Percentage of sarcomatoid component as a prognostic indicator for survival in sarcomatoid renal cell carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 499-499
Author(s):  
Mehrad Adibi ◽  
Arun Z. Thomas ◽  
Leonardo Borregales ◽  
Megan M. Merrill ◽  
Kanishka Sircar ◽  
...  

499 Background: Renal cell carcinoma with sarcomatoid component (sRCC) is characterized by the microscopic spectrum of spindle cells within a background of RCC. The presence of sarcomatoid elements is associated with higher stage of presentation and decreased patient survival. The objective of this study is to examine the clinicopathological characteristics associated with overall survival (OS), specifically examining the percentage of sarcomatoid component (PSC) to stratify risk. Methods: We retrospectively reviewed data for all radical nephrectomy patients with pathologically confirmed sarcomatoid component from 1987−2011. All slides were re−reviewed by a GU pathologist to ascertain PSC. Patient characteristics were tabulated overall and by disease status (metastatic vs. localized). Cutpoints in the percent sarcomatoid providing a meaningful difference in OS were identified by recursive partitioning analysis (RPA) as univariate and combined with patient characteristics. Factors selected included age, gender, race, clinical stage, tumor histology, and treatment. The Kaplan−Meier method and two−sided log−rank test was used to assess differences in OS. Results: Among 186 patients with sRCC, 64 (34%) had localized and 122 (66%) metastatic disease. Patients were primarily white (76%) males (63%) with clear cell histology (73%), and did not receive neoadjuvant or adjuvant therapy (87%). The median follow−up time was 12.1 months (range, 0.1 to 242.2 months). The median OS was 12.6 months (95% confidence interval (CI) 10.7−14.9 months). Two subgroups were identified with a cut−point of 12.5% for PSC after univariate RPA. Patients with PSC ≥ %12.5 were at higher risk of death compared to patients with <%12.5 (45% vs. 61% 1 year OS; p value=0.04). Mutlivariate RPA revealed clinical stage and percent sarcomatoid were significantly associated with OS. Patients with localized disease were most likely to be alive at 1 year (74%). Among patients with metastatic disease with PSC<%42.5 had 1−year OS of 44% vs. 27% for patients with ≥%42.5 cutoff (p<0.001). Conclusions: The PSC appears to be a prognostic factor in the OS of patients with RCC, with larger percentage of involvement portending a worse survival.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 485-485 ◽  
Author(s):  
James Harnett ◽  
Elizabeth A. MacLean ◽  
Helen Bhattacharyya ◽  
Laura A. Cisar ◽  
Caroline Hoang ◽  
...  

485 Background: Few studies compare targeted treatments for renal cell carcinoma (RCC) so understanding real world treatment patterns and healthcare utilization may inform decision making. This study evaluated treatment naïve RCC patients initiating sunitinib (SUN) or pazopanib (PAZ) and the potential impact of administration schedules on duration of therapy (persistence) assessments using claims data. Methods: This retrospective cohort analysis used de-identified Truven Marketscan Medicare Supplemental claims data. Included patients were ≥20 years, diagnosed with RCC with ≥1 prescription (Rx) for SUN or PAZ between Oct. 2009–Sept. 2013 and continuously enrolled ≥6 months prior to and 12 months after index. Patient characteristics, treatment patterns, persistence, RCC-related and all-cause costs were evaluated. Chi-square, Student t-test, or Wilcoxon signed-rank test were used to compare groups (α=0.05). A generalized linear model was used to evaluate costs controlling for patient demographics and characteristics, index medication dose, persistence and index medication. As the recommendation for most patients receiving SUN is 4 weeks on, 2 weeks off, a sensitivity analysis was conducted imputing 42 days supply (DS) for SUN Rx with 28 or 30 DS. Results: 291 patients initiated SUN (76.6%) and PAZ (23.4%). There were no significant (NS) differences between groups in demographics, Charlson Comorbidity Index scores, or proportion with pre-index inpatient admission. Mean time from earliest RCC diagnosis to index was longer for PAZ compared to SUN (518 vs. 398 days, p<0.05). There was NS difference in mean persistence in the non-imputed (154 vs. 175 days, p=0.20) and imputed DS (182 vs. 175, p=0.69) analyses for SUN and PAZ, respectively. Adjusted mean RCC-related ($65,993 vs. $65,254, p=0.68) and all-cause ($92,121 vs. 87,962, p=0.18) costs were NS different between SUN and PAZ cohorts, respectively. Conclusions: This analysis indicates NS differences in treatment persistence or costs for Medicare Supplemental patients with RCC initiating SUN or PAZ. Understanding the implications of SUN’s dosing schedule on DS values for persistence and other calculations is critical.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3036-3036 ◽  
Author(s):  
Marios Giannakis ◽  
Haoxin Li ◽  
Chelsea Jin ◽  
Shuba Gopal ◽  
Kaushal Desai ◽  
...  

