Robust intensity-modulated proton therapy with simultaneous integrated boost reduces the low-dose to surrounding tissues in pancreatic cancer patients

Purpose or Objective
Neoadjuvant or primary radiochemotherapy (RCT) are treatment options for patients with borderline resectable or unresectable locally advanced non-metastatic pancreatic cancer, respectively. Currently, the potential of RCT is hampered by an insufficient dose prescription to the target, limited by the close-by radiosensitive organs at risk (OAR). Dose-escalation to the gross tumor volume (GTV) along with the current standard dose to the elective volume using a simultaneous integrated boost approach (SIB) may lead to improved therapeutic outcome. In this in-silico feasibility study on SIB dose-escalation, we compared volumetric modulated arc therapy (VMAT) using photons with robust intensity-modulated proton therapy (IMPT).

Material and Methods
For each of five locally advanced pancreatic cancer patients, a VMAT and a robust multi-field optimized IMPT treatment plan were optimized on free-breathing treatment planning CTs using the RayStation treatment planning system (V5.99, RaySearch Laboratories AB, Sweden). For the photon treatment plan, the doses prescribed to 95% of the GTV and of the planning target volume (PTV: clinical target volume, CTV, plus a 5 mm margin) were to be at least 95% of 66Gy and 51Gy respectively, both in 30 fractions. For the proton plan, robust optimization to the CTV (instead of the PTV) with a setup uncertainty of 5mm and a density uncertainty of 3.5% was chosen, thus prescribing the dose of 51Gy(RBE) to 95% of the CTV (GTV with a margin and elective volume). The OAR dose constraints adhered to local guidelines and QUANTEC. For each treatment plan, doses to GTV, CTV, and OARs as well as the volume of normal tissue outside the CTV receiving a dose of ≥ 20Gy(RBE) (V20Gy) were compared.

Results
All treatment plans reached the prescribed doses to the GTV and CTV/PTV, irrespective of the technique. In some patients, doses to the bowel, stomach and liver exceeded the constraints since that OARs were next to or within the target volume. While the VMAT technique reduced the V50Gy of the bowel (median V50Gy: VMAT 20.4ccm vs. IMPT 23.3ccm) and stomach (median V50Gy: VMAT 1.2ccm vs. IMPT 4.5ccm), the radiation doses to the remaining gastrointestinal organs were lower for IMPT, e.g. liver (median V30Gy: VMAT 93.6ccm vs. IMPT 39.2ccm) and kidneys (median V20Gy of left/right kidney: VMAT 21.0ccm/16.1ccm vs. IMPT 13.8ccm/12.1ccm). Overall, the IMPT technique showed a lower dose deposition outside the targets for the surrounding normal tissue (median V20Gy: VMAT 1483.4ccm vs. IMPT 756.2ccm).

Conclusion
Disregarding the inter- and intra-fractional organ motion, dose escalation is possible for both treatment techniques. In comparison to VMAT, IMPT reduced the dose to the surrounding normal tissue, including relevant organs at risk. However, robust optimization increased the high-dose level to OARs overlapping with the target volume. Further patients will be included in this study and presented during the DKFK 2019.