Comprehensive molecular and genomic characterization of pancreatic tropism in metastatic renal cell carcinoma.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 633-633 ◽  
Author(s):  
Nirmish Singla ◽  
Jacob Choi ◽  
Oreoluwa Onabolu ◽  
Layton Woolford ◽  
Christina Stevens ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Normal Tissue ◽  
Pancreatic Metastasis ◽  
Matched Normal Tissue ◽  
Pancreatic Metastases ◽  
Metastatic Sites ◽  
Pdx Models

633 Background: Patients with metastatic renal cell carcinoma (mRCC) involving the pancreas have been shown to exhibit a relatively indolent course, yet the biologic explanation is unclear. We sought to characterize the genomic landscape of patients with mRCC harboring pancreatic metastases to identify molecular drivers of pancreatic tropism. Methods: mRCC patients harboring pancreatic metastases from UTSW and Cleveland Clinic were identified. Clinicopathologic data and oncologic outcomes were analyzed. Samples were obtained from primary tumors, metastatic sites (including pancreatic or other distant metastases), and matched normal tissue. Whole exome (WES) and RNA sequencing of tumors was conducted. Patient-derived xenograft (PDX) models were generated from a subset of patients, and the engrafted tumors were analyzed. Results: 31 mRCC patients with pancreatic metastases were included with 54 tumor samples derived from the primary tumor or thrombus (24), pancreatic metastasis (21), or other metastatic sites (9). Median follow-up was 101 months. Clinicopathologic characteristics were similar between the two institutional cohorts, and all but one patient were favorable or intermediate IMDC risk. All patients had clear cell histology. 8 patients (26%) were metastatic at diagnosis, and median time to metastasis in the remaining patients was 74 months (IQR 32-120). Overall (OS) and cancer-specific (CSS) survival did not vary by IMDC risk group. Morphologically, tumors largely displayed low-grade acinar patterns. WES with matched normal tissue and RNAseq were completed with adequate quality for 48 and 30 samples, respectively. 14 PDX lines were generated, of which 5 (36%) engrafted stably (≥2 passages). WES from 2 tumorgraft specimens revealed preservation of specific mutations in the corresponding human samples. Conclusions: mRCC patients with pancreatic metastases exhibit remarkably favorable survival outcomes. The relatively indolent biology of these tumors is reflected histologically and genomically and can be recapitulated in PDX models. Understanding tumor heterogeneity may help refine prognostic models for mRCC and hold implications for improved personalization of therapy.

Concordance of Pathologic Features Between Metastatic Sites and the Primary Tumor in Surgically Resected Metastatic Renal Cell Carcinoma

Urology ◽  
2016 ◽  
Vol 96 ◽  
pp. 106-113 ◽  
Author(s):  
Sarah P. Psutka ◽  
John C. Cheville ◽  
Brian A. Costello ◽  
Suzanne B. Stewart-Merrill ◽  
Christine M. Lohse ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Primary Tumor ◽  
Renal Cell ◽  
Pathologic Features ◽  
Metastatic Sites

scholarly journals Prognosis of patients with metastatic renal cell carcinoma and pancreatic metastases

2015 ◽  
Vol 117 (5) ◽  
pp. 761-765 ◽  
Author(s):  
Sarathi Kalra ◽  
Bradley J. Atkinson ◽  
Marc Ryan Matrana ◽  
Surena F. Matin ◽  
Christopher G. Wood ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Pancreatic Metastases

Combination therapy with nivolumab and tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17090-e17090
Author(s):  
Benjamin Garmezy ◽  
Tian Zhang ◽  
Andrew Leonard Laccetti ◽  
Minas P. Economides ◽  
Amishi Yogesh Shah ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Weight Loss ◽  
Combination Therapy ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Systemic Treatments ◽  
Metastatic Sites

