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Brian I Rini - One of the best experts on this subject based on the ideXlab platform.
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active surveillance in metastatic Renal Cell Carcinoma a prospective phase 2 trial
Lancet Oncology, 2016Co-Authors: Brian I Rini, Laura S Wood, Tanya B Dorff, Paul Elson, Cristina Suarez Rodriguez, Dale R Shepard, Jordi Humbert, Linda Pyle, Yuning Wong, James H FinkeAbstract:Summary Background A subset of patients with metastatic Renal-Cell Carcinoma show indolent growth of metastases. Because of the toxicity and non-curative nature of systemic therapy, some of these patients could benefit from initial active surveillance. We aimed to characterise the time to initiation of systemic therapy in patients with metastatic Renal-Cell Carcinoma under active surveillance. Methods In this prospective phase 2 trial, we enrolled patients with treatment-naive, asymptomatic, metastatic Renal-Cell Carcinoma from five hospitals in the USA, Spain, and the UK. Patients were radiographically assessed at baseline, every 3 months for year 1, every 4 months for year 2, then every 6 months thereafter. Patients continued on observation until initiation of systemic therapy for metastatic Renal-Cell Carcinoma; a decision that was made at the discretion of the treating physician and patient. The primary endpoint of the study was time to initiation of systemic therapy in the per-protocol population. The follow-up of patients is ongoing. Findings Between Aug 21, 2008, and June 7, 2013, we enrolled 52 patients. Median follow-up of patients in the study was 38·1 months (IQR 29·4–48·9). In the 48 patients included in analysis, median time on surveillance from registration on study until initiation of systemic therapy was 14·9 months (95% CI 10·6–25·0). Multivariate analysis showed that higher numbers of International Metastatic Database Consortium (IMDC) adverse risk factors (p=0·0403) and higher numbers of metastatic disease sites (p=0·0414) were associated with a shorter surveillance period. 22 (46%) patients died during the study period, all from metastatic Renal-Cell Carcinoma. Interpretation A subset of patients with metastatic Renal-Cell Carcinoma can safely undergo surveillance before starting systemic therapy. Additional investigation is required to further define the benefits and risks of this approach. Funding None.
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cytoreductive nephrectomy in patients with synchronous metastases from Renal Cell Carcinoma results from the international metastatic Renal Cell Carcinoma database consortium
European Urology, 2014Co-Authors: Daniel Y C Heng, Brian I Rini, B Beuselinck, Sumanta K. Pal, Connor J Wells, Jae-lyun Lee, Georg A Bjarnason, Jennifer J Knox, Christian K Kollmannsberger, Takeshi YuasaAbstract:Abstract Background The benefit of cytoreductive nephrectomy (CN) for overall survival (OS) is unclear in patients with synchronous metastatic Renal Cell Carcinoma (mRCC) in the era of targeted therapy. Objective To determine OS benefit of CN compared with no CN in mRCC patients treated with targeted therapies. Design, setting, and participants Retrospective data from patients with synchronous mRCC ( n =1658) from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were used to compare 982 mRCC patients who had a CN with 676 mRCC patients who did not. Outcome measurements and statistical analysis OS was compared and hazard ratios (HRs) adjusted for IMDC poor prognostic criteria. Results and limitations Patients who had CN had better IMDC prognostic profiles versus those without (favorable, intermediate, or poor in 9%, 63%, and 28% vs 1%, 45%, and 54%, respectively). The median OS of patients with CN versus without CN was 20.6 versus 9.5 mo ( p p Conclusions CN is beneficial in synchronous mRCC patients treated with targeted therapy, even after adjusting for prognostic factors. Patients with estimated survival times Patient summary We looked at the survival outcomes of metastatic Renal Cell Carcinoma patients who did or did not have the primary tumor removed. We found that most patients benefited from tumor removal, except for those with four or more IMDC risk factors.
