20 results on '"Heng, D. Y. C."'
Search Results
2. A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel
- Author
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Chi, K. N., Kheoh, T., Ryan, C. J., Molina, A., Bellmunt, J., Vogelzang, N. J., Rathkopf, D. E., Fizazi, K., Kantoff, P. W., Li, J., Azad, A. A., Eigl, B. J., Heng, D. Y. C., Joshua, A. M., de Bono, J. S., and Scher, H. I.
- Published
- 2016
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- View/download PDF
3. Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials
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Heng, D. Y. C., Choueiri, T. K., Rini, B. I., Lee, J., Yuasa, T., Pal, S. K., Srinivas, S., Bjarnason, G. A., Knox, J. J., MacKenzie, M., Vaishampayan, U. N., Tan, M. H., Rha, S. Y., Donskov, F., Agarwal, N., Kollmannsberger, C., North, S., and Wood, L. A.
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- 2014
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4. Risk and Predictors of Suicide in Colorectal Cancer Patients: A Surveillance, Epidemiology, and End Results Analysis
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Samawi, H. H., primary, Shaheen, A. A., additional, Tang, P. A., additional, Heng, D. Y. C., additional, Cheung, W. Y., additional, and Vickers, M. M., additional
- Published
- 2017
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- View/download PDF
5. Real-world outcomes of nivolumab and cabozantinib in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium.
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Stukalin, I., Wells, J. C., Graham, J., Yuasa, T., Beuselinck, B., Kollmansberger, C., Ernst, D. S., Agarwal, N., Le, T., Donskov, F., Hansen, A. R., Bjarnason, G. A., Srinivas, S., Wood, L. A., Alva, A. S., Kanesvaran, R., Fu, S. Y. F., Davis, I. D., Choueiri, T. K., and Heng, D. Y. C.
- Subjects
RENAL cell carcinoma ,VASCULAR endothelial growth factor receptors - Abstract
Objectives In the present study, we explored the real-world efficacy of the immuno-oncology checkpoint inhibitor nivolumab and the tyrosine kinase inhibitor cabozantinib in the second-line setting. Methods Using the International Metastatic Renal Cell Carcinoma Database Consortium (imdc) dataset, a retrospective analysis of patients with metastatic renal cell carcinoma (mrcc) treated with nivolumab or cabozantinib in the second line after prior therapy targeted to the vascular endothelial growth factor receptor (vegfr) was performed. Baseline characteristics and imdc risk factors were collected. Overall survival (os) and time to treatment failure (ttf) were calculated using Kaplan-Meier curves. Overall response rates (orrs) were determined for each therapy. Multivariable Cox regression analysis was performed to determine survival differences between cabozantinib and nivolumab treatment. Results The analysis included 225 patients treated with nivolumab and 53 treated with cabozantinib. No significant difference in median os was observed: 22.10 months [95% confidence interval (ci): 17.18 months to not reached] with nivolumab and 23.70 months (95% ci: 15.52 months to not reached) with cabozantinib (p = 0.61). The ttf was also similar at 6.90 months (95% ci: 4.60 months to 9.20 months) with nivolumab and 7.39 months (95% ci: 5.52 months to 12.85 months) with cabozantinib (p = 0.20). The adjusted hazard ratio (hr) for nivolumab compared with cabozantinib was 1.30 (95% ci: 0.73 to 2.3), p = 0.38. When adjusted by imdc criteria and age, the hr was 1.32 (95% ci: 0.74 to 2.38), p = 0.35. Conclusions Real-world imdc data indicate comparable os and ttf for nivolumab and cabozantinib. Both agents are reasonable therapeutic options for patients progressing after initial first-line vegfr-targeted therapy. [ABSTRACT FROM AUTHOR]
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- 2019
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- View/download PDF
6. First-, second-, third-line therapy for mRCC: benchmarks for trial design from the IMDC
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Ko, J J, primary, Choueiri, T K, additional, Rini, B I, additional, Lee, J-L, additional, Kroeger, N, additional, Srinivas, S, additional, Harshman, L C, additional, Knox, J J, additional, Bjarnason, G A, additional, MacKenzie, M J, additional, Wood, L, additional, Vaishampayan, U N, additional, Agarwal, N, additional, Pal, S K, additional, Tan, M-H, additional, Rha, S Y, additional, Yuasa, T, additional, Donskov, F, additional, Bamias, A, additional, and Heng, D Y C, additional
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- 2014
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7. Anti-VEGF therapy in mRCC: differences between Asian and non-Asian patients
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Wang, Y, primary, Choueiri, T K, additional, Lee, J-L, additional, Tan, M-H, additional, Rha, S Y, additional, North, S A, additional, Kollmannsberger, C K, additional, McDermott, D F, additional, and Heng, D Y C, additional
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- 2014
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8. Risk of infections in renal cell carcinoma (RCC) and non-RCC patients treated with mammalian target of rapamycin inhibitors
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Kaymakcalan, M D, primary, Je, Y, additional, Sonpavde, G, additional, Galsky, M, additional, Nguyen, P L, additional, Heng, D Y C, additional, Richards, C J, additional, and Choueiri, T K, additional
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- 2013
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9. Returning research results to clinical trial participants: A survey of patients with cancer.