e17090 Background: Two immunotherapy (IO) and tyrosine kinase inhibitor (TKI) combinations are FDA-approved for patients (pts) with metastatic renal cell carcinoma (mRCC). Here we present a multicenter off-protocol experience with IO/TKI combinations after progression on monotherapy. Methods: We performed a retrospective analysis of pts with mRCC who received combination non-FDA approved off-protocol IO/TKI combination therapy from 11/2015 – 1/2019 at MD Anderson Cancer Center and Duke Cancer Institute. Results: 48 pts met criteria for study inclusion. At therapy start: median (med) age 65 years; 75% clear cell histology; 68.8% IMDC intermediate risk (20.8% favorable, 10.4% poor); 81.3% prior nephrectomy; med metastatic sites: 2; med prior systemic treatments: 2; most common metastatic sites: lung (58.3%), lymph node (52.1%), and bone (43.8%). Pts received nivolumab (nivo) in combination with the following: cabozantinib (n = 24, 50%), pazopanib (13, 27.1%), axitinib (6, 12.5%), lenvatinib (2, 4.2%), ipilimumab/cabozantinib (3, 6.3%). Med PFS was 13.7 months and med OS was not reached. The two largest cohorts received nivo + cabozantinib (N+C; med dose 40 mg daily) or nivo + pazopanib (N+P; med dose 400 mg daily). The N+C cohort had higher med metastatic sites (3 vs 2) and was more pretreated with agents unique to their IO/TKI combination (med 2 vs 0). In the N+P group, more pts had started on TKI prior to addition of nivo at progression (69.2% vs 45.8%), and fewer had IO monotherapy with TKI addition (30.8% vs 50%). With a med follow up of 14.0 months after combination start, the N+C cohort had a med PFS of 7.3 months (initiated TKI first: 4.8, IO first: 8.2) and med OS of 18.2 months (TKI first: 11.8, IO first: 24.3). The N+P cohort had med follow up of 20.5 months after combination, med PFS of 21.3 months (TKI first: 16.5, IO first: 21.8), and med OS was not reached. In the N+C group, 87.5% experienced any grade adverse event (AE), most common included fatigue (79.2%), diarrhea (42.7%), nausea (29.2%), hypertension (29.2%), and weight loss (25.0%). In the N+P group, 92.3% experienced any grade AE, including fatigue (76.9%), hypertension (38.5%), diarrhea (30.8%), nausea (30.8%), and weight loss (30.8%). There were no grade ≥3 AEs. Conclusions: Slow disease progression on nivo or TKI may be safely controlled with addition of IO/TKI therapy. Med PFS after addition of nivo to TKI appears similar (N+C) and improved (N+P) compared to nivo monotherapy (Checkmate-025). Med PFS after addition of TKI to IO was also similar (N+C) and improved (N+P) compared to historical controls.

Prognosis of patients with metastatic renal cell carcinoma and pancreatic metastases.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 527-527 ◽  
Author(s):  
Sarathi Kalra ◽  
Bradley J. Atkinson ◽  
Marc Ryan Matrana ◽  
Surena F. Matin ◽  
Christopher G. Wood ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Laboratory Data ◽  
Pancreatic Metastasis ◽  
Prognostic Impact ◽  
Pancreatic Metastases ◽  
Baseline Characteristics ◽  
Sites Of Metastases

527 Background: Pancreatic metastases are seen in a relatively small percentage of patients with renal cell carcinoma (mRCC). The prognostic impact of pancreatic metastases in patients receiving treatment for mRCC has not been extensively studied, and drivers of pancreatic metastases are not known. Methods: Retrospective review of mRCC patients in an outpatient clinic was done from January 2006 to November 2011. Patient characteristics including demographics, laboratory data, and outcomes were analyzed. Comparison of baseline characteristics was done using chi2and t-test and overall survival (OS) was estimated using Kaplan-Meier methods. Predictors of OS were analyzed using Cox regression. Results: A total of 228 patients were reviewed of which 44 (19.3%) had metastases to the pancreas and 184 (81.7%) had metastasis to sites other than the pancreas. The distribution of baseline characteristics and other factors was equal in both cohorts. 4 patients had isolated metastases to the pancreas, however, the majority of patients (68%) with pancreatic metastases had at least three different organ sites of metastases, as compared to 29% in patients without pancreatic metastases (p<0.01). Distribution of organ sites of metastases was similar (p>0.05), excluding pancreas. Median OS was 39 months (95% confidence interval [CI], 24-57) for patients with pancreatic metastases, compared to 26 months (95% CI, 21-31) for patients without pancreatic metastases (p-value <0.01). Conclusions: Despite a higher number of affected organ sites in the pancreatic metastasis cohort, mRCC behavior in this cohort appears to be more indolent, as demonstrated by a higher median OS. These findings suggest that host or tumor features associated with pancreatic metastases induce a less aggressive tumor phenotype. [Table: see text]

Association of PD-1 and PD-L1 protein expression in matched primary and metastatic renal cell carcinoma tumors.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 418-418 ◽  
Author(s):  
Brian I. Rini ◽  
Jennifer Yearly ◽  
Hari Dhakal ◽  
Christopher Przybycin
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Linear Regression Analysis ◽  
Matched Pair ◽  
Primary Tumors ◽  
Metastatic Site ◽  
Metastatic Sites

