المؤلفون: McDermott, David F., Lee, Jae-Lyun, Bjarnason, Georg A., Larkin, James M. G., Gafanov, Rustem Airatovich, Kochenderfer, Mark D., Jensen, Niels Viggo, Donskov, Frede, Malik, Jahangeer, Poprach, Alexandr, Tykodi, Scott S., Gordoa, Teresa Alonso, Cho, Daniel C., Geertsen, Poul F., Duran, Miguel Angel Climent, Simone, Christopher Di, Du, Xiaoqi, Perini, Rodolfo F., Rodriguez-Lopez, Karla, Atkins, Michael B.

المصدر: McDermott , D F , Lee , J-L , Bjarnason , G A , Larkin , J M G , Gafanov , R A , Kochenderfer , M D , Jensen , N V , Donskov , F , Malik , J , Poprach , A , Tykodi , S S , Gordoa , T A , Cho , D C , Geertsen , P F , Duran , M A C , Simone , C D , Du , X , Perini , R F , Rodriguez-Lopez , K & Atkins , M B 2020 , ' First-line ....

العلاقة: https://portal.findresearcher.sdu.dk/da/publications/c5030676-a743-4298-97b4-654c3752ce72Test

الإتاحة: https://doi.org/10.1200/JCO.2020.38.15_suppl.5069Test
https://portal.findresearcher.sdu.dk/da/publications/c5030676-a743-4298-97b4-654c3752ce72Test

المؤلفون: McDermott, David F., Lee, Jae Lyun, Bjarnason, Georg A., Larkin, James M.G., Gafanov, Rustem A., Kochenderfer, Mark D., Jensen, Niels Viggo, Donskov, Frede, Malik, Jahangeer, Poprach, Alexandr, Tykodi, Scott S., Alonso-Gordoa, Teresa, Cho, Daniel C., Geertsen, Poul F., Climent Duran, Miguel Angel, DiSimone, Christopher, Silverman, Rachel Kloss, Perini, Rodolfo F., Schloss, Charles, Atkins, Michael B.

المصدر: McDermott , D F , Lee , J L , Bjarnason , G A , Larkin , J M G , Gafanov , R A , Kochenderfer , M D , Jensen , N V , Donskov , F , Malik , J , Poprach , A , Tykodi , S S , Alonso-Gordoa , T , Cho , D C , Geertsen , P F , Climent Duran , M A , DiSimone , C , Silverman , R K , Perini , R F , Schloss , C & Atkins , M B 2021 , ' Open-Label, ....

مصطلحات موضوعية: Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized/therapeutic use, Antineoplastic Agents, Immunological/therapeutic use, Carcinoma, Renal Cell/drug therapy, Female, Follow-Up Studies, Humans, Kidney Neoplasms/drug therapy, Male, Middle Aged, Non-Randomized Controlled Trials as Topic, Prognosis, Survival Rate

الوصف: PURPOSE: Pembrolizumab, a programmed death 1 inhibitor, demonstrated promising single-agent activity in untreated patients with various cancer types. The phase II KEYNOTE-427 study evaluated efficacy and safety of single-agent pembrolizumab in treatment-naive patients with advanced clear cell renal cell carcinoma (ccRCC; cohort A) and advanced non-ccRCC (cohort B). Results of cohort A are reported. METHODS: In this open-label, single-arm phase II study, patients with advanced ccRCC received pembrolizumab 200 mg every 3 weeks for ≤ 24 months. The primary end point was objective response rate by RECIST, version 1.1. RESULTS: In the total population (N = 110), median time from enrollment to data cutoff was 35.9 (range, 29.5-40.3) months. Objective response rate was 36.4% with four (3.6%) complete responses and 36 (32.7%) partial responses; disease control rate was 58.2% (95% CI, 48.4 to 67.5). Most patients (68.2%) had a decrease in target lesions, including 30.9% with a reduction ≥ 60%. Median duration of response was 18.9 (range, 2.3-37.6+) months; 64.1% of responders had a response ≥ 12 months (Kaplan-Meier). Median progression-free survival was 7.1 months (95% CI, 5.6 to 11.0). Median overall survival was not reached; 12-month and 24-month overall survival rates were 88.2% and 70.8%, respectively. Durable responses were observed across all International Metastatic RCC Database Consortium categories. Grade 3-5 treatment-related adverse events were reported in 30.0% of patients, of which colitis and diarrhea were most frequent. CONCLUSION: Single-agent pembrolizumab showed promising antitumor activity as a first-line treatment in patients with advanced ccRCC, with durable responses across International Metastatic RCC Database Consortium categories. Safety and tolerability profile of pembrolizumab monotherapy was comparable to what has been previously described in other tumor types.

