Dose escalation for locally advanced pancreatic cancer: How high can we go?

Abstract

Purpose: There are limited treatment options for locally advanced, unresectable pancreatic cancer (LAPC) and no likelihood of cure without surgery. Radiation offers an option for local control, but radiation dose has previously been limited by nearby bowel toxicity. Advances in on-board imaging and treatment planning may allow for dose escalation not previously feasible and improve local control. In preparation for development of clinical trials of dose escalation in LAPC, we undertook a dosimetric study to determine the maximum possible dose escalation while maintaining known normal tissue constraints.

Methods and materials: Twenty patients treated at our institution with either SBRT or dose-escalated hypofractionated IMRT (DE-IMRT) were re-planned using dose escalated SBRT to 70 Gy in 5 fractions to the GTV and 40 Gy in 5 fractions to the PTV. Standard accepted organ at risk (OAR) constraints were used for planning. Descriptive statistics were generated for homogeneity, conformality, OAR's and GTV/PTV.

Results: Mean iGTV coverage by 50 Gy was 91% (±0.07%), by 60 Gy was 61.3% (±0.08%) and by 70 Gy was 24.4% (±0.05%). Maximum PTV coverage by 70 Gy was 33%. Maximum PTV coverage by 60 Gy was 77.5%. The following organ at risk (OAR) constraints were achieved for 90% of generated plans: Duodenum V20 < 30 cc, V30 < 3 cc, V35 < 1 cc; Small Bowel V20 < 15 cc, V30 < 1 cc, V35 < 0.1 cc; Stomach V20 < 20 cc, V30 < 2 cc, V35 < 1 cc. V40 < 0.5 cc was achieved for all OAR.

Conclusions: Dose escalation to 60 Gy is dosimetrically feasible with adequate GTV coverage. The identified constraints for OAR's will be used in ongoing clinical trials.

Figure. 1

Selected images from a typical simulation using intravenous contrast and without oral contrast. Patients are immobilized with an upper-body vac-lock cradle and instructed to be NPO for 3 hours to reduce gastric and duodenal filling. Patients were instructed to perform a comfortable inspiration breath hold with respiratory feedback provided by a real-time management system (Varian Medical Systems, Palo Alto, CA). One or 2 noncontrast scans are taken (A) before the administration of a 150 cc bolus of intravenous contrast, infused at a rate of 3 to 5 cc/second, followed by 4 to 6 scans at 30-second intervals after contrast administration (B-E).

Figure. 2

Target and organ-at-risk contouring technique using breath-hold scans. The gastrointestinal planning risk volume and high-dose prescription target volumes are defined in panels A-F. Target and organs at risk were delineated using an internal target volume based on all inspiration breath-hold scans to account for motion. An integrated gross target volume was also delineated using all available pretreatment imaging fused to simulation imaging, including pancreatic protocol (multiphasic computed tomography) and abdominal magnetic resonance imaging, where available.

Figure. 3

Sample plans for 3 individual dose-escalation stereotactic body radiation therapy patients. Representative targets and isodose lines for (A-C) patients 1 to 3, with the critical regions magnified for emphasis in (D-F). These examples demonstrate excellent coverage of prescription target volume (PTV)-70 by the 70 Gy isodose line. The PTV-40 (yellow color wash) was created by adding 3 mm to the integrated gross target volume structure and subtracting the gastrointestinal planning risk volume (green). The PTV-70 structure (green color wash) was created by a 3 mm contraction in 3 dimensions from the integrated gross target volume structure. For all plans, a high level of conformality was maintained, and careful attention was paid that the 40 Gy isodose line (orange) did not cross the internal target volume for gastrointestinal mucosa (beige).

Figure. 4

Distribution of organ-at-risk constraints and gross/planning target volume coverage for all dose-escalation stereotactic body radiation therapy plans. Plan parameters (A) included the homogeneity index (D_max/D_min and D95/D_min), conformality index (prescription isodose volume/planning target volume), and gradient index (0.5 prescription iodose volume/planning target volume). Conformality was overall very high (mean: confidence interval, 0.98 ± 24). Integrated gross target volume coverage (B) was evaluated for percent coverage by the 40 Gy, 50 Gy, 60 Gy, and 70 Gy isodose lines. Mean integrated gross target volume coverage by 50 Gy was 91% (±0.07%), by 60 Gy 61.3% (±0.08%), and by 70 Gy 24.4% (±0.05%). Distributions for V20, V35, and V35 are given for the duodenum (C), small bowel (D), and stomach (E).