Prognostic value of a systemic inflammatory response index in metastatic renal cell carcinoma and construction of a predictive model.
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ABSTRACT:
SUBMITTER: Gu L
PROVIDER: S-EPMC5581015 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
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Prognostic value of a systemic inflammatory response index in metastatic renal cell carcinoma and construction of a predictive model.
Gu Liangyou L Ma Xin X Wang Lei L Li Hongzhao H Chen Luyao L Li Xintao X Zhang Yu Y Xie Yongpeng Y Zhang Xu X
Oncotarget 20160716 32
Inflammation act as a crucial role in carcinogenesis and tumor progression. In this study, we aim to investigate the prognostic significance of systemic inflammatory biomarkers in metastatic renal cell carcinoma (mRCC) and develop a survival predictive model. One hundred and sixty-one mRCC patients who had undergone cytoreductive nephrectomy were enrolled from January 2006 to December 2013. We created a systemic inflammation response index (SIRI) basing on pretreatment hemoglobin and lymphocyte ...[more]
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Project description:IntroductionGene-expression signatures for prognosis have been reported in localized renal cell carcinoma (RCC). The aim of this study was to test the predictive power of two different signatures, ClearCode34, a 34-gene signature model [Eur Urol 2014;66:77-84], and an 8-gene signature model [Eur Urol 2015;67:17-20], in the setting of systemic therapy for metastatic disease.Materials and methodsMetastatic RCC (mRCC) patients from five institutions who were part of TCGA were identified and clinical data were retrieved. We trained and implemented each gene model as described by the original study. The latter was demonstrated by faithful regeneration of a figure and results from the original study. mRCC patients were dichotomized to good or poor prognostic risk groups using each gene model. Cox proportional hazard regression and concordance index (C-Index) analysis were used to investigate an association between each prognostic risk model and overall survival (OS) from first-line therapy.ResultsOverall, 54 patients were included in the final analysis. The primary endpoint was OS. Applying the ClearCode34 model, median survival for the low-risk-ccA (n = 17)-and the high-risk-ccB (n = 37)-subtypes were 27.6 and 22.3 months (hazard ratio (HR): 2.33; p = .039), respectively. ClearCode34 ccA/ccB and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) classifications appear to represent distinct risk criteria in mRCC, and we observed no significant overlap in classification (p > .05, chi-square test). On multivariable analyses and adjusting for IMDC groups, ccB remained independently associated with a worse OS (p = .044); the joint model of ccA/ccB and IMDC was significantly more accurate in predicting OS than a model with IMDC alone (p = .045, F-test). This was also observed in C-Index analysis; a model with both ccA and ccB subtypes had higher accuracy (C-Index 0.63, 95% confidence interval [CI] = 0.51-0.75) and 95% CIs of the C-Index that did not include the null value of 0.5 in contrast to a model with IMDC alone (0.60, CI = 0.47-0.72). The 8-gene signature molecular subtype model was a weak but insignificant predictor of survival in this cohort (p = .13). A model that included both the 8-gene signature and IMDC (C-Index 0.62, CI = 0.49-0.76) was more prognostic than IMDC alone but did not reach significance, as the 95% CI included the null value of 0.5. These two genomic signatures share no genes in common and are enriched in different biological pathways. The ClearCode34 included genes ARNT and EPAS1 (also known as HIF2a), which are involved in regulation of gene expression by hypoxia-inducible factor.ConclusionThe ClearCode34 but not the 8-gene molecular model improved the prognostic predictive power of the IMDC model in this cohort of 54 patients with metastatic clear cell RCC. The Oncologist 2017;22:286-292 IMPLICATIONS FOR PRACTICE: The clinical and laboratory factors included in the International Metastatic Renal Cell Carcinoma Database Consortium model provide prognostic information in metastatic renal cell carcinoma (mRCC). The present study shows that genomic signatures, originally validated in localized RCC, may add further complementary prognostic information in the metastatic setting. This study may provide new insights into the molecular basis of certain mRCC subgroups. The integration of clinical and molecular data has the potential to redefine mRCC classification, enhance the understanding of mRCC biology, and potentially predict response to treatment in the future.
