Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

Abstract

in current treatment plans of intensity-modulated proton therapy, high-energy beams are usually assigned larger weights than low-energy beams. Using this form of beam delivery strategy cannot effectively use the biological advantages of low-energy and high-linear energy transfer (LET) protons present within the Bragg peak. However, the planning optimizer can be adjusted to alter the intensity of each beamlet, thus maintaining an identical target dose while increasing the weights of low-energy beams to elevate the Let therein. the objective of this study was to experimentally validate the enhanced biological effects using a novel beam delivery strategy with elevated LET. We used Monte Carlo and optimization algorithms to generate two different intensity-modulation patterns, namely to form a downslope and a flat dose field in the target. We spatially mapped the biological effects using high-content automated assays by employing an upgraded biophysical system with improved accuracy and precision of collected data. In vitro results in cancer cells show that using two opposed downslope fields results in a more biologically effective dose, which may have the clinical potential to increase the therapeutic index of proton therapy.Worldwide the number of proton therapy centers has increased dramatically in recent years 1 . The expansion of proton therapy centers can be attributed to multiple factors. The first and foremost advantage of protons is that a Bragg-peak dose profile appears at the end of the range of a proton beam. The use of different beam modulation and shaping techniques makes it possible to deliver a uniform high dose to the tumors while sparing the surrounding normal tissues 2 . The uniform target dose can be achieved using the passive-scattering proton therapy (PSPT) technique or the more advanced intensity-modulated proton therapy (IMPT) technique employing scanned beams. Importantly, some clinical trials have indicated the advantages of proton therapy over traditional photon-based therapy 3-6 . However, there are still many challenging issues in modern proton therapy. One of the them is that the radiobiological characteristics of proton therapy have yet to be completely understood. In current clinical practice, the relative biological effectiveness (RBE) of protons to reference photons, such as x-rays from a

Spot-Scanning Hadron Arc (SHArc) Therapy: A Study With Light and Heavy Ions

“…For the 1F/2F/3F treatments, maximum LET D (LET D , max ) was located at the distal-end/outside of the target, while for SHArc treatments, LET D , max was located within the central core of the target volume (~8 keV･µm -1 , ~30keV･µm -1 and ~150keV･µm -1 for p, 4 He and 12 C ions, respectively and intra-field iso-energy configurations, described in recent works (e.g. PATCH optimization) [45]. The PATCH technique, however, substantially increases entrance dose (Fig.…”

Proton Therapy for Major Salivary Gland Cancer: Clinical Outcomes

“…In our cohort, 9 patients (12%) were treated who had undergone prior radiation, and they tolerated re-treatment well. With future advancements in treatment optimization, a further benefit with IMPT may come in the form of optimizing plans based on linear energy transfer and RBE, which, by altering beamlet intensity (increasing the weighting of low-energy beams), the linear energy transfer can be elevated within a target and still maintain the same physical dose [ 9 , 21 ]. That would be ideal for SGCs, given the propensity for certain histologic subtypes (ie, adenoid cystic carcinoma) to harbor resistant cancer stem cells and may further improve the therapeutic index of PBT [ 22 ].…”

“…Robust single-field and multifield optimization (SFO/MFO) allow treatment of complex volumes and maintenance of dosimetric equipoise in surrounding structures at both the proximal and distal extent [7,8]. From a biologic perspective, patients with radioresistant tumors that are prone to recurrence may also stand to benefit from future advances in IMPT that allow linear energy transfer and relative biological effectiveness (RBE)-optimized radiation planning [9]. Further, the ability to safely reirradiate (with cumulative doses) is made possible with advancements in particle therapy [2,[10][11][12].…”

Proton Therapy for Prostate Cancer: Challenges and Opportunities

“…By contrast, biological treatment planning and LET-guided dose optimization have been developed and commercially available for testing and clinic planning studies. They are mainly used in generating reference plans with LET-based dose optimization for guiding the planning of complex treatment involving critical normal tissue structures [ 84 , 85 , 86 ]. Subject to satisfactory demonstration of clinical evidence, LET-based dose optimization may potentially improve the quality of PT treatment plans.…”