D. Holyoake

Modelling duodenum radiotherapy toxicity using cohort dose-volume-histogram data

Background and purpose Gastro-intestinal toxicity is dose-limiting in abdominal radiotherapy and correlated with duodenum dose-volume parameters. We aimed to derive updated NTCP model parameters using published data and prospective radiotherapy quality-assured cohort data. Material and methods A systematic search identified publications providing duodenum dose-volume histogram (DVH) statistics for clinical studies of conventionally-fractionated radiotherapy. Values for the Lyman-Kutcher-Burman (LKB) NTCP model were derived through sum-squared-error minimisation and using leave-one-out cross-validation. Data were corrected for fraction size and weighted according to patient numbers, and the model refined using individual patient DVH data for two further cohorts from prospective clinical trials. Results Six studies with published DVH data were utilised, and with individual patient data included outcomes for 531 patients in total (median follow-up 16 months). Observed gastro-intestinal toxicity rates ranged from 0% to 14% (median 8%). LKB parameter values for unconstrained fit to published data were: n = 0.070, m = 0.46, TD50(1) [Gy] = 183.8, while the values for the model incorporating the individual patient data were n = 0.193, m = 0.51, TD50(1) [Gy] = 299.1. Conclusions LKB parameters derived using published data are shown to be consistent to those previously obtained using individual patient data, supporting a small volume-effect and dependence on exposure to high threshold dose.

EP-1474: The dosimetric effect of interfraction motion on the duodenum in pancreatic radiotherapy

could involve schedules employing fewer fractions than CFRT, but more than in a typical SBRT treatment while partly escalating the fractional dose. It was the purpose of this study to investigate heterogeneous fractionation patterns with respect to the dose per fraction, taking into account the spatial and dynamic aspects of the tumour oxygenation and the effect of accelerated repopulation of tumour cells in treatments extending over several weeks. Materials and Methods: Three-dimensional in silico tumours with heterogeneous oxygenation were simulated based on previous calculations from intervessel distance distributions. Homogeneous dose delivery was simulated employing 2 Gy per fraction as baseline and partly escalating the dose to 3 and 4 Gy per fraction corresponding to fractions delivered prior to or directly following a short interruption of the treatment as represented by the weekends. Survival was assessed on voxel level with the linear-quadratic (LQ) model taking into account the dose-modifying effect of the oxygenation. The effect of accelerated repopulation was incorporated assuming a kick-off time of 14 days and a potential doubling time of 5 days for NSCLC. Local control was evaluated as tumour control probability (TCP) through a Poisson-based model and dose-response curves were generated by systematically varying the total dose. Results: For tumours with a negligible level of spread-out hypoxia (left panel of Figure 1) and assuming that accelerated repopulation starts after two weeks, partly increasing the fractional dose could substantially improve local control even if no reoxygenation takes place. If however the effects of repopulation are neglected and the hypoxia is geometrically concentrated instead of being spread out throughout the tumour, the impact of reoxygenation is far more important than partly escalating the fractional dose, even for small hypoxic fractions (right panel of Figure 1).

PO-0713: Conformity analysis of target-volume definition for margin-directed boost in pancreatic cancer SBRT

Results: To date, 23 patients from 21 centres entered in the trial have been analysed. Mean Grey Level <399.745, Skewness >2.215, Kurtosis >0.6 were associated with improved PFS (p=0.0227, p=0.0218, p=0.0460 respectively) for medium filter 3.0. For filter 4.0, improved PFS was associated with Mean Grey Level <454.055 (p=0.0227) and Skewness >0.840 (p=0.0371). Mean Grey Levels of <565.535 (p=0.0251) and <542.5(p=0.0251) were associated with improved PFS for filters 5.0 and 6.0 respectively. For OS, mean grey levels of <34.845 (p=0.0182), <399.745 (p=0.0381) and <454.055 (p=0.0381) were associated with improved survival for filters 0.0, 3.0 and 4.0 respectively. An entropy level <5.6 was also found to be significant (p=0.0428) for improved overall survival using filter 2.0.

