Hematology, Transfusion and Cell Therapy (Apr 2024)
COST SIMULATION OF GSTP1 C.313 A>G GENOTYPING FOR OTOTOXICITY RISK ASSESSMENT IN HEAD AND NECK SQUAMOUS CELL CARCINOMA PATIENTS UNDERGOING CISPLATIN-BASED CHEMORADIOTHERAPY
Abstract
Introduction/Justification: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy worldwide, with substantial morbidity and mortality. Cisplatin-based chemoradiotherapy is a standard treatment modality for most HNSCC patients, but it is associated with significant adverse effects, including ototoxicity. Glutathione S-transferase pi 1 (GSTP1) is a gene involved in the detoxification of cisplatin, and single nucleotide variants as GSTP1 c.313 A>G have been linked to differential susceptibility to ototoxicity in HNSCC patients under therapy. It is unknown, however, if genotyping selection could improve patient outcomes and reduce treatment costs. Objectives: This study aims to investigate the potential cost reduction of GSTP1 c.313 A>G genotyping in identifying HNSCC patients at risk of cisplatin-induced ototoxicity, with the goal of optimizing therapeutic decision-making and reducing the economic burden associated with audiological support interventions (ASIs). Materials and Methods: A decision analytic model was designed, where patients with low-risk genotypes (GSTP1 c.313 AA) would receive cisplatin, while those with high-risk (GSTP1 c.313 AG/GG) would hypothetically receive docetaxel. Transitional probabilities were then calculated using Metropolis-Hastings algorithm. Costs included genotyping, therapy, and ASIs provision. A probabilistic Markov model was developed to simulate the clinical and economic outcomes associated with GSTP1 genotyping in HNSCC patients receiving cisplatin-based chemoradiotherapy. Transition probabilities, treatment costs, and the probabilities of adverse events were incorporated into the model over a ten-year time horizon. Sensitivity analyses were conducted to assess the robustness of the results. Results: The median total cost per patient in the conventional arm was R$ 2,025.05 (credibility interval R$ 1,975.58 to R$ 2,047.75). Simulation results indicated that implementing genotyping could result in significant cost reductions in the first year, with savings ranging from R$ 92.53 to R$140.06 per patient, depending on the number of simultaneous genotyping tests performed (in this case, 3 and 5 samples, respectively). Over a ten-year period, cumulative cost savings of R$75,689.10 were projected for 250 patients, primarily attributed to decreased expenditures on ASIs and audiological support services. Conclusion: The analysis demonstrated that GSTP1 c.313 A>G genotyping has the potential to yield cost savings in the management of cisplatin-induced ototoxicity in HNSCC patients. Genotyping for GSTP1 polymorphisms represents a promising approach to identify HNSCC patients at increased risk of cisplatin-induced ototoxicity, allowing for personalized treatment strategies. These findings highlight the importance of integrating pharmacogenetic testing into clinical practice to enhance patient outcomes and healthcare resource utilization. Further research and implementation efforts are warranted to validate this strategy in routine HNSCC management.