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Project description:Introduction: Vimentin, a classical marker of epithelial-mesenchymal transition, reflects the invasiveness of cancer cells. Its role in the genesis and progression of tumor has been reported in various cancers, including renal cell carcinoma. However, the impact of vimentin on tumor microenvironment, particularly its implication with tumor-infiltrating immune cells, is unknown. Methods: We conducted this study in 231 patients with metastatic renal cell carcinoma (mRCC) to determine the potential relationship between vimentin and immune status. Using immunohistochemical staining, expression of vimentin, CD8, FOXP3, programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) were evaluated in resected tumor tissue. Kaplan-Meier analysis and Cox regression models were used for survival analysis. Chi-square test, Fisher exact test, and Mann-Whitney U-test were used for comparison between vimentin high and low groups. Results: High expression of vimentin, stroma PD-L1, and PD-1 indicated poor overall survival, whereas low regulatory T cell or high CD8+ T cell infiltration indicated long overall survival. Stroma PD-L1 (P = 0.030), vimentin (P = 0.026) expression, and CD8+ T cell infiltration (P < 0.001) were independent prognostic factors in mRCC. High vimentin expression was accompanied by high PD-1, PD-L1 expression, and increased regulatory T cell infiltration (all P < 0.001), indicating immunosuppression in the tumor microenvironment. Conclusions: We revealed that vimentin expression was associated with immunosuppression in mRCC, and the immune-suppressive status might be possibly posed by PD-1/PD-L1. Patients with high vimentin expression may acquire potential benefit from the recently approved PD-1/PD-L1 inhibitors. However, further clinical trials are needed to validate our findings.
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Project description:The purpose of the study was to identify a comprehensive prognostic system of pretreatment clinical parameters in 425 patients (pts) with metastatic renal-cell carcinoma treated with different subcutaneous (s.c.) recombinant cytokine-based home therapies in consecutive trials. Treatment consisted of (A) s.c. interferon-alpha 2a (INF-alpha), s.c. interleukin-2 (IL-2) (n=102 pts), (B) s.c. IFN-alpha 2a, s.c. IL-2, and i.v. 5-fluorouracil (5-FU) (n=235 pts) or (C) s.c. IFN-alpha 2a, s.c. IL-2, and i.v. 5-FU combined with p.o. 13-cis-retinoic acid (13cRA) (n=88 pts). Kaplan-Meier survival analysis, log-rank statistics, and Cox regression analysis were employed to identify risk factors and to create a multiple risk factor model. The following pretreatment risk factors were identified by univariate analysis: (1) three and more metastatic sites, (2) presence of liver, lymph node or bone metastases, (3) neutrophil count > or = 6500 cells microl(-1), (4) serum lactate dehydrogenase level (LDH) > or = 220 U l(-1), and (5) serum C-reactive protein level (CRP) > or = 11 mg l(-1). Cox regression analysis with forward stepwise variable selection identified neutrophil count as the major prognostic factor (hazard ratio=1.9, P<0.001), while serum levels of LDH and CRP, time between diagnosis of tumour and onset of metastatic disease, number of metastatic sites, and bone metastases were significant but somewhat less important prognostic variables within the multiple risk factor model (hazard ratio < or = 1.5). Patients were assigned to one of the three risk groups according to cumulative risk defined as the sum of simplified risk s.c.ores for six pretreatment variables. Low-, intermediate-, and high-risk patients achieved a median overall survival of 32+ months (95% CI 24, 43; 5-year survival of 27%), 18+ months (95% CI 15, 20; 5-year survival of 11%), and 8+ months (95% CI 6, 10; 5-year survival of 5%), respectively. These prognostic categories are helpful both in individual patient care and in the assessment of patients entering prospective clinical trials.
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Project description:Immune/stromal-associated genes may be promising biomarkers for cancer diagnosis and the determination of clinical cancer treatment options. The aim of the present study was to identify prognostic stromal/immune-associated genes in renal cell carcinoma (RCC). RCC gene expression data (885 cases) were obtained from The Cancer Genome Atlas database. Immune/stromal scores were calculated by using the ESTIMATE package in R. Immune/stromal scores were significantly associated with Tumor-Node-Metastasis stage, clinical stage and overall survival rate (P<0.05). There were 419 differentially expressed genes (DEGs) based on immune scores and 738 DEGs based on stromal scores. Among these DEGs, 406 DEGs based on stromal scores and 252 DEGs based on immune scores were significantly associated with overall survival rate (P<0.05). The biological functions of these DEGs were primarily enriched in the 'immune response' and 'regulation of cell migration and proliferation'. These DEGs were observed in a protein-protein interaction network. A LASSO Cox regression model was used to build a prognostic 6 gene-based classifier, including the IL21R, ATP6V1C2, GBP1, P2RY10, GBP4 and TNNC2 genes [area under the curve (AUC) =0.776]. The predictive model which combined this classifier with clinical prognostic factors had a high accuracy in predicting patient survival in RCC (combined AUC =0.899). Taken together, these results demonstrated that there are significant associations between immune/stromal scores and clinicopathological staging. A set of tumor microenvironment-associated genes that have powerful prognostic value in patients with RCC were identified in the present study.