EP-1720: Impact of contouring variability on tumour control and normal tissue toxicity in liver SBRT

Results: An inverse correlation of the radio-sensitivity parameter assessed by the model was found with respect the dR2* (-0.65) for the Oxy group. A further subdivision according to positive and negative values of dR2* showed a larger average radio-sensitivity for the Oxy rats with <0 and a significant difference in the two distributions according to the Wilcoxon-Mann-Whitney test (p<0.05). Finally, the Pearson correlation coefficient (R^2>0.9) revealed a strong agreement of the FF-ANN output with the target radiosensitivity.

Conformity analysis to demonstrate reproducibility of target volumes for Margin-Intense Stereotactic Radiotherapy for borderline-resectable pancreatic cancer

Background and purpose Margin-directed neoadjuvant radiotherapy for borderline-resectable pancreatic cancer (BRPC) aims to facilitate clear surgical margins. A systematic method was developed for definition of a boost target volume prior to a formal phase-I study. Material and methods Reference structures were defined by two oncologists and one radiologist, target structures were submitted by eight oncologist investigators and compared using conformity indices. Resultant risk of duodenal bleed (NTCP) was modelled. Results For GTV, reference volume was 2.1 cm3 and investigator mean was 6.03 cm3 (95% CI 3.92–8.13 cm3), for boost volume 1.1 cm3 and 1.25 cm3 (1.02–1.48 cm3). Mean Dice conformity coefficient for GTV was 0.47 (0.38–0.56), and for boost volume was significantly higher at 0.61 (0.52–0.70, p = 0.01). Discordance index (DI) for GTV was 0.65 (0.56–0.75) and for boost volume was significantly lower at 0.39 (0.28–0.49, p = 0.001). NTCP using reference contours was 2.95%, with mean for investigator contour plans 3.93% (3.63–4.22%). Correlations were seen between NTCP and GTV volume (p = 0.02) and NTCP and DI (correlation coefficient 0.83 (0.29–0.97), p = 0.01). Conclusions Better conformity with reference was shown for boost volume compared with GTV. Investigator GTV volumes were larger than reference, had higher DI scores and modelled toxicity risk. A consistent method of target structure definition for margin-directed pancreatic radiotherapy is demonstrated.

SU-D-BRA-06: Duodenal Interfraction Motion with Abdominal Compression

PURPOSE To quantify the effect of abdominal compression on duodenal motion during pancreatic radiotherapy. METHODS Seven patients treated for pancreatic cancer were selected for analysis. Four patients were treated with abdominal compression and three without. The duodenum was contoured by the same physician on each CBCT (five CBCTs for patients with compression, four for non-compression patients). CBCTs were rigidly registered using a soft tissue match and contours were copied to the delivered plans which were all radical (BED > 50 Gy). The distance between the duodenum on the planning CT and each CBCT was quantified by calculating the root mean square (RMS) distance. The DVHs of each abdominal compression patient was converted to an EQD2 DVH (alpha/beta = 10) using an in-house tool and volumes receiving at least 25, 35, 45, and 50 Gy were recorded. RESULTS The maximum variation in duodenal volumes on the CBCTs for the four abdominal compression patients were 19.1 cm3 (32.8%), 19.1 cm3 (20.6%), 19.9 cm3 (14.3%), and 12.9 cm3 (27.3%) compared to 15.2 cm3 (17.6%), 34.7 cm3 (83.4%), and 56 cm3 (60.2%) for non-compression patients. The average RMS distance between the duodenum on the planning CT and each CBCT for all abdominal compression patients was 0.3 cm compared to 0.7 cm for non-compressed patients. The largest (and average) difference between the planning CT and CBCTs in volume of duodenum receiving more than 25, 35, 45 and 50 Gy for abdominal compression patients was 11% (5%), 9% (3%), 9% (2%), and 6% (1%). CONCLUSION Abdominal compression reduces variation in volume and absolute position of the duodenum throughout treatment. This is seen as an improvement but does not eliminate the need to consider dosimetric effects of motion. Abdominal compression is particularly useful in SBRT when only a few fractions are delivered. Alon Witztum is supported by an MRC/Gray Institute DPhil Studentship. Daniel Holyoake is supported by a CRUK/Nuffield Clinical Research Fellowship. Sam Warren and Mike Partridge are supported by CRUK grant C5255/A15935. Maria Hawkins received an MRC Fellowship MC_PC_12001/2.