👉 preclinical data suggest that protons and photons differ in their biological effects on cancer stem cells, with protons offering potential advantages, although the heterogeneity of cancer stem cells and the different proton irradiation modalities make the comparison of the results not so easy.
👉 although Proton Arc Therapy (PAT) may not produce better physical dose distributions than intensity modulated proton therapy, the radiobiological considerations associated with particular PAT techniques could offer the possibility of an increased therapeutic index.
👉 Proton minibeam therapy (PMBT) is a form of spatially fractionated radiotherapy wherein broad beam radiation is replaced with segmented minibeams—either parallel, planar minibeam arrays generated by a multislit collimator or scanned pencil beams that converge laterally at depth to create a uniform dose layer at the tumor. By doing so, the spatial pattern of entrance dose is considerably modified while still maintaining tumor dose and efficacy. Recent studies using computational modeling, phantom experiments, in vitro and in vivo preclinical models, and early clinical feasibility assessments suggest that unique physical and biological attributes of PMBT can be exploited for future clinical benefit
👉 the combination of FLASH and minibeams using proton beams, in spite of their complexity, may help to optimize the benefits of several or all the reviewed aspects, through the following concepts:
(1) the intrinsic advantages of protons to reduce the integral mid and low doses, will be volumetrically combined in synergy with the FLASH and minibeam effects as a whole;
(2) to reduce mid and high equivalent doses in critical organs around the tumour volume using the FLASH effect with high dose rates achievable with proton beams, both with passive or pencil beam approaches;
(3) to reduce healthy tissue complications by the minibeams space modulation in every beam path, where protons can be focalized with a steep penumbra and hence a high peak to valley ratio;
(4) to deliver an homogeneous dose to the target at any depth using the multiple scattering of proton minibeams in depth, and/or with multiple fields, or even setting a controlled inhomogeneous “vertex” doses escalation approach, optimizing intensity modulated proton therapy with robust solutions;
(5) to modify present approaches of immunological responses by the combination of concentration of lattice doses in very short time with a slight increase in LET, and the microstructure in time and space of both effects and
(6) to deliver single or hypofractionated treatments in very short time per fraction, facilitating the treatment of moving organs, specially when using pencil beam approaches and the associated risk of interplay effects, as well as the optimal use of minibeams with minimal risk of movement during the fraction.
Proton beams have in consequence one of the highest potentials to optimize the use of FLASH and Minibeams effects in radiation therapy, individually or in a synergistic combination.
👉 Re-irradiation can offer a potentially curative solution in case of progression after initial therapy; however, a second course of radiotherapy can be associated with an increased risk of severe side-effects. Particle therapy with protons and especially carbon ions spares surrounding tissue better than most photon techniques, thus it is of high potential for re-irradiation. Irradiation of tumors of the brain, head and neck and skull base involves several delicate risk organs, e.g. optic system, brainstem, salivary gland or swallowing muscles. Adequate local control rates with tolerable side-effects have been described for several tumors of these locations as meningioma, adenoid cystic carcinoma, chordoma or chondrosarcoma and head and neck tumors.
👉 proton therapy results in lower dose levels in multiple organs at risk, which translates into reduced acute toxicity (i.e. up to 3 months after radiotherapy), while preserving tumour control. Next to reducing mucositis, tube feeding, xerostomia and distortion of the sense of taste, protons can improve general well-being by decreasing fatigue and nausea. Proton therapy results in decreased rates of tube feeding dependency and severe weight loss up to 1 year after radiotherapy, and may decrease the risk of radionecrosis of the mandible.
👉 IMPT was able to statistically significantly decrease the radiation doses to the OARs. IMPT was superior in achieving the highest tumour dose while also decreasing the dose to the organs at risk.
👉 Along with high cure rates, the rate of (late) toxicities is reduced using this radiotherapy modality
Articles cited above and many more are available in Proton therapy special feature, The British Journal of Radiology 2020 93:1107