Individual isotoxic radiation dose escalation based on V20 and advanced technologies benefits unresectable stage III non-small cell lung cancer patients treated with concurrent chemoradiotherapy: long term follow-up

Under the assumption that the highest therapeutic ratio could be achieved by increasing the total tumor dose (TTD) to the limits of normal tissues, the phase I trial was conducted in patients with unresectable stage III non-small cell lung cancer treated with concurrent chemoradiotherapy, to determine the feasibility and effects of individual isotoxic radiation dose escalation based on bilateral lung V20 and advanced technologies. Consecutive eligible patients were assigned to cohorts of eight. V20 of each cohort was increased from 27% to 30%, 33%, 35%, 37%, and so on. The criterion for cessation of dose escalation was defined as ≥ 2 patients in each cohort experienced dose limiting toxicity. Isotoxic dose escalation was based on V20, functional imaging was used to improve the accuracy of radiotherapy. To test the power of escalation dose, patients with TTD over 66 Gy were assigned to the higher dose group (HD), while the others to the standard dose one (SD). In result, the recommended value of V20 was 35%. For all patients, follow-up ranged from 1 to 112 months, median overall and progression free survivals were 25.0 and 13.0 months, respectively. The 1-, 3-, 5- and 8-year overall survival (OS) rates were 72.5%, 22.5%, 17.5%, and 10.0%, respectively. Especially, the OS and local recurrence-free survival of patients in HD group were significantly longer than those in SD one (P=0.035, P=0.007, respectively) without increasing severe toxicity. Thus, individual isotoxic dose escalation based on V20 with advanced technologies was feasible and effective.