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-III Non-Small Cell Lung Cancer: A Phase I Study

Publication date: Available online 3 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Melenda D. Jeter, Daniel Gomez, Quynh-Nhu Nguyen, Ritsuko Komaki, Xiaodong Zhang, Xiaorong Zhu, Michael O'Reilly, Frank V. Fossella, Ting Xu, Xiong Wei, Hui Wang, Wenjuan Yang, Anne Tsao, Radhe Mohan, Zhongxing Liao
PurposeThis phase I portion of a prospective phase I/II study sought to establish 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-IIIB non-small cell lung cancer (NSCLC) receiving concurrent chemoradiation therapy.MethodsPatients had pathologically proven NSCLC, either unresectable stage II-IIIB disease or recurrent disease after surgical resection, who could tolerate concurrent chemoradiation. Radiation doses were selectively escalated to the SIB volume (SIBV; internal gross tumor volume + 5 mm margin), and the dose to the planning target volume (PTV; internal gross target volume + 8 mm margin for CTV + 5 mm) was kept at 60 Gy (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.ResultsFifteen patients (6 IMRT, 9 IMPT) were enrolled. The highest doses to the SIB were 72 Gy in the IMRT group and 78 Gy (CGE) in the IMPT group. Nine patients (6 IMRT, 3 IMPT) received an SIB dose of 72 Gy (CGE) (BED=89.3 Gy (CGE)) and 6 patients (IMPT) received an SIB dose of 78 Gy (CGE) (BED=98.3 Gy (CGE)). Dose-limiting (grade ≥3) toxicity (esophagitis) developed in 1 of the 9 patients given 72 Gy (CGE) SIB. Grade ≥3 pneumonitis developed in 2 of the 6 patients treated to 78 Gy (CGE) IMPT SIB; one (grade 3) at 3 months after treatment, and the other (grade 5, possibly related to treatment) at 2 months after treatment. Only 1 patient developed a marginal tumor recurrence with a median follow-up of 25 months (range 4.3-47.4 months).ConclusionWe recommend that an SIB dose of 72 Gy (CGE) be used as the highest SIB dose for the planned randomized phase II study.

Teaser

Local failure is common after conventionally fractionated, standard-dose chemoradiation for NSCLC. Theoretically, higher doses could confer a survival benefit, but this has not been confirmed in a phase III trial using conventional techniques. Dose escalation by new strategies seems promising. Our study is trying to find the optimal dose and fractionation by image-guided IMRT or IMPT with a simultaneous integrated boost. This article presents our preliminary results of a phase I study.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-III Non-Small Cell Lung Cancer: A Phase I Study


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