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Elzinga, K., primary, Fernandez, C. V., additional, Heng, D. Y. C., additional, and Tang, P. A., additional
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- 2011
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10. State-of-the-Art Treatment of Metastatic Renal Cell Carcinoma
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Heng, D. Y. C., primary and Kollmannsberger, C., additional
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- 2009
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11. Progression-free survival as a clinical trial endpoint in advanced renal cell carcinoma.
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Hotte, S. J., Bjarnason, G. A., Heng, D. Y. C., Jewett, M. A. S., Kapoor, A., Kollmannsberger, C., Maroun, J., Mayhew, L. A., North, S., Reaume, M. N., Ruether, J. D., Soulieres, D., Venner, P. M., Winquist, E. W., Wood, L., Yong, J. H. E., and Saad, F.
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RENAL cell carcinoma ,RENAL cancer ,DISEASE progression ,ONCOLOGY ,DATA integrity - Abstract
Traditionally, overall survival (OS) has been considered the "gold standard" for evaluating new systemic oncologic therapies, because death is easy to define, is easily compared across disease sites, and is not subject to investigator bias. However, as the available options for continuing therapy increase, the use of OS as a clinical trial endpoint has become problematic because of the increasing crossover and contamination of trials. As a result, the approval of promising new therapies may be delayed. Many clinicians believe that progression-free survival (PFS) is a more viable option for evaluating new therapies in metastatic and advanced renal cell carcinoma. As with all endpoints, PFS has inherent biases, and those biases must be addressed to ensure that trial results are not compromised and that they will be accepted by regulatory authorities. In this paper, we examine the issues surrounding the use of PFS as a clinical trial endpoint, and we suggest solutions to ensure that data integrity is maintained. [ABSTRACT FROM AUTHOR]
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- 2011
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12. Progression-free survival as a clinical trial endpoint in advanced renal cell carcinoma
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Hotte, S. J., Bjarnason, G. A., Heng, D. Y. C., Jewett, M. A. S., Kapoor, A., Kollmannsberger, C., Maroun, J., Mayhew, L. A., scott North, Reaume, M. N., Ruether, J. D., Soulieres, D., Venner, P. M., Winquist, E. W., Wood, L., Yong, J. H. E., and Saad, F.
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clinical trial endpoints ,regulatory approval ,overall survival ,Kidney cancer ,progression-free survival - Abstract
Traditionally, overall survival (os) has been considered the &ldquo, gold standard&rdquo, for evaluating new systemic oncologic therapies, because death is easy to define, is easily compared across disease sites, and is not subject to investigator bias. However, as the available options for continuing therapy increase, the use of os as a clinical trial endpoint has become problematic because of the increasing crossover and contamination of trials. As a result, the approval of promising new therapies may be delayed.
13. Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma.
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Choueiri, T. K., Powles, T., Albiges, L., Burotto, M., Szczylik, C., Zurawski, B., Ruiz, E. Yanez, Maruzzo, M., Zaizar, A. Suarez, Fein, L. E., Schutz, F. A., Heng, D. Y. C., Wang, F., Mataveli, F., Chang, Y.-L., van Kooten Losio, M., Suarez, C., and Motzer, R. J.
