Oxygen ions produced greater pancreatic cancer cell killing than carbon ions and photons

Oxygen-ion irradiation showed higher biological effectiveness and more persistent DNA damage than carbon ions or photons in pancreatic cancer cells.

KEY POINTS

  • This in vitro study compared photon, carbon-ion, and oxygen-ion irradiation in PANC-1 and BxPC-3 human pancreatic cancer cell lines, with and without gemcitabine. Experiments were conducted under normoxic conditions.
  • Oxygen ions produced the greatest reduction in clonogenic survival. At 10% survival, relative biological effectiveness was 4.2 versus 2.6 for oxygen versus carbon ions in PANC-1 cells and 4.4 versus 2.8 in BxPC-3 cells.
  • At 50% survival, relative biological effectiveness was 5.8 versus 2.4 in PANC-1 cells and approximately 4.4 versus 2.9 in BxPC-3 cells for oxygen versus carbon ions.
  • Gemcitabine produced pronounced radiosensitization with photons and carbon ions, whereas its interaction with oxygen ions was mainly additive. Oxygen ions nevertheless retained high intrinsic cytotoxicity.
  • Oxygen-ion irradiation generated larger and more persistent γH2AX foci, prolonged DNA-damage response activity, and more complex micronuclear damage. However, the oxygen beam used a dose-averaged linear energy transfer of approximately 145 keV/µm, higher than the carbon-ion value of 92 keV/µm and above levels typically used clinically.

CLINICAL TAKEAWAY

Oxygen ions showed a clear radiobiological advantage over carbon ions and photons in pancreatic cancer cell lines, supporting further investigation for highly radioresistant disease. However, the findings are preclinical, were generated at high experimental linear energy transfer, and include no in vivo efficacy or normal-tissue toxicity data, so they are preliminary and not practice-changing.

SOURCE

Clinical and Translational Radiation Oncology