J. Lilley

Radiation-induced second primary cancer risks from modern external beam radiotherapy for early prostate cancer: impact of stereotactic ablative radiotherapy (SABR), volumetric modulated arc therapy (VMAT) and flattening filter free (FFF) radiotherapy

Risks of radiation-induced second primary cancer following prostate radiotherapy using 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), flattening filter free (FFF) and stereotactic ablative radiotherapy (SABR) were evaluated. Prostate plans were created using 10 MV 3D-CRT (78 Gy in 39 fractions) and 6 MV 5-field IMRT (78 Gy in 39 fractions), VMAT (78 Gy in 39 fractions, with standard flattened and energy-matched FFF beams) and SABR (42.7 Gy in 7 fractions with standard flattened and energy-matched FFF beams). Dose-volume histograms from pelvic planning CT scans of three prostate patients, each planned using all 6 techniques, were used to calculate organ equivalent doses (OED) and excess absolute risks (EAR) of second rectal and bladder cancers, and pelvic bone and soft tissue sarcomas, using mechanistic, bell-shaped and plateau models. For organs distant to the treatment field, chamber measurements recorded in an anthropomorphic phantom were used to calculate OEDs and EARs using a linear model. Ratios of OED give relative radiation-induced second cancer risks. SABR resulted in lower second cancer risks at all sites relative to 3D-CRT. FFF resulted in lower second cancer risks in out-of-field tissues relative to equivalent flattened techniques, with increasing impact in organs at greater distances from the field. For example, FFF reduced second cancer risk by up to 20% in the stomach and up to 56% in the brain, relative to the equivalent flattened technique. Relative to 10 MV 3D-CRT, 6 MV IMRT or VMAT with flattening filter increased second cancer risks in several out-of-field organs, by up to 26% and 55%, respectively. For all techniques, EARs were consistently low. The observed large relative differences between techniques, in absolute terms, were very low, highlighting the importance of considering absolute risks alongside the corresponding relative risks, since when absolute risks are very low, large relative risks become less meaningful. A calculated relative radiation-induced second cancer risk benefit from SABR and FFF techniques was theoretically predicted, although absolute radiation-induced second cancer risks were low for all techniques, and absolute differences between techniques were small.

Prostate Stereotactic Ablative Radiation Therapy Using Volumetric Modulated Arc Therapy to Dominant Intraprostatic Lesions

Purpose To investigate boosting dominant intraprostatic lesions (DILs) in the context of stereotactic ablative radiation therapy (SABR) and to examine the impact on tumor control probability (TCP) and normal tissue complication probability (NTCP). Methods and Materials Ten prostate datasets were selected. DILs were defined using T2-weighted, dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Four plans were produced for each dataset: (1) no boost to DILs; (2) boost to DILs, no seminal vesicles in prescription; (3) boost to DILs, proximal seminal vesicles (proxSV) prescribed intermediate dose; and (4) boost to DILs, proxSV prescribed higher dose. The prostate planning target volume (PTV) prescription was 42.7 Gy in 7 fractions. DILs were initially prescribed 115% of the PTVProstate prescription, and PTVDIL prescriptions were increased in 5% increments until organ-at-risk constraints were reached. TCP and NTCP calculations used the LQ-Poisson Marsden, and Lyman-Kutcher-Burman models respectively. Results When treating the prostate alone, the median PTVDIL prescription was 125% (range: 110%-140%) of the PTVProstate prescription. Median PTVDIL D50% was 55.1 Gy (range: 49.6-62.6 Gy). The same PTVDIL prescriptions and similar PTVDIL median doses were possible when including the proxSV within the prescription. TCP depended on prostate α/β ratio and was highest with an α/β ratio = 1.5 Gy, where the additional TCP benefit of DIL boosting was least. Rectal NTCP increased with DIL boosting and was considered unacceptably high in 5 cases, which, when replanned with an emphasis on reducing maximum dose to 0.5 cm3 of rectum (Dmax0.5cc), as well as meeting existing constraints, resulted in considerable rectal NTCP reductions. Conclusions Boosting DILs in the context of SABR is technically feasible but should be approached with caution. If this therapy is adopted, strict rectal constraints are required including Dmax0.5cc. If the α/β ratio of prostate cancer is 1.5 Gy or less, then high TCP and low NTCP can be achieved by prescribing SABR to the whole prostate, without the need for DIL boosting.