وصف الملف: application/pdf

العلاقة: https://pure.au.dk/portal/en/publications/bae5aee9-7f1b-4552-855b-cfdb62d318f9Test

الإتاحة: https://doi.org/10.1200/JCO.20.02363Test
https://pure.au.dk/portal/en/publications/bae5aee9-7f1b-4552-855b-cfdb62d318f9Test
https://pure.au.dk/ws/files/274416924/jco.20.02363.pdfTest
http://www.scopus.com/inward/record.url?scp=85103228704&partnerID=8YFLogxKTest

المؤلفون: Motzer, Robert J., Escudier, Bernard, McDermott, David F., Arén Frontera, Osvaldo, Melichar, Bohuslav, Powles, Thomas, Donskov, Frede, Plimack, Elizabeth R., Barthélémy, Philippe, Hammers, Hans J., George, Saby, Grünwald, Viktor, Porta, Camillo, Neiman, Victoria, Ravaud, Alain, Choueiri, Toni K., Rini, Brian I., Salman, Pamela, Kollmannsberger, Christian K., Tykodi, Scott S., Grimm, Marc Oliver, Gurney, Howard, Leibowitz-Amit, Raya, Geertsen, Poul F., Amin, Asim, Tomita, Yoshihiko, McHenry, M. Brent, Saggi, Shruti Shally, Tannir, Nizar M.

المصدر: Motzer , R J , Escudier , B , McDermott , D F , Arén Frontera , O , Melichar , B , Powles , T , Donskov , F , Plimack , E R , Barthélémy , P , Hammers , H J , George , S , Grünwald , V , Porta , C , Neiman , V , Ravaud , A , Choueiri , T K , Rini , B I , Salman , P , Kollmannsberger , C K , Tykodi , S S , Grimm , M O , Gurney , H , Leibowitz-Amit ....

مصطلحات موضوعية: clinical trials, phase III as topic, CTLA-4 antigen, immunotherapy, kidney neoplasms, programmed cell death 1 receptor

الوصف: Background The extent to which response and survival benefits with immunotherapy-based regimens persist informs optimal first-line treatment options. We provide long-term follow-up in patients with advanced renal cell carcinoma (aRCC) receiving first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the phase 3 CheckMate 214 trial. Survival, response, and safety outcomes with NIVO+IPI versus SUN were assessed after a minimum of 42 months of follow-up. Methods Patients with aRCC were enrolled from October 16, 2014, through February 23, 2016. Patients stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and region were randomized to nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks for four doses, followed by nivolumab (3 mg/kg) every 2 weeks; or SUN (50 mg) once per day for 4 weeks (6-week cycle). Primary endpoints: overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) per independent radiology review committee in IMDC intermediate-risk/poor-risk patients. Secondary endpoints: OS, PFS, and ORR in the intention-to-treat (ITT) population and safety. Favorable-risk patient outcomes were exploratory. Results Among ITT patients, 550 were randomized to NIVO+IPI (425 intermediate/poor risk; 125 favorable risk) and 546 to SUN (422 intermediate/poor risk; 124 favorable risk). Among intermediate-risk/poor-risk patients, OS (HR, 0.66; 95% CI, 0.55-0.80) and PFS (HR, 0.75; 95% CI, 0.62-0.90) benefits were observed, and ORR was higher (42.1% vs 26.3%) with NIVO+IPI versus SUN. In ITT patients, both OS benefits (HR, 0.72; 95% CI, 0.61-0.86) and higher ORR (39.1% vs 32.6%) were observed with NIVO+IPI versus SUN. In favorable-risk patients, HR for death was 1.19 (95% CI, 0.77-1.85) and ORR was 28.8% with NIVO+IPI versus 54.0% with SUN. Duration of response was longer (HR, 0.46-0.54), and more patients achieved complete response (10.1%-12.8% vs 1.4%-5.6%) with NIVO+IPI versus SUN regardless of risk group. The incidence of ...

