Treatment of pancreatic cancer tumors with intensity-modulated radiation therapy (IMRT) using the volume at risk approach (VARA): Employing dose-volume histogram (DVH) and normal tissue complication probability (NTCP) to evaluate small bowel toxicity

Abstract

The emergent use of a combined modality approach (chemotherapy and radiation) in pancreatic cancer is associated with increased gastrointestinal toxicity. Intensity-modulated radiation therapy (IMRT) has the potential to deliver adequate dose to the tumor volume while decreasing the dose to critical structures such as the small bowel. We evaluated the influence of IMRT with inverse treatment planning on the dose-volume histograms (DVHs) of normal tissue compared to standard 3-dimensional conformal radiation treatment (3D-CRT) in patients with pancreatic cancer. Between July 1999 and May 2001, 10 randomly selected patients with adenocarcinoma of the pancreatic head were planned simultaneously with 3D-CRT and inverse-planned IMRT using the volume at risk approach (VaRA) and compared for various dosimetric parameters. DVH and normal tissue complication probability (NTCP) were calculated using IMRT and 3D-CRT plans. The aim of the treatment plan was to deliver 61.2 Gy to the gross tumor volume (GTV) and 45 Gy to the clinical treatment volume (CTV) while maintaining critical normal tissues to below specified tolerances. IMRT plans were more conformal than 3D-CRT plans. The average dose delivered to one third of the small bowel was lower with the IMRT plan compared to 3D-CRT. The IMRT plan resulted in one third of the small bowel receiving 30.2 ± 12.9 Gy vs. 38.5 ± 14.2 Gy with 3D-CRT ( p = 0.006). The median volume of small bowel that received greater than either 50 or 60 Gy was reduced with IMRT. The median volume of small bowel exceeding 50 Gy was 19.2 ± 11.2% (range 3% to 45%) compared to 31.4 ± 21.3 (range 7% to 70%) for 3D-CRT ( p = 0.048). The median volume of small bowel that received greater than 60 Gy was 12.5 ± 4.8% for IMRT compared to 19.8 ± 18.6% for 3D-CRT ( p = 0.034). The VaRA approach employing IMRT techniques resulted in a lower dose per volume of small bowel that exceeded 60 Gy. We used the Lyman-Kutcher models to compare the probability of small bowel injury employing IMRT compared to 3D-CRT. The BIOPLAN model predicted a small bowel complication probability of 9.3 ± 6% with IMRT compared to 24.4 ± 18.9% with 3D-CRT delivery of dose ( p = 0.021). IMRT with an inverse treatment plan has the potential to significantly improve radiation therapy of pancreatic cancers by reducing normal tissue dose, and simultaneously allow escalation of dose to further enhance locoregional control.