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Iacovelli R.,University of Rome La Sapienza | Carteni G.,A Cardarelli Hospital | Sternberg C.N.,San Camillo Forlanini Hospital | Milella M.,Regina Elena Cancer Institute | And 20 more authors.
European Journal of Cancer | Year: 2013

Aim: A number of targeted therapies (TTs) are effective in metastatic renal cell carcinoma (mRCC) but clinical outcomes with the sequential use of three TTs have been poorly investigated, this study evaluates their outcome. Methods: Patients with clear cells mRCC treated with three TTs were retrospectively studied. Therapies were classified as vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) or mammalian target of rapamycin inhibitors (mTORi). Progression free survival (PFS), overall survival (OS) and total PFS (tPFS)-defined as the time from start of first-line to progression on third-line treatment-were estimated using the Kaplan-Meier method and curves were compared with log-rank test. Results: A total of 2065 patients with mRCC were consecutively treated with first-line TT in 23 centres in Italy. Overall 281/2065 patients (13%) were treated with three TTs. Median OS and tPFS were 44.7 and 34.1 months, respectively and were longer in patients receiving the sequence vascular endothelial growth factor inhibitors (VEGFi)-VEGFi-mTORi compared with those receiving VEGFi-mTORi-VEGFi with a statistical difference in OS (50.7 versus 37.8 months, p = 0.004; 36.5 versus 29.3 months, p = 0.059, respectively). Conclusions: Few patients received three lines of TTs. The sequence VEGFi-VEGFi-mTORi was associated with improved survival with respect to VEGFi-mTORi-VEGFi and primary resistance to first-line was a negative predictive and prognostic factor.© 2013 Elsevier Ltd. All rights reserved.


Iacovelli R.,Fondazione IRCCS Instituto Nazionale Dei Tumori | Farcomeni A.,University of Rome La Sapienza | Sternberg C.N.,San Camillo Forlanini Hospital | Carteni G.,A Cardarelli Hospital | And 22 more authors.
Journal of Urology | Year: 2015

Purpose Several prognostic models have been proposed for metastatic renal cell carcinoma but none has been validated in patients who receive third line targeted agents. We evaluated prognostic factors in patients with metastatic renal cell carcinoma who received a third line targeted agent. Materials and Methods We retrospectively reviewed data on 2,065 patients with clear cell metastatic renal cell carcinoma who were treated with targeted therapy at a total of 23 centers in Italy. Included in final analysis were 281 patients treated with 3 targeted agents. Overall survival was the main outcome. Cox proportional hazards regression followed by bootstrap validation was used to identify independent prognostic factors. Results Three clinical characteristics (ECOG performance status greater than 1, metastasis at diagnosis and liver metastasis) and 2 biochemical factors (hemoglobin less than the lower limit of normal and neutrophil count greater than the upper limit of normal, respectively) were prognostic. Patients were classified into 3 risk categories, including low - zero or 1, intermediate - 2 and high risk - more than 2 risk factors. Median overall survival was 19.7, 10.1 and 5.5 months, and 1-year overall survival was 71%, 43% and 15%, respectively. The major limitation was the retrospective nature of this study and absent external validation. Conclusions This nomogram included clinical and biochemical prognostic factors. In clinical trials it may be useful to select patients and define the prognosis. © 2015 American Urological Association Education and Research, Inc.


Granata A.,St Giovanni Of Dio Hospital | Zanoli L.,University of Catania | Clementi S.,Oncology Unit | Fatuzzo P.,Oncology Unit | And 2 more authors.
British Journal of Radiology | Year: 2014

In renal diagnosis, the B-mode ultrasound is used to provide an accurate study of the renal morphology, whereas the colour and power Doppler are of strategic importance in providing qualitative and quantitative information about the renal vasculature, which can also be obtained through the assessment of the resistive index (RI). To date, this is one of the most sensitive parameters in the study of kidney diseases and allows us to quantify the changes in renal plasma flow. If a proper Doppler ultrasound examination is carried out and a critical analysis of the values obtained is performed, the RI measurement at the interlobar artery level has been suggested in the differential diagnosis between nephropathies. The aim of this review is to highlight the pathological conditions in which the study of intrarenal RI provides useful information about the pathophysiology of renal diseases in both the native and the transplanted kidneys. © 2014 The Authors.


PubMed | Regina Elena Cancer Institute, Santa Maria Annunziata Hospital, Sen A Perrino Hospital, Instituto Tumori Giovanni Paolo II Bari and 19 more.
Type: Comparative Study | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2014

A number of targeted therapies (TTs) are effective in metastatic renal cell carcinoma (mRCC) but clinical outcomes with the sequential use of three TTs have been poorly investigated, this study evaluates their outcome.Patients with clear cells mRCC treated with three TTs were retrospectively studied. Therapies were classified as vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) or mammalian target of rapamycin inhibitors (mTORi). Progression free survival (PFS), overall survival (OS) and total PFS (tPFS)--defined as the time from start of first-line to progression on third-line treatment--were estimated using the Kaplan-Meier method and curves were compared with log-rank test.A total of 2065 patients with mRCC were consecutively treated with first-line TT in 23 centres in Italy. Overall 281/2065 patients (13%) were treated with three TTs. Median OS and tPFS were 44.7 and 34.1 months, respectively and were longer in patients receiving the sequence vascular endothelial growth factor inhibitors (VEGFi)-VEGFi-mTORi compared with those receiving VEGFi-mTORi-VEGFi with a statistical difference in OS (50.7 versus 37.8 months, p = 0.004; 36.5 versus 29.3 months, p = 0.059, respectively).Few patients received three lines of TTs. The sequence VEGFi-VEGFi-mTORi was associated with improved survival with respect to VEGFi-mTORi-VEGFi and primary resistance to first-line was a negative predictive and prognostic factor.

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