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John L Gore - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of initial surgery vs initial systemic therapy for Metastatic Kidney Cancer in the targeted therapy era analysis of a population based cohort
Urology, 2017Co-Authors: Liam C Macleod, Scott S Tykodi, Sarah K Holt, Jonathan D Harper, Anobel Y Odisho, John L GoreAbstract:Objective To use econometric methods to assess comparative overall survival of patients with Metastatic renal cell carcinoma (mRCC) managed with initial cytoreductive nephrectomy (CN) vs initial systemic therapy. Randomized data demonstrate improved survival for CN preceding cytokine-based therapy in mRCC. This benefit may be attenuated in the contemporary mRCC era given more effective systemic therapies. Methods Patients over age 65 with mRCC from the Surveillance, Epidemiology, and End Results registries linked with Medicare claims from 2006 to 2011 were categorized by initial treatment. We applied sequential survival analysis methods to assess the association between initial CN and overall survival (OS) including Cox proportional hazards models, propensity scoring, and instrumental variable analysis to account for measured and unmeasured selection bias. Results Of 537 patients analyzed, 190 had initial CN followed by targeted therapy and 347 had initial targeted therapy. Median OS in the initial CN group was 17.4 months (interquartile range 9.8-32.0), compared with 9.2 months (interquartile range 4.3-18.0) for initial targeted therapy. Cox proportional hazards analysis revealed initial CN was associated with improved OS (hazard ratio 0.50, 95% confidence interval [CI] 0.38-0.65). Propensity matching demonstrated a survival advantage for initial CN of 5.8 months (95% CI 1.9-9.7). Accounting for unmeasured confounding with instrumental variable analysis demonstrated a trend toward improved survival with initial CN (hazard ratio 0.29 [95% CI 0.08-1.00]). Conclusion Initial CN is associated with improved survival compared with initial systemic therapy in a contemporary population-based mRCC cohort.
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impact of cytoreductive nephretomy on timing of systemic therapy in Metastatic Kidney Cancer
Journal of Clinical Oncology, 2017Co-Authors: Liam C Macleod, Scott S Tykodi, Atreya Dash, George R. Schade, Daniel W Lin, Jonathan D Harper, John L GoreAbstract:503Background: High rates of disease control with systemic therapy (ST) in the post-cytokine era for Metastatic renal cell carcinoma (mRCC) cause apprehension that cytoreductive nephrectomy (CN) may delay effective therapy. We therefore evaluated factors associated with early mortality and time to ST after CN. We hypothesized markers of poor performance status and morbid CN would be associated with postoperative mortality and therapeutic delays. Methods: The National Cancer Database was screened for adult mRCC cases having CN followed by ST, years 2006-2013. We classified a delay in systemic therapy as interval > 45 days (median time to ST in the cohort). Multivariable logistic regression was performed, identifying factors associated with perioperative mortality and delays to initiation of ST. Results: Of 10,913 patients with initial CN (45% of mRCC), 30- and 90-day mortality were 3% and 11%, respectively. 6,362 later received ST (87% targeted therapy, 13% immunotherapy), median start was 45 days post-ope...
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Litmus test or destination systemic therapy? Trends in referral for surgery after initial systemic therapy in Metastatic Kidney Cancer.
Journal of Clinical Oncology, 2017Co-Authors: Liam C Macleod, Scott S Tykodi, Atreya Dash, George R. Schade, John L GoreAbstract:502Background: With nine new targeted and immunotherapeutic agents for Metastatic Kidney Cancer (mRCC) since 2005, there is no randomized data supporting sequencing cytoreductive nephrectomy (CN) and newer systemic therapies (ST). Increased disease control with ST engenders concern that CN may shorten life or delay therapy. Thus, in all the best prognostic candidates, initial ST as a “litmus” test may be advocated prior to CN. We evaluated use of CN after initial ST, hypothesizing receipt of deferred CN to be associated with increased survival time, markers of increased performance status, less rapid disease, and socioeconomic status. Methods: The National Cancer Database was screened for adult patients with biopsy-proven mRCC treated with initial systemic therapy between 2006-2013. Covariates included demographic, oncologic, hospital-level, and geographic variables. Unadjusted and multivariable logistic regression was performed, identifying factors associated with CN after initial ST. Results: Of 14,651 ...
