The Woodruff School

SUMMARY

Dose-Volume effects have been shown to increase the radiation dose tolerance of critical organs-at-risk (OARs) in multiple normal tissues such as the brainstem, spinal cord, parotid glands and in animal models. The irradiated volume must be kept “small” on the order of millimeters for tissues to experience additional protection from dose-volume effects. For example, the brainstem may tolerate single-session dose over 45 Gray during trigeminal neuralgia radiosurgery! Additionally, mouse ears have demonstrated minimal toxicity from more than 60 Gy of single-fraction dose when the beam width was kept below 2 mm. Spatially Fractionated Radiation Therapy (SFRT) aims to deliver heterogeneous peak and valley dose regions to the tumor in contrast to homogeneous dose techniques such as intensity modulated radiotherapy (IMRT). A form of SFRT called minibeam radiation therapy (MBRT) typically uses beams on the order of sub-millimeter to a few millimeters which is within the size range for exploitation of dose-volume effects, but the connection between SFRT, MBRT and dose-volume effects has not been thoroughly explored. Glioma and glioblastoma are aggressive, radioresistant primary brain tumors with bleak prognosis and minimal treatment options, but LINAC-based photon MBRT in an animal study demonstrated complete tumor response for glioma when compared to stereotactic radiosurgery which only showed partial tumor remission. These results motivated this thesis work to develop novel techniques for delivering LINAC-based MBRT for overcoming radioresistance of aggressive tumors such as glioma/glioblastoma. In this defense, we will discuss the novel techniques of 2D “en face” honeycomb LINAC-MBRT, 3D “mini-LATTICE”, and “4π-MBRT” that have developed from the work of this thesis. We will show that with modifications to existing commercially available medical linear accelerators, LINAC-MBRT can be implemented with MV-photon beams to increase the therapeutic ratio and treatment outcomes of radioresistant diseases such as glioma/glioblastoma.

SUBJECT:	Ph.D. Dissertation Defense

BY:	Zachary Carter

TIME:	Friday, July 12, 2024, 10:00 a.m.

PLACE:	Boggs, 3-47

TITLE:	Design and optimization of mini-beam GRID and LATTICE therapy using linear accelerators

COMMITTEE:	Dr. C.K. Chris Wang, Chair (NREMP) Dr. Kenneth Brooks (NREMP) Dr. Eric Elder (NREMP) Dr. Justin Roper (NREMP) Dr. Anna Erickson (NREMP)

SUMMARY Dose-Volume effects have been shown to increase the radiation dose tolerance of critical organs-at-risk (OARs) in multiple normal tissues such as the brainstem, spinal cord, parotid glands and in animal models. The irradiated volume must be kept “small” on the order of millimeters for tissues to experience additional protection from dose-volume effects. For example, the brainstem may tolerate single-session dose over 45 Gray during trigeminal neuralgia radiosurgery! Additionally, mouse ears have demonstrated minimal toxicity from more than 60 Gy of single-fraction dose when the beam width was kept below 2 mm. Spatially Fractionated Radiation Therapy (SFRT) aims to deliver heterogeneous peak and valley dose regions to the tumor in contrast to homogeneous dose techniques such as intensity modulated radiotherapy (IMRT). A form of SFRT called minibeam radiation therapy (MBRT) typically uses beams on the order of sub-millimeter to a few millimeters which is within the size range for exploitation of dose-volume effects, but the connection between SFRT, MBRT and dose-volume effects has not been thoroughly explored. Glioma and glioblastoma are aggressive, radioresistant primary brain tumors with bleak prognosis and minimal treatment options, but LINAC-based photon MBRT in an animal study demonstrated complete tumor response for glioma when compared to stereotactic radiosurgery which only showed partial tumor remission. These results motivated this thesis work to develop novel techniques for delivering LINAC-based MBRT for overcoming radioresistance of aggressive tumors such as glioma/glioblastoma. In this defense, we will discuss the novel techniques of 2D “en face” honeycomb LINAC-MBRT, 3D “mini-LATTICE”, and “4π-MBRT” that have developed from the work of this thesis. We will show that with modifications to existing commercially available medical linear accelerators, LINAC-MBRT can be implemented with MV-photon beams to increase the therapeutic ratio and treatment outcomes of radioresistant diseases such as glioma/glioblastoma.