Dose escalation model for limited-stage small-cell lung cancer

Background and purpose: To construct a model for the local dose-response relationship of limited-stage small-cell lung cancer (LS-SCLC) along with subsequent models for dose-per-fraction escalation. Materials and methods: Reported doses and 2-year progression free survival (PFS_2year) rates from LS-SCLC studies were used to construct a dose-response model. Modeling incorporated effects of chemotherapy, incomplete repair of sublethal damage and variations in both kick-off time for rapid reproliferation and effective tumor cell doubling time. Response was modeled as a function of overall treatment duration in order to shed light on the optimum radiotherapy treatment duration. Subsequent models were constructed for more aggressive radiotherapy by means of dose-per-fraction escalation for once a day (QD) and twice a day (BID) fractionation schedules. Results: Modeling response as a function of treatment duration resulted in an optimum treatment duration of 3 weeks for both fractionation schedules. Modeling for dose-per-fraction escalation resulted in an increase in the expected local PFS_2year for both fractionation schedules with possible gains in a BID schedule with lower expected late complication rates than a QD schedule yielding the same expected local PFS_2year. Conclusions: This modeling suggests more aggressive treatment through escalation of dose-per-fraction, which may result in substantial gains in local PFS_2year. This points towards treatment durations of 3 weeks as being optimal with a BID schedule predicting possible gains in local PFS_2year at lower rates of expected late complications than a QD schedule.