Simultaneous Integrated Boost for Radiation Dose Escalation to the Gross Tumor Volume With Intensity Modulated (Photon) Radiation Therapy or Intensity Modulated Proton Therapy and Concurrent Chemotherapy for Stage II to III Non-Small Cell Lung Cancer: A Phase 1 Study

Abstract

To establish, in the phase 1 portion of a prospective phase 1/2 study, the maximum tolerated dose of image guided intensity modulated radiation therapy (IMRT) or proton therapy (IMPT), both with a simultaneous integrated boost (SIB), for patients with stage II to IIIB non-small cell lung cancer receiving concurrent chemoradiation therapy. Patients had pathologically proven non-small cell lung cancer, either unresectable stage II to IIIB disease or recurrent disease after surgical resection, and could tolerate concurrent chemoradiation. Radiation doses were selectively escalated to the SIB volume (internal gross tumor volume+5-mm margin), and the dose to the planning target volume (internal gross tumor volume+8-mm margin for clinical target volume+5mm) was kept at 60Gy [cobalt gray equivalent (CGE)] over 30 fractions. Patients were randomized between the IMRT and IMPT groups if slots were available on the treatment machines for both groups. Otherwise, patients were allocated to IMRT or IMPT, whichever had an open treatment slot on the machine without randomization. Fifteen patients (6 IMRT, 9 IMPT) were enrolled. The highest doses to the SIB were 72Gy in the IMRT group and 78Gy(CGE) in the IMPT group. Nine patients (6 IMRT, 3 IMPT) received an SIB dose of 72Gy(CGE) [biologically effective dose=89.3Gy(CGE)], and 6 patients (IMPT) received an SIB dose of 78Gy(CGE) [biologically effective dose=98.3Gy(CGE)]. Dose-limiting (grade ≥3) toxicity (esophagitis) developed in 1 of the 9 patients given 72Gy(CGE) SIB. Grade ≥3 pneumonitis developed in 2 of the 6 patients treated to 78Gy(CGE) IMPT SIB: 1 (grade 3) at 3months after treatment and the other (grade 5, possibly related to treatment) at 2months after treatment. Only 1 patient developed a marginal tumor recurrence with a median follow-up of 25months (range, 4.3-47.4months). We recommend that an SIB dose of 72Gy(CGE) be used as the highest SIB dose for the planned randomized phase 2 study.