K. Aitken

Initial UK Experience of Stereotactic Body Radiotherapy for Extracranial Oligometastases: Can We Change the Therapeutic Paradigm?

AIMS To retrospectively review the toxicity and early outcome data from patients who have received stereotactic body radiotherapy (SBRT) for extracranial oligometastases at a single UK institution. MATERIALS AND METHODS Eligible patients had ≤3 extracranial metastases and performance status ≤2. Prior systemic therapy and radical treatment of oligometastastic relapse with any standard treatment modality was permitted. Patients with synchronous metastatic disease were excluded unless they had evidence of controlled primary disease after radical therapy. Follow-up consisted of clinical examination, biochemical and radiological assessments in accordance with standard clinical care. Progression events were defined using RECIST. Toxicity was evaluated using CTCAE v4.0. Local control, progression-free survival (PFS), freedom from widespread distant metastasis (defined as disease not amenable to further radical salvage therapy) and overall survival were calculated. RESULTS Between July 2011 and April 2014, 73 patients with 87 metastases received SBRT (range 1-3 per patient). The median follow-up was 14.5 months (range 0-26.4). The median PFS was 14.5 months (1 year PFS 57%, 2 year 28%); 1 year overall survival 96%, 2 year 79.8%; 2 year local control 88%. At 2 years, 46% of patients were free from widespread distant metastases. No ≥ grade 3 acute or late toxicity was observed. CONCLUSION At this time point, observed toxicity is minimal with excellent local control rates. This promising treatment paradigm requires further investigation in the context of a randomised controlled trial to establish if the addition of SBRT to standard care improves survival outcomes.

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.

Risk-adapted strategy partial liver irradiation for the treatment of large volume metastatic liver disease

The liver is a common site of metastases from many solid organ malignancies. In patients with oligometastatic liver disease, systemic therapy, generally in combination with surgical resection, is considered standard of care. In colorectal cancer, this combined approach has improved fi ve-year survival rates to 50 – 60% [1]. However, only 10 – 25% of patients will be initially appropriate for surgery, due to unfavourable disease distribution or co-morbidities [2]. For the remainder, a number of non-surgical invasive and non-invasive ablative techniques may be used as alternative modalities to achieve local control. Of these, partial liver irradiation (PLI), (also known as stereotactic body radiation therapy, SBRT) represents an attractive non-invasive option, with a rapidly expanding body of evidence supporting its use. High rates of LC (60 – 90% at two years), together with an acceptable toxicity profi le ( 10% G3 toxicity) have led to it being increasingly integrated into the therapeutic pathway [3,4]. Here it competes with alternative local options such as radiofrequency ablation (RFA), cryotherapy, microwave, selective internal radiation therapy (SIRT) and trans-arterial chemoembolisation (TACE). Small, favourably located lesions may be successfully ablated by a number of these techniques with similar local control outcomes, as demonstrated in a recent matched pair analysis of RFA compared to SBRT [5]. More challenging is the management of large volume lesions, often situated adjacent to critical structures, where many of these techniques are unsuitable or are known to result in inferior LC results. In this sub-group signifi cantly less reported experience exists, both in the use of PLI and alternative strategies. We have approached the safe treatment of large lesions with SBRT by individualising the radiation dose, using a normal tissue complication probability (NTCP) model. This effectively allows individualisation of tumour dose according to the modelled risk of radiation-induced liver disease (RILD) for each patient, a toxicity of particular concern when treating large lesions. The prescribed dose is dependent on the volume of normal liver tissue exposed to radiation and has been previously described [6]. This report evaluates the safety and effi cacy of a biologically driven prescription method for moderately hypofractionated RT strategy, in a heavily pretreated group of patients with, in general, larger volume liver metastases.

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.