KEY POINTS
- Investigators measured proton biological effectiveness in Panc-1 and COLO 357 FG pancreatic ductal adenocarcinoma cells using a high-throughput 96-well platform sampling 12 discrete depths along an 81.4-MeV pristine proton Bragg curve.
- Radiation quality was characterized using dose-mean lineal energy, ranging from 1.9 to 20.0 keV/µm across the proton positions; parallel 6-MV photons at 0.8 keV/µm served as the biological reference.
- At approximately equal physical dose, biological response changed markedly with radiation quality: wells receiving about 5.4 Gy at 6.2 keV/µm showed substantially greater surviving cell density than wells receiving 5.3 Gy at 16.3 keV/µm near the distal region.
- RBE at 10% viability remained around 1.0 through the entrance and Bragg-peak region, then increased rapidly distally. In Panc-1 cells, RBE rose to 1.57 at 14.8, 3.03 at 18.7, and 4.56 at 20.0 keV/µm.
- COLO 357 FG showed an even steeper rise: RBE reached 1.59, 3.61, and 6.05 at the same three positions. The difference between the two cell lines was not statistically significant at individual positions because confidence intervals overlapped.
- COLO 357 FG also showed an unusual approximately linear proton dose-response with a near-zero quadratic component, despite demonstrating a conventional linear-quadratic response to photons, suggesting potentially different repair behavior with higher-quality proton exposures.
- These very high RBE values should not be transferred directly into clinical plans. The experiment used a pristine Bragg curve; clinical spread-out Bragg peaks generally have lower lineal energies around 5–10 keV/µm, and the endpoint was crystal-violet proliferation rather than clonogenic survival.
CLINICAL TAKEAWAY
A fixed proton RBE of 1.1 clearly does not describe every microscopic region of a proton beam, and the distal edge deserves particular biological attention in PDAC as well as adjacent normal tissues. This is mechanistic laboratory evidence, not a justification for changing clinical prescriptions or intentionally creating high-RBE hotspots.