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NIVOLUMAB , *IPILIMUMAB , *PROGRESSION-free survival , *EXPERIMENTAL groups , *CARCINOMA , *RENAL cell carcinoma - Abstract
BACKGROUND The efficacy and safety of treatment with cabozantinib in combination with nivolumab and ipilimumab in patients with previously untreated advanced renal-cell carcinoma are unknown. METHODS In this phase 3, double-blind trial, we enrolled patients with advanced clear-cell renal-cell carcinoma who had not previously received treatment and had intermediate or poor prognostic risk according to the International Metastatic Renal-Cell Carcinoma Database Consortium categories. Patients were randomly assigned to receive 40 mg of cabozantinib daily in addition to nivolumab and ipilimumab (experimental group) or matched placebo in addition to nivolumab and ipilimumab (control group). Nivolumab (3 mg per kilogram of body weight) and ipilimumab (1 mg per kilogram) were administered once every 3 weeks for four cycles. Patients then received nivolumab maintenance therapy (480 mg once every 4 weeks) for up to 2 years. The primary end point was progression-free survival, as determined by blinded independent review according to Response Evaluation Criteria in Solid Tumors, version 1.1, and was assessed in the first 550 patients who had undergone randomization. The secondary end point was overall survival, assessed in all patients who had undergone randomization. RESULTS Overall, 855 patients underwent randomization: 428 were assigned to the experimental group and 427 to the control group. Among the first 550 patients who had undergone randomization (276 in the experimental group and 274 in the control group), the probability of progression-free survival at 12 months was 0.57 in the experimental group and 0.49 in the control group (hazard ratio for disease progression or death, 0.73; 95% confidence interval, 0.57 to 0.94; P=0.01); 43% of the patients in the experimental group and 36% in the control group had a response. Grade 3 or 4 adverse events occurred in 79% of the patients in the experimental group and in 56% in the control group. Follow-up for overall survival is ongoing. CONCLUSIONS Among patients with previously untreated, advanced renal-cell carcinoma who had intermediate or poor prognostic risk, treatment with cabozantinib plus nivolumab and ipilimumab resulted in significantly longer progression-free survival than treatment with nivolumab and ipilimumab alone. Grade 3 or 4 adverse events were more common in the experimental group than in the control group. (Funded by Exelixis; COSMIC-313 ClinicalTrials.gov number, NCT03937219.). [ABSTRACT FROM AUTHOR]
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- 2023
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- View/download PDF
14. Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium
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Christopher Sweeney, Eric Winquist, Darren R. Feldman, Ugo De Giorgi, Daniel Y.C. Heng, Silke Gillessen, Michal Chovanec, Jourik A. Gietema, Robert Huddart, Costantine Albany, Fay H. Cafferty, Peter Grimison, Aaron R. Hansen, Carsten Bokemeyer, Karim Fizazi, Jörg Beyer, Christian D. Fankhauser, Nicolas Sauvé, Alexey Tryakin, Torgrim Tandstad, Olof Ståhl, Helene F. S. Negaard, Ronald de Wit, Anja Lorch, Andrea Necchi, David J. Vaughn, Angelika Terbuch, Axel Heidenreich, Cora N. Sternberg, Marcus Hentrich, Xavier Garcia-del-Muro, Gedske Daugaard, Laurence Collette, Jonathan Shamash, Gillessen, S., Sauve, N., Collette, L., Daugaard, G., de Wit, R., Albany, C., Tryakin, A., Fizazi, K., Stahl, O., Gietema, J. A., de Giorgi, U., Cafferty, F. H., Hansen, A. R., Tandstad, T., Huddart, R. A., Necchi, A., Sweeney, C. J., Garcia-Del-Muro, X., Heng, D. Y. C., Lorch, A., Chovanec, M., Winquist, E., Grimison, P., Feldman, D. R., Terbuch, A., Hentrich, M., Bokemeyer, C., Negaard, H., Fankhauser, C., Shamash, J., Vaughn, D. J., Sternberg, C. N., Heidenreich, A., Beyer, J., Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
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Male ,0301 basic medicine ,Oncology ,Cancer Research ,Lung Neoplasms ,International Cooperation ,medicine.medical_treatment ,Metastasis ,chemistry.chemical_compound ,PROGNOSTIC-FACTORS ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Young adult ,Etoposide ,Age Factors ,BLEOMYCIN ,Middle Aged ,Neoplasms, Germ Cell and Embryonal ,Prognosis ,Cèl·lules germinals ,ETOPOSIDE ,030220 oncology & carcinogenesis ,SURVIVAL ,TRIAL ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,610 Medicine & health ,Bleomycin ,CLASSIFICATION ,TESTICULAR CANCER ,CISPLATIN ,Young Adult ,03 medical and health sciences ,Testicular Neoplasms ,Metàstasi ,Internal medicine ,Germ cells ,medicine ,Humans ,Testicular cancer ,Aged ,Tumors ,BEP ,Cisplatin ,Chemotherapy ,Errata ,business.industry ,medicine.disease ,Clinical trial ,030104 developmental biology ,MARKER DECLINE ,chemistry ,Germ cell tumors ,610 Medizin und Gesundheit ,business - Abstract
PURPOSE The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. MATERIALS AND METHODS Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,542 patients with complete information on potentially relevant variables. The results were validated in an independent data set. RESULTS Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided ( https://www.eortc.org/IGCCCG-Update ). CONCLUSION The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.
