High-dose concurrent chemo-proton therapy for Stage III NSCLC: preliminary results of a Phase II study.

Y Oshiro,N Hizawa,Y Sato,T Okumura,H Ishikawa,Y Goto,K Kurishima,S Homma,M Sakai,H Sakurai,M Mizumoto,M Onizuka

doi:10.1093/jrr/rru034

Abstract

The aim of this report is to present the preliminary results of a Phase II study of high-dose (74 Gy RBE) proton beam therapy (PBT) with concurrent chemotherapy for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients were treated with PBT and chemotherapy with monthly cisplatin (on Day 1) and vinorelbine (on Days 1 and 8). The treatment doses were 74 Gy RBE for the primary site and 66 Gy RBE for the lymph nodes without elective lymph nodes. Adapted planning was made during the treatment. A total of 15 patients with Stage III NSCLC (IIIA: 4, IIIB: 11) were evaluated in this study. The median follow-up period was 21.7 months. None of the patients experienced Grade 4 or 5 non-hematologic toxicities. Acute pneumonitis was observed in three patients (Grade 1 in one, and Grade 3 in two), but Grade 3 pneumonitis was considered to be non-proton-related. Grade 3 acute esophagitis and dermatitis were observed in one and two patients, respectively. Severe ( ≥ Grade 3) leukocytopenia, neutropenia and thrombocytopenia were observed in 10 patients, seven patients and one patient, respectively. Late radiation Grades 2 and 3 pneumonitis was observed in one patient each. Six patients (40%) experienced local recurrence at the primary site and were treated with 74 Gy RBE. Disease progression was observed in 11 patients. The mean survival time was 26.7 months. We concluded that high-dose PBT with concurrent chemotherapy is safe to use in the treatment of unresectable Stage III NSCLC.

Highlights

The prognosis of unresectable advanced non-small-cell lung cancer (NSCLC) remains poor despite advances in radiotherapy and medication
Obstructive pneumonia could not be controlled in one patient, and the chemotherapy agents were changed before the start of treatment
The other patient could not continue with the Proton beam therapy (PBT) because of the Great East Japan Earthquake, and photon radiotherapy was used as an alternative

Summary

Introduction

The prognosis of unresectable advanced non-small-cell lung cancer (NSCLC) remains poor despite advances in radiotherapy and medication. Concurrent chemoradiotherapy is the first treatment choice for unresectable advanced NSCLC. In the 2000s, dose escalation studies were encouraged, and doses > 70 Gy were delivered with concurrent chemotherapy [1,2,3,4,5,6]. The prognoses were favorable in many Phase I/II studies, with median survivals of > 20 months and toxicities that appeared tolerable [3,4,5,6]. In the Phase III study, there was no apparent survival benefit [7]. Proton beam therapy (PBT) has been utilized in advanced lung cancer [9,10,11]

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