisticated risk model. Methods: From January 2008 to January 2018, 179 mRCC patients with a pretreatment and SII were retrospectively investigated. All patients were classified into either a high-SII group or a low-SII group based on the cutoff value of a SII at 730, as reported in previous studies; the overall survival (OS) rates in each group were compared. Results: The median age was 65 years old. Males and females comprised 145 and 34 cases, respectively. The categories of favorable-, intermediate-, and poor-risk groups in the IMDC model were assessed in 39, 102, and 38 cases, respectively. The median of the observation period was 24 months. The low-SII and high-SII groups consisted of 73 and 106 cases, respectively. The 50% OS in the high-SII group was 21.4 months, which was significantly worse than that in the low-SII group (49.7 months; p<0.0001). Multivariate analysis showed that a high SII was an independent predictive factor for a worse OS. Next, we constructed a modified IMDC risk model that included the SII instead of a neutrophil count and a platelet count. By using this modified IMDC model, all cases were re-classified into four groups of 33, 52, 81, and 13 cases with 50% OS of 88.8, 45.9, 29.4, and 4.8 months, respectively. Conclusions: The systemic immune-inflammation index is useful for establishing a more sophisticated prognostic model that can stratify mRCC patients into four groups with different prognoses.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 398-398 ◽  
Author(s):  
Jenny J. Ko ◽  
Wanling Xie ◽  
Daniel Yick Chin Heng ◽  
Nils Kroeger ◽  
Jae-Lyun Lee ◽  
...  

398 Background: Prior prognostic models for 2nd-line systemic therapy have not been studied in the setting of contemporary sequential targeted therapy (TT). We sought to validate the IMDC prognostic model in patients with mRCC receiving next-line TT after progression on 1st-line TT. Methods: Patients who received 2nd-line TT after progressing on 1st-line TT for mRCC at 19 centres were analyzed. For the patients who had immunotherapy (22%) prior to their 1st TT, we examined their second TT (ie 3rd-line therapy). The endpoint was median overall survival (OS) since the initiation of 2nd-line therapy. Additionally, we compared the IMDC model with the 3-factor-MSKCC model (Motzer et al JCO 2004) used for previously-treated patients. Results: 1,021 patients treated with a second TT were included. Median time on 2nd-line TT was 3.9 months (range 0-76+). 871 (85%) of patients had stopped 2nd-line TT by the time of analysis. Median OS since 2nd-line TT was 12.5 months (95% CI: 11.3-14.3 months), with 369 (36.1%) of patients remaining alive. 5 out of 6 pre-defined factors in IMDC model (anemia, thrombocytosis, neutrophilia, KPS <80%, and <1 year from diagnosis to treatment) measured at the time of 2nd-line TT were independent predictors of poorer OS (HR between 1.39 and 1.58, p<0.05). Hypercalcemia was not statistically significant in multivariable analysis (p=0.3008) likely due to the low incidence of hypercalcemia (9%). The concordance index using all 6 prognostic factors was 0.70, and was 0.66 with the 3-factor-MSKCC model. When patients were divided into 3 risk categories using IMDC criteria, median OS was 35.8 months (95% CI 28.3-47.8) in the favorable risk group (n=76), 16.6 months (95% CI 14.9-17.9) in the intermediate risk group (n=529), and 5.4 months (95% CI 4.7-6.8) in the poor risk group (n=261). Conclusions: The IMDC prognostic model has been validated in and can be applied to patients previously treated with TT, in addition to previously validated populations in 1st-line TT and non-clear cell setting.


2016 ◽  
Vol 15 (3) ◽  
pp. e532
Author(s):  
Campillo J.M. Velis ◽  
Marckert F.J. Ancizu ◽  
Suárez M. Hevia ◽  
Narro I. Merino ◽  
Cortés A. García ◽  
...  

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 586-586 ◽  
Author(s):  
Solomon L. Woldu ◽  
Justin T. Matulay ◽  
Timothy N Clinton ◽  
Nirmish Singla ◽  
Yuval N Freifeld ◽  
...  

586 Background: Targeted therapy (TT) is the first-line option for metastatic renal cell carcinoma (mRCC) however, it is not curative and associated with a high-cost and adverse events. Preliminary data suggests TT may be safely delayed in appropriately selected patient, however the utilization and impact of delayed TT has not been evaluated on larger-scale. Methods: The National Cancer Database (NCDB) was queried from 2006-2012 for patients with mRCC treated with cytoreductive nephrectomy and TT. Time to initiation of TT was defined as ‘early’ (within 2 months), ‘moderately delayed’ (2-4 months), and ‘delayed’ (4-6 months), and ‘late’ ( > 6 months) based on time from diagnosis to initiation of therapy. Multivariable logistic regression was performed to determine factors associated with delayed TT. The impact time to initiation of TT on OS was estimated by Kaplan-Meier and Cox multivariable survival analysis. Results: For2,716 patients in the analysis, the median (interquartile range [IQR]) follow-up was 18.8 (9.1-32.9) months, and 71.8% of patients had died at last follow-up. The median (IQR) time from diagnosis to initiation of TT was 2.1 (1.3-3.23) months, with the longest delay being 20.1 months. 1,255 patients (46.2%) had early TT, 1,072 patients (39.5%) had moderately delayed TT, 284 patients (10.5%) had delayed TT, and 105 patients (3.9%) had late TT. Delay in TT was not found to be a predictor of mortality in multivariable analysis; early TT (reference), moderately delayed TT (HR 0.98, p = 0.74), delayed TT (HR 0.95, p = 0.51), and late TT (HR 0.86, p = 0.20). Time from diagnosis to initiation of TT and time from initiation of TT to patient death were not correlated after control for covariates ( r= 0.04, p = 0.08). Conclusions: Delay in initiation of TT for mRCC was not an independent predictor of worse OS. Although this study is subject to limitations of observation study design and selection bias, the results are consistent with the notion that in carefully selected patients, outcomes might not be compromised with initial observation. Prospective, randomized evaluation is warranted.


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