Purpose: To demonstrate that the large variations in radiosensitivity between cell lines is the same relative size for higher LET radiation as for x-rays.
Methods: We compiled clonogenic survival data we measured with data from the literature for human cancer cell lines (n=38) exposed to x-rays and protons (9.9 keV/μm) or carbon (C) ions (13.3-77.1 keV/μm), parameterizing each cell’s radiosensitivity as the dose required to achieve 10% survival, D10%. For each radiation quality, we quantified the relative variability in radiosensitivity between cell lines using the coefficient of variation, COV(D10%). For each particle radiation quality, we compared the COV(D10%) to that for the same subset of cells exposed to x-rays via two-tailed z-tests. We further stratified the data into three histological subsets (brain, pancreatic and non-small cell lung cancer) based on tumor type, including only tumors for which no distinction is made in clinical dose prescription. Then, within each histological category, we compared the COV(D10%) values between radiation qualities.
Results: Even for high LET C-ions, there were remarkable variations in radiosensitivity between cell lines, with COV(D10%) values of 28±6% at 77.1 keV/μm compared to 34±7% for x-rays. Consequently, we could not detect significant differences in the COV(D10%) values for x-rays and any particle radiation quality. The same was true even after we stratified the data into histologic subsets. Indeed, within histologic subsets, we still found remarkable differences in radiosensitivity at high LETs, with brain cancer cells varying 43±18% to 77.1 keV/μm C-ions, non-small cell lung cancer cells varying 24±7% to 60.5 keV/μm C-ions and pancreatic cancer cells varying 16±4% to 60.5 keV/μm C-ions, compared to 37±15%, 34±10% and 15±4%, to x-rays, respectively.
Conclusion: Even for cell lines of the same histology, there are remarkable variations in intrinsic radiosensitivity that do not differ significantly between photon, proton or C-ion radiation.
Funding Support, Disclosures, and Conflict of Interest: This research was supported in part by RP170040, 1R21CA252411-01, Emerson Collective, and MD Anderson Cancer Center. Dr. Sawakuchi has research agreements with Alpha Tau Medical and Artios Pharma. Dr. Shaitelman has a research agreement with Exact Sciences.