Overall survival and response to radiation and targeted therapies among patients with renal cell carcinoma brain metastases

2020 ◽  
Vol 132 (1) ◽  
pp. 188-196 ◽  
Author(s):  
Aditya Juloori ◽  
Jacob A. Miller ◽  
Shireen Parsai ◽  
Rupesh Kotecha ◽  
Manmeet S. Ahluwalia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Cumulative Incidence ◽  
Renal Cell ◽  
Radiation Necrosis ◽  
Local Failure ◽  
The Impact

OBJECTIVEThe object of this retrospective study was to investigate the impact of targeted therapies on overall survival (OS), distant intracranial failure, local failure, and radiation necrosis among patients treated with radiation therapy for renal cell carcinoma (RCC) metastases to the brain.METHODSAll patients diagnosed with RCC brain metastasis (BM) between 1998 and 2015 at a single institution were included in this study. The primary outcome was OS, and secondary outcomes included local failure, distant intracranial failure, and radiation necrosis. The timing of targeted therapies was recorded. Multivariate Cox proportional-hazards regression was used to model OS, while multivariate competing-risks regression was used to model local failure, distant intracranial failure, and radiation necrosis, with death as a competing risk.RESULTSThree hundred seventy-six patients presented with 912 RCC BMs. Median OS was 9.7 months. Consistent with the previously validated diagnosis-specific graded prognostic assessment (DS-GPA) for RCC BM, Karnofsky Performance Status (KPS) and number of BMs were the only factors prognostic for OS. One hundred forty-seven patients (39%) received vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Median OS was significantly greater among patients receiving TKIs (16.8 vs 7.3 months, p < 0.001). Following multivariate analysis, KPS, number of metastases, and TKI use remained significantly associated with OS.The crude incidence of local failure was 14.9%, with a 12-month cumulative incidence of 13.4%. TKIs did not significantly decrease the 12-month cumulative incidence of local failure (11.4% vs 14.5%, p = 0.11). Following multivariate analysis, age, number of BMs, and lesion size remained associated with local failure. The 12-month cumulative incidence of radiation necrosis was 8.0%. Use of TKIs within 30 days of SRS was associated with a significantly increased 12-month cumulative incidence of radiation necrosis (10.9% vs 6.4%, p = 0.04).CONCLUSIONSUse of targeted therapies in patients with RCC BM treated with intracranial SRS was associated with improved OS. However, the use of TKIs within 30 days of SRS increases the rate of radiation necrosis without improving local control or reducing distant intracranial failure. Prospective studies are warranted to determine the optimal timing to reduce the rate of necrosis without detracting from survival.

Sarcomatoid Renal Cell Carcinoma: Biologic Behavior, Prognosis, and Response to Combined Surgical Resection and Immunotherapy

1999 ◽  
Vol 17 (2) ◽  
pp. 523-523 ◽  
Author(s):  
Thomas Cangiano ◽  
Joseph Liao ◽  
John Naitoh ◽  
Frederick Dorey ◽  
Robert Figlin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Surgical Resection ◽  
Median Duration ◽  
Renal Cell ◽  
High Dose ◽  
Risk Of Death

PURPOSE: Sarcomatoid variants of renal cell carcinoma (RCC) are aggressive tumors that respond poorly to immunotherapy. We report the outcomes of 31 patients with sarcomatoid RCC treated with a combination of surgical resection and immunotherapy. PATIENTS AND METHODS: Patients were identified from the database of the University of California Los Angeles Kidney Cancer Program. We retrospectively reviewed the cases of 31 consecutive patients in whom sarcomatoid RCC was diagnosed between 1990 and 1997. Clinical stage, sites of metastasis, pathologic stage, and type of immunotherapy were abstracted from the medical records. The primary end point analyzed was overall survival, and a multivariate analysis was performed to distinguish any factors conferring an improved survivorship. RESULTS: Twenty-six percent of patients were male and 74% were female, and the median age was 59 years (range, 34 to 73 years). Length of follow-up ranged from 2 to 77 months (mean, 21.4 months). Twenty-eight patients (84%) had known metastases at the time of radical nephrectomy (67% had lung metastases and 40% had bone, 21% had liver, 33% had lymphatic, and 15% had brain metastases). Twenty-five patients (81%) received immunotherapy, including low-dose interleukin (IL)-2–based therapy (five patients), tumor-infiltrating lymphocyte–based therapy plus IL-2 (nine patients), high-dose IL-2–based therapy (nine patients), dendritic cell vaccine–based therapy (one patient), and interferon alpha–based therapy alone (one patient). Two patients (6%) achieved complete responses (median duration, 46+ months) and five patients (15%) achieved partial responses (median duration, 36 months). One- and 2-year overall survival rates were 48% and 37%, respectively. Using a multivariate analysis, age, sex, and percentage of sarcomatoid tumor (< or > 50%) did not significantly correlate with survival. Improved survival was found in patients receiving high-dose IL-2 therapy compared with patients treated with surgery alone or any other form of immunotherapy (P = .025). Adjusting for age, sex, and percentage of sarcomatoid tumor, the relative risk of death was 10.4 times higher in patients not receiving high-dose IL-2 therapy. Final pathologic T stage did not correlate significantly with outcome, but node-positive patients had a higher death rate per year of follow-up than did the rest of the population (1.26 v 0.76, Cox regression analysis). CONCLUSION: Surgical resection and high-dose IL-2–based immunotherapy may play a role in the treatment of sarcomatoid RCCs in select patients.