وصف الملف: application/pdf

الإتاحة: https://doi.org/10.1136/jitc-2020-000891Test
https://researchers.mq.edu.au/en/publications/16efdcde-4b5e-4c18-804a-e2d1896c4c6aTest
https://research-management.mq.edu.au/ws/files/127646137/Publisher_version_open_access_.pdfTest
http://www.scopus.com/inward/record.url?scp=85088040485&partnerID=8YFLogxKTest

المؤلفون: Powles, Thomas, Motzer, Robert J., Escudier, Bernard, Pal, Sumanta, Kollmannsberger, Christian, Pikiel, Joanna, Gurney, Howard, Rha, Sun Young, Park, Se Hoon, Geertsen, Poul F., Gross-Goupil, Marine, Grande, Enrique, Suárez, Cristina, Markby, David W., Arroyo, Alan, Dean, Mark, Choueiri, Toni K., George, Daniel, Universitat Autònoma de Barcelona

الوصف: Altres ajuts: We thank the patients, their families, the investigators and site staff, and the study teams who participated in the METEOR trial. This study was funded by Exelixis, Inc. Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). Editorial support was provided by Fishawack Communications (Conshohocken, PA, USA) and funded by Exelixis. ; In the phase 3 METEOR trial, cabozantinib improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) versus everolimus in patients with advanced renal cell carcinoma (RCC), after prior antiangiogenic therapy. Outcomes were evaluated for subgroups defined by prior therapy with sunitinib or pazopanib as the only prior VEGFR inhibitor, or prior anti-PD-1/PD-L1 therapy. For the prior sunitinib subgroup (N = 267), median PFS for cabozantinib versus everolimus was 9.1 versus 3.7 months (HR 0.43, 95% CI 0.32-0.59), ORR was 16% versus 3%, and median OS was 21.4 versus 16.5 months (HR 0.66, 95% CI 0.47-0.93). For the prior pazopanib subgroup (N = 171), median PFS for cabozantinib versus everolimus was 7.4 versus 5.1 months (HR 0.67, 95% CI 0.45-0.99), ORR was 19% versus 4%, and median OS was 22.0 versus 17.5 months (HR 0.66, 95% CI 0.42-1.04). For prior anti-PD-1/PD-L1 therapy (N = 32), median PFS was not reached for cabozantinib versus 4.1 months for everolimus (HR 0.22, 95% CI 0.07-0.65), ORR was 22% versus 0%, and median OS was not reached versus 16.3 months (HR 0.56, 95% CI 0.21-1.52). Cabozantinib was associated with improved clinical outcomes versus everolimus in patients with advanced RCC, irrespective of prior therapy, including checkpoint inhibitor therapy.

وصف الملف: application/pdf

العلاقة: British Journal of Cancer; Vol. 119 (september 2018), p. 663-669; https://ddd.uab.cat/record/228008Test; urn:10.1038/s41416-018-0164-0; urn:oai:ddd.uab.cat:228008; urn:pmid:30197417; urn:pmcid:PMC6173766; urn:pmc-uid:6173766; urn:articleid:15321827v119p663; urn:scopus_id:85053437700; urn:oai:pubmedcentral.nih.gov:6173766

الإتاحة: https://ddd.uab.cat/record/228008Test

المؤلفون: Soerensen, Anne V, Geertsen, Poul F, Christensen, Ib J, Hermann, Gregers G, Jensen, Niels V, Fode, Kirsten, Petersen, Astrid, Sandin, Rickard, Donskov, Frede

المصدر: Soerensen , A V , Geertsen , P F , Christensen , I J , Hermann , G G , Jensen , N V , Fode , K , Petersen , A , Sandin , R & Donskov , F 2016 , ' A five-factor biomarker profile obtained week 4-12 of treatment for improved prognostication in metastatic renal cell carcinoma : Results from DARENCA study 2 ' , Acta Oncologica , vol. 55 , no. 3 , pp. 341-348 . https://doi.org/10.3109/0284186X.2015.1091499Test

