PRONTOX - proton therapy to reduce acute normal tissue toxicity in locally advanced non-small-cell lung carcinomas (NSCLC): study protocol for a randomised controlled trial

Sebastian Zschaeck, Monique Simon, Steffen Löck, Esther G C Troost, Kristin Stützer, Patrick Wohlfahrt, Steffen Appold, Sebastian Makocki, Rebecca Bütof, Christian Richter, Michael Baumann, Mechthild Krause, Sebastian Zschaeck, Monique Simon, Steffen Löck, Esther G C Troost, Kristin Stützer, Patrick Wohlfahrt, Steffen Appold, Sebastian Makocki, Rebecca Bütof, Christian Richter, Michael Baumann, Mechthild Krause

Abstract

Background: Primary radiochemotherapy with photons is the standard treatment for locally advanced-stage non-small cell lung cancer (NSCLC) patients. Acute radiation-induced side effects such as oesophagitis and radiation pneumonitis limit patients' quality of life, and the latter can be potentially life-threatening. Due to its distinct physical characteristics, proton therapy enables better sparing of normal tissues, which is supposed to translate into a reduction of radiation-induced side effects.

Methods/design: This is a single-centre, prospective, randomised controlled, phase II clinical trial to compare photon to proton radiotherapy up to 66 Gy (RBE) with concomitant standard chemotherapy in patients with locally advanced-stage NSCLC. Patients will be allocated in a 1:1 ratio to photon or proton therapy, and treatment will be delivered slightly accelerated with six fractions of 2 Gy (RBE) per week.

Discussion: The overall aim of the study is to show a decrease of early and intermediate radiation-induced toxicity using proton therapy. For the primary endpoint of the study we postulate a decrease of radiation-induced side effects (oesophagitis and pneumonitis grade II or higher) from 39 to 12%. Secondary endpoints are locoregional and distant failure, overall survival and late side effects.

Trial registration: Registered at ClinicalTrials.gov with Identifier NCT02731001 on 1 April 2016.

Keywords: Locally advanced; Non-small-cell lung cancer (NSCLC); Phase II trial; Photon radiotherapy; Proton radiotherapy; Randomised clinical trial; Toxicity.

Figures

Fig. 1
Fig. 1
Flowchart of planning procedures and patient allocation
Fig. 2
Fig. 2
Flowchart of both randomised treatment arms and primary endpoint
Fig. 3
Fig. 3
Dose distribution of one patient with locally advanced non-small cell lung cancer (NSCLC) planned with intensity-modulated radiation therapy (IMRT) (left) or protons (right) showing lower doses to organs at risk (OAR) by proton therapy

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