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Project description:BackgroundPredictive markers can help tailor treatment to the individual in metastatic renal cell carcinoma (mRCC). De Ritis ratio (DRR) is associated with oncologic outcomes in various solid tumors.ObjectiveTo assess the value of DRR in prognosticating survival in mRCC patients treated with tyrosine-kinase inhibitors (TKI).MethodsOverall, 220 mRCC patients treated with TKI first-line therapy were analyzed. An optimal cut-off point for DRR was determined with Youden's J. We used multiple strata for DRR, performed descriptive, Kaplan-Meier and multivariable Cox-regression analyses to assess associations of DRR with progression-free (PFS) and overall survival (OS).ResultsPatients above the optimal cut-off point for DRR of ≥ 1.58 had fewer liver metastases (p = 0.01). There was no difference in PFS (p > 0.05) between DRR groups. DRR above the median of 1.08 (HR 1.42; p = 0.03), DRR ≥ 1.1(HR 1.44; p = 0.02), ≥ 1.8 (HR 1.56; p = 0.03), ≥ 1.9 (HR 1.59; p = 0.02) and ≥ 2.0 (HR 1.63; p = 0.047) were associated with worse OS. These associations did not remain after multivariable adjustment. In the intermediate MSKCC group, DRR was associated with inferior OS at cut-offs ≥ 1.0 (HR 1.78; p = 0.02), ≥ 1.1 (HR 1.81; p = 0.01) and above median (HR 1.88; p = 0.007) in multivariable analyses. In patients with clear-cell histology, DRR above median (HR 1.54; p = 0.029) and DRR ≥ 1.1 (HR 1.53; p = 0.029) were associated with OS in multivariable analyses.ConclusionThere was no independent association between DRR and survival of mRCC patients treated with TKI in the entire cohort. However, OS of patients with intermediate risk and clear-cell histology were affected by DRR. DRR could be used for tailored decision-making in these subgroups.
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Project description:BackgroundThe prognostic nutritional index (PNI) is an indicator of nutritional immune status. Recently, the PNI has been found to be significantly associated with the clinical outcome of various solid tumors. Few patients with newly diagnosed breast cancer are in a state of malnutrition. In contrast, breast cancer is usually an overnutrition-related disease. This study aimed to explore the relationship of an excessively high PNI with sensitivity to neoadjuvant therapy and the prognosis of patients with locally advanced breast cancer.MethodsA total of 202 patients from two clinical trials, SHPD002 and SHPD003, were included. Binary logistic regression analysis was used to assess the association between the PNI and pathological complete response (pCR). Univariate and multivariate survival analyses were performed to assess the prognostic factors used to predict disease-free survival (DFS).ResultsAn excessively high PNI was more difficult to achieve pCR (OR =0.322; 95% CI, 0.132-0.788, P=0.013) and was associated with a worse DFS (log-rank P=0.013). The PNI was an independent prognostic factor for DFS in all patients (HR =3.027; 95% CI, 1.207-7.592, P=0.018), the premenopausal (HR =8.292; 95% CI, 1.670-41.17, P=0.010), clinical T3 and T4 (HR =3.405; 95% CI, 1.141-10.16, P=0.028), ER negative (HR =9.698; 95% CI, 1.205-78.07, P=0.033), HER2 negative (HR =3.765; 95% CI, 1.101-12.88, P=0.035) and pCR subgroups (HR =11.912; 95% CI, 1.326-107.0, P=0.027).ConclusionsAn excessively high PNI was a risk factor for sensitivity to neoadjuvant therapy and prognosis of patients with locally advanced breast cancer.
| S-EPMC6989918 | biostudies-literature
Project description:Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18-25 year old controls and 50-80 year old controls, respectively. mRCC patients with high hPG80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients.