scholarly journals Overall survival in renal cell carcinoma after introduction of targeted therapies: a Norwegian population-based study

2017 ◽  
Vol Volume 10 ◽  
pp. 371-385 ◽  
Author(s):  
Christian Beisland ◽  
Tom Johannesen ◽  
Olbjorn Klepp ◽  
Ulrika Axcrona ◽  
Knut Martin Torgersen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Population Based ◽  
Population Based Study ◽  
Norwegian Population

Data to decisions: The impact of online education on immunotherapy in advanced renal cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17076-e17076
Author(s):  
Kinjal Parikh ◽  
Katie Lucero ◽  
Charlotte Warren ◽  
Emily Sherene Van Laar ◽  
Ann Carothers ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Online Education ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Advanced Renal Cell Carcinoma ◽  
Online Video ◽  
Educational Activities ◽  
The Impact

e17076 Background: Cytokine therapy was initially the only immunotherapy for patients with advanced renal cell carcinoma (RCC). The advent of targeted therapies ushered in a new area of precision medicine in the treatment paradigm. Recently, immunotherapy in the form of immune checkpoint inhibitors has shown improved outcomes as compared to targeted therapies and has become a mainstay in treatment. As immunotherapy use moves into earlier stages of disease and combination therapies are explored, education remains essential to optimize patient outcomes. Through the partnership between Medscape Oncology and the Society for Immunotherapy of Cancer, educational activities were designed to increase the knowledge and competence among oncologists surrounding the role of immunotherapy in patients with advanced RCC and uncover remaining educational needs. Methods: The 2 educational activities included a 30-minute online, video discussion with 2 faculty presenters and synchronized slides and a text-based online activity with 2 patient cases and interactive questions. Educational effectiveness was assessed with repeated paired pre/post assessment where learners served as their own controls. The first activity launched September 19, 2018, the second activity launched December 19, 2018, and the data were collected and are reported through December 27, 2019. Results: A total of 9474 learners participated from September 2018-December 2019 including 1029 oncologists. Participation in education resulted in significant improvements for oncologist who answered all pre/post questions for an activity during the study period (n = 302). Improvements in knowledge and competency were observed in the following areas: Knowledge regarding the latest clinical trial data on the use of cancer immunotherapies for the treatment of RCC (49% vs. 74%, p < .001). Knowledge regarding the immune checkpoint inhibitor regimens on the care of patients with RCC (49% vs. 70%, p < .001). Competence related to choosing the most appropriate regimen for patients with mRCC across the continuum of care (54% vs. 76%, p < .001). Conclusions: Participation in online, video- and case-based CME-certified educational activities resulted in statistically significant gains in oncologist knowledge and competency surrounding the use of immunotherapy in advanced RCC. These results demonstrate the value and benefit of multi-modal and sequential activities on improving knowledge and competence outcomes for oncologists caring for patients with advanced renal cell carcinoma.

The impact of metastasis location on overall survival among patients with renal cell carcinoma.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 621-621
Author(s):  
Devin Patel ◽  
Fady Ghali ◽  
Margaret Meagher ◽  
Margaret Meagher ◽  
Aaron Bradshaw ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Renal Cell ◽  
Lung Metastases ◽  
Univariate Analysis ◽  
The Impact ◽  
Disease Location

