Structure
Unresectable/neoadjuvant recommendationsa
Adjuvant/resected recommendationsb
Kidney (right and left)
Not more than 30 % of the total volume can receive ≥18 Gy. If only one kidney is functional, not more than 10 % of the volume can receive ≥18 Gy
If two functioning kidneys are present, no more than 50 % of the right and 65 % of the left kidney should receive >18 Gy. For IMRT planning, mean dose to bilateral kidneys should be ≤18 Gy.
If only one kidney is present, not more than 15 % should receive ≥18 Gy, and no more than 30 % should receive ≥14 Gy
Stomach, duodenum, jejunum
Max dose ≤55 Gy; not more than 30 % of the volume
can be between 45 and 55 Gy
Max dose ≤55 Gy; <10 % of each organ volume can receive between 50 and 53.99 Gy. <15 % of each organ volume can receive 45–49.99 Gy
Liver
Mean dose cannot exceed 30 Gy
Mean liver dose ≤25 Gy
Spinal cord
Max dose to a volume of at least 0.03 cc must be ≤45 Gy
Max dose ≤45 Gy
Intensity-modulated radiation therapy (IMRT):
IMRT allows for conformal target coverage while minimizing high dose to organs at risk (OARs) [21, 22]:
OARs include the stomach, duodenum, bowel, liver, kidneys, and spinal cord.
Utilization of intensity-modulated radiation therapy (IMRT) and fiducials should be considered when RT dose is above 55 Gy and when OARs are adjacent or overlapping with the PTV. Placement of fiducials and image-guided radiation therapy with cone beam CT images should also be considered to ensure tumor coverage and avoid OARs.
In the adjuvant setting, preoperative diagnostic scans along with the operative note, pathology report, and surgical clips are used to identify areas at risk of residual disease:
Tumor bed, peripancreatic elective lymph nodes, and surgical anastomoses (pancreaticojejunostomy, hepaticojejunostomy, gastrojejunostomy) are contoured as the clinical target volume (CTV).
If not using breath-hold techniques, an internal target volume (ITV) expansion is placed based on maximum and minimum excursion as defined by 4D CT simulation scans.
A planning target volume (PTV) expansion is placed according to physics capabilities and image guidance usage to account for patient setup error and is usually between 0.5 and 1 cm.
In neoadjuvant, borderline, and locally advanced/unresectable settings, anatomic and functional scans can assist with assessment of gross tumor and involved lymph nodes:
GTV is expanded by 5–15 mm to encompass regions at risk for harboring microscopic disease.
CTV is expanded to ITV and PTV based on target/breathing motion and image guidance capabilities, respectively.
Surgical clips and stents are contoured and expanded by 5 mm to assist with image guidance during daily setup using cone beam CT.
8.4.2 Short-Course Hypofractionation
Stereotactic body radiation therapy (SBRT):
SBRT should be delivered on trial or at experienced centers.
SBRT is typically delivered in 3–5 fractions over 1–2 weeks.
In the neoadjuvant/definitive/adjuvant settings, SBRT dose generally consists of 25–40 Gy in 5–12 Gy fractions [25].
In the palliative setting, SBRT dose generally consists of 25 Gy in 5 Gy fractions.
SBRT requires placement of 1–5 (preferably ≥3) fiducial markers for targeting purposes. The fiducial markers are placed directly into the tumor and/or periphery under endoscopic ultrasound (preferred) or CT guidance [26].
It is imperative to evaluate the DVH of the PTV and the critical OARs. No clear dose constraints for SBRT exist, but Table 8.2 outlines published dose constraints that have been utilized [27–29].
Table 8.2
Published dose constraints to surrounding organs at risk (OARs) for 3–5 fraction SBRT regimens
Mahadevan et al. (2011)
Chuong et al. (2013)
Herman et al. (2015)
SBRT regimen
8–12 Gy × 3 fractions
Dose painting technique: 7–10 Gy × 5 fractions to the region of vessel involvement; 5–6 Gy × 5 fractions to the remainder of the tumor
6.6 Gy × 5 fractions
Disease stage
LAPC
BRPC and LAPC
LAPC
kidney (right and left)
75 % < 12 Gy
Mean < 10 Gy
75 % < 12 Gy
Stomach, duodenum, jejunum
Dmax < 10Gy/fraction
Dmax 35 Gy
Mean < 20 Gy
<5 cc < 30 Gy
<1 cc < 35 Gy
9 cc < 15 Gy
3 cc < 20 Gy
1 cc < 33 Gy
Liver
30 % < 15 Gy
10 % < 30 Gy
50 % < 12 Gy
Spinal sord
Maximum 12 Gy
Maximum 20 Gy
1 cc < 8 Gy
PTV/GTV coverage
Rx isodose line covers ≥95 % of the PTV
A 5 mm or smaller expansion margin (extending up to the outer bowel wall) was included to determine the final planning target volume. Elective nodes not included
GTV to PTV expansion is 3 to 5 mm and treated in 25 to 30 Gy while simultaneously delivering 35 to 50 Gy delivered to the tumor vessel interface. Elective nodes were not included to limit dose to nearby normal structures
No more than 1 cc of the mPTV received >130 % of the prescription dose (49.2 Gy) and >90 % of the modified PTV received 100 % of the prescription dose (33 Gy). If these constraints could not be met, then 100 % of the GTV received ≥25 Gy
SBRT should be avoided if direct invasion of the bowel or stomach is observed on CT, MRI, or endoscopy as these patients may be at a higher risk of an ulcer or bleeding.