الوصف: BACKGROUND: Several biomarkers of treatment efficacy have been associated with a better prognosis in patients with metastatic renal cell carcinoma (mRCC). The prognostic significance of biomarkers in the early treatment phase is unclear. MATERIAL AND METHODS: In a complete national cohort of mRCC patients receiving first-line tyrosine kinase inhibitors (TKI) or interleukin-2 based immunotherapy (IT) from 2006 to 2010, overall survival (OS) was analysed for baseline International mRCC Database Consortium (IMDC) classification factors and on-treatment time-dependent biomarkers obtained day 1 each cycle week 4-12 after treatment initiation with multivariate analysis and bootstrap validation. RESULTS: A total of 735 patients received first-line TKI (59%) or IT (41%). Median OS was overall 14.0 months and 33.4, 18.5, and 5.8 months for baseline IMDC favourable, intermediate, and poor risk groups, respectively (p < 0.0001). Systolic blood pressure ≥140 mmHg, neutrophils < lower level of normal (LLN), platelets < LLN, sodium ≥ LLN, and LDH ≤1.5 times upper level of normal after treatment initiation were significantly associated with favourable OS independent of baseline IMDC risk group in multivariate analyses stratified for TKI and IT (p ≤ 0.04). Concordance (C)-index for IMDC classification alone was 0.625 (95% CI 0.59-0.66) and combined with the five-factor biomarker profile 0.683 (95% CI 0.64-0.72). For patients with good (3-5 factors) and poor (0-2 factors) biomarker profile median OS were 23.5 and 9.6 months, respectively (p < 0.0001). Adding the five-factor biomarker profile significantly improved prognostication in IMDC intermediate (25.7 vs. 12.0 months, p < 0.0001) and poor (12.8 vs. 6.4 months, p < 0.0001) risk groups. A trend was seen in IMDC favourable risk group (38.9 vs. 28.7 months, p = 0.112). CONCLUSION: On-treatment hypertension, neutropenia, thrombocytopenia, LDH below 1.5 times upper level of normal, and normal sodium, obtained week 4-12 of treatment, are independent biomarkers of ...

العلاقة: https://portal.findresearcher.sdu.dk/da/publications/4e963283-937e-4ced-8f2f-414ef4d50a3eTest

الإتاحة: https://doi.org/10.3109/0284186X.2015.1091499Test
https://portal.findresearcher.sdu.dk/da/publications/4e963283-937e-4ced-8f2f-414ef4d50a3eTest
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819832/pdf/ionc-55-341.pdfTest

المؤلفون: Soerensen, Anne V, Geertsen, Poul F, Christensen, Ib J, Hermann, Gregers G, Jensen, Niels V, Fode, Kirsten, Petersen, Astrid, Sandin, Rickard, Donskov, Frede

المصدر: Soerensen , A V , Geertsen , P F , Christensen , I J , Hermann , G G , Jensen , N V , Fode , K , Petersen , A , Sandin , R & Donskov , F 2015 , ' A five-factor biomarker profile obtained week 4-12 of treatment for improved prognostication in metastatic renal cell carcinoma : Results from DARENCA study 2 ' , Acta Oncologica . https://doi.org/10.3109/0284186X.2015.1091499Test

الوصف: BACKGROUND: Several biomarkers of treatment efficacy have been associated with a better prognosis in patients with metastatic renal cell carcinoma (mRCC). The prognostic significance of biomarkers in the early treatment phase is unclear. MATERIAL AND METHODS: In a complete national cohort of mRCC patients receiving first-line tyrosine kinase inhibitors (TKI) or interleukin-2 based immunotherapy (IT) from 2006 to 2010, overall survival (OS) was analysed for baseline International mRCC Database Consortium (IMDC) classification factors and on-treatment time-dependent biomarkers obtained day 1 each cycle week 4-12 after treatment initiation with multivariate analysis and bootstrap validation. RESULTS: A total of 735 patients received first-line TKI (59%) or IT (41%). Median OS was overall 14.0 months and 33.4, 18.5, and 5.8 months for baseline IMDC favourable, intermediate, and poor risk groups, respectively (p < 0.0001). Systolic blood pressure ≥140 mmHg, neutrophils < lower level of normal (LLN), platelets < LLN, sodium ≥ LLN, and LDH ≤1.5 times upper level of normal after treatment initiation were significantly associated with favourable OS independent of baseline IMDC risk group in multivariate analyses stratified for TKI and IT (p ≤ 0.04). Concordance (C)-index for IMDC classification alone was 0.625 (95% CI 0.59-0.66) and combined with the five-factor biomarker profile 0.683 (95% CI 0.64-0.72). For patients with good (3-5 factors) and poor (0-2 factors) biomarker profile median OS were 23.5 and 9.6 months, respectively (p < 0.0001). Adding the five-factor biomarker profile significantly improved prognostication in IMDC intermediate (25.7 vs. 12.0 months, p < 0.0001) and poor (12.8 vs. 6.4 months, p < 0.0001) risk groups. A trend was seen in IMDC favourable risk group (38.9 vs. 28.7 months, p = 0.112). CONCLUSION: On-treatment hypertension, neutropenia, thrombocytopenia, LDH below 1.5 times upper level of normal, and normal sodium, obtained week 4-12 of treatment, are independent biomarkers of ...