418 Background: Therapy targeting programmed death (PD)-1 and PD-L1 proteins has activity in metastatic renal cell carcinoma (mRCC). Expression of these proteins on tumor and infiltrating immune cells is associated with a higher response to drugs inhibiting this pathway. However, these associations have been made based on primary tumor expression, while therapy is directed against metastatic deposits. Methods: Patients with mRCC and metastases (all clear cell; 3 with sarcomatoid changes) who had undergone resection of both the primary and at least one metastatic tumor were included. Samples were evaluated for PD-1 and PD-L1 expression by immunohistochemistry using anti-PD-1 clone NAT105 and Merck proprietary anti-PD-L1 clone 22C3. Stained sections were scored for PD-1 and PD-L1 using a semi-quantitative 0 to 5 scale (0 = negative, 1 = rare, 2 = low, 3 = moderate, 4= high, 5 = very high). PD-1 expression was limited to cells with lymphoid morphology, PD-L1 expression was evaluated for both tumor and non-tumor (inflammatory, endothelial) cells. Linear regression analysis was performed to assess significance of correlations. Results: Fifty matched primary and metastatic RCC tissue sets were analyzed with 48 evaluable matched pairs. PD-1 score greater than 3 (considered positive) was detected in 9 primary tumors (18%) and 9 metastatic sites (18%). PD-L1 score greater than 3 was detected in 9 primary tumors (18%) and 12 metastatic sites (24%). There was a correlation between PD-1 scores for primary and metastatic pairs (R2=0.194; p<0.002) and between PD-L1 scores for primary and metastatic pairs (R2=0.319; p<0.0001). There was an association between PD-1 score and PD-L1 score for primary tumors (R2=0.513; p<0.0001) and for metastatic sites (R2=0.449; p<0.0001). For PD-1 score, there were 10 pairs (21%) in which either the primary or metastatic site score was ≥3, but the matched pair was < 3. For PD-L1 score, there were 9 pairs (19%) in which either the primary or metastatic site score was ≥3, but the matched pair was < 3. Conclusions: The expression of PD1 and PD-L1 in primary clear cell RCC tumors is correlated with metastatic site expression, although there are a substantial percentage of tumors with discordance.

Number of metastatic sites rather than location dictates overall survival of patients with node-negative metastatic renal cell carcinoma

Urology ◽  
2003 ◽  
Vol 61 (2) ◽  
pp. 314-319 ◽  
Author(s):  
Ken-Ryu Han ◽  
Allan J Pantuck ◽  
Matthew H.T Bui ◽  
Oleg Shvarts ◽  
Danielo G Freitas ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Node Negative ◽  
Metastatic Sites

Pancreatic metastasis from renal cell carcinoma: Presentation, recurrence, survival, and response to antiangiogenic therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16137-e16137 ◽  
Author(s):  
B. Albouy ◽  
B. Billemont ◽  
C. Massard ◽  
M. Gross-Goupil ◽  
O. Rixe ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Surgical Resection ◽  
Renal Cell ◽  
Antiangiogenic Therapy ◽  
Prolonged Survival ◽  
Pancreatic Metastasis ◽  
Free Survival ◽  
Pancreatic Metastases ◽  
Antiangiogenic Therapies

e16137 Background: Pancreas represents an uncommon site of metastasis in renal cell carcinoma (RCC). The natural history of pancreatic metastases is largely unknown, and efficacy of targeted agents has never been assessed. We examined the outcome in a series of RCC patients (pts) with pancreatic metastases, treated by either surgery or antiangiogenic therapy. Methods: We reviewed the charts of RCC pts treated for pancreatic metastases, between 2001 and 2008, in Institut Gustave Roussy and Pitié-Salpetrière Hospital. Data base was reviewed to determine presentation, clinical symptoms, pancreatic metastases treatment, use of systemic therapy, disease-free survival (DFS) or progression-free survival (PFS) and overall survival (OS) after treatment. Results: A total of 40 pts with pancreatic metastases from RCC have been analyzed. Median age was 63 years (range: 48–81), sex ratio M/F was 29/11, and metastases occurred initially (synchroneous) in 9 pts, while they were metachronous in 31 pts. Most of the metastases were asymptomatic (87%), detected on routine CT scans, while only 12% were symptomatic (pain, cholestasis). Surgical resection of pancreatic metastases was performed in 8 (20%) patients, and DFS and OS were 45 and 66 months. In patients with multiple metastatic sites (lung : 20 (50%); liver : 8 (20%); thyroid : 3(7%)), therapeutic approaches have included antiangiogenic therapies (75%): sorafenib (20 pts), sunitinib (7 pts), bevacizumab (2 pts), Torisel (1 pt). Best response was partial response in 30% of pts and stable disease in 50% of pts. Median PFS and OS were 21 months and 30 months. Conclusions: Patients with RCC pancreatic metastases seem to have a longer survival than the usual metastatic RCC pts. Surgical resection must be discussed in pauci-metastatic disease, as it can be associated with prolonged survival. Antiangiogenic therapies are active in these patients with high response rate and prolonged survival. No significant financial relationships to disclose.