Stereotactic Ablative Radiotherapy (SABR) in Patients with Medically Inoperable Peripheral Early Stage Lung Cancer: Outcomes for the First UK SABR Cohort

AIMS To report outcomes for the first UK cohort treated for early stage peripheral lung cancer using stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS Patients were included who received SABR between May 2009 and May 2012. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. Patients were treated according to the UK SABR Consortium Guidelines. Univariate and multivariate Cox regression was used to determine factors that influenced overall survival and local control. RESULTS In total, 273 patients received SABR for 288 lesions in the time period examined. The median follow-up was 19.7 months. The median overall survival for all patients was 27.3 months, with 1, 2 and 3 year overall survival of 78.0, 54.9 and 38.6%, respectively. The 1, 2 and 3 year rates of local control were 98.2, 95.7 and 95.7%, respectively. All patients completed the planned course of treatment and rates of Common Toxicity Criteria grade 3+ toxicity were low. On multivariate analysis, patients with Medical Research Council (MRC) breathlessness scores of 3-5 had worse overall survival compared with patients with scores of 1-2 (hazard ratio: 2.10; 95% confidence interval: 1.25-3.59) and the presence of histological diagnosis conferred improved overall survival (hazard ratio: 0.54; 95% confidence interval: 0.31-0.93), probably reflecting that patients who are considered well enough to undergo biopsy are generally fitter overall. No factors were identified that significantly influenced local control. CONCLUSIONS SABR is an effective and well-tolerated treatment option for patients with early stage peripheral lung cancer who are not suitable for surgery. No patient cohort was identified in whom SABR was considered inappropriate. This series adds to the existing positive data that support SABR for this patient group.

Lung stereotactic ablative radiotherapy (SABR): dosimetric considerations for chest wall toxicity

OBJECTIVE To investigate chest wall pain in patients with peripheral early stage lung cancer treated with stereotactic ablative radiotherapy (SABR), and to identify factors predictive of Common Terminology Criteria of Adverse Events Grade 2 + chest wall pain. METHODS Patients who received 55 Gy in five fractions were included. A chest wall structure was retrospectively defined on planning scans, and chest wall dosimetry and tumour-related factors recorded. Logistic regression was performed to identify factors predictive of ≥Grade 2 chest wall pain. RESULTS 182 patients and 187 tumours were included. There were 20 (10.9%) episodes of ≥Grade 2 chest wall pain. Multivariate logistic regression demonstrated that the maximum dose received by 1 cm(3) of chest wall (Dmax1 cm(3)) and tumour size were significant predictors of ≥Grade 2 chest wall pain [Dmax1 cm(3) odds ratio : 1.104, 95% confidence interval : 1.012-1.204, p = 0.025; tumour size (mm) odds ratio : 1.080, 95% confidence interval : 1.026-1.136, p = 0.003]. This model was an adequate fit to the data (Hosmer and Lemeshow test non-significant) and a fair discriminator for chest wall pain (area under receiver-operating characteristic curve: 0.74). Using the multivariate logistic regression model, parameters for Dmax1 cm(3) are provided, which predict <10% and <20% risks of ≥Grade 2 chest wall pain for different tumour sizes. CONCLUSION Grade 2+ chest wall pain is an uncommon side effect of lung SABR. Larger tumour size and increasing Dmax1 cm(3) are significant predictors of ≥Grade 2 chest wall pain. When planning lung SABR, it is prudent to try to avoid hot volumes in the chest wall, particularly for larger tumours. ADVANCES IN KNOWLEDGE This article demonstrates that Grade 2 or greater chest wall pain following lung SABR is more common when the tumour is larger in size and the Dmax1 cm(3) of the chest wall is higher. When planning lung SABR, the risk of chest wall pain may be reduced if maximum doses are minimized, particularly for larger tumours.

