EditorialDo protons have a role in the treatment of locally advanced NSCLC with radiotherapy?
Introduction
Photon external bean radiotherapy remains the cornerstone of radical treatment for inoperable locally advanced non-small cell lung cancer (LA-NSCLC) given concomitantly with platinum-based chemotherapy [1]. With a median overall survival of approximately 25–29 months [2], [3], research efforts continue to explore how both advanced radiotherapy techniques and novel systemic therapy and radiotherapy combination treatments can improve outcomes for this patient group. The goal of radical treatment is to achieve optimal therapeutic benefit with a high probability of tumour control for minimal toxicity. The Radiation Therapy Oncology Group (RTOG) randomised phase III 0617 study [3] comparing standard dose (60 Gy) to dose escalated radiotherapy (74 Gy) given with concomitant systemic therapy has highlighted in the modern era the importance of the dose received by normal tissues and toxicity in relation to overall survival, with the maximum grade of oesophageal toxicity and the proportion of heart receiving radiation dose both being predictive factors of inferior survival.
Section snippets
Advances in photon technology
The last two decades have seen many technical advances in photon radiotherapy. For treatment planning, the objective is to attain conformity of the planned dose to the target volume within minimal dose to surrounding normal tissues. There have been incremental advances in planning with improved robustness of photon planning algorithms and the ability to plan intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). There have also been important advances in assessment
The promise of proton therapy
A relevant limitation of photon based radiotherapy is its characteristic dose deposition curve within normal tissue with a long tail of dose fall-off limiting the conformality of target dose distributions. This important physical aspect is potentially improved by use of proton compared to photon therapy due to the characteristic advantage of the Bragg peak deposition of dose within tissue that is associated with lower entrance dose and minimal exit dose. The improved dosimetry of proton
Retrospective clinical data for proton therapy
Over the last few years there has been increasing use of protons for radical NSCLC treatment, albeit without randomised evidence to provide clear evidence of benefit. The recent retrospective analysis of survival outcomes from the U.S. national cancer database comparing proton versus photon therapy is the largest published dataset in treatment of NSCLC [11]. The study in patients with stage I–IV NSCLC includes 348 treated with protons and over 240,000 patients treated with photons between 2004
Randomised clinical data for proton therapy
Despite the challenge, randomised data are on their way. The results of a multi-institution randomised phase II trial comparing photon IMRT to passively scattered proton therapy (PSPT) in LA-NSCLC with concomitant chemotherapy (NCT00915005) were presented in abstract form at the American Society of Clinical Oncology (ASCO) annual meeting in 2016 [13]. Patients in the study had paired radiotherapy plans created using both treatment modalities to either 74 Gy if achievable or to 66 Gy if
Evolving proton technology and clinical experience
Proton technology is at a disadvantage to photon therapy due to its relative infancy in technological development. For example, over the course of the phase II randomised trial mentioned above, PSPT using wide proton beams that are conformally shaped to the target volume using customized apertures and compensators, was largely been replaced with intensity-modulated proton therapy (IMPT), which uses magnetic steering of multiple narrow proton beams (pencil beam scanning (PBS)) with modulation of
Proving the promise of protons
Rigorous and comprehensive evaluation of proton therapy remains challenging [15]. The RTOG 1308 trial team should be congratulated on their recruitment so far and on-going work to provide level I evidence to guide clinical practice, particularly in a landscape where the majority of ongoing proton trials are not randomised [16]. There is a limited window of opportunity to conduct these trials before loss of collective clinical equipoise and widespread availability of proton therapy ‘off-trial’
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Preclinical models of radiation-induced lung damage: Challenges and opportunities for small animal radiotherapy
2019, British Journal of Radiology