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Renal Cell Carcinoma
2009Co-Authors: Brian I Rini, Steven C Campbell, Bernard EscudierAbstract:Considerable progress has been made in the treatment of patients with Renal Cell Carcinoma, with innovative surgical and systemic strategies revolutionising the management of this disease. In localised disease, partial nephrectomy for small tumours and radical nephrectomy for large tumours continue to be the gold-standard treatments, with emphasis on approaches that have reduced invasiveness and preserve Renal function. Additionally, cytoreductive nephrectomy is often indicated before the start of systemic treatment in patients with metastatic disease as part of integrated management strategy. The effectiveness of immunotherapy, although previously widely used for treatment of metastatic Renal Cell Carcinoma, is still controversial, and is mainly reserved for patients with good prognostic factors. Development of treatments that have specific targets in relevant biological pathways has been the main advance in treatment. Targeted drugs, including inhibitors of the vascular endothelial growth factor and mammalian target of rapamycin pathways, have shown robust effectiveness and offer new therapeutic options for the patients with metastatic disease.
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recent advances in molecularly targeted therapy in advanced Renal Cell Carcinoma
Therapy, 2009Co-Authors: Jenny J Kim, Brian I RiniAbstract:In the last few years, enhanced understanding of the biology of clear Cell Renal Cell Carcinoma has led to the development of molecular signaling inhibitors, which, with their superior anti-tumor activity demonstrated in randomized clinical trials, have led to a paradigm shift in the treatment of advanced Renal Cell Carcinoma from cytokine-based therapy to signaling-inhibitor therapy. Relevant therapeutic signaling pathways that have emerged are VEGF receptor and mammalian target of rapamycin pathways, and signaling inhibitors sunitinib, sorafenib, temsirolimus and, most recently, everolimus are approved by the FDA for treatment of advanced Renal Cell Carcinoma in the USA. Newer agents with promising anti-tumor activity are in continued development, as are efforts to uncover additional therapeutic targets. Currently, the optimal use of available agents, such as sequence and combination strategies, as well as their role in the adjuvant and neoadjuvant setting, remain unclear and investigative efforts are underway.
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hypothyroidism in patients with metastatic Renal Cell Carcinoma treated with sunitinib
Journal of the National Cancer Institute, 2007Co-Authors: Brian I Rini, Ila Tamaskar, Jorge A Garcia, Laura S Wood, Robert Dreicer, Phillip Shaheen, Renee Salas, Sethu Reddy, Ronald M BukowskiAbstract:Sunitinib is an inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors, and it has antitumor activity in metastatic Renal Cell Carcinoma and gastrointestinal stromal tumors. To further investigate the fatigue associated with sunitinib therapy, thyroid function tests were performed on patients with metastatic Renal Cell Carcinoma who were receiving sunitinib. Seventy-three patients with metastatic Renal Cell Carcinoma were treated with sunitinib at the Cleveland Clinic Taussig Cancer Center, and 66 of them had thyroid function test results available. Fifty-six (85%) of the 66 patients had one or more abnormality in their thyroid function test results, consistent with hypothyroidism, and 47 (84%) of the 56 patients with abnormal thyroid function tests had signs and/or symptoms possibly related to hypothyroidism. Thyroid hormone replacement was undertaken in 17 patients, and symptoms improved in nine of them. Thyroid function test abnormalities appear to be common in patients with metastatic Renal Cell Carcinoma treated with sunitinib, and routine monitoring is warranted.
Michael L Blute - One of the best experts on this subject based on the ideXlab platform.
