Перспективы применения комбинированных технологий в протонной терапии злокачественных новообразований

Abstract

Purpose: Evaluating the possibilities to increase proton radiotherapy therapeutic efficacy by means of combined (binary) technologies: simultaneous application of proton radiation and special drugs.
 Material and methods: Published studies assessing antitumor efficacy of proton radiation together with simultaneous tumor radiosensitizing chemical compounds administration in treating cancer are being reviewed and analyzed.
 Results: Two approaches to increase therapeutic efficacy of proton radiotherapy using drugs, which have abnormally large value of proton interaction cross section comparing to soft tissues, can be outlined recently. They are: 1) utilization of proton induced nuclear reactions producing high LET secondary radiation to increase absorbed dose in tumor; 2) utilization of protons and proton track’s secondary electrons interaction with high-Z nanoparticles (Z>52), that leads to redistribution of released proton energy in soft tissues and its localization in tumor volume.
 Limited number of the studies devoted to application of 11B(p,3a) nuclear reaction in proton therapy and contradictoriness of the obtained result do not allow to judge so far about the future prospects of the boron containing drugs utilization in proton therapy to increase its antitumor efficacy. However, this approach looks very attractive because of the already existing boron drugs successfully being applied in boron neutron capture therapy. Analysis of the metal nanoparticle application in radiotherapy showed that despite of the promising results showing impressive tumor suppression increase represented in many scientific papers only three pharmaceuticals based on nanoparticles reached Phase I/II Clinical Trials. Radiosensitizing mechanism of metal nanoparticles in radiotherapy is still unrevealed, unstudied and not formalized thus interfering nanoparticle based pharmaceuticals to be approved for Clinical Trials. Quantitative relationship between nanoparticles’ properties (i.e. chemical composition, shape, surface coating etc.), irradiation parameters and final biological effect (therapeutic efficacy) is still undetermined. 
 Conclusion: Fundamental and applied studies should be carried out to determine and describe the processes underlying in the basis of combined methods of proton radiotherapy. That would allow to perform both proper treatment planning, similar to conventional radiotherapy, as well as the prognosis of the therapy final outcomes in curing malignant tumors.