Lattice or Oxygen-Guided Radiotherapy: What If They Converge? Possible Future Directions in the Era of Immunotherapy

Abstract

Palliative radiotherapy has a great role in the treatment of large tumor masses. However, treating a bulky disease could be difficult, especially in critical anatomical areas. In daily clinical practice, short course hypofractionated radiotherapy is delivered in order to control the symptomatic disease. Radiation fields generally encompass the entire tumor mass, which is homogeneously irradiated. Recent technological advances enable delivering a higher radiation dose in small areas within a large mass. This goal, previously achieved thanks to the GRID approach, is now achievable using the newest concept of LATTICE radiotherapy (LT-RT). This kind of treatment allows exploiting various radiation effects, such as bystander and abscopal effects. These events may be enhanced by the concomitant use of immunotherapy, with the latter being ever more successfully delivered in cancer patients. Moreover, a critical issue in the treatment of large masses is the inhomogeneous intratumoral distribution of well-oxygenated and hypo-oxygenated areas. It is well known that hypoxic areas are more resistant to the killing effect of radiation, hence the need to target them with higher aggressive doses. This concept introduces the “oxygen-guided radiation therapy” (OGRT), which means looking for suitable hypoxic markers to implement in PET/CT and Magnetic Resonance Imaging. Future treatment strategies are likely to involve combinations of LT-RT, OGRT, and immunotherapy. In this paper, we review the radiobiological rationale behind a potential benefit of LT-RT and OGRT, and we summarize the results reported in the few clinical trials published so far regarding these issues. Lastly, we suggest what future perspectives may emerge by combining immunotherapy with LT-RT/OGRT.

A Novel Radiotherapeutic Approach to Treat Bulky Metastases Even From Cutaneous Squamous Cell Carcinoma: Its Rationale and a Look at the Reliability of the Linear-Quadratic Model to Explain Its Radiobiological Effects

“…Moving from a low palliative radiation dose prescription toward a higher radical one causes some concerns about normal tissue tolerance, especially for the treatment of bulky tumors. Spatially fractionated RT (SFRT), specifically lattice RT, overcomes such an issue by delivering a highly heterogeneous radiation dose to large targets in order to spare the neighboring organs at risk (OARs) ( 11 ). Such a peculiar dose delivery method could face the typical non-homogeneous tumor growth by selecting the hypoxic regions to be boosted for overcoming their relative radioresistance ( 12 ).…”

Whole Brain Irradiation or Stereotactic RadioSurgery for five or more brain metastases (WHOBI-STER): A prospective comparative study of neurocognitive outcomes, level of autonomy in daily activities and quality of life

“…The treatment will be delivered using five non-coplanar arcs and a mono-isocentric technique supported by a dedicated Treatment Planning System (TPS), that is the BrainLab Elements MultiMet™. In case of many lesions (>10–15) this TPS allows to achieve a highly conformal dose distribution in a similar peak-valley fashion to another radiotherapy technique, that is the Spatially Fractionated one, characterized by a steep dose fall-off between high dose subvolumes within extracranial bulky tumors [26] .The daily portal images (EPID) matched with the Digital Reconstructed Radiographs (DRRs) will be employed for an accurate patient set-up (ExacTrac™ X-ray system).…”

Radiotherapy in Current Neuro-Oncology: There Is Still Much to Reveal

“…To further enhance its potential, proton therapy could be adopted for unconventional use: an almost homogeneous high dose can be delivered deep into the target through a physical grid, whose submillimetric holes would permit sparing of the overlying healthy brain tissue between micron-sized beams [20]. Such a microbeam array fits into the broader framework of spatially fractionated radiotherapy (SFRT), whose biological mechanisms are currently generating great interest among scientists [21].…”