S. Harrow

UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy

Six UK studies investigating stereotactic ablative radiotherapy (SABR) are currently open. Many of these involve the treatment of oligometastatic disease at different locations in the body. Members of all the trial management groups collaborated to generate a consensus document on appropriate organ at risk dose constraints. Values from existing but older reviews were updated using data from current studies. It is hoped that this unified approach will facilitate standardised implementation of SABR across the UK and will allow meaningful toxicity comparisons between SABR studies and internationally.

Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study

Introduction The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of ‘isotoxic’ radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable. Methods and analysis Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years. Ethics and dissemination The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West—Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally. Trial registration number NCT01836692; Pre-results.

An assessment of cone beam CT in the adaptive radiotherapy planning process for non-small-cell lung cancer patients

OBJECTIVE To investigate the potential use of cone beam CT (CBCT) in adaptive radiotherapy (ART) planning process for non-small-cell lung cancer (NSCLC). METHODS 17 retrospective patients with NSCLC Stage T1-T4, who had completed a course of radiotherapy with weekly CBCT imaging were selected for the study. The patients had been delineated and planned for three-dimensional (3D) conformal treatment (prescription: 55 Gy in 20 fractions) based on free-breathing four-dimensional CT data. Of these initial 17 patients, 12 had full quantitative data on gross tumour volume (GTV) position and volume throughout treatment. GTV delineation was carried out on weekly CBCT by a clinical oncologist. For each patient, mean percentage change in GTV and centre of mass (COM) displacement (based on 3D vectors) were calculated throughout treatment. Volume overlap between GTVs was calculated. Correlation of the COM displacement and planning GTV (pGTV) was assessed. A linear mixed model with patients as random effects was fitted to the data to assess potential benefit from using ART for these patients. RESULTS Comparison of CBCT-based GTV acquired prior to Fraction 1 (cbctGTV1) to pGTV showed mean 20 ± 19% volume increase using a related sample Wilcoxon signed rank test p = 0.04. Correlation was identified between volume reductions and dose delivered (beta = -0.003, p < 0.001)-a highly statistically significant association. Compared with cbctGTV1, the mean ratios ± standard deviation were cbctGTV2, 0.93 ± 0.08; cbctGTV3, 0.84 ± 0.12; and cbctGTV4, 0.75 ± 0.14. The dice similarity coefficient was 0.81 ± 0.14, 0.78 ± 0.17, 0.73 ± 0.19, respectively. The COM was consistent throughout treatment (mean 0.35 ± 0.24 cm). A fitted model predicts that a mean change of 30% volume relative to cbctGTV1 occurs at a dose of approximately 50 Gy. CONCLUSION Using a 30% reduction in volume, ART would not be of benefit for all radiotherapy-alone-treated patients with NSCLC assessed in this study. For individual patients and patients with atelectasis, CBCT imaging was able to identify volume change. ADVANCES IN KNOWLEDGE For patients treated with 55 Gy in 20 fractions, target volume changes throughout treatment have been demonstrated using CBCT and can be used to highlight patients who may benefit from ART.

Re-irradiation for Locally Recurrent Lung Cancer: Evidence, Risks and Benefits

In spite of recent improvements in both the technical delivery of radiotherapy and systemic therapy in the treatment of non-small cell lung cancer, local recurrence rates after radiotherapy remain a significant challenge. In the setting of local relapse after radiotherapy, treatments such as surgical resection or radiofrequency ablation are often not appropriate owing to disease and patient factors. Re-irradiation may be a potential treatment option. This overview considers the published evidence and potential treatment strategies.

The Challenges Faced in Developing Novel Drug Radiation Combinations in Non-small Cell Lung Cancer

Lung cancer is the most common cancer diagnosed in the UK. Outcomes for patients with this disease remain poor and new strategies to treat this disease require investigation. One potential option is to combine novel agents with radiotherapy in clinical studies. Here we discuss some of the important issues to consider when combining novel agents with radiotherapy, together with potential solutions as discussed at a recent Clinical Translational Radiotherapy Group (CTRad) workshop.

UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy: Reply to Ghafoor et al.

MadamdWethankDrGhafoor and colleagues [1] for their insightful letter and interest in our consensus on stereotactic ablative radiotherapy dose constraints and warmly welcome discussion of the consensus constraints. We also thank Dr Ghafoor et al. for providing valuable data and clinical experience that are not reported in this detail in the available literature to date. However, in the data provided there is no information on the size of the lesions, the fitness of the patients treated, thepatient’s lung functionor thecombinedV20. With reference to the treatment of multiple lung lesions, in our consensus paper we advised that it may be preferable to treat individual lesions on alternate days, which has been the practice of a number of UK centres [2]. The rationale for this was to reduce the dose per fraction to the whole lung and therefore reduce the risk of clinically significant pneumonitis and late fibrosis. We accept that the evidence base for this recommendation regarding treatment on alternate days is lacking and hence we did suggest that more than one lung tumour could be treated on the same day if the combined V20 for all plans was below the tolerance for a single lesion, for small metastases in otherwise fit patients or in the situation of two or more lung lesions in close proximity to each other. In these scenarios it may be preferable to plan and treat these lesions on the same day to avoid any set-up uncertainty. We agree that it is highly desirable to assess the optimal sequencing of multiple stereotactic ablative radiotherapy treatments to lung lesions through clinical studies. Cognisant of this, we encourage clinicians to recruit the currently open UK studies (e.g. CORE, SARON and HALT), which permit the treatment of multiple lung lesions and which will hopefully provide important information regarding the treatment of multiple lesions in the lung [3e5]. G.G. Hanna*, F. McDonaldy, L. Murrayz, S. Harrowx, D. Landaujj, M. Ahmedy, K.N. Franksz *Centre for Cancer Research and Cell Biology, Queen’s University of Belfast, Belfast, UK yDepartment of Radiotherapy, Royal Marsden NHS Foundation Trust & Institute of Cancer Research, London, UK zDepartment of Clinical Oncology, St James’s Institute of Oncology, Leeds Cancer Centre, Leeds, UK xDepartment of Radiotherapy, Beatson West of Scotland Cancer Centre, Glasgow, UK jjDepartment of Oncology, Guy’s and St Thomas’ Hospital, London, UK

EP-1937: UK stereotactic ablative radiotherapy trials normal tissue dose constraints tolerance consensus

Results: A total of 1847 pts (904 right-sided and 943 leftsided) were treated with either 40 Gy/15 fx (912 pts) or 50 Gy/25 fx (935 pts). 388 of the left-sided pts were treated with gated RT, and 440 without. No information about gating was available for the remaining 115 pts. Dmax(CTV) was less than 110% of the prescription dose in 99.4% of the plans. More than 2 cm3 of the CTV received 107-110% of the dose in 1% of the hypo-fractionated plans. For the normofractionated plans, this deviation was observed in 3.5% of the plans. For 92.3% of the hypo-fractionated plans, less than 2% of the CTV was covered with doses above 105%, whereas 3.9% and 3.5% of the plans had minor and major deviations, respectively. For 80.8% of the pts, the part of the CTV covered with at least 95% of the prescription dose was in compliance with the guidelines. Minor and major deviations were observed for 12.6% and 6.6% of the pts, respectively. By taking laterality into consideration, 90.8% of the right-sided pts were in compliance with the guidelines compared to only 71.2% of the left-sided pts. For the left-sided pts with available information about gating, it was found that 87.4% and 59.3% of the pts treated with and without gated RT, respectively, were in compliance, thus indicating that shielding of the heart resulted in CTV under-dosage. This was supported by compliance to the protocol heart dose guidelines for 941 left-sided pts. Only one hypo-fractionated pt showed a major deviation in V35Gy and a minor deviation in V17Gy (data missing for one pt). The lung dose satisfied the protocol guidelines for 99.4% of the pts.