| S-EPMC7864155 | biostudies-literature
Project description:PURPOSE:We aimed to determine the prognostic significance of computed tomography imaging parameters of unresectable primary renal tumor lesions, obtained at baseline and at first follow-up, on overall survival in naïve, unresectable metastatic renal cell carcinoma patients during first-line systemic therapy. MATERIALS AND METHODS:Clinicopathological parameters of 56 patients treated between 2007 and 2015, including imaging parameters (such as the longest tumor diameter, necrotic area diameter, and attenuation in primary renal tumor lesions on baseline vs. follow-up computed tomography), were retrospectively reviewed to derive predictive factors of overall survival. The best overall response was measured according to the RECIST v1.1. RESULTS:The median treatment period was 206.3 days and the median follow-up was 14.6 months. Forty-four (78.6%) patients progressed after a median 4.6 months of progression-free survival, and 6 (10.7%) patients survived with a median overall survival of 12.5 months. Multivariate analysis showed that the baseline tumor diameter (hazard ratio [HR] 0.903) and mean attenuation (HR 0.936), change of tumor diameter (HR 0.714) and necrosis diameter (HR 0.861), change in the percentage of tumor diameter (HR 1.483) and of necrosis diameter (HR 1.028) between baseline and follow-up computed tomography images; treatment duration (HR 0.986) and baseline serum hemoglobin (HR 1.790) and albumin level (HR 0.060) were significant factors for overall survival (p<0.05). CONCLUSION:The study showed that baseline and first follow-up computed tomography findings of primary renal lesions during first-line systemic therapy are useful and significant predictors of OS in patients with naïve unresectable mRCC.
| S-EPMC5451027 | biostudies-other
Project description:BackgroundThe specific impacts of sarcopenic obesity (SO) on hepatocellular carcinoma (HCC) and the association between SO and systemic inflammation remain unclear. This study aimed to investigate the prognostic value and association of SO and systemic inflammation with outcomes after hepatectomy for HCC and develop novel nomograms based on SO and inflammatory indexes for survival prediction.MethodsWe retrospectively enrolled 452 patients with HCC who underwent radical hepatectomy between January 2012 and March 2015 in Fujian Provincial Hospital as the training cohort. In addition, 275 patients during the same period were enrolled as the external validation cohort. Patients were classified into different groups according to the presence of sarcopenia and obesity. Different inflammation indexes were evaluated to select the best predictor of overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate logistic regression were performed to investigate the associations between inflammatory indexes and SO. The inflammatory indexes with the highest predictive values and SO were selected for subgroup analyses to establish a novel classification system: the SOLMR grade. SOLMR grades identified in the multivariate Cox analysis were selected to construct novel nomograms for OS and RFS.ResultsSO (P<0.001) was an independent risk factor for OS and RFS. The lymphocyte-monocyte ratio (LMR) had the highest areas under the receiver operating characteristic (ROC) curves (AUCs) for OS (P<0.001) and RFS (P<0.001) and was identified as an independent factor of SO (P=0.001). SO and the LMR were selected to establish the SOLMR grade. Multivariate Cox analysis revealed that SOLMR grade was a significant independent predictor of OS (P<0.001) and RFS (P<0.001). Nomograms based on SOLMR grades were generated and accurately predicted 1-, 3- and 5-year OS and RFS in HCC patients. The C-index of the novel nomograms was higher than those of the other conventional staging systems (P<0.001).ConclusionsBoth SO and the LMR were independent risk factors for OS and RFS in HCC patients after hepatectomy. The LMR was an independent factor of SO. The novel nomograms developed from the SOLMR grading system combining SO with the LMR provide good prognostic estimates of the outcomes of HCC patients.
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Project description:Sunitinib has become mainstay first line treatment for patients with metastatic renal clear cell carcinoma (mRCC). Still, useful predictive markers of response are lacking and urgently needed for clinical decision making.In the present study we investigated the predictive value of standard serum markers as well as clinical markers, including C-reactive protein (CRP), Neutrophil to Lymphocyte ratio (NLR) and early hypertension (eHTN) in an unselected prospective patient population treated with sunitinib for mRCC. Forty-six patients were enrolled in a prospective single-arm study of predictive markers for sunitinib response. Response rates according to RECIST 1.1 were used as primary end-point. Secondary objectives were to evaluate prognostic value of the candidate markers with regard to progression free survival (PFS) and overall survival (OS). In addition, toxicity rates and quality of life was recorded.Median PFS and OS was 9.1 months and 15.0 months, respectively. Of 38 patients evaluable for response, 1 patient had complete response (CR), 7 had partial response (PR), 18 had stable disease (SD) and 12 had progressive disease (PD). Normal CRP at baseline was significantly associated with objective response (CR + PR) (p = 0.01). Normal CRP was also significantly associated with improved PFS and OS (Log rank, p = 0.05 and <0.01, respectively). Early hypertension, NLR and IMDC risk score were not significantly associated with response rates or survival.Baseline CRP was a significant predictive factor of sunitinib response and a prognostic factor of survival. Baseline CRP might be a useful biomarker in the treatment planning of mRCC. Due to the relatively small sample size, our results need to be confirmed in larger studies.
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