A randomised phase II trial of Stereotactic Ablative Fractionated radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the lung (TROG 13.01 SAFRON II)

Abstract

BackgroundStereotactic ablative body radiotherapy (SABR) is emerging as a non-invasive method for precision irradiation of lung tumours. However, the ideal dose/fractionation schedule is not yet known. The primary purpose of this study is to assess safety and efficacy profile of single and multi-fraction SABR in the context of pulmonary oligometastases.Methods/DesignThe TROG 13.01/ALTG 13.001 clinical trial is a multicentre unblinded randomised phase II study. Eligible patients have up to three metastases to the lung from any non-haematological malignancy, each < 5 cm in size, non-central targets, and have all primary and extrathoracic disease controlled with local therapies. Patients are randomised 1:1 to a single fraction of 28Gy versus 48Gy in four fractions of SABR. The primary objective is to assess the safety of each treatment arm, with secondary objectives including assessment of quality of life, local efficacy, resource use and costs, overall and disease free survival and time to distant failure. Outcomes will be stratified by number of metastases and origin of the primary disease (colorectal versus non-colorectal primary). Planned substudies include an assessment of the impact of online e-Learning platforms for lung SABR and assessment of the effect of SABR fractionation on the immune responses. A total of 84 patients are required to complete the study.DiscussionFractionation schedules have not yet been investigated in a randomised fashion in the setting of oligometastatic disease. Assuming the likelihood of similar clinical efficacy in both arms, the present study design allows for exploration of the hypothesis that cost implications of managing potentially increased toxicities from single fraction SABR will be outweighed by costs associated with delivering multiple-fraction SABR.Trials registrationACTRN12613001157763, registered 17th October 2013

Radiosensitivity of Lung Metastases by Primary Histology and Implications for Stereotactic Body Radiation Therapy Using the Genomically Adjusted Radiation Dose

“…27 The ongoing TROG 13.01 SAFFRON II study is assessing 28 Gy in one fraction versus 48 Gy in four fractions in pulmonary oligometastases. 28 However, the BEDs of these two fractionation schemes are very similar: 106.4 and 105.6, respectively. With high rates of local control, decreasing toxicity and treatment burden is the primary goal of the TROG 13.01 study.…”

Independent review of 4DCT scans used for SABR treatment planning

“…Review guidelines for 4DCT image sets were developed based on commissioning work 16 and experiences from quality assurance for several clinical trials. 17,18 An in-house training programme was developed for medical physicists to establish a minimum skillset for performing 4DCT reviews in the context of SABR. A patient-specific review checklist was designed to aid in the review process and facilitate data collection, which has been provided as supplementary material.…”

Treatment-Related Adverse Effects in Lung Cancer Patients after Stereotactic Ablative Radiation Therapy

“…Radiation-induced lung fibrosis can appear six months to one year post-SABR [ 31 ] and is characterised by the proliferation of fibroblasts and myofibroblasts which deposit connective tissue such as collagen, and extracellular matrix into the pulmonary tissue, causing the alveoli to collapse [ 30 , 31 ]. This comes as a result of cytokines and other cellular components migrating to the site of irradiation and causing a continual inflammatory process [ 30 ] which can lead to respiratory distress and right-sided heart failure [ 30 , 32 ].…”