GTV is contoured and expanded to ITV, in the absence of breath-hold techniques, or directly to PTV if using ABC.
The stomach, duodenum, and bowel are contoured as “proximal organs at risk” and expanded by 2 mm to result in a “proximal OAR + 2 mm” structure.
The pancreas PTV expansion is limited by the “proximal OAR + 2 mm” structure to increase the feasibility of delivering high-dose to target volume with rapid dose falloff to adjacent normal tissues (Fig. 8.1).
Fig. 8.1
Anterior-posterior (top) and lateral (bottom) views of local recurrence plots for (a) surgery alone (orange), (b) chemotherapy (red), (c) chemoradiation (green), and (d) all groups. The celiac artery (yellow) and superior mesenteric artery (blue) are contoured (Adapted from Dholakia et al. IJROBP 2013)
SBRT can be used for re-irradiation of locoregional recurrences, usually with 5 Gy × 5:
Three publications have reported on SBRT re-irradiation after an initial median dose of 50.4 Gy CRT.
Lominska et al. at the University of Kansas reported on a median of 23 Gy SBRT delivered to 28 previously irradiated patients [30]. Median OS was 5.9 months from SBRT, and local control was 86 %. Late grade 3 GI toxicity was 7 % [30].
Wild et al. at Johns Hopkins reported a multi-institutional experience of 18 patients who received re-irradiation [31]. Median OS after SBRT was 8.8 months, and local control was 62 %. Only 1 patient (6 %) experienced a grade 3 GI toxicity.
Dagoglu et al. at Beth Israel published on their experience of 30 patients treated with 25 Gy SBRT re-irradiation [32]. Median OS was 14.0 months from SBRT, and local control was 78 %. Late grade 3 toxicity was 7 % and consistent with bowel obstruction.
Daily cone beam CT with alignment to bone and shift to fiducials, use of a hexapod, and NPO status with standardized fluid intake 2 h prior to SBRT ensures treatment safety and reproducibility.
Intraoperative radiation therapy (IORT):
The role of IORT is controversial and should only be performed at specialized centers.
IORT is delivered with electron beam RT (IOERT) or high-dose-rate brachytherapy (HDR-IORT);
An IORT dose of 10–20 Gy is generally delivered in combination with neoadjuvant or adjuvant CRT to 45–50.4 Gy EBRT.
It is sometimes used in cases where surgical resection may result in close or involved margins [33].
The target volume is determined clinically with feedback from the surgeon(s).
Areas at high risk for recurrence typically include the uncinate and/or SMA margin. These are determined at the time of surgery:
A 1–2 cm margin should be placed around the area at risk.
Ideally, the area treated should be photographed and mapped out with surgical clips to determine if the recurrence was within the irradiated field.
All normal structures should be displaced and/or shielded with lead from the IORT field.
The most critical OARs include the bowel and anastomoses if a bypass is performed.
The target volume may include the tumor and peripancreatic lymph nodes with IOERT:
Specialized treatment planning tools are needed for IOERT.
Proton beam therapy (PBT):
Proton therapy takes advantage of the Spread Out Bragg Peak to deposit high-dose RT into the at-risk areas while minimizing exit dose, thereby increasing the therapeutic window.
Hong et al. performed a phase I/II study of preoperative short-course PBT and capecitabine for resectable pancreatic cancer at the Massachusetts General Hospital [34]:
Thirty-five patients were treated in phase II with a dose of 25 GyE in five fractions.
Only two (4 %) experienced a grade ≥3 toxicity.
Eleven of 48 patients (22 %) did not undergo resection.
Median OS and 2-year OS rate were 17.3 months and 42 %, respectively. For the 37 resected patients, median OS was 27.0 months, and locoregional failure and distant metastases occurred in 16.2 % and 73 %, respectively. The effectiveness of PBT for LAPC was reported from two institutions, but no published reports describe long-term outcomes. Further investigations are needed to evaluate long-term impact of PBT on survival because the median follow-up period was limited to 1 year in both these reports [35, 36].Related posts:
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