ABSTRACT
BACKGROUND: Particle therapy provides steep dose gradients to facilitate dose escalation in challenging anatomical sites which has been shown not only to improve local control but also overall survival in patients with ACC. Cost-effectiveness of intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost vs IMRT alone was performed in order to objectivise and substantiate more widespread use of this technology in ACC. METHODS: Patients with pathologically confirmed ACC received a combination regimen of IMRT plus C12 boost. Patients presenting outside C12 treatment slots received IMRT only. Clinical results were published; economic analysis on patient-level data was carried out from a healthcare purchaser's perspective based on costs of healthcare utilization. Cost histories were generated from resource use recorded in individual patient charts and adjusted for censoring using the Lin I method. Cost-effectiveness was measured as incremental cost-effectiveness ratio (ICER). Sensitivity analysis was performed regarding potentially differing management of recurrent disease. RESULTS: The experimental treatment increased overall costs by 18,076 (13,416 - 22,922) at a mean survival benefit of 0.86 years. Despite improved local control, following costs were also increased in the experimental treatment. The ICER was estimated to 26,863 /LY. After accounting for different management of recurrent disease in the two cohorts, the ICER was calculated to 20,638 /LY. CONCLUSION: The combined treatment (IMRT+C12 boost) substantially increased initial and overall treatment cost. In view of limited treatment options in ACC, costs may be acceptable though. Investigations into quality of life measures may support further decisions in the future.
Subject(s)
Carcinoma, Adenoid Cystic/radiotherapy , Head and Neck Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/economics , Carcinoma, Adenoid Cystic/economics , Combined Modality Therapy/economics , Combined Modality Therapy/methods , Cost-Benefit Analysis , Decision Making , Head and Neck Neoplasms/economics , Heavy Ion Radiotherapy/economics , Humans , Neoplasm Recurrence, Local/economics , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/methods , Random Allocation , Retrospective StudiesABSTRACT
Adenoid cystic carcinoma (ACC) is a malignant salivary gland tumor, which shows frequent recurrence and metastasis, ultimately with a poor outcome. We previously demonstrated that p27 down-regulation is frequently found and is due to an enhancement of its degradation in ACC. In this study, we transfected nondegradable p27 mutant (T187A) and wild-type gene into ACC cell line. Transfection of T187A mutant gene was more effective on inhibition of cell growth of ACC cells, suggesting that aberration of p27 degradation may be present in ACC. As F-box protein S-phase kinase-associated protein 2 (Skp2), which is necessary for ubiquitin-mediated degradation of p27, is involved in p27 down-regulation in various cancers, we examined the Skp2 expression and its association with p27 expression in 50 ACC cases. We found Skp2 expression in 36% of ACC cases and inverse association between the expression of Skp2 and p27. Moreover, Skp2 small interfering ribonucleic acid (siRNA) transfection decreased Skp2 protein and accumulation of p27 protein and inhibited the cell growth of ACC cells in vitro. These findings, overall, suggest that Skp2 may play an important role in ACC development through the down-regulation of p27 and that Skp2 siRNA can be a novel modality of cancer gene therapy for suppression of p27 down-regulation in ACC.