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- 2021
15. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.
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Choueiri, T. K., Escudier, B., Powles, T., Mainwaring, P. N., Rini, B. l., Donskov, F., Hammers, H., Hutson, T. E., Lee, J.-L., Peltola, K., Roth, B. J., Bjamason, G. A., Geczi, L., Ream, B., Maroto, P., Heng, D. Y. C., Schmidinger, M., Kantoff, P. W., Borgman-Hagey, A., and Hessel, C.
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AMIDES , *ANTINEOPLASTIC agents , *KIDNEY tumors , *PROGNOSIS , *PYRIDINE , *QUALITY of life , *RENAL cell carcinoma , *RESEARCH funding , *SURVIVAL analysis (Biometry) , *RAPAMYCIN , *THERAPEUTICS - Abstract
Background: Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.Methods: We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression-free survival. Secondary efficacy end points were overall survival and objective response rate.Results: Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P<0.001). The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). A planned interim analysis showed that overall survival was longer with cabozantinib than with everolimus (hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005) but did not cross the significance boundary for the interim analysis. Adverse events were managed with dose reductions; doses were reduced in 60% of the patients who received cabozantinib and in 25% of those who received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus.Conclusions: Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.). [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
16. Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium
- Author
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Eric Winquist, Darren R. Feldman, Ignacio Duran, Andrea Necchi, Silke Gillessen, Alexey Tryakin, David J. Vaughn, Angelika Terbuch, Axel Heidenreich, Christopher Sweeney, Enrique Gonzalez-Billalabeitia, Anna Patrikidou, Aaron R. Hansen, Daniel Y.C. Heng, Jonathan Shamash, Costantine Albany, Peter Grimison, Robert Huddart, Anja Lorch, Carsten Bokemeyer, Torgrim Tandstad, Cora N. Sternberg, Ugo De Giorgi, Marko Bebek, Jörg Beyer, Gedske Daugaard, Nicolas Sauvé, Richard Cathomas, Ronald de Wit, Laurence Collette, Christian D. Fankhauser, Helene F. S. Negaard, Olof Ståhl, Stéphane Culine, Ben Tran, Michal Chovanec, Samson Assele, Marcus Hentrich, Fay H. Cafferty, Dan Stark, Jourik A. Gietema, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Beyer, J., Collette, L., Sauve, N., Daugaard, G., Feldman, D. R., Tandstad, T., Tryakin, A., Stahl, O., Gonzalez-Billalabeitia, E., de Giorgi, U., Culine, S., de Wit, R., Hansen, A. R., Bebek, M., Terbuch, A., Albany, C., Hentrich, M., Gietema, J. A., Negaard, H., Huddart, R. A., Lorch, A., Cafferty, F. H., Heng, D. Y. C., Sweeney, C. J., Winquist, E., Chovanec, M., Fankhauser, C., Stark, D., Grimison, P., Necchi, A., Tran, B., Heidenreich, A., Shamash, J., Sternberg, C. N., Vaughn, D. J., Duran, I., Bokemeyer, C., Patrikidou, A., Cathomas, R., Assele, S., and Gillessen, S.
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,International Cooperation ,medicine.medical_treatment ,MEDLINE ,03 medical and health sciences ,Collaborative group ,CISPLATIN ,0302 clinical medicine ,GERM-CELL CANCER ,Testicular Neoplasms ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm Metastasis ,610 Medicine & health ,Cisplatin ,Chemotherapy ,L-Lactate Dehydrogenase ,business.industry ,Cancer ,CHEMOTHERAPY ,Prognosis ,medicine.disease ,Seminoma ,030104 developmental biology ,Germ cell cancer ,Multicenter study ,030220 oncology & carcinogenesis ,Metastatic seminoma ,business ,medicine.drug - Abstract
PURPOSE The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium. MATERIALS AND METHODS Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients. RESULTS Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH. CONCLUSION PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.