621 Background: Current staging guidelines define all patients with metastatic renal cell carcinoma (RCC) as a singular group. We sought to compare the impact of metastatic disease location on overall survival (OS) in patients with RCC. Methods: We queried our institutional database of consecutive patients with metastatic RCC. A confirmatory analysis was performed using the National Cancer Database (NCDB) for cases between 2010 to 2015. Only cases from which all metastatic disease location was known were used. Patients were grouped into having brain or bone metastases, liver or lung metastases or other metastases. From our institutional database, we performed a univariate analysis to determine the impact of metastasis location on OS. From the NCDB, univariable and multivariable Cox proportional hazards and Kaplan-Meier survival analysis with log-rank testing was performed. Multivariable models were adjusted for age, comorbidity, race, gender, and treatment with either palliative care, chemotherapy or immunotherapy. Results: A total of 95 patients were analyzed from our institutional database, with 30 (31.9%) having brain/bone metastases, 20 (21.3%) having lung/liver metastases, and 44 (46.8%) having other site metastases. On univariate analysis, patients with brain/bone metastases had significantly worse OS (HR 1.87; 95% CI 1.01-3.47). However, no significant difference was seen in patients with liver/lung metastases (HR 1.44; 95% CI 0.64-3.27). A total of 25,528 patients met inclusion for our NCDB analysis, of which 12,119 (47.5%) had brain/bone metastases, 10,004 (39.2%) had liver/lung metastases, and 3,405 (13.3%) had other site metastases. On univariate analysis, patients with lung/liver (HR 1.46; 95% CI 1.38-1.53) and patients with bone/brain (HR 1.69; 95% CI 1.60-1.77) had progressively worse OS with non-overlapping confidence intervals. Multivariable analysis again showed that patients with lung/liver disease (HR 1.51; 95% CI 1.43-1.59) and brain/bone disease (HR 1.66; 95% CI 1.60-1.75) had progressively worse OS. Conclusions: Our results highlight the heterogeneity of patients with metastatic renal cell carcinoma. Location of metastatic disease may drive differences in survival.

Prognostic value of simple blood biomarkers of systemic inflammation for metastatic renal cell carcinoma (mRCC) patients who undergo cytoreductive nephrectomy (CNx).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 350-350
Author(s):  
Jigi Moudgil-Joshi ◽  
Mark Stares ◽  
Alex Laird ◽  
Steve Leung ◽  
Jahangeer Malik ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Inflammatory Response ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Cytoreductive Nephrectomy

350 Background: The role of cytoreductive nephrectomy (CNx) in patients with metastatic renal cell carcinoma (mRCC) is currently in question. Assessing the benefits and risks of CNx is challenging, with a lack of validated prognostic tools. Biomarkers of the systemic inflammatory response have prognostic utility in mRCC and are included in the IMDC score used to predict survival in patients with mRCC treated with systemic therapy. We sought to investigate their role in patients with mRCC who had undergone CNx. Methods: A cohort of 68 patients, suitable for first-line VEGFR inhibitor (VEGFRi) systemic therapy, who had undergone CNx for mRCC, were identified from a clinical database of patients referred to a regional mRCC service. Inflammatory biomarkers from routine blood tests (haemoglobin, white cell count, neutrophil count, platelets, C-reactive protein (CRP), albumin) and the IMDC score, measured at the time of diagnosis of mRCC, were recorded. The relationship between these and overall survival and time to VEGFRi (tVEGFRi) was examined using Kaplan-Meier and Cox-regression methods. Results: Data were available for 68 patients. Median survival was 33.7 months. On multivariate analysis, albumin ( < 35g g/dL v ≥35 g/dL) and CRP (≤ 10 mg/L v > 10 mg/L) were independently associated with overall survival (p = 0.027 and p = 0.034 respectively). Albumin stratified survival from 24.7 to 87.2 months (p < 0.0001) and CRP from 29.4 to 82.3 months (p = 0.004). 40 (59%) patients subsequently commenced VEGFRi therapy. Median tVEGFRi was 18.1 months, with only 5 (7%) patients commencing treatment within 3 months. 16 (24%) patients yet to receive systemic therapy remain alive after a median 54.0 months follow-up. On multivariate analysis, albumin was also predictive of tVEGFRi (p = 0.037), stratifying tVEGFRi from 6.07 to 45.7 months (p = 0.002). Conclusions: These results highlight that biomarkers of the systemic inflammatory response are strong prognostic factors in mRCC patients who have undergone CNx. Albumin and CRP, but not IMDC, predict survival in this patient group. Significantly, the population investigated here differ from those included in the CARMENA and SURTIME studies, with a majority undergoing surveillance prior to VEGFRi therapy. Our results support a role for CNx in patients where deferred systemic therapy strategies may be employed. Albumin may assist in clinical decision making when considering when to start systemic therapy. We advocate further studies to investigate the prognostic role of these simple, routine clinical tests in patients with mRCC undergoing CNx.

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