A Prospective 4π Radiation Therapy Clinical Study in Recurrent High-Grade Glioma Patients

To evaluate the feasibility, safety, dosimetric benefits, delivery efficiency, and patient comfort in the clinical implementation of 4π radiation therapy.

Eleven patients with recurrent high-grade glioma were recruited for the trial. 4π plans integrating beam orientation and fluence-map optimization were created using an in-house column-generation algorithm. The collision-free beam solution space throughout the 4π steradian was determined using a computer-aided-design model of the Varian TrueBeam system and a human subject. Twenty beams were optimized for each case and imported into Eclipse for intensity modulated radiation therapy planning. Beam orientations with neighboring couch kicks were merged for increased delivery efficiency, generating plans with an average of 16 beam orientations. Volumetric modulated arc therapy (VMAT) plans with 3-4 arcs were also generated for each case, and the plan achieving superior dosimetric quality was selected for treatment. Patient comfort was surveyed after every fraction. Multiple 2-dimensional X-ray images were obtained to measure intrafractional motion.

Of 11 patients, 9 were treated with 4π. Mean and maximum organ at risk doses were equal or significantly lower (P < .05) with 4π than with VMAT. Particularly substantial dose reduction of 2.92 Gy in the average accumulated brainstem maximum dose enabled treatments that would otherwise not satisfy safe dose constraints with VMAT. One patient was not treated because neither plan met the dosimetric criteria. The other was treated with VMAT owing to comparable dosimetry resulting from a planning target volume located in a separate co-plane superior to organs at risk. Treatments were well tolerated, with an average patient comfort score of 8.6/10. Intrafractional motion was <1.5 mm for all delivered fractions, and the average delivery time was 34.1 minutes.

The feasibility, safety, dosimetric benefits, delivery efficiency, and patient comfort of 4π radiation therapy have been clinically demonstrated with a prospective clinical trial. The results elucidate the potential and challenges of wider clinical implementations.