Back to the Future: Helium Ion Therapy 2020

Abstract

Helium ions (4He) remained clinically unexploited worldwide since the shutdown of the clinical trials at the Lawrence Berkeley Laboratory (LBL) despite their favorable physical and biophysical characteristics. 4He afford minimal lateral scattering compared to protons, with a significantly reduced fragmentation tail compared to carbon ions and enhancement of bio-effects with relative biological effectiveness (RBE) values ranging between 1.3 and ∼3. Here, we outline milestones and on-going preparations for 4He clinical trials set for this year at our facility. Investigation of physical and biological phenomena of 4He was performed. Dosimetry was conducted in both homogenous and heterogenous (clinical-like) settings, verifying prediction of the first (non-clinical) 4He Monte Carlo (MC) and GPU-accelerated based treatment planning system (gTPS). Towards translation in patients, these systems are supporting development and integration of the first clinical treatment planning system. Additionally, in vitro, in vivo and in silico biological studies were carried out to establish robust prediction of biological effects for 4He. Prescription doses, fractionation schemes, tissue radio-sensitivity (α/βx) assignment, algorithm for effective dose calculation, and RBE model were selected for the upcoming clinical trials using 4He. In water and in anthropomorphic head phantoms, measurements yielded dose values within ∼2% against MC and gTPS predictions. For RBE modeling, measured RBE in vitro and in vivo indicates clinically relevant uncertainty of ±5-10% across different RBE model as a function of the various endpoints (dose, linear energy transfer and tissue type). Based on improved performance in the studied cell lines and tissues, as well as its accessibility in the literature, the modified microdosimetric kinetic model (mMKM) was selected as the clinical model for 4He RBE prediction. Through interdisciplinary collaboration between physicians, physicists and radiobiologists, we have addressed the prospective challenges and clinical decisions necessary for translating active scanning 4He to the clinic. Developed physical/biological models were successfully integrated in both research and commercial systems and validated against in vitro/in vivo experimental data. Together, these efforts mark an important step towards clinical translation 4He ion-beam therapy with state-of-the-art technologies.