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utilization and sequencing of targeted therapy and cytoreductive nephrectomy in non clear cell Metastatic Kidney Cancer
Journal of Clinical Oncology, 2016Co-Authors: Liam C Macleod, Scott S Tykodi, Sarah K Holt, John L GoreAbstract:615 Background: Many patients with Metastatic Kidney Cancer (mRCC) are ineligible for trials due to non-clear cell histology. Efficacy of targeted therapy agents in non-clear cell mRCC is still being investigated. We hypothesized that sequencing CN upfront is associated with improved overall survival. We analyze a population-based cohort of non-clear cell mRCC patients in the targeted therapy era. Methods: Patients from the SEER-Medicare files (2005-2011) with non-clear cell mRCC were categorized as having received upfront targeted therapy or upfront CN. Additional exclusions were age < 66 to avoid confounding by uncaptured non-Medicare coverage, and competing stage IV Cancer. Targeted therapy was identified through Medicare Part D files. Cox proportional hazards regression determined association between treatment groups, clinical and Cancer-related characteristics, and the main outcome, median overall survival (OS). Propensity matching controlled for measurable confounding in treatment selection. Results...
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initial compared to deferred cytoreductive nephrectomy for Metastatic Kidney Cancer and its association with improved survival in the targeted therapy era
Journal of Clinical Oncology, 2016Co-Authors: Liam C Macleod, Scott S Tykodi, Sarah K Holt, John L GoreAbstract:607 Background: Since 2005 seven new agents were approved for Metastatic renal cell carcinoma (mRCC), demarcating a transition from the cytokine to the targeted therapy era. Trials demonstrated a survival benefit for upfront cytoreductive nephrectomy (CN) pre-2005. However, upfront versus delayed CN relative to targeted therapy has not been reported in the trial arena. We hypothesized that upfront CN confers a survival benefit in the targeted therapy era. We analyze survival in a population based cohort exposed to targeted therapies with upfront CN compared to deferred CN. Methods: Patients from SEER registries (2005-2011) with mRCC were categorized into: 1.) CN followed by targeted therapy or 2). initial targeted therapy. Additional exclusions were age < 66, due to chance of uncaptured non-Medicare care, competing non-renal stage IV Cancer and non-clear cell histology. Targeted therapy was identified from Medicare Part D files (bevacizumab, sunitinib, sorafenib, axitinib, pazopanib, temsirolmus, everolim...
Liam C Macleod - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of initial surgery vs initial systemic therapy for Metastatic Kidney Cancer in the targeted therapy era analysis of a population based cohort
Urology, 2017Co-Authors: Liam C Macleod, Scott S Tykodi, Sarah K Holt, Jonathan D Harper, Anobel Y Odisho, John L GoreAbstract:Objective To use econometric methods to assess comparative overall survival of patients with Metastatic renal cell carcinoma (mRCC) managed with initial cytoreductive nephrectomy (CN) vs initial systemic therapy. Randomized data demonstrate improved survival for CN preceding cytokine-based therapy in mRCC. This benefit may be attenuated in the contemporary mRCC era given more effective systemic therapies. Methods Patients over age 65 with mRCC from the Surveillance, Epidemiology, and End Results registries linked with Medicare claims from 2006 to 2011 were categorized by initial treatment. We applied sequential survival analysis methods to assess the association between initial CN and overall survival (OS) including Cox proportional hazards models, propensity scoring, and instrumental variable analysis to account for measured and unmeasured selection bias. Results Of 537 patients analyzed, 190 had initial CN followed by targeted therapy and 347 had initial targeted therapy. Median OS in the initial CN group was 17.4 months (interquartile range 9.8-32.0), compared with 9.2 months (interquartile range 4.3-18.0) for initial targeted therapy. Cox proportional hazards analysis revealed initial CN was associated with improved OS (hazard ratio 0.50, 95% confidence interval [CI] 0.38-0.65). Propensity matching demonstrated a survival advantage for initial CN of 5.8 months (95% CI 1.9-9.7). Accounting for unmeasured confounding with instrumental variable analysis demonstrated a trend toward improved survival with initial CN (hazard ratio 0.29 [95% CI 0.08-1.00]). Conclusion Initial CN is associated with improved survival compared with initial systemic therapy in a contemporary population-based mRCC cohort.