الإتاحة: https://doi.org/10.3109/0284186X.2015.1091499Test
https://pure.au.dk/portal/da/publications/a-fivefactor-biomarker-profile-obtained-week-412-of-treatment-for-improved-prognostication-in-metastatic-renal-cell-carcinomaTest(40c6d83f-52e1-4c01-b0a4-959af55c7b19).html

المؤلفون: Soerensen, Anne V, Donskov, Frede, Kjellberg, Jakob, Ibsen, Rikke, Hermann, Gregers G, Jensen, Niels V, Fode, Kirsten, Geertsen, Poul F

المصدر: Soerensen , A V , Donskov , F , Kjellberg , J , Ibsen , R , Hermann , G G , Jensen , N V , Fode , K & Geertsen , P F 2015 , ' Health economic changes as a result of implementation of targeted therapy for metastatic renal cell carcinoma : national results from DARENCA study 2 ' , European Urology , vol. 68 , no. 3 , pp. 516-522 . https://doi.org/10.1016/j.eururo.2014.12.017Test

مصطلحات موضوعية: Cost analysis, Economic analysis, Implementation, Metastatic renal cell carcinoma, National, Observational, Population-based, Targeted therapy

الوصف: BACKGROUND: Limited data exist on the economic consequences of implementing targeted therapy (TT) for metastatic renal cell carcinoma (RCC) in a real-world setting. OBJECTIVE: To analyze health care and productivity costs for TT implementation in a national cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: Costs were measured per patient per year during a 2-yr follow-up during 2002-2005 (immunotherapy only) and 2006-2009 (TT implementation). All Danish patients with a diagnosis code for RCC and a procedure code for TT or immunotherapy were linked to the Danish National Patient Registry (contains information on all contacts with primary and secondary health sector). Health care and productivity costs were retrieved from the Danish case-mix system and Coherent Social Statistics, respectively. Drug costs were calculated separately from procedure codes and retail prices. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Generalized linear models were used to analyze costs adjusted for age, gender, and civil status. RESULTS AND LIMITATIONS: A total of 439 patients were included for 2006-2009 and 192 for 2002-2005. Comparison of the health care cost per patient per year between 2006-2009 and 2002-2005 revealed lower inpatient costs (€11 899 vs €19 944, adjusted relative risk [RR] 0.64), higher outpatient costs (€14 308 vs €6209, RR 2.39), lower radiotherapy costs (€194 vs €633, RR 0.31), higher radiology costs (€676 vs €191, RR 3.73), and higher separately calculated drug costs (€12 040 vs €3103, RR 3.82, all p<0.001) for the former. Total health care costs per patient per year did not significantly differ (€27 676 vs €27 856, RR 1.05, p=0.5) between the two periods. Income from employment did not significantly differ between 2006-2009 and 2002-2005 (RR 1.11, p=0.11) and costs associated with loss of productivity were €7852 and €8265, respectively. CONCLUSIONS: A different pattern of health care costs were observed but total health care costs per patient per year did not significantly differ after implementation ...