3036 Background: Immune-checkpoint inhibition has been shown to be effective in a variety of cancers, including renal cell carcinoma (RCC) and melanoma. However, only a subset of patients with RCC and melanoma respond to anti-PD1 therapy. Given the importance of metabolism in the tumor immune microenvironment, we performed serum metabolomics in nivolumab-treated patients towards identifying novel non-invasive correlates of response and progression-free survival in immunotherapy-treated patients. Methods: We performed liquid chromatography-mass spectrometry on pre- and on-treatment serum samples from 79 patients with advanced melanoma (CA209-038 study) and 82 patients with metastatic RCC (CA209-009 study) receiving nivolumab. We precisely measured more than one-hundred named metabolites at baseline (prior to starting nivolumab), at 4 weeks and at 6 (melanoma) or 9 weeks (RCC) after initiation of treatment and correlated these with best overall response as well as progression-free survival (PFS). Results: In melanoma patients treated with nivolumab, the difference in mean levels of kynurenine (the product of IDO / TDO activity in tryptophan catabolism) between weeks 4 and 6 compared to baseline was significantly different between responders and non-responders (t-test with unequal variance p-value = 0.043 and p-value = 0.044 respectively). In RCC patients, we observed that patients with no response to nivolumab had significantly higher adenosine levels, than those who responded, at baseline and at 4 weeks after initiation of treatment (158% and 138% higher, t-test p-value = 0.0019 and p-value = 0.0011 respectively). RCC nivolumab-treated patients with higher (top quartile) baseline adenosine levels also had a significantly worse PFS (log rank test p-value = 0.004). Conclusions: In this first-of-its kind metabolomic analysis of peripheral blood from nivolumab-treated patients, we find that the change in kynurenine levels in melanoma patients correlates to response. In addition, higher baseline levels of adenosine in RCC patients are associated with worse PFS and lack of response to nivolumab. These results suggest a possible role for serum metabolites as biomarkers of benefit to PD1 inhibition.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5059-5059
Author(s):  
Mausam Patel ◽  
Thomas Kim ◽  
Chenghui Li ◽  
Ahmed Safar ◽  
Sanjay Maraboyina

5059 Background: Stereotactic body radiotherapy (SBRT) is being increasingly used for renal cell carcinoma (RCC) treatment in non-surgical candidates. However, no studies have compared survival between nephrectomy and SBRT. The National Cancer Database (NCDB) database was used to assess overall survival in patients undergoing SBRT vs nephrectomy. Methods: All cases of T1-T4, N0, M0 RCC diagnosed between 2004 and 2016 were extracted from the NCDB. Only patients undergoing either nephrectomy or SBRT, but not both, were included in the final analysis. Primary outcome was overall survival, defined as time in months from diagnosis to death due to any cause. Descriptive statistics were calculated for all variables. Univariate survival analysis was performed using the Kaplan Meier method and log rank test. Multivariate Cox proportional hazards regression models were performed to determine the predictive performance of covariates with respect to overall survival, reported as hazard ratio [HR] with 95% CIs. Nephrectomy patients were propensity score matched to SBRT patients for sub-cohort survival analysis. Comparisons were considered statistically significant at P < 0.05. Results: There were 243,754 patients meeting inclusion criteria with 243,488 undergoing nephrectomy and 266 undergoing SBRT. Five year OS rates were 53% and 80% for SBRT and nephrectomy, respectively (P < 0.001). On multivariate Cox regression, SBRT was associated with an increased risk of death as compared to nephrectomy (HR, 2.05; 95% CI, 1.72 – 2.44; P < 0.001). Sex, race, insurance coverage, comorbidity index, tumor grade, lymphovascular invasion status, T-stage, tumor size, and academic status of treatment facility were also independent predictors of survival. After propensity score matching of 266 SBRT patients to 266 nephrectomy patients, there were no significant differences in baseline characteristics between the groups. However, SBRT continued to demonstrate worse survival and an increased risk of death as compared to nephrectomy (HR, 1.85; 95% CI, 1.41 – 2.44; P < 0.001). Conclusions: Among node-negative, non-metastatic RCC patients, SBRT is associated with inferior survival outcomes as compared to nephrectomy, even after correcting for underlying differences in demographics, tumor characteristics, socioeconomic status, and comorbidities. These results indicate that nephrectomy should remain the standard of care for RCC patients, with SBRT reserved for non-surgical candidates.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4566-4566
Author(s):  
Claud Grigg ◽  
Sally Trufan ◽  
Peter E Clark ◽  
Stephen Boyd Riggs ◽  
Jason Zhu ◽  
...  

