Image-guided intensity-modulated radiotherapy for pancreatic carcinoma

Abstract

Purpose: To present the techniques and preliminary outcomes of ultrasound-based image-guided intensity-modulated radiotherapy (IG-IMRT) for pancreatic cancer.

Materials and methods: Retrospective analysis of 41 patients treated between November 2000 and March 2005 with IG-IMRT to mean total doses of 55 Gy (range, 45-64 Gy). We analyzed the clinical feasibility of IG-IMRT, dosimetric parameters, and outcomes, including acute gastrointestinal toxicity (RTOG grading). Survival was assessed for adenocarcinoma (n = 35) and other histologies.

Results: Mean daily image-guidance corrective shifts were 4.8 +/- 4.3 mm, 7.5 +/- 7.2 mm, and 4.6 +/- 5.9 mm along the x-, y-, and z-axes, respectively (mean 3D correction vector, 11.7 +/- 8.4 mm). Acute upper gastrointestinal toxicity was grade 0-1 in 22 patients (53.7%), grade 2 in 16 patients (39%), and grade 3 in 3 patients (7.3%). Lower gastrointestinal toxicity was grade 0-1 in 32 patients (78%), grade 2 in 7 patients (17.1%), and grade 4 in 2 patients (4.9%). Treatment was stopped early in 4 patients following administration of 30 to 54 Gy. Median survival for adenocarcinoma histology was 10.3 months (18.6 months in patients alive at analysis; n = 8) with actuarial 1- and 2-year survivals of 38% and 25%, respectively.

Conclusion: Daily image-guidance during delivery of IMRT for pancreatic carcinoma is clinically feasible. The data presented support the conclusion that safety margin reduction and moderate dose escalation afforded by implementation of these new radiotherapy technologies yields preliminary outcomes at least comparable with published survival data.

Figure 1

Typical intensity-modulated radiotherapy (IMRT) dose prescription for initial (upper screen) and boost planning target volume (PTV) (lower screen).

Figure 2

IMRT dose distribution for initial planning target volume (PTVi) and PTV boost. Displayed are the 100% (blue), 90% (red), 70% (yellow), and 50% (green) isodose lines. The respective clinical target volumes and PTVs are shaded in light tones of red to allow anatomy display.

Figure 3

Structure delineation for a BAT study displayed in an axial slice and sagittal reconstruction, as well as 3D rendering (upper figures). The lower figures show those structure outlines superimposed onto real-time acquired ultrasound images. Depicted are the mass in the pancreatic head (blue), biliary stent (red), arteries (aorta and superior mesenteric artery in orange), extrahepatic portal vein system (green), and liver outline (which is not used for alignments in pancreatic cancer) in yellow. Note that the color coding between CT simulation and BAT alignments varies. Anatomical structures are named on ultrasound images.

Figure 4

Display of frequency (y-axis) of directional shifts (left figures, x-axis), and absolute shifts (right figures, x-axis) along the x-, y-, and z-axes. Fitted onto the frequency of observed length of shifts are Gaussian distributions. The lowest figure displays the frequency (y-axis) and length of the 3D magnitude vector of corrective shifts (x-axis).

Figure 5

This set of figures documents the effect of hollow organ filling on pancreatic tumor displacement recognized by ultrasound-based image guidance. The left figure shows an extended stomach at the time of original treatment CT simulation. Following consistent 3D corrective shifts >25 mm derived from ultrasound-based image guidance, the patient was re-simulated to assess the cause of shift magnitude. CT-CT comparison confirmed that the significant altered state of stomach filling had changed the target location by a calculated 3D magnitude vector of 25.1 mm (anteroposterior displacement of the displayed surgical clip 17.6 mm, left/right 6.3 mm, craniocaudally 16.7 mm). Treatment was re-planned based on the second CT scan and subsequent image guidance suggested shifts were within the range of the entire cohort.

Figure 6

Linear regression plot of dose exposure of the kidneys with increasing PTVi volume and increased total prescribed dose.

Figure 7

Kaplan-Meier actuarial survival curves for the entire cohort (top); for adjuvant radiotherapy vs. definitive radiotherapy of locally advanced disease (middle), and survival following complete vs. incomplete resection (low).