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differences in organ system of distant metastasis by Renal Cell Carcinoma subtype
The Journal of Urology, 2008Co-Authors: Nathan E Hoffmann, Michael D Gillett, John C Cheville, Christine M Lohse, Bradley C Leibovich, Michael L BluteAbstract:Purpose: The majority of the published data regarding the rates of Renal Cell Carcinoma metastasis to specific locations has examined Renal Cell Carcinoma as a whole. We evaluated site of distant metastasis by Renal Cell Carcinoma histological subtype.Materials and Methods: We studied 910 patients treated with radical nephrectomy for clear Cell, papillary or chromophobe Renal Cell Carcinoma at the Mayo Clinic between 1970 and 2000 who had distant metastasis at nephrectomy or who had metastasis during followup. The sites of metastases were compared by histological subtype using the chi-square and Fisher exact tests.Results: There were 853 (94%) patients with clear Cell, 39 (4%) with papillary and 18 (2%) with chromophobe Renal Cell Carcinoma. Median followup for the 65 patients who were still alive at last followup was 11.6 years. Patients with clear Cell Renal Cell Carcinoma were more likely to have metastasis to the lungs (53.6%) compared to those with papillary (33.3%) and chromophobe (33.3%) Renal Cell...
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the role of nephron sparing surgery for metastatic pm1 Renal Cell Carcinoma
The Journal of Urology, 2006Co-Authors: Amy E Krambeck, Horst Zincke, Christine M Lohse, Bradley C Leibovich, Eugene D Kwon, Michael L BluteAbstract:Purpose: Studies have demonstrated increased time to progression when cytoreductive nephrectomy is performed for metastatic Renal Cell Carcinoma. We evaluated the role of nephron sparing surgery in these patients.Materials and Methods: We selected all patients with pM1 Renal Cell Carcinoma treated with nephron sparing surgery or radical nephrectomy, and all patients with pM0 Renal Cell Carcinoma undergoing nephron sparing surgery for solitary kidney from 1970 to 2002 from the Mayo Clinic Nephrectomy Registry.Results: We identified 16 patients who underwent nephron sparing surgery for pM1 Renal Cell Carcinoma. Solitary kidney was present in 12, 3 had bilateral synchronous disease and 1 had elective nephron sparing surgery. Cancer specific survival rates at 1, 3 and 5 years were 81%, 49% and 49%, respectively. We identified 404 patients who underwent radical nephrectomy for pM1 Renal Cell Carcinoma. Cancer specific survival rates at 1, 3 and 5 years were 51%, 21% and 13%, respectively. The pM1 nephron spari...
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the effect of bilaterality pathological features and surgical outcome in nonhereditary Renal Cell Carcinoma
The Journal of Urology, 2003Co-Authors: Michael L Blute, John C Cheville, Christine M Lohse, Nancy B Itano, Amy L Weaver, Horst ZinckeAbstract:ABSTRACTPurpose: We evaluated the differences in cancer specific, distant metastasis-free and local recurrence-free survival in patients with sporadic subtype concordant bilateral synchronous Renal Cell Carcinoma and those with unilateral Renal Cell Carcinoma, controlling for the covariates of subtype, stage, tumor size, grade and necrosis. We also analyzed early surgical complications and long-term Renal function in patients who underwent staged surgery and those who underwent a single operation for bilateral synchronous Renal Cell CarcinomaMaterials and Methods: We retrospectively evaluated 44 patients with sporadic subtype concordant bilateral synchronous Renal Cell Carcinoma treated at our institution between 1970 and 1998. There were 32 patients with bilateral synchronous clear Cell Renal Cell Carcinoma and 12 with bilateral synchronous papillary Renal Cell Carcinoma. These patients were compared with 1,714 with sporadic unilateral clear Cell Renal Cell Carcinoma and 322 with sporadic unilateral papi...
Lori Wood - One of the best experts on this subject based on the ideXlab platform.
