Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma

Abstract

Objective: To improve medulloblastoma proton therapy. Although considered ideal for proton therapy, there are potential disadvantages. Expected benefits include reduced radiation-induced cancer and circulatory complications, while avoiding small brain volumes of dose in-homogeneity when compared with conventional X-rays. Several aspects of proton therapy might contribute to reduced tumour control due to (a) the use of more homogenous dose levels which can result in under-dosage, (b) differences in relative biological effectiveness (RBE) between that prescription RBE of 1.1 and the RBE of brain and spinal cord (likely to exceed 1.1) and in medulloblastoma cells (where RBE is likely to be below 1.1). Such changes, although speculative for RBE, might result in potential underdosage of tumour cells and a higher bio-effect in brain tissue.

Methods: Dose distributions for X-ray and proton treatment are compared, with allocation of likely RBE values for fast growing medullolastoma cells and stable central nervous system tissue.

Results: These physical and radiobiological factors are shown to combine to give a higher risk of tumour recurrence with further risks on tumour control when dose reduction schedules used for X-ray therapy are replicated for proton therapy for "low-risk" patients.

Conclusion: The dose distributions and prescribed doses of proton therapy, taking into account RBE, in children and adults with medulloblastoma, need to be reconsidered.

Figure 1

Three-dimensional plot of relative biological effectiveness (RBE) and parameters A and B, which link α/β with RBE_max and RBE_min, respectively.

Figure 2

(a) Dose distribution across brain in temporoparietal region for parallel opposed fields using 6 MeV X-rays, showing non-uniformity of dose with excess dose near to the brain surfaces and in more anterior and posterior areas. (b) Dose profile across widest section of the plan shown in (a) where the maximum dose is 103%. Normally the dose is prescribed at midline, although could be prescribed as a maximum subcutaneous dose at 104%, which is shown in (a) more anteriorly.

Figure 3

Schematic diagram of depth dose profiles for X-rays and protons (assuming the proton dose is homogeneous) between two parallel opposed lateral fields for tissues between the meningeal surfaces. The plot does not show the dose decreases that occur close to the surface of the patient's skull owing to the breakdown of electronic equilibrium, but which are shown in Figure 2b.

Figure 4

Recurrence of medulloblastoma in an 8-year-old child after using low-dose fractionated treatment to 24 Gy and relative biological effectiveness=1.1. The recurrence is in superficial brain tissue at the level of maximum tissue separation and where the skull bone (black) is of minimum thickness.