- Published
- 2021
17. Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma receiving first-line combination immunotherapies: results from the International Metastatic Renal Cell Carcinoma Database Consortium.
- Author
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Takemura K, Yuasa T, Lemelin A, Ferrier E, Wells JC, Saad E, Saliby RM, Basappa NS, Wood LA, Jude E, Pal SK, Donskov F, Beuselinck B, Szabados B, Powles T, McKay RR, Gebrael G, Agarwal N, Choueiri TK, and Heng DYC
- Subjects
- Humans, Male, Female, Middle Aged, Prognosis, Lymphocyte Count, Aged, Lymphopenia, Retrospective Studies, Databases, Factual, Adult, Carcinoma, Renal Cell therapy, Carcinoma, Renal Cell mortality, Carcinoma, Renal Cell immunology, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology, Kidney Neoplasms immunology, Kidney Neoplasms therapy, Kidney Neoplasms drug therapy, Kidney Neoplasms mortality, Immunotherapy methods
- Abstract
Background: Lymphocytes are closely linked to mechanisms of action of immuno-oncology (IO) agents. We aimed to assess the prognostic significance of absolute lymphocyte count (ALC) in patients with metastatic renal cell carcinoma (mRCC)., Patients and Methods: Using the International mRCC Database Consortium (IMDC), patients receiving first-line IO-based combination therapy were analysed. Baseline patient characteristics, objective response rates (ORRs), time to next treatment (TTNT), and overall survival (OS) were compared., Results: Of 966 patients included, 195 (20%) had lymphopenia at baseline, and they had a lower ORR (37% versus 45%; P < 0.001), shorter TTNT (10.1 months versus 24.3 months; P < 0.001), and shorter OS (30.4 months versus 48.2 months; P < 0.001). Among 125 patients with lymphopenia at baseline, 52 (42%) experienced ALC recovery at 3 months, and they had longer OS (not reached versus 30.4 months; P = 0.012). On multivariable analysis for OS, lymphopenia was an independent adverse prognostic factor (hazard ratio 1.68; P < 0.001). Incorporation of lymphopenia into the IMDC criteria improved OS prediction accuracy (C-index from 0.688 to 0.707)., Conclusions: Lymphopenia was observed in one-fifth of treatment-naive patients with mRCC and may serve as an indicator of unfavourable oncologic outcomes in the contemporary IO era., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
18. Application of Hereditary Renal Cell Carcinoma Risk Criteria to a Large Prospective Database.
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Kushnir I, Kirk L, Mallick R, Kim RH, Graham GE, Breau RH, Lattouf JB, Violette PD, Pautler SE, Care M, Kapoor A, Jewett MAS, Wood L, Tanguay S, Heng DYC, Basappa NS, So A, Pouliot F, and Reaume NM
- Subjects
- Adult, Data Management, Female, Humans, Male, Prospective Studies, Risk Factors, Carcinoma, Renal Cell epidemiology, Database Management Systems standards, Kidney Neoplasms epidemiology
- Abstract
Aims: To evaluate the clinical impact of the Canadian criteria for identifying patients and families at risk for hereditary renal cell carcinoma (RCC)., Materials and Methods: The Canadian hereditary RCC risk criteria were applied to patients from 16 centres in the Canadian Kidney Cancer information system (CKCis) prospective database. The primary end point was the proportion of patients who met at least one criterion., Results: Between January 2011 and May 2017, 8388 patients were entered in the database; 291 had inadequate risk data; 2827 (35%) met at least one criterion for genetic testing (at-risk population). Most (83%) met just one criterion. The criterion of non-clear cell histology contributed the largest proportion of at-risk patients (59%), followed by age ≤ 45 years (28%). Sixty-one patients had documentation of genetic testing, with 56 being classified at-risk (2% of at-risk). Twenty patients (35%) of the patients at risk and tested for hereditary RCC were found to harbour a germline mutation., Conclusions: Application of the Canadian hereditary RCC risk criteria to a large prospective database resulted in 35% of patients being identified at risk for hereditary RCC who could qualify for genetic testing. However, the true incidence of hereditary RCC in this population is unknown as most patients did not have documented genetic testing carried out and, thus, the sensitivity and specificity of the criteria cannot be determined. The low proportion of at-risk patients who underwent genetic testing is disappointing and highlights that there may be gaps in reporting, knowledge and/or barriers in access to genetic testing., (Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
