Proton therapyPhotons, protons or carbon ions for stage I non-small cell lung cancer – Results of the multicentric ROCOCO in silico study
Introduction
The introduction of stereotactic body radiation therapy (SBRT) has led to an increase in radiotherapy use in early stage non-small cell lung cancer (NSCLC) patients and fewer untreated patients, which has driven up population-based survival for lung cancer [1]. SBRT is a form of high-precision radiotherapy, using large (ablative) radiation doses per fraction, generally in one to eight fractions over one to three weeks. A Biologically Effective Dose (BED) of more than 100 Gy has allowed for high local tumor control rates (>90%), comparable to those obtained with surgery, supporting its consideration in operable patients [2], [3], [4]. A pooled meta-analysis of the STARS and ROSEL trials has indicated non-inferiority of SBRT compared to surgery with respect to survival and disease progression, albeit in a small patient population with limited follow up. Furthermore, treatment related toxicity was generally low and found to be favorable compared to surgery, even though damage to central structures and the chest wall have been reported [4], [5]. The photon-based SBRT techniques have evolved over the years from 3-dimensional (3D) conformal photon radiotherapy (3D-CRT) to intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT).
In recent years, there has been a massive expansion in particle therapy centers (mainly proton therapy) in clinical operation. Charged particles are characterized by the presence of the so-called ‘Bragg peak’, i.e., dose deposition at an energy-dependent tissue depth, and a sharp dose falloff at the distal edge with no further dose deposition. Some centers use particles for (stereotactic) treatment of lung cancer and report outcomes seemingly comparable to photon radiotherapy despite the known difficulties with the delivery of particle beams to a moving tumor in the lung (e.g., range uncertainties, interplay effect) [6], [7]. Several dosimetric studies on particles have shown a significant reduction in dose to surrounding organs at risk (OAR) and thus short- and long-term toxicities [8], [9], [10], [11], [12].
While there are multiple options for delivery of photon- or particle-based radiation therapy in early stage lung cancer patients, it is currently not known which technique is best in terms of target coverage and low dose to OARs. A randomized controlled trial comparing these techniques would require a very large patient cohort to show significant differences in local control and/or toxicity and likely be fraught with accrual difficulties. Hence, the multicenter international Radiation Oncology Collaborative Comparison (ROCOCO) was initiated in 2007 conducting several comparative in silico trials in multiple primary tumor sites, including lung cancer [8], [13].
In this study on twenty-five patients with stage I NSCLC, we compared the doses to the OARs and the dose escalation probability for one SBRT fractionation schedule using five contemporary radiotherapy techniques with either photons (IMRT, VMAT and CyberKnife), double scattered protons (DSP) or intensity-modulated carbon ions (IMIT).
Section snippets
Patients
Twenty-five consecutive patients with stage I NSCLC who underwent SBRT at MAASTRO clinic (Department of Radiotherapy, Maastricht University Medical Center+, The Netherlands) between February 2011 and June 2013 were included in this in silico planning study. The maximum tumor diameter was 3 cm and all tumors were at least 2 cm separated from the mediastinal structures and bronchial tree [14]. Most tumors were located peripherally, with 15 tumors (or their planning target volume; PTV) overlapping
Results
Due to a technical obstacle, only twenty-four out of the 25 datasets were available for analysis.
The mean CTV was 20.7 cm3 (range 5.34–71.01 cm3). The anatomical distribution of the 24 lung tumors is shown in Fig. 1A–C. The mean dose to the target volumes and OARs after rescaling the dose to 99% of the CTV receiving at least 60 Gy is shown in Table 1. Mid-CTV dose distributions for a typical case are shown in Fig. 2. The Dmean and D2% to the CTV were significantly lower for DSP and IMIT than
Discussion
Several in silico planning studies are available in the literature comparing a type of stereotactic photon treatment with either carbon-ion or proton treatment for stage I NSCLC [9], [10], [11], [17]. However, the current international planning study is the largest in silico study to date and the first to compare multiple photon-based stereotactic radiotherapy plans (IMRT, VMAT and Cyberknife) with each other and with multiple particle therapy plans (DSP, IMIT) for early stage NSCLC.
In general,
Conflicts of interest
None.
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