Reducing Heart Toxicity In Medulloblastoma Using Proton Therapy


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Abdossalam Madkhali1,Mike Partridge1
1University of Oxford

Abstract

Background

Radiation therapy is known to cause acute and long term side effects. Some of those side effects are a major reason of mortality in cancer survivors. Heart disease after radiotherapy for Hodgkin and breast cancer patients is a major cause for mortality that it is offsetting the benefits of treatment (EBCTCG, 2016). In this work, potential benefits of using proton therapy in treatment of medulloblastoma to reduce heart toxicity is discussed and compared with benefit gained in reduction of secondary cancer.

Method

Increase in risk for rate of major coronary events for 3DCRT and proton plans for a patient with medulloblastoma (MB) was calculated using published model (Darby et al,2014), the NTCP for cardiac perfusion deficits was  modelled using LKB model and relevant parameters (Das et al, 2005), and finally, the mortality risk from ischemic heart disease (IHD) was modelled using relative seriality model and relevant parameters (Kallman et al,1992, Eriksson et al,2000). Risk of mortality from radiotherapy-induced secondary cancer (SC) was modelled as well using voxel-by-voxel dose maps and models that includes cell-kill components, linear quadratic (LQ) and linear model (LIN) (Timlin et al,2015).

Results

The heart mean dose in 3DCRT was 16.1 Gy, and 0.1 Gy in the proton plan. Risk of major coronary events were 119% (3DCRT ), 0.7% (proton). NTCP was 34.5%(3DCRT), 0.8%(proton). Risk of mortality from IHD was 1.61%(3DCRT) and 0.01%(proton), while mortality from SC was for 3DCRT: 1.08%(LQ), 0.10%(LIN) and for proton: 0.32%(LQ) and 0.03%(LIN)

Conclusion

Proton therapy for MB is expected to decreases risk of major cardiac events, mortality due to IHD and mortality from RT-induced secondary cancer significantly, when compared to 3DCRT. With cardiac late side effects being a major and important clinical burden post-RT,  and some would say more than secondary cancer risk, these results strengthen the argument to use proton therapy.

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