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impact of cytoreductive nephretomy on timing of systemic therapy in Metastatic Kidney Cancer
Journal of Clinical Oncology, 2017Co-Authors: Liam C Macleod, Scott S Tykodi, Atreya Dash, George R. Schade, Daniel W Lin, Jonathan D Harper, John L GoreAbstract:503Background: High rates of disease control with systemic therapy (ST) in the post-cytokine era for Metastatic renal cell carcinoma (mRCC) cause apprehension that cytoreductive nephrectomy (CN) may delay effective therapy. We therefore evaluated factors associated with early mortality and time to ST after CN. We hypothesized markers of poor performance status and morbid CN would be associated with postoperative mortality and therapeutic delays. Methods: The National Cancer Database was screened for adult mRCC cases having CN followed by ST, years 2006-2013. We classified a delay in systemic therapy as interval > 45 days (median time to ST in the cohort). Multivariable logistic regression was performed, identifying factors associated with perioperative mortality and delays to initiation of ST. Results: Of 10,913 patients with initial CN (45% of mRCC), 30- and 90-day mortality were 3% and 11%, respectively. 6,362 later received ST (87% targeted therapy, 13% immunotherapy), median start was 45 days post-ope...
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Litmus test or destination systemic therapy? Trends in referral for surgery after initial systemic therapy in Metastatic Kidney Cancer.
Journal of Clinical Oncology, 2017Co-Authors: Liam C Macleod, Scott S Tykodi, Atreya Dash, George R. Schade, John L GoreAbstract:502Background: With nine new targeted and immunotherapeutic agents for Metastatic Kidney Cancer (mRCC) since 2005, there is no randomized data supporting sequencing cytoreductive nephrectomy (CN) and newer systemic therapies (ST). Increased disease control with ST engenders concern that CN may shorten life or delay therapy. Thus, in all the best prognostic candidates, initial ST as a “litmus” test may be advocated prior to CN. We evaluated use of CN after initial ST, hypothesizing receipt of deferred CN to be associated with increased survival time, markers of increased performance status, less rapid disease, and socioeconomic status. Methods: The National Cancer Database was screened for adult patients with biopsy-proven mRCC treated with initial systemic therapy between 2006-2013. Covariates included demographic, oncologic, hospital-level, and geographic variables. Unadjusted and multivariable logistic regression was performed, identifying factors associated with CN after initial ST. Results: Of 14,651 ...
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utilization and sequencing of targeted therapy and cytoreductive nephrectomy in non clear cell Metastatic Kidney Cancer
Journal of Clinical Oncology, 2016Co-Authors: Liam C Macleod, Scott S Tykodi, Sarah K Holt, John L GoreAbstract:615 Background: Many patients with Metastatic Kidney Cancer (mRCC) are ineligible for trials due to non-clear cell histology. Efficacy of targeted therapy agents in non-clear cell mRCC is still being investigated. We hypothesized that sequencing CN upfront is associated with improved overall survival. We analyze a population-based cohort of non-clear cell mRCC patients in the targeted therapy era. Methods: Patients from the SEER-Medicare files (2005-2011) with non-clear cell mRCC were categorized as having received upfront targeted therapy or upfront CN. Additional exclusions were age < 66 to avoid confounding by uncaptured non-Medicare coverage, and competing stage IV Cancer. Targeted therapy was identified through Medicare Part D files. Cox proportional hazards regression determined association between treatment groups, clinical and Cancer-related characteristics, and the main outcome, median overall survival (OS). Propensity matching controlled for measurable confounding in treatment selection. Results...
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initial compared to deferred cytoreductive nephrectomy for Metastatic Kidney Cancer and its association with improved survival in the targeted therapy era
Journal of Clinical Oncology, 2016Co-Authors: Liam C Macleod, Scott S Tykodi, Sarah K Holt, John L GoreAbstract:607 Background: Since 2005 seven new agents were approved for Metastatic renal cell carcinoma (mRCC), demarcating a transition from the cytokine to the targeted therapy era. Trials demonstrated a survival benefit for upfront cytoreductive nephrectomy (CN) pre-2005. However, upfront versus delayed CN relative to targeted therapy has not been reported in the trial arena. We hypothesized that upfront CN confers a survival benefit in the targeted therapy era. We analyze survival in a population based cohort exposed to targeted therapies with upfront CN compared to deferred CN. Methods: Patients from SEER registries (2005-2011) with mRCC were categorized into: 1.) CN followed by targeted therapy or 2). initial targeted therapy. Additional exclusions were age < 66, due to chance of uncaptured non-Medicare care, competing non-renal stage IV Cancer and non-clear cell histology. Targeted therapy was identified from Medicare Part D files (bevacizumab, sunitinib, sorafenib, axitinib, pazopanib, temsirolmus, everolim...