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outcome of patients with metastatic sarcomatoid Renal Cell Carcinoma results from the international metastatic Renal Cell Carcinoma database consortium
Clinical Genitourinary Cancer, 2015Co-Authors: Christos Kyriakopoulos, Jae-lyun Lee, Georg A Bjarnason, Jennifer J Knox, Namita Chittoria, Toni K Choueiri, Nils Kroeger, Sandy Srinivas, Scott Ernst, Lori WoodAbstract:Outcome and prognosis of metastatic sarcomatoid Renal Cell Carcinoma (sRCC) in the targeted therapy era are not well described. In this retrospective series of 230 patients with metastatic sRCC, we examined the role of antievascular endothelial growth factor (VEGF) agents as a treatment option. The validity of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model in patients with metastatic sRCC was confirmed. Sarcomatoid histology was found to be an independent factor for adverse prognosis. Background: Sarcomatoid Renal Cell Carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. Patients and Methods: Clinical, prognostic, and treatment parameters in metastatic Renal Cell Carcinoma patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed. Results: Two thousand two hundred eighty-six patients were identified (sRCC: n ¼ 230 and nonsRCC: n ¼ 2056). sRCC patients had significantly worse IMDC prognostic criteria compared with non-sRCC (11% vs. 19% favorable risk; 49% vs. 57% intermediate risk, and 40% vs. 24% poor risk; P < .0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) was shorter in the sRCC group (18.8 vs. 42.9 months; P < .0001). There was no significant difference in the incidence of central nervous system metastases (6%-8%) or underlying clear Cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as firstline therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P < .0001, for both). sRCC patients had significantly less use of second- (P ¼ .018)
Jae-lyun Lee - One of the best experts on this subject based on the ideXlab platform.
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outcome of patients with metastatic sarcomatoid Renal Cell Carcinoma results from the international metastatic Renal Cell Carcinoma database consortium
Clinical Genitourinary Cancer, 2015Co-Authors: Christos Kyriakopoulos, Jae-lyun Lee, Georg A Bjarnason, Jennifer J Knox, Namita Chittoria, Toni K Choueiri, Nils Kroeger, Sandy Srinivas, Scott Ernst, Lori WoodAbstract:Outcome and prognosis of metastatic sarcomatoid Renal Cell Carcinoma (sRCC) in the targeted therapy era are not well described. In this retrospective series of 230 patients with metastatic sRCC, we examined the role of antievascular endothelial growth factor (VEGF) agents as a treatment option. The validity of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model in patients with metastatic sRCC was confirmed. Sarcomatoid histology was found to be an independent factor for adverse prognosis. Background: Sarcomatoid Renal Cell Carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. Patients and Methods: Clinical, prognostic, and treatment parameters in metastatic Renal Cell Carcinoma patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed. Results: Two thousand two hundred eighty-six patients were identified (sRCC: n ¼ 230 and nonsRCC: n ¼ 2056). sRCC patients had significantly worse IMDC prognostic criteria compared with non-sRCC (11% vs. 19% favorable risk; 49% vs. 57% intermediate risk, and 40% vs. 24% poor risk; P < .0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) was shorter in the sRCC group (18.8 vs. 42.9 months; P < .0001). There was no significant difference in the incidence of central nervous system metastases (6%-8%) or underlying clear Cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as firstline therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P < .0001, for both). sRCC patients had significantly less use of second- (P ¼ .018)
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cytoreductive nephrectomy in patients with synchronous metastases from Renal Cell Carcinoma results from the international metastatic Renal Cell Carcinoma database consortium
European Urology, 2014Co-Authors: Daniel Y C Heng, Brian I Rini, B Beuselinck, Sumanta K. Pal, Connor J Wells, Jae-lyun Lee, Georg A Bjarnason, Jennifer J Knox, Christian K Kollmannsberger, Takeshi YuasaAbstract:Abstract Background The benefit of cytoreductive nephrectomy (CN) for overall survival (OS) is unclear in patients with synchronous metastatic Renal Cell Carcinoma (mRCC) in the era of targeted therapy. Objective To determine OS benefit of CN compared with no CN in mRCC patients treated with targeted therapies. Design, setting, and participants Retrospective data from patients with synchronous mRCC ( n =1658) from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were used to compare 982 mRCC patients who had a CN with 676 mRCC patients who did not. Outcome measurements and statistical analysis OS was compared and hazard ratios (HRs) adjusted for IMDC poor prognostic criteria. Results and limitations Patients who had CN had better IMDC prognostic profiles versus those without (favorable, intermediate, or poor in 9%, 63%, and 28% vs 1%, 45%, and 54%, respectively). The median OS of patients with CN versus without CN was 20.6 versus 9.5 mo ( p p Conclusions CN is beneficial in synchronous mRCC patients treated with targeted therapy, even after adjusting for prognostic factors. Patients with estimated survival times Patient summary We looked at the survival outcomes of metastatic Renal Cell Carcinoma patients who did or did not have the primary tumor removed. We found that most patients benefited from tumor removal, except for those with four or more IMDC risk factors.