وصف الملف: application/pdf

العلاقة: https://portal.findresearcher.sdu.dk/da/publications/a4a0d8ab-6609-48fa-9c89-802235bd045dTest

الإتاحة: https://doi.org/10.1016/j.eururo.2014.12.017Test
https://portal.findresearcher.sdu.dk/da/publications/a4a0d8ab-6609-48fa-9c89-802235bd045dTest
https://findresearcher.sdu.dk/ws/files/121294368/Hepatic_encephalopathy_treatment_and_its_effect_on_driving_abilities.pdfTest

المؤلفون: Sørensen, Anne V., Donskov, Frede, Hermann, Gregers G., Jensen, Niels V., Petersen, Astrid, Spliid, Henrik, Sandin, Rickard, Fode, Kirsten, Geertsen, Poul F.

المصدر: Sørensen , A V , Donskov , F , Hermann , G G , Jensen , N V , Petersen , A , Spliid , H , Sandin , R , Fode , K & Geertsen , P F 2014 , ' Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: Results from the Danish Renal Cancer Group (DARENCA) study-2 ' , European Journal of Cancer , vol. 50 , no. 3 , pp. 553–562 . https://doi.org/10.1016/j.ejca.2013.10.010Test

مصطلحات موضوعية: Metastatic renal cell carcinoma, National cohort, Overall survival, Targeted therapy, Population-based study, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, name=SDG 3 - Good Health and Well-being

الوصف: Aim To evaluate the implementation of targeted therapy on overall survival (OS) in a complete national cohort of patients with metastatic renal cell carcinoma (mRCC). Methods All Danish patients with mRCC referred for first line treatment with immunotherapy, TKIs or mTOR-inhibitors between 2006 and 2010 were included. Baseline and outcome data were collected retrospectively. Prognostics factors were identified using log-rank tests and Cox proportional hazard model. Differences in distributions were tested with the Chi-square test. Results 1049 patients were referred; 744 patients received first line treatment. From 2006 to 2010 we observed a significant increase in the number of referred patients; a significant increase in treated patients (64% versus 75%, P = 0.0188); a significant increase in first line targeted therapy (22% versus 75%, P < 0.0001); a significant increase in second line treatment (20% versus 40%, P = 0.0104), a significant increased median OS (11.5 versus 17.2 months, P = 0.0435) whereas survival for untreated patients remained unchanged. Multivariate analysis validated known prognostic factors. Moreover, treatment start years 2008 (HR 0.74, 95% CI, 0.55–0.99; P = 0.0415), 2009 (HR 0.72, 95% CI, 0.54–0.96; P = 0.0277) and 2010 (HR 0.63, 95% CI, 0.47–0.86; P = 0.0035) compared to 2006, and more than two treatment lines received for patients with performance status 0–1 (HR 0.76, 95% CI, 0.58–0.99; P = 0.0397) and performance status 2–3 (HR 0.19, 95% CI, 0.06–0.60; P = 0.0051) were significantly associated with longer OS. Conclusion This retrospective study documents that the implementation of targeted therapy has resulted in significantly improved treatment rates and overall survival in a complete national cohort of treated mRCC patients.

وصف الملف: application/pdf

العلاقة: https://orbit.dtu.dk/en/publications/824187fc-a2cc-44c4-8067-e459ea967748Test

الإتاحة: https://doi.org/10.1016/j.ejca.2013.10.010Test
https://orbit.dtu.dk/en/publications/824187fc-a2cc-44c4-8067-e459ea967748Test
https://backend.orbit.dtu.dk/ws/files/125729249/1_s2.0_S0959804913009489_main.pdfTest

المؤلفون: Soerensen, Anne V, Donskov, Frede, Hermann, Gregers G, Jensen, Niels V, Petersen, Astrid, Spliid, Henrik, Sandin, Rickard, Fode, Kirsten, Geertsen, Poul F

المصدر: Soerensen , A V , Donskov , F , Hermann , G G , Jensen , N V , Petersen , A , Spliid , H , Sandin , R , Fode , K & Geertsen , P F 2014 , ' Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma : results from the Danish Renal Cancer Group (DARENCA) study-2 ' , European Journal of Cancer , vol. 50 , no. 3 , pp. 553-562 . https://doi.org/10.1016/j.ejca.2013.10.010Test