Martin Marszalek - One of the best experts on this subject based on the ideXlab platform.
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long term relative survival rs in patients with primary Metastatic Kidney Cancer primary mrcc an analysis of 2 167 patients from the austrian national Cancer registry ancr
Annals of Oncology, 2019Co-Authors: Monika Hackl, Stephan Madersbacher, Henrike E Karimkos, M Rauchenwald, Martin MarszalekAbstract:Abstract Background The introduction of thyrosinkinase inhibitors (TKI) changed the treatment of mRCC. To elaborate the potential impact of TKI therapies, we studied trends in OS for patients diagnosed with primary mRCC between 1998 - 2015 in Austria. Methods All patients with primary mRCC (≥18 years), diagnosed from 1998 - 2015 were derived from the ANCR (n = 2,490). Patients diagnosed from 2004-2005 (n = 323) were excluded (transition period of systemic therapies). To evaluate survival differences between patients treated before and after the introduction of Sunitinib (preTKI-era and TKI-era), 3 periods were defined: 1998 - 2003 (preTKI-era; N = 937), 2006 - 2010 (TKI-era P1; N = 687) and 2011 - 2015 (TKI-era P2; N = 543). Follow-up was complete until Dec. 31st, 2016. The Cox proportional hazard model was used to calculate hazard ratios (HR). Results A total of 2,167 patients were included, median age was 70 yrs in the 3 eras. The incidence of T1 tumors increased from 6.9% in the preTKI-era to 10% in the TKI-era while T4 tumors decreased from 15% to 8% (p = 75 years of + 0.2% (p =.03) and for T3/T4 tumors of + 6% (p =.002). The Relative Excess Risk of dying (RER) for patients treated in the TKI-eras was reduced compared to the preTKI-era (HR 0.78, 95% CI 0.76-0.95) adjusted for sex, age, T-stage and surgery. Survival advantage for patients undergoing surgery remained significant (HR: 0.46, 95% CI 0.41-0.52) after adjustment for TKI-era, sex, age, T-stage. Conclusions Patients treated in the TKI era show improved RS compared to the cytokine era. Most benefit was observed in non-surgical patients, younger patients and for T3/T4 disease. Surgery contributed to an additional survival benefit. Legal entity responsible for the study Priv. Doz. Dr. Martin Marszalek. Funding Pfizer Austria. Disclosure All authors have declared no conflicts of interest.
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long term overall survival os in patients with primary Metastatic Kidney Cancer an analysis of 1468 patients from the austrian national Cancer registry ancr
European Urology Supplements, 2017Co-Authors: Martin Marszalek, Henrike E Karimkos, Stephan Madersbacher, M Rauchenwald, Monika HacklAbstract:489Background: The introduction of thyrosinkinase inhibitors (TKI) changed the treatment of Metastatic Kidney Cancer fundamentally. To elaborate the potential impact of TKI therapies, we studied tr...
Shahrokh F Shariat - One of the best experts on this subject based on the ideXlab platform.
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median time to progression with tki based therapy after failure of immuno oncology therapy in Metastatic Kidney Cancer a systematic review and meta analysis
European Journal of Cancer, 2021Co-Authors: Mike Wenzel, Shahrokh F Shariat, Marina Deuker, Luigi Nocera, Claudia Colla Ruvolo, Christoph Wurnschimmel, Zhe Tian, Fred Saad, Alberto Briganti, Derya TilkiAbstract:Abstract Background The efficacy of tyrosine kinase inhibitor (TKI)-based therapy after previous immuno-oncology therapy (IO) failure has been addressed before. However, summary efficacy estimates have never been generated in these reports. We addressed this void. Material and methods We systematically examined TKI efficacy after IO-failure and generated weighted median progression-free survival (PFS) estimates for Pazopanib, Axitinib, Cabozantinib, Sunitinib. A systematic review according to PRISMA was conducted. PubMed and abstracts were queried. Only studies proving median PFS were included. Weighted medians were computed for each TKI alternative. Results Of 245 articles, nine eligible studies were included in the current study with 952 analysed patients. Weighted PFS medians after any previous IO-based therapy were respectively 13.7 (range from 4.6 to 24.4), 8.1 (range from 4.7 to 13.2), 8.5 (range from 4.7 to 15.2) and 6.9 months (range from 2.9 to 11.6) for Pazopanib, Axitinib, Cabozantinib, Sunitinib. Specific second-line weighted PFS median was 14.8 months (range from 5.6 to 24.4), 10.1 months (range from 6.4 to 13.2), 8.7 months (range from 4.7 to 15.2) and 6.0 months (range from 2.9 to 8.0) for Pazopanib, Axitinib, Cabozantinib, Sunitinib, respectively, after first-line IO. Conclusion Pazopanib results in the longest weighted median PFS, after previous IO-failure, regardless of treatment line, as well as in specific second-line, post-first-line IO failure settings. Pending novel studies, Pazopanib appears to represent the most promising treatment option after prior IO.