19. Transforming the Perioperative Treatment Paradigm in Non-Metastatic RCC-A Possible Path Forward.
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Harshman LC, Drake CG, Haas NB, Manola J, Puligandla M, Signoretti S, Cella D, Gupta RT, Bhatt R, Van Allen E, Lara P, Choueiri TK, Kapoor A, Heng DYC, Shuch B, Jewett M, George D, Michaelson D, Carducci MA, McDermott D, and Allaf M
- Abstract
In 2017, there is no adjuvant systemic therapy proven to increase overall survival in non-metastatic renal cell carcinoma (RCC). The anti-PD-1 antibody nivolumab improves overall survival in metastatic treatment refractory RCC and is generally tolerable. Mouse solid tumor models have revealed a benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy. Two ongoing phase 2 studies of perioperative nivolumab in RCC patients have shown preliminary feasibility and safety with no surgical delays or complications. The recently opened PROSPER RCC trial (A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy; EA8143) will examine if the addition of perioperative nivolumab to radical or partial nephrectomy can improve clinical outcomes in patients with high risk localized and locally advanced RCC. With the goal of increasing cure and recurrence-free survival (RFS) rates in non-metastatic RCC, we are executing a three-pronged, multidisciplinary approach of presurgical priming with nivolumab followed by resection and adjuvant PD-1 blockade. We plan to enroll 766 patients with clinical stage ≥T2 or node positive M0 RCC of any histology in this global, randomized, unblinded, phase 3 National Clinical Trials Network study. The investigational arm will receive two doses of nivolumab 240 mg IV prior to surgery followed by adjuvant nivolumab for 9 months. The control arm will undergo the current standard of care: surgical resection followed by observation. Patients are stratified by clinical T stage, node positivity, and histology. The trial is powered to detect a 14.4% absolute benefit in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 years (HR = 0.70). The study is also powered to detect a significant overall survival benefit (HR 0.67). Key safety, feasibility, and quality of life endpoints are incorporated. PROSPER RCC exemplifies team science with a host of planned correlative work to investigate the impact of the baseline immune milieu and changes after neoadjuvant priming on clinical outcomes.
- Published
- 2017
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20. Association between treatment effects on disease progression end points and overall survival in clinical studies of patients with metastatic renal cell carcinoma.
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Delea TE, Khuu A, Heng DY, Haas T, and Soulières D
- Subjects
- Disease Progression, Disease-Free Survival, Endpoint Determination, Humans, Molecular Targeted Therapy, Randomized Controlled Trials as Topic, Survival Analysis, Treatment Outcome, Carcinoma, Renal Cell drug therapy, Kidney Neoplasms drug therapy
- Abstract
Background: The relationship between progression-free survival and time to progression (PFS/TTP) and overall survival (OS) has been demonstrated in a variety of solid tumours but not in metastatic renal cell carcinoma (mRCC)., Methods: A systematic literature search was conducted to identify controlled trials of cytokine or targeted therapies for mRCC reporting information on treatment effects on PFS/TTP and OS for one or more comparison. The associations between treatment effects on PFS/TTP and OS were analysed using linear regression., Results: Thirty-one studies representing 10943 patients, 75 treatment groups, and 41 comparisons were identified. The correlation coefficient between the negative log of the hazard ratio (HR) for PFS/TTP (-ln HR(PFS/TTP)) vs the negative log of the HR for OS (-ln HR(OS)) was 0.80 (P<0.0001). In linear regression, the coefficient on -ln HR(PFS/TTP) vs -ln HR(OS) was 0.64 (95% confidence interval (CI): 0.470.81; R(2)=0.63), suggesting each 10% relative risk reduction (RRR) for PFS/TTP was associated with a 6% RRR for OS. A 1-month gain in median PFS/TTP was associated with a 1.17-month gain in median OS (95% CI: 0.59,1.76; R(2)=0.28)., Conclusion: In trials of treatments for mRCC, treatment effects on PFS/TTP are strongly associated with treatment effects on OS.
- Published
- 2012
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