Cost-Effectiveness of Subsequent Whole-Brain Radiotherapy or Hippocampal-Avoidant Whole-Brain Radiotherapy Versus Stereo

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ORIGINAL RESEARCH ARTICLE

Cost‑Effectiveness of Subsequent Whole‑Brain Radiotherapy or Hippocampal‑Avoidant Whole‑Brain Radiotherapy Versus Stereotactic Radiosurgery or Surgery Alone for Treatment of Melanoma Brain Metastases Anh Dam Tran1 · Gerald Fogarty2 · Anna K. Nowak3,4 · Vakaramoko Diaby5 · Angela Hong6 · Caroline Watts6,7 · Rachael L. Morton1,6

© Springer Nature Switzerland AG 2020

Abstract Background  A randomized phase III trial comparing whole-brain radiotherapy (WBRT) to observation following definitive local treatment of intracranial melanoma metastases with neurosurgery and/or stereotactic surgery (SRS) is underway. Objective  We sought to assess the pre-trial cost-effectiveness of WBRT, hippocampal-avoidant WBRT (HA-WBRT), and observation (SRS or surgery alone) for this population to guide trial data collection efforts and reduce decision uncertainty.  Methods  A time-dependent Markov model followed patients treated with neurosurgery or SRS who received subsequent WBRT, HA-WBRT or observation over a 5-year time horizon. Model inputs were sourced from published literature and results tested for robustness using probabilistic sensitivity analysis. Value of information (VOI) analysis was undertaken to guide data collection for the randomized trial. Results  Over 5 years, the WBRT strategy produced 1.74 QALYs (2.38 life-years) at a mean cost of $40,128 (costs in 2017 Australian dollars); HA-WBRT produced 1.88 QALYs (2.38 life-years) and cost $42,977; and SRS/surgery alone produced 1.65 QALYs (2.13 life-years) at a cost of $46,281. Probabilistic sensitivity analysis showed HA-WBRT was the preferred strategy in 77% of simulations. Cost-effectiveness results were most sensitive to utilities of the controlled-disease health state in the WBRT group, and costs of HA-WBRT. The EVPI for a randomized trial was estimated at $6,888 per person. Conclusions  HA-WBRT may be cost-effective for the treatment of melanoma brain metastases. The results predicted in our model can be validated with prospective trial data when available.

1 Introduction Nearly half (44%) of patients with American Joint Cancer Committee (AJCC) stage III/IV melanoma will develop brain metastases [1]. Recent data from phase III trials Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s4025​8-020-00560​-1) contains supplementary material, which is available to authorized users. * Anh Dam Tran [email protected] 1

comparing stereotactic radiosurgery (SRS) and SRS plus whole-brain radiotherapy (WBRT), or hippocampal-avoidant whole-brain radiotherapy (HA-WBRT) showed no difference in survival, despite a higher risk of intracranial recurrence in the SRS or surgery alone groups [2–4]. Melanoma is perceived as a radioresistant tumour, and the value of WBRT as an addition to SRS/neurosurgery is highly debated [5, 6].

4



Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia

5



Health Economics and Outcomes Research, Department of Pharmaceutical Outcomes and