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impact of patients gender on efficacy of immunotherapy in patients with Metastatic Kidney Cancer a systematic review and meta analysis
Clinical Genitourinary Cancer, 2020Co-Authors: Melanie R Hassler, Mohammad Abufaraj, Shoji Kimura, Judith Stanglkremser, Kilian M Gust, Petr Glybochko, Manuela Schmidinger, Pierre I Karakiewicz, Shahrokh F ShariatAbstract:Abstract Background Recent meta-analyses on checkpoint inhibitors in Cancer report conflicting data regarding the association of patient sex with inhibitor efficacy. In advanced Kidney Cancer, checkpoint inhibitors have shown improved outcomes in first- and second-line settings compared to standard of care, but the role of patient sex on treatment outcome is unclear. We aimed to assess the efficacy of immunotherapy according to patient sex in advanced Kidney Cancer. Methods We performed a systematic review and meta-analysis according to PRISMA guidelines. A literature search was performed using Pubmed, Scopus®, Web of Science™ and The Cochrane Library to identify eligible studies published until February 16, 2019. Studies were included if they reported on the differential outcomes of male and female patients with Metastatic Kidney Cancer receiving immunotherapy. Our outcomes of interest were overall survival or progression-free survival. Results Four randomized controlled trials comprising a total of 3664 patients (2715 males and 949 females) met our inclusion criteria. Both men and women with Metastatic Kidney Cancer had an OS- and PFS advantage with immunotherapy compared to standard-of-care, but no statistically significant difference between the sexes was observed (OS HR for men 0.69, 0.59-0.8, p = 0.40; HR for women 0.62, 0.48-0.81, p = 0.13; PFS HR for men 0.7, 0.59-0.82, p = 0.24; HR for women 0.68, 0.52-0.90, p = 0.105). Conclusion In advanced Kidney Cancer patients receiving checkpoint inhibitors, there seems to be no association of patient sex with treatment outcome.
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higher perioperative morbidity and in hospital mortality in patients with end stage renal disease undergoing nephrectomy for non Metastatic Kidney Cancer a population based analysis
BJUI, 2012Co-Authors: Jan Schmitges, Maxine Sun, Quocdien Trinh, Jens Hansen, Marco Bianchi, Claudio Jeldres, Paul Perrotte, Roland Dahlem, Shahrokh F ShariatAbstract:Study Type – Therapy (population cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Patients with renal failure more frequently harbour RCC due to predisposing factors such as cystic disease of the Kidney. The benefit of nephrectomy might be outweighed by adverse perioperative events, however, which may be more prevalent in patients with end-stage renal disease (ESRD). In a population-based study focusing on patients after non-elective colorectal surgery, patients with ESRD had an increased risk of mortality and complications. To date, small-scale studies have reported complication rates in patients with ESRD after nephrectomy for RCC with conflicting results. However, no formal contemporary analysis has been compiled within a nephrectomy cohort of adequate size. The present population-based case–control study showed that patients with ESRD are at substantially higher risk of in-hospital mortality and in-hospital complications. Specifically, we demonstrated higher cardiac-related complications, transfusion and haemorrhage/haematoma rates in patients with ESRD than in others. Moreover, patients with ESRD are more likely to have prolonged length of stay in hospital, and incur higher hospital charges. Based on the findings of the present study, use of biopsy and active surveillance for small, carefully selected renal masses might be considered in patients with ESRD at high risk of morbidity and mortality after surgery. OBJECTIVE • To examine the effect of end-stage renal disease (ESRD) on six short-term nephrectomy outcomes. PATIENTS AND METHODS • The Nationwide Inpatient Sample was used to assess the rates of blood transfusions, intra-operative and postoperative complications, length of hospital stay (LOS) within the highest quartile (>5 days), total hospital charges within the highest quartile (>$33 391) and in-hospital mortality. • Propensity-based matching was performed to adjust for potential baseline differences between patients with ESRD and others. • Multivariable logistic regression analyses further adjusted for confounding variables. RESULTS • Overall, 46 225 patients underwent open radical, open partial, laparoscopic radical or laparoscopic partial nephrectomy for non-Metastatic Kidney Cancer between 1998 and 2007. • Of those, 941 patients with ESRD were identified (2.0%). • For patients with ESRD and others, the following rates were recorded, respectively: blood transfusions, 17.4 vs 9.1% (P < 0.001); intra-operative complications, 3.5 vs 3.3% (P= 0.81); postoperative complications, 19.2 vs 15.6% (P= 0.007); length of stay within the highest quartile, 55.4 vs 30.1% (P < 0.001); total hospital charges within the highest quartile, 50.4 vs 26.3% (P < 0.001); in-hospital mortality, 2.4 vs 0.5% (P < 0.001). • In multivariable logistic regression analyses, patients with ESRD were more likely to receive a blood transfusion (odds ratio [OR]= 2.05, P < 0.001), to experience any postoperative complication (OR = 1.25, P= 0.019), to have a LOS within the highest quartile (OR = 3.06, P < 0.001), to have hospital charges within the highest quartile (OR = 3.10, P < 0.001), and to die during hospitalization (OR = 4.85, P < 0.001). CONCLUSIONS • Patients with ESRD are at substantially higher risk of adverse outcomes after nephrectomy. • Most importantly, the in-hospital mortality rate is fivefold higher.
Scott S Tykodi - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of initial surgery vs initial systemic therapy for Metastatic Kidney Cancer in the targeted therapy era analysis of a population based cohort
Urology, 2017Co-Authors: Liam C Macleod, Scott S Tykodi, Sarah K Holt, Jonathan D Harper, Anobel Y Odisho, John L GoreAbstract:Objective To use econometric methods to assess comparative overall survival of patients with Metastatic renal cell carcinoma (mRCC) managed with initial cytoreductive nephrectomy (CN) vs initial systemic therapy. Randomized data demonstrate improved survival for CN preceding cytokine-based therapy in mRCC. This benefit may be attenuated in the contemporary mRCC era given more effective systemic therapies. Methods Patients over age 65 with mRCC from the Surveillance, Epidemiology, and End Results registries linked with Medicare claims from 2006 to 2011 were categorized by initial treatment. We applied sequential survival analysis methods to assess the association between initial CN and overall survival (OS) including Cox proportional hazards models, propensity scoring, and instrumental variable analysis to account for measured and unmeasured selection bias. Results Of 537 patients analyzed, 190 had initial CN followed by targeted therapy and 347 had initial targeted therapy. Median OS in the initial CN group was 17.4 months (interquartile range 9.8-32.0), compared with 9.2 months (interquartile range 4.3-18.0) for initial targeted therapy. Cox proportional hazards analysis revealed initial CN was associated with improved OS (hazard ratio 0.50, 95% confidence interval [CI] 0.38-0.65). Propensity matching demonstrated a survival advantage for initial CN of 5.8 months (95% CI 1.9-9.7). Accounting for unmeasured confounding with instrumental variable analysis demonstrated a trend toward improved survival with initial CN (hazard ratio 0.29 [95% CI 0.08-1.00]). Conclusion Initial CN is associated with improved survival compared with initial systemic therapy in a contemporary population-based mRCC cohort.
