Comparing the outcome of proton beam irradiation with experimental x-ray and clinical photons in a sophisticated 3-D assay setup

Background and Aim:

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer with a median survival of <6 months. The role of radiotherapy in PDAC treatment is consistently under debate. Recent studies imply the superiority of proton versus photon irradiation and propose a benefit for pancreatic cancer patients. We therefore aimed at a systematical comparison of the treatment outcome of PDAC cells when exposed to different beams (photons, protons). Our study included the technical setup, establishment, and application of a multicellular 3-D assay to assess the putatively „curative“ biological endpoint of spheroid control probabilities (SCP).

Materials and Methods:

Four PDAC cell line models were applied in 96-well liquid-overlay spheroid culture. A clinical LINAC (6 MV) at a dose rate of 3 Gy/min and an experimental X-ray tube (220 kV) at a dose rate of 1.3 Gy/min were used for photon irradiation. For proton exposure, spheroids were placed within a spread-out Bragg peak (SOBP) of a double scattered proton beam (150 MeV) and irradiated with a dose rate of 3, 6 and 10 Gy/min. After single-dose irradiation (0-30 Gy), radioresponse was evaluated by a 60-day post-treatment monitoring of spheroid integrity, recovery, and volume growth.

Results and Conclusions:

For proton irradiation, variations in the dose rate were proven to neither alter the SCP nor the spheroid volume growth behavior. SCP and SCD50 (spheroid control dose 50%) turned out to be reproducible read-outs for 3-D culture treatment outcome. Experimental and clinical photon beams led to similar response of PDAC 3-D models. However, all spheroids showed a higher sensitivity to protons reflected by a significant reduction in the SCD50 values and an RBE of 1.2-1.5. New combinatorial treatment strategies with protons are now under evaluation.