4566 Background: Clear cell renal cell carcinoma (ccRCC) is nearly twice as common in men as in women, and women with non-metastatic RCC have a better prognosis than men. The etiology for these disparities is not known, though sex-specific differences in risk factor prevalence and tumor biology have been reported. The differential impact of systemic therapies, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), on prognosis in women and men with metastatic ccRCC is not defined. Methods: Clinicopathologic features and survival of patients with clinical stage IV ccRCC were obtained from the National Cancer Database (NCDB). Patients were grouped by date of metastatic diagnosis into three eras that correspond to major advances in systemic therapy: 2004-2005 (pre-TKI), 2006-2014 (TKI), and 2015-2016 (ICI). Uni- and multi-variable chi-square, logistic regression, and survival analyses were used for comparisons. Survival differences were assessed using Kaplan-Meier curves. Results: 15,025 male and 7,100 female patients with metastatic ccRCC were identified. Demographic features were similar between cohorts though females were slightly older (median 64.8 vs 62.7 mo, p < 0.0001), more likely to be black (6.5% vs 6.0%, p = 0.0119) or receiving Medicare benefits (46.4% vs 39.9%, p < 0.0001). In the combined cohort, median overall survival (OS) was higher in patients diagnosed in the ICI vs TKI (23.0 vs 16.5 mo) and pre-TKI eras (14.4 mo, log-rank p < 0.0001). Compared with men of the same age groups, OS was inferior for women age 50-64 yr (median 18.4 vs 21.1mo, p = 0.0084) and > 64 yr (15.3 vs 12.6mo, p = 0.0001), but not < 50 yr (20.3 vs 21.7mo, p = 0.6290). In the ICI era, median OS improved by a lesser absolute but similar relative amount for women compared to men (+5.6mo [+39%] and +7.2mo [+41%]), respectively). After controlling for age, race, Charlson-Deyo score, initial treatment modality, and insurance and socioeconomic status, women remained at increased risk of death in both the ICI era (HR 1.12 [95% CI 1.04-1.22], p = 0.004) and the TKI era (HR 1.08 [1.04-1.12], p < 0.001). Conclusions: Women with metastatic ccRCC have a worse prognosis than men which is not explained by demographic differences. This disparity is observed in both the TKI and ICI eras. This finding contrasts with previous studies suggesting women with localized RCC have a favorable prognosis compared with men. Further investigation into the sex-specific biology of metastatic ccRCC is warranted.


2017 ◽  
Vol 10 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Reza Mehrazin ◽  
Essel Dulaimi ◽  
Robert G. Uzzo ◽  
Karthik Devarjan ◽  
Jianming Pei ◽  
...  

Background: The proto-oncogene c-MYC, located on chromosome 8q, can be upregulated through gain of 8q, causing alteration in biology of renal cell carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC through chromosome 8q gain and to correlate findings with cancer-specific mortality (CSM), and overall survival (OS). Methods: Cytogenetic analysis by conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on 414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in chromosome 8q status on CSM, OS, and its correlation with clinicopathological variables were evaluated. CSM and OS were assessed using log-rank test and the Cox proportional hazards model. Results: A total of 297 RCC tumors with cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors (9 clear cell and 9 papillary RCC), using conventional method ( n = 11) or CMA ( n = 7). Gain of 8q was associated with higher T stage ( p < 0.001), grade ( p < 0.001), nodal involvement ( p = 0.005), and distant metastasis ( p < 0.001). No association between gain of 8q and age ( p = 0.23), sex ( p = 0.46), and Charlson comorbidity index (CCI, p = 0.59) were seen. Gain of 8q was associated with an 8.38-fold [95% confidence interval (CI), 3.83–18.34, p < 0.001] and 3.31-fold (95% CI, 1.56–7.04, p = 0.001) increase in CSM and decrease in OS, respectively, at a median follow up of 56 months. Conclusion: Chromosome 8q harbors the proto-oncogene c-MYC, which can be upregulated by gain of 8q. Our findings suggest that gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.


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