Comparing dose-volume histogram and radiobiological endpoints for ranking intensity-modulated arc therapy and 3D-radiotherapy treatment plans for locally-advanced pancreatic cancer

Pancreatic adenocarcinoma patients have a poor prognosis, with the fi ve-year overall survival rate 5% [1]. Treatment options for these patients may include pre-operative or defi nitive chemo-radiotherapy (CRT). Patterns of failure suggest that inclusion of elective lymph nodes in the treatment volume may improve local control [2]. These extended volumes, in conjunction with large margins to account for breathing motion, generate substantial planning treatment volumes (PTV) which may increase the risk of gastro-intestinal (GI) toxicity. Several publications have investigated the use of intensity-modulated radiotherapy (IMRT) [3 – 7] and intensity-modulated arc therapy (IMAT) [8 – 11] for treatment of pancreatic cancer, where the improved dose conformation may reduce dose to surrounding normal tissue, and allow dose escalation for improved local control. Despite studies showing a correlation between dosimetric parameters and GI toxicity for three-dimensional (3D)-RT and IMRT [12] there is some debate over dose constraints for stomach, duodenum and small bowel. Differences in organ delineation and prescribed dose may limit the comparison of dose-volume histogram (DVH) parameters, and a standard dose-volume analysis is often limited to only a few points in the DVH data, which may not always correspond directly to a clinical outcome. However, radiobiological modelling evaluates treatment plans by analysing the entire DVH and reducing this multifactorial comparison into a single clinically relevant parameter. As the parameters used for modelling normal tissue complication probability (NTCP) are derived from observed rates of toxicity in clinical trials, these parameters should be cited as a range of values (e.g. covering a 95% confi dence interval). Each parameter set is specifi c for a selected endpoint and is also dependent on the patient cohort and the treatment technique used. Careful comparison of the predicted complications with observed clinical toxicity is required to validate each set of NTCP parameters which may be found in the literature [13]. Nonetheless, radiobiological modelling may be useful for assessing different planning techniques and dose prescriptions, and has been applied to compare predicted toxicity to stomach and duodenum for a dose escalation study using tomotherapy plans for pancreatic cancer [5]. The current study compares the use of NTCP models and dose-volume metrics to analyse RapidArc (IMAT) and three-dimensional conformal treatment (3D-RT) plans for locally-advanced pancreatic cancer (LAPC). Using commercially available biological evaluation software module (Eclipse, Varian, Palo Alto