Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer |
| |
| Institution: | 1. Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center/Geisel School of Medicine, Lebanon, NH;2. The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, NH;3. Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA;4. Geisel School of Medicine, Lebanon, NH;1. Vanderbilt-Ingram Cancer Center, Nashville, TN;2. Department of Medicine (Hematology & Oncology), Vanderbilt University Medical Center; Nashville, TN;3. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN;4. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN;5. Department of Surgical Pathology, Duke University Health System, Durham, NC;1. Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany;2. Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany;3. Profile Area Clinical Studies and Biostatistics, Halle (Saale), Germany;4. Department of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany;1. Division of Clinical Research, Instituto Nacional de Câncer (INCA), Rio de Janeiro (RJ), Brazil;2. Department of Abdomino-Pelvic Surgery, Instituto Nacional de Câncer (INCA), Rio de Janeiro (RJ), Brazil;3. Department of Radiology, Instituto Nacional de Câncer (INCA), Rio de Janeiro (RJ), Brazil;4. Department of Radiotherapy, Instituto Nacional de Câncer (INCA), Rio de Janeiro (RJ), Brazil;5. Department of Endoscopy, Instituto Nacional de Câncer (INCA), Rio de Janeiro (RJ), Brazil;6. Department of Pathology, Instituto Nacional de Câncer (INCA), Rio de Janeiro (RJ), Brazil;1. A.C. Camargo Cancer Center - Fundação Antônio Prudente, São Paulo, Brazil;2. Hospital Bonorino Udaondo, Buenos Aires, Argentina;1. Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;2. Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA;3. Medical Department, Division of Oncology and Hematology, Charité Universitaetsmedizin Berlin, Germany;4. Department of Medicine III, University Hospital, LMU Munich, Munich, Germany |
| |
| Abstract: | BackgroundAdjuvant fluoropyrimidine-based chemotherapy substantially reduces recurrence and mortality after resection of stage 3 colon cancer. While standard doses of 5-fluorouracil and capecitabine are safe for most patients, the risk of severe toxicity is increased for the approximately 6% of patients with dihydropyimidine dehydrogenase (DPD) deficiency caused by pathogenic DPYD gene variants. Pre-treatment screening for pathogenic DPYD gene variants reduces severe toxicity but has not been widely adopted in the United States.MethodsWe conducted a cost-effectiveness analysis of DPYD genotyping prior to fluoropyrimidine-based adjuvant chemotherapy for stage 3 colon cancer, covering the c.1129-5923C>G (HapB3), c.1679T>G (*13), c.1905+1G>A (*2A), and c.2846A>T gene variants. We used a Markov model with a 5-year horizon, taking a United States healthcare perspective. Simulated patients with pathogenic DPYD gene variants received reduced-dose fluoropyrimidine chemotherapy. The primary outcome was the incremental cost-effectiveness ratio (ICER) for DPYD genotyping.ResultsCompared with no screening for DPD deficiency, DPYD genotyping increased per-patient costs by $78 and improved survival by 0.0038 quality-adjusted life years (QALYs), leading to an ICER of $20,506/QALY. In 1-way sensitivity analyses, The ICER exceeded $50,000 per QALY when the cost of the DPYD genotyping assay was greater than $286. In probabilistic sensitivity analysis using a willingness-to-pay threshold of $50,000/QALY DPYD genotyping was preferred to no screening in 96.2% of iterations.ConclusionAmong patients receiving adjuvant chemotherapy for stage 3 colon cancer, screening for DPD deficiency with DPYD genotyping is a cost-effective strategy for preventing infrequent but severe and sometimes fatal toxicities of fluoropyrimidine chemotherapy. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
