A. Dornisch1, K. R. Tringale2, and J. D. Murphy1; 1Department of Radiation Medicine and Applied Sciences, UC San Diego, La Jolla, CA, 2Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA
Purpose/Objective(s): Photon involved-field radiation therapy (IFRT) represents a primary treatment for palliation of symptoms due to leptomeningeal metastasis (LM); however, because LM disseminates throughout the neuroaxis, IFRT cannot comprehensively halt the progression of disease. Recently, a randomized trial found pCSI, as compared to IFRT, may reduce the risk of CNS progression and improve overall survival in patients with LM. However, a course of proton therapy can cost substantially more than photon therapy. Given the increasing number of patients with LM (now >10% of all cancer patients), it is imperative that we understand the financial impact of implementing this expensive treatment more widely. Here, we evaluated the cost effectiveness of pCSI for solid tumor LM. Materials/
Methods: We built a microsimulation model for patients with solid tumor LM who received either pCSI or IFRT with whole brain radiation therapy. The model incorporates costs, quality of life (measured by health utility), and probabilities of CNS progression and death. We extracted probabilities for progression and death from a phase II trial of pCSI versus IFRT, and health utilities from published literature. We assessed costs from the healthcare payer perspective. We measured cost-effectiveness with the incremental cost-effectiveness ratio (ICER) with ICERs less than $150,000 per quality-adjusted life-year (QALY) considered cost-effective. One-way and probabilistic sensitivity analyses were used to test model uncertainty. Results: Simulating the clinical course of 1,000,000 patients with solid tumor leptomeningeal metastasis, we found that compared to IFRT, pCSI increased overall cost by $5651 and improved effectiveness by 0.09 QALYs, resulting in an ICER of $62,800/QALY. The model was most sensitive to assumptions about ongoing costs of cancer care and long-term health utility (=6 months after cranial radiation therapy). If the monthly cost of cancer care increased from our base estimate of $2438 to $3775, or the health utility =6 months after cranial radiation decreased from 0.16 to 0.06, then pCSI was no longer cost effective (ICER >$150,000/QALY). The base model assumed that pCSI reduced the risk of death by >85% (hazard ratio [HR] 0.13). pCSI remained cost-effective with any reduction in risk of death (HRs up to 0.99). The model was not sensitive to assumptions about rate of CNS progression, cost of radiation therapy, or model time horizon. Probabilistic sensitivity analysis demonstrated that pCSI was cost-effective in >99% of iterations. Conclusion: This study found that proton craniospinal irradiation may represent a cost-effective treatment option by reducing the risk of death among patients with solid tumor leptomeningeal metastasis. Additional research defining efficacy and optimal target populations who benefit most from pCSI will help confirm these findings.