الوصف: AIM: To evaluate the implementation of targeted therapy on overall survival (OS) in a complete national cohort of patients with metastatic renal cell carcinoma (mRCC). METHODS: All Danish patients with mRCC referred for first line treatment with immunotherapy, TKIs or mTOR-inhibitors between 2006 and 2010 were included. Baseline and outcome data were collected retrospectively. Prognostics factors were identified using log-rank tests and Cox proportional hazard model. Differences in distributions were tested with the Chi-square test. RESULTS: 1049 patients were referred; 744 patients received first line treatment. From 2006 to 2010 we observed a significant increase in the number of referred patients; a significant increase in treated patients (64% versus 75%, P=0.0188); a significant increase in first line targeted therapy (22% versus 75%, P<0.0001); a significant increase in second line treatment (20% versus 40%, P=0.0104), a significant increased median OS (11.5 versus 17.2 months, P=0.0435) whereas survival for untreated patients remained unchanged. Multivariate analysis validated known prognostic factors. Moreover, treatment start years 2008 (HR 0.74, 95% CI, 0.55-0.99; P=0.0415), 2009 (HR 0.72, 95% CI, 0.54-0.96; P=0.0277) and 2010 (HR 0.63, 95% CI, 0.47-0.86; P=0.0035) compared to 2006, and more than two treatment lines received for patients with performance status 0-1 (HR 0.76, 95% CI, 0.58-0.99; P=0.0397) and performance status 2-3 (HR 0.19, 95% CI, 0.06-0.60; P=0.0051) were significantly associated with longer OS. CONCLUSION: This retrospective study documents that the implementation of targeted therapy has resulted in significantly improved treatment rates and overall survival in a complete national cohort of treated mRCC patients.

العلاقة: https://vbn.aau.dk/da/publications/801502b9-39e6-4a4b-8414-ba19aa4255d5Test

الإتاحة: https://doi.org/10.1016/j.ejca.2013.10.010Test
https://vbn.aau.dk/da/publications/801502b9-39e6-4a4b-8414-ba19aa4255d5Test

المؤلفون: Schmidt, Henrik, Johansen, Julia Sidenius, Gehl, Julie, Geertsen, Poul F., Fode, Kirsten, von der Maase, Hans

المصدر: Cancer ; volume 106, issue 5, page 1130-1139 ; ISSN 0008-543X 1097-0142

الوصف: BACKGROUND YKL‐40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. Cancer cells, macrophages, and neutrophils secrete YKL‐40. Its function in cancer is unknown. High serum YKL‐40 levels have been associated with a poor prognosis in patients with several solid tumors. The prognostic impact of serum YKL‐40 in metastatic melanoma was evaluated. METHODS YKL‐40 was measured in serial serum samples from 110 patients with metastatic melanoma obtained immediately before and during treatment and from 245 healthy subjects. RESULTS Patients had higher serum YKL‐40 values than healthy subjects ( P < 0.001). Pretreatment serum YKL‐40 was elevated in 45% of the patients and correlated to site of metastases ( P = 0.03) and poor performance status ( P = 0.002). Multivariate Cox analysis showed that serum YKL‐40 (hazard ratio [HR] = 1.9; 95% confidence interval [CI], 1.2–2.8; P = 0.004) and serum lactate dehydrogenase (LDH) (HR = 1.9; 95% CI, 1.2–2.9; P = 0.004) were independent prognostic factors for survival. A combination variable of elevated serum YKL‐40 and LDH quadrupled the risk of early death (HR = 4.4; 95% CI, 2.5–7.7; P < 0.001) compared with patients with normal levels. The combination of YKL‐40 and LDH had a stronger prognostic impact than the American Joint Committee on Cancer (AJCC) Stage IV classification. Furthermore, serum samples were available from 12 patients during followup. In 9 of 11 patients a significant increase in serum YKL‐40 was observed together with disease progression. In one patient with a lasting complete response, serum YKL‐40 remained normal. CONCLUSIONS An elevated serum YKL‐40 was an independent prognostic factor for poor survival in patients with metastatic melanoma. When combining serum YKL‐40 and LDH, patients could be separated into three prognostic groups based on the number of elevated biomarkers. The findings should be validated in an independent study. Cancer 2006. © 2006 American Cancer Society.

الإتاحة: https://doi.org/10.1002/cncr.21678Test