Hypercoagulability as a prognostic factor for survival in patients with metastatic renal cell carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16134-e16134
Author(s):  
I. Tsimafeyeu V. ◽  
A. Madzhuga ◽  
L. Demidov
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Case Control Study ◽  
Response Rate ◽  
Case Control ◽  
Metastatic Sites ◽  
Control Study

e16134 Background: In experimental systems, interference with coagulation can affect tumor biology. We suggested that abnormal coagulation could be a negative predictor for response to immunotherapy and survival among patients with metastatic renal cell carcinoma (MRCC). Methods: To address this issue, retrospective analysis of 289 previously untreated MRCC patients entering on institutional review board-approved clinical trials was conducted between 2003 and 2006. In addition, two groups of MRCC patients with (n = 28) or without (n = 28) hypercoagulability were compared in a case-control study. Baseline and treatment characteristics were well balanced. Results: Hypercoagulability was present at treatment start in 40% of patients. Median baseline fibrinogen was 6.2 mg/dl. Serious disorders were found in 68% of patients. Abnormal coagulation was strongly associated with a number of metastatic sites (2 and more metastatic sites vs. 0–1 (p = 0.001). Patients with high extent of hypercoagulability had significantly higher number of metastatic sites (p = 0.02). On univariate analysis, patients with hypercoagulability had significantly shorter overall survival than patients with normal coagulation; median survivals of 8.9 and 16.3, respectively (p = 0.001). Short survival and low response rate also were significantly associated with hypercoagulability in a case-control study. Median cancer-specific survival was 8.2 months and 14.6 months, respectively (p = 0.0011). Disease control rate (overall response + stable disease) was significantly higher in patients with normal coagulation: 71.4 versus 42.9% (p = 0.003). We did not reveal VTE-related deaths. Conclusions: Hypercoagulability disorders were found to be prognostic factor for response rate to systemic therapy and survival in patients with MRCC. No significant financial relationships to disclose.

Clinical outcomes according to ethnicity in patients with metastatic renal cell carcinoma (mRCC) treated with VEGF-targeted therapy (TT).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16065-e16065
Author(s):  
Dominick Bosse ◽  
Wanling Xie ◽  
Connor Wells ◽  
Aly-Khan A. Lalani ◽  
Frede Donskov ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Risk Groups ◽  
Eligibility Criteria ◽  
Best Response ◽  
Metastatic Sites

e16065 Background: Discrepancies in clinical outcomes between different ethnic groups are well known in cancer patients. Differences in mRCC patients receiving VEGF-TT are less well characterized. We thought to report on baseline characteristics and treatment outcomes in African-Americans (AA) and Hispanic patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Methods: Caucasians, AA and Hispanics with mRCC treated with 1stline VEGF-TT were identified from the IMDC. We created 2 matched cohorts: 1) AA vs. Caucasians and 2) Hispanics vs. Caucasians, both matched for age (<50; 50-59; 60-69; <70-year-old), gender, years of treatment (2003-07; 2008-12; 2013-16) and geography (Canada, USA, Europe). Weighted Cox and logistic regressions were used to compare OS, time-to-treatment failure (TTF) and best response, adjusted for nephrectomy status, IMDC risk groups, number of metastatic sites (1 v. >1) and histology (clear-cell vs. else). Results: 73 AA and 71 Hispanics met eligibility criteria and were matched with 1236 and 901 eligible Caucasians, respectively. AA had more non-clear cell histology (26% v. 11%), time from diagnosis to therapy<1 year (67% v. 55%) and anemia (75% v. 54%) vs. Caucasians. Differences were not significant for Hispanics. Clinical outcomes are presented in Table. Conclusions: Adjusted for clinical prognostic factors, Hispanics with mRCC have statistically shorter TTF and survival than Caucasians. AA had a trend toward shorter TTF (not significant) but similar survival than Caucasians. Underlying genetic/biological differences, along with potential cultural variations, may impact survival in Hispanic mRCC patients. [Table: see text]

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