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impact of cytoreductive nephretomy on timing of systemic therapy in Metastatic Kidney Cancer
Journal of Clinical Oncology, 2017Co-Authors: Liam C Macleod, Scott S Tykodi, Atreya Dash, George R. Schade, Daniel W Lin, Jonathan D Harper, John L GoreAbstract:503Background: High rates of disease control with systemic therapy (ST) in the post-cytokine era for Metastatic renal cell carcinoma (mRCC) cause apprehension that cytoreductive nephrectomy (CN) may delay effective therapy. We therefore evaluated factors associated with early mortality and time to ST after CN. We hypothesized markers of poor performance status and morbid CN would be associated with postoperative mortality and therapeutic delays. Methods: The National Cancer Database was screened for adult mRCC cases having CN followed by ST, years 2006-2013. We classified a delay in systemic therapy as interval > 45 days (median time to ST in the cohort). Multivariable logistic regression was performed, identifying factors associated with perioperative mortality and delays to initiation of ST. Results: Of 10,913 patients with initial CN (45% of mRCC), 30- and 90-day mortality were 3% and 11%, respectively. 6,362 later received ST (87% targeted therapy, 13% immunotherapy), median start was 45 days post-ope...
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Litmus test or destination systemic therapy? Trends in referral for surgery after initial systemic therapy in Metastatic Kidney Cancer.
Journal of Clinical Oncology, 2017Co-Authors: Liam C Macleod, Scott S Tykodi, Atreya Dash, George R. Schade, John L GoreAbstract:502Background: With nine new targeted and immunotherapeutic agents for Metastatic Kidney Cancer (mRCC) since 2005, there is no randomized data supporting sequencing cytoreductive nephrectomy (CN) and newer systemic therapies (ST). Increased disease control with ST engenders concern that CN may shorten life or delay therapy. Thus, in all the best prognostic candidates, initial ST as a “litmus” test may be advocated prior to CN. We evaluated use of CN after initial ST, hypothesizing receipt of deferred CN to be associated with increased survival time, markers of increased performance status, less rapid disease, and socioeconomic status. Methods: The National Cancer Database was screened for adult patients with biopsy-proven mRCC treated with initial systemic therapy between 2006-2013. Covariates included demographic, oncologic, hospital-level, and geographic variables. Unadjusted and multivariable logistic regression was performed, identifying factors associated with CN after initial ST. Results: Of 14,651 ...
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utilization and sequencing of targeted therapy and cytoreductive nephrectomy in non clear cell Metastatic Kidney Cancer
Journal of Clinical Oncology, 2016Co-Authors: Liam C Macleod, Scott S Tykodi, Sarah K Holt, John L GoreAbstract:615 Background: Many patients with Metastatic Kidney Cancer (mRCC) are ineligible for trials due to non-clear cell histology. Efficacy of targeted therapy agents in non-clear cell mRCC is still being investigated. We hypothesized that sequencing CN upfront is associated with improved overall survival. We analyze a population-based cohort of non-clear cell mRCC patients in the targeted therapy era. Methods: Patients from the SEER-Medicare files (2005-2011) with non-clear cell mRCC were categorized as having received upfront targeted therapy or upfront CN. Additional exclusions were age < 66 to avoid confounding by uncaptured non-Medicare coverage, and competing stage IV Cancer. Targeted therapy was identified through Medicare Part D files. Cox proportional hazards regression determined association between treatment groups, clinical and Cancer-related characteristics, and the main outcome, median overall survival (OS). Propensity matching controlled for measurable confounding in treatment selection. Results...
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initial compared to deferred cytoreductive nephrectomy for Metastatic Kidney Cancer and its association with improved survival in the targeted therapy era
Journal of Clinical Oncology, 2016Co-Authors: Liam C Macleod, Scott S Tykodi, Sarah K Holt, John L GoreAbstract:607 Background: Since 2005 seven new agents were approved for Metastatic renal cell carcinoma (mRCC), demarcating a transition from the cytokine to the targeted therapy era. Trials demonstrated a survival benefit for upfront cytoreductive nephrectomy (CN) pre-2005. However, upfront versus delayed CN relative to targeted therapy has not been reported in the trial arena. We hypothesized that upfront CN confers a survival benefit in the targeted therapy era. We analyze survival in a population based cohort exposed to targeted therapies with upfront CN compared to deferred CN. Methods: Patients from SEER registries (2005-2011) with mRCC were categorized into: 1.) CN followed by targeted therapy or 2). initial targeted therapy. Additional exclusions were age < 66, due to chance of uncaptured non-Medicare care, competing non-renal stage IV Cancer and non-clear cell histology. Targeted therapy was identified from Medicare Part D files (bevacizumab, sunitinib, sorafenib, axitinib, pazopanib, temsirolmus, everolim...