Jennifer J Knox - One of the best experts on this subject based on the ideXlab platform.
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outcome of patients with metastatic sarcomatoid Renal Cell Carcinoma results from the international metastatic Renal Cell Carcinoma database consortium
Clinical Genitourinary Cancer, 2015Co-Authors: Christos Kyriakopoulos, Jae-lyun Lee, Georg A Bjarnason, Jennifer J Knox, Namita Chittoria, Toni K Choueiri, Nils Kroeger, Sandy Srinivas, Scott Ernst, Lori WoodAbstract:Outcome and prognosis of metastatic sarcomatoid Renal Cell Carcinoma (sRCC) in the targeted therapy era are not well described. In this retrospective series of 230 patients with metastatic sRCC, we examined the role of antievascular endothelial growth factor (VEGF) agents as a treatment option. The validity of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model in patients with metastatic sRCC was confirmed. Sarcomatoid histology was found to be an independent factor for adverse prognosis. Background: Sarcomatoid Renal Cell Carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. Patients and Methods: Clinical, prognostic, and treatment parameters in metastatic Renal Cell Carcinoma patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed. Results: Two thousand two hundred eighty-six patients were identified (sRCC: n ¼ 230 and nonsRCC: n ¼ 2056). sRCC patients had significantly worse IMDC prognostic criteria compared with non-sRCC (11% vs. 19% favorable risk; 49% vs. 57% intermediate risk, and 40% vs. 24% poor risk; P < .0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) was shorter in the sRCC group (18.8 vs. 42.9 months; P < .0001). There was no significant difference in the incidence of central nervous system metastases (6%-8%) or underlying clear Cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as firstline therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P < .0001, for both). sRCC patients had significantly less use of second- (P ¼ .018)
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cytoreductive nephrectomy in patients with synchronous metastases from Renal Cell Carcinoma results from the international metastatic Renal Cell Carcinoma database consortium
European Urology, 2014Co-Authors: Daniel Y C Heng, Brian I Rini, B Beuselinck, Sumanta K. Pal, Connor J Wells, Jae-lyun Lee, Georg A Bjarnason, Jennifer J Knox, Christian K Kollmannsberger, Takeshi YuasaAbstract:Abstract Background The benefit of cytoreductive nephrectomy (CN) for overall survival (OS) is unclear in patients with synchronous metastatic Renal Cell Carcinoma (mRCC) in the era of targeted therapy. Objective To determine OS benefit of CN compared with no CN in mRCC patients treated with targeted therapies. Design, setting, and participants Retrospective data from patients with synchronous mRCC ( n =1658) from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were used to compare 982 mRCC patients who had a CN with 676 mRCC patients who did not. Outcome measurements and statistical analysis OS was compared and hazard ratios (HRs) adjusted for IMDC poor prognostic criteria. Results and limitations Patients who had CN had better IMDC prognostic profiles versus those without (favorable, intermediate, or poor in 9%, 63%, and 28% vs 1%, 45%, and 54%, respectively). The median OS of patients with CN versus without CN was 20.6 versus 9.5 mo ( p p Conclusions CN is beneficial in synchronous mRCC patients treated with targeted therapy, even after adjusting for prognostic factors. Patients with estimated survival times Patient summary We looked at the survival outcomes of metastatic Renal Cell Carcinoma patients who did or did not have the primary tumor removed. We found that most patients benefited from tumor removal, except for those with four or more IMDC risk factors.
