The relative biological effectiveness of carbon ion radiation therapy for early stage lung cancer.

ABSTRACT:

Background and purpose

Carbon ion radiation therapy (CIRT) is recognized as an effective alternative treatment modality for early stage lung cancer, but a quantitative understanding of relative biological effectiveness (RBE) compared to photon therapy is lacking. In this work, a mechanistic tumor response model previously validated for lung photon radiotherapy was used to estimate the RBE of CIRT compared to photon radiotherapy, as a function of dose and the fractionation schedule.

Materials and methods

Clinical outcome data of 9 patient cohorts (394 patients) treated with CIRT for early stage lung cancer, representing all published data, were included. Fractional dose, number of fractions, treatment schedule, and local control rates were used for model simulations relative to standard photon outcomes. Four parameters were fitted: α, α/β, and the oxygen enhancement ratios of cells either accessing only glucose, not oxygen (OER_I), or cells dying from starvation (OER_H). The resulting dose-response relationship of CIRT was compared with the previously determined dose-response relationship of photon radiotherapy for lung cancer, and an RBE of CIRT was derived.

Results

Best-fit CIRT parameters were: α = 1.12 Gy^-1 [95%-CI: 0.97-1.26], α/β = 23.9 Gy [95%-CI: 8.9-38.9], and the oxygen induced radioresistance of hypoxic cell populations were characterized by OER_I = 1.08 [95%-CI: 1.00-1.41] (cells lacking oxygen but not glucose), and OER_H = 1.01 [95%-CI: 1.00-1.44] (cells lacking oxygen and glucose). Depending on dose and fractionation, the derived RBE ranges from 2.1 to 1.5, with decreasing values for larger fractional dose and fewer number of fractions.

Conclusion

Fitted radiobiological parameters were consistent with known carbon in vitro radiobiology, and the resulting dose-response curve well-fitted the reported data over a wide range of dose-fractionation schemes. The same model, with only a few fitted parameters of clear mechanistic meaning, thus synthesizes both photon radiotherapy and CIRT clinical experience with early stage lung tumors.

SUBMITTER: Jeong J 

PROVIDER: S-EPMC7770609 | biostudies-literature |

REPOSITORIES: biostudies-literature