This is a mono-centric, prospective, two-arms, feasibility study in which the investigator will enroll up to 22 patients with locally advanced or metastatic cancers with at least one bulky (≥6cm) lesion. This study uses a novel, recently developed unconventional radiotherapy technique, consisting of a short course (3 fractions) high dose partial irradiation targeting exclusively the hypoxic segment of unresectable bulky tumors while sparing the peritumoral immune microenvironment for induction of immune-mediated tumoricidal bystander and abscopal effects.~The present study will explore the potential biological and physical advantages of particle-based radiotherapy to deliver a highly conformal radiation dose to the hypoxic tumor segment defined by using hypoxia-specific Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone) Positron Emission Tomography-Computer Tomography (64Cu-ATSM PET-CT) and dynamic contrast enhanced Magnetic Resonance Tomography imaging. Based on tumor location, volume and risk factors related to nearby organs at risk, patients will be divided in the high-dose or reduced-dose group which will be treated with different dose-schedules according to risk factors.~Additionally, radiotherapy will be administered at the precise timing, determined individually for each patient, based on the serially mapped homeostatic immune fluctuations by monitoring blood levels of the inflammatory markers. The objective is to synchronize the radiation treatment with the favorable, most reactive anti-tumor immune response phase, in order to break tumor´s immune-tolerance locally and systemically.
This study uses a novel, recently developed unconventional radiotherapy technique which consists of three high-dose fractions directed to special segments of unresectable bulky tumors.