Abstract Purpose To show that radiation response across cancer cell lines of the same anatomic site and histologic type varies remarkably for protons and carbon (C) ions. Materials and Methods We measured and obtained from the literature clonogenic survival of human cancer cell lines of the lung (n=18), brain (n=10) and pancreas (n=10) exposed to photons, protons, and C-ions to assess their variability in response. We also treated cancer cell lines with DNA repair inhibitors prior to irradiation to assess how DNA repair capacity affects their variability in response. We quantified the variability in response by calculating the relative range (range/mean) and the coefficient of variation (COV) of the dose at 10% survival fraction (D 10% ) and relative biological effectiveness (RBE 10% ). Results The relative range of D 10% for lung cancer cell lines varied from 55-92% for photons, protons, and C-ions, with the relative range in RBE varying from 16-45% for protons and C-ions. For brain and pancreatic cancer cell lines, the relative range of D 10% varied from 95-112%, and 39-75%, respectively, with the relative range in RBE varying from 27-33% and 25-50%, respectively. However, the COVs in D 10% were approximately equal across radiation qualities, varying from 0.24±0.07–0.35±0.10, 0.35±0.09–0.69±0.62 and 0.13±0.03– 0.21±0.04 for lung, brain and pancreatic cancer cell lines, respectively. Greater relative ranges in D 10% were observed in the cell lines with inhibited DNA repair, varying from 108%-157% for photons, protons, and C-ions, with relative ranges in RBE varying from 29-67%. The COVs in the D 10% were also greater for the cell lines treated with inhibitors of DNA repair, varying from 0.34±0.09–0.41±0.06. Conclusion Cell lines of the same anatomic site and histologic type have a remarkable variability in response, not only to photons but also to protons and C-ions. We attributed this variability to differences in DNA repair capacity. Category Biological Physics and Response Prediction

Cell lines of the same anatomic site and histologic type show large variability in radiosensitivity and relative biological effectiveness to protons and carbon ions