Pelvic re-irradiation using stereotactic ablative radiotherapy (SABR): A systematic review

BACKGROUND AND PURPOSE To perform a systematic review regarding the use of stereotactic ablative radiotherapy (SABR) for the re-irradiation of recurrent malignant disease within the pelvis, to guide the clinical implementation of this technique. MATERIAL AND METHODS A systematic search strategy was adopted using the MEDLINE, EMBASE and Cochrane Library databases. RESULTS 195 articles were identified, of which 17 were appropriate for inclusion. Studies were small and data largely retrospective. In total, 205 patients are reported to have received pelvic SABR re-irradiation. Dose and fractionation schedules and re-irradiated volumes are highly variable. Little information is provided regarding organ at risk constraints adopted in the re-irradiation setting. Treatment appears well-tolerated overall, with nine grade 3 and six grade 4 toxicities amongst thirteen re-irradiated patients. Local control at one year ranged from 51% to 100%. Symptomatic improvements were also noted. CONCLUSIONS For previously irradiated patients with recurrent pelvic disease, SABR re-irradiation could be a feasible intervention for those who otherwise have limited options. Evidence to support this technique is limited but shows initial promise. Based on the available literature, suggestions for a more formal SABR re-irradiation pathway are proposed. Prospective studies and a multidisciplinary approach are required to optimise future treatment.

A practical method of identifying data loss in 4DCT

BACKGROUND AND PURPOSE The design, testing and clinical implementation of a simple quality assurance tool which allows quick and accurate identification of regions of data loss and data interpolation in 4DCT data sets is reported. MATERIALS AND METHODS A 4DCT model, dependent on gantry rotation time and pitch, was developed to allow an understanding of the data collection and reconstruction processes. To test this model, 4DCT scans of a phantom were acquired using a Siemens SOMATOM Sensation 40 slice CT scanner. A radio-opaque rod mounted under the couch top was present during the phantom scans. RESULTS The model predicts that periodic regions of data loss occur when the respiration rate drops below a critical value. These results are verified by experimental data. Regions of data loss result in breaks in the imaged radio-opaque rod. CONCLUSIONS Regions of data loss in 4DCT data sets can be difficult to detect. Mounting a radio-opaque rod under the couch top allows regions of data loss and data interpolation to be quickly assessed on a patient by patient basis. This quality assurance tool has been successfully implemented into clinical use. The results of this work have implications for quality assurance programmes for 4DCT scanning.

PO-0853: A method for automatic selection of parameters in NTCP modelling

Purpose: In this study we present a fully automatic method to generate multiparameter normal tissue complication probability (NTCP) models and compare its results with a published model of the same patient cohort. Methods and Materials: Data were analysed from 345 rectal cancer patients treated with external radiotherapy to predict the risk of patients developing grade 1 or ≥2 cystitis. In total 23 clinical factors were included in the analysis as candidate predictors of cystitis. Principal component analysis (PCA) was used to decompose the bladder dose volume histogram (DVHs) into 8 principal components (PCs), explaining more than 95% of the variance. The dataset of clinical factors and PCs was divided into training (70%) and test (30%) datasets, with the training dataset used by the algorithm to compute an NTCP model. The first step of the algorithm was to obtain a bootstrap sample, followed by multicollinearity reduction using the variance inflation factor (VIF) and genetic algorithm optimisation to determine an ordinal logistic regression model that minimises the Bayesian information criterion (BIC). The process was repeated 100 times and the model with the minimum BIC was recorded on each iteration. The most frequent model was selected as the final ‘automatically generated model’ (AGM). The published model and AGM were fitted on the training datasets and the risk of cystitis was calculated. Results: The two models had no significant differences in predictive performance both for the training and test datasets (p-value>0.05), and found similar clinical and dosimetric factors as predictors. Both models exhibited good explanatory performance on the training dataset (p-values>0.44) which was reduced on the test datasets (p-values<0.05). Conclusions: The predictive value of the AGM is equivalent to the expert-derived published model. It demonstrates potential in saving time, tackling problems with a large number of parameters and standardising variable selection in NTCP modelling.

PO-0827: Elekta AgilityTM FFF for Lung VMAT SABR.

Conclusions: The Eclipse planning system is able to achieve a comparable plan quality for Elekta VMAT delivery technique to that of fixed field IMRT in terms of target coverage and critical structure sparing using optimizing templates without operator interference. Plans with 2 arcs show less exceeding of the objectives than plans with 1 arc. In the VMAT cases where the objectives are not met, adapting the optimizing parameters once results in an improvement of the target coverage and OAR sparing.