Study design and patients
This planning study evaluated 13 patients with LAPC in the pancreatic head (n=10) or body (n=3) who were treated with IMRT in our institution. The clinical stages (Union for International Cancer Control 7th edition) were T3N0M0 in 5 patients, T4N0M0 in 7 patients, and T4N1M0 in 1 patient. The eligible criteria to this study are as follows: 1) primary tumors are located in the head or body of the pancreas, located close to the duodenum, 2) Planning tumor volume (PTV) sizes are less than 410 cm3 and 3) PTV is included in the field size of the Vero4DRT system (maximum, 15 cm × 15 cm).
Simulation and delineation of the target organ and organs at risk
Patients were immobilized with a vacuum pillow (BodyFIX, Medical Intelligence, Schwabmuchen, Germany) in a supine position with both arms raised above the head. Expiratory breath-hold treatment-planning CT was performed via an intravenous contrast-enhancing agent(without oral contrast agents) using either a LightSpeed RT scanner (GE Medical Systems, Waukesha, WI, USA) with slice thickness of 2.5 mm or SOMATOM Definition AS (Siemens Medical Systems, Erlangen, Germany) with slice thickness of 2 mm.
The gross tumor volume (GTV) included the tumor and metastatic lymph nodes. The clinical target volume (CTV) was defined as the GTV plus a 5-mm margin as well as the retropancreatic space and the para-aortic lymph node region between 10 mm superior to the celiac axis and 10 mm inferior to the superior mesenteric artery. The (PTV) was defined as CTV plus a 5-mm margin. The target organs and OARs were contoured based on the end-expiration phase CT. OARs were defined for the stomach, duodenum, small bowel, large bowel, kidneys, liver, and spinal cord. The planning OAR volumes (PRVs) were created with a 5-mm margin for the duodenum, small bowel, and spinal cord and a 10-mm margin for the stomach.
Treatment planning
The co-VMAT and DWA plans were created for the Vero4DRT system (Hitachi, Tokyo, Japan) using RayStation version 6.2. Dose distribution was calculated using collapsed-cone convolution algorithm with a dose grid of 2.5 mm (LightSpeed RT scanner) or 2.0 mm (SOMATOM Definition AS). The prescribed dose was 48 Gy in 15 fractions to 95% of PTV boost volume, defined as PTV excluding PRVs, while keeping the 36 Gy isodose line covering 98% of PTV volume.
DWA treatment plans were created via synchronous rotation of the O-ring and the gantry with optimal sequencing of dynamic multileaf collimators. A single non-coplanar trajectory called pancreas peaks up trajectory (Fig. 1) was applied to the DWA plans. The trajectory was divided into 5 segments. The O-ring rotated from 20° to 0°, 0° to 25°, 25° to 335°, 335° to 10°, and 10° to 340° during the first, second, third, fourth, and fifth segments, respectively. Simultaneously, the gantry rotated clockwise from 182° to 234°, 234° to 314°, 314° to 42°, 42° to 100°, and 100° to 178° in the five segments, respectively. The co-VMAT treatment plans consisted of one arc that rotated clockwise from 181˚ to 179˚.
We applied the same prescription policy and the same constraints to both the DWA and co-VMAT plans. Optimization was performed until the following criteria were met: (1) the maximum dose to the PTV was set to be <56 Gy, and (2) the dose to the OARs and PRVs should meet the dose constraints (Table 1) while keeping the dose coverage to PTV as mentioned above. If the PRV dose constraints cannot be fulfilled, a 5% reduction of the prescribed dose (45.6 Gy to 95% of PTVboost-34.2 Gy to 98% of PTV) was allowed. The dose constraints were based on the previous papers from our department [7,20,21].
Patient-specific quality assurance
The patient-specific quality assurance of co-VMAT and DWA was performed using the ArcCHECK (Sun Nuclear Corp., Melbourne, FL, USA). The measured dose distribution was compared with the calculated results of treatment plans. The gamma analysis with global 3%/3-mm gamma criteria was conducted to compare the calculated and delivered dose distributions[22]. The gamma passing rate for areas receiving isodoses above 10% was calculated using a global difference approach for the absolute dose. In addition, data on the MU and beam-on time for co-VMAT plans and DWA plans were collected.
Plan evaluation and statistical analysis
The dose volume indices (DVIs) for the following parameters were compared between co-VMAT plans and DWA plans: dose irradiated to 98%, 95%, 50%, and 2% of GTV and PTV (D98%, D95%, D50%, and D2%); irradiated volumes of the stomach, duodenum, large bowel, and small bowel to 39, 42, 45, and 48 Gy (V39Gy, V42Gy, V45Gy, and V48Gy); mean dose (Dmean) and V20Gy of the kidney; Dmean of the liver; maximum dose (Dmax) of the spinal cord; and near-maximum dose (D2cm3) of the PRV for the spinal cord. The DVIs, gamma passing rate, MU values, and beam-on time were compared using the paired t-test on two paired samples. All statistical analyses were performed using R (version 3.5.1). A p value of <0.05 was considered statistically significant.