# Impact of Dosimetric Parameters on Tumor Control in Stereotactic Radiotherapy for Pancreatic Cancer: A Prospective Study on 104 Patients Treated with Simultaneous Integrated Protection (SIP)

## TL;DR

This study shows that using a specific radiotherapy technique called SIP can effectively treat pancreatic cancer with high local control and low toxicity.

## Contribution

The study identifies dosimetric parameters impacting tumor control in pancreatic cancer treated with SIP, a novel planning strategy.

## Key findings

- A mean dose to the PTV_SIP of at least 28 Gy is associated with better local control.
- PTV_SIP volume greater than 4 cc and whole PTV greater than 69 cc are linked to worse outcomes.
- SIP planning achieved excellent local control with low toxicity in pancreatic cancer patients.

## Abstract

Treating pancreatic cancer with stereotactic radiotherapy, a precise, high-dose radiotherapy modality, is challenging. The pancreatic gland moves with respiration, and more importantly, the duodenum, stomach, small bowel, and colon are highly sensitive to radiation. As a consequence, treating lesions in contact with such organs is highly complex. Moreover, planning in pancreatic cancer radiotherapy is highly related to physician experience and skill, and limited data are available concerning the major dosimetric variables influencing tumor control. In our prospective, single-arm study, 104 patients were treated with 45 Gy in six fractions, with the simultaneous integrated protection technique to better manage the area of intersection between critical organs and tumor. Our study showed excellent local control with low toxicity. We also identified important dosimetric variables impacting local cancer control, with an area of intersection between tumor and gut receiving a mean dose of at least 28 Gy being related to better local control. Our results may guide the design of future stereotactic radiotherapy trials for pancreatic cancer.

Background: One of the challenges in treating pancreatic ductal adenocarcinoma (PDAC) with stereotactic radiotherapy (SRT) is to manage lesions abutted to the duodenum, bowel and stomach. Simultaneous integrated protection (SIP) is one of the proposed approaches to increase plan reproducibility and quality. However, no clinical data are available regarding the dosimetric objectives impacting local control probability. Methods: This is a prospective, single-arm study. Key inclusion criteria were as follows: PDAC histology; tumor abutment with duodenum, stomach, or small bowel; and SRT schedule consisting of 45 Gy in six fractions. Delineation of the PTV overlapped with critical OARs (PTV_SIP) and PTV outside critical OARs (PTV_Dominant) was mandatory. Dose constraints were as follows: (near) maximum dose, D2cc, and D20cc to critical OARs 38 Gy, 32 Gy, and 24 Gy, respectively. This study was designed to prospectively investigate the main clinical and dosimetric parameters impacting freedom from local recurrence (FFLR). Results: From June 2019 to January 2024, 104 patients were enrolled. One-year FFLR was 91.7%. Fifteen events of local failure occurred (17.6%). Mapping of local relapses showed a relapse inside the PTV_SIP area in nine patients and outside the PTV_SIP in six cases (NS). Whole PTV > 69 cc, PTV_SIP > 4 cc, PTV-SIP/whole PTV ratio > 7%, (near) Dmin to PTV_SIP < 25 Gy, mean dose to PTV_SIP < 28 Gy, and (near) Dmin to PTV_Dominant < 29 Gy were associated with worse FFLR. Multivariable analysis showed PTV_SIP absolute volume of more than 4 cc, mean dose to PTV_SIP < 28 Gy and whole PTV > 69 cc were independently related to worse FFLR. One case of acute G4 toxicity and two cases of acute G3 toxicity occurred, with two late toxicity deaths not certainly due to treatment. Conclusions: In this prospective study, SIP planning strategy with six fractions is safe and effective in pancreatic targets with critical contact with critical OARs. Given its potential advantages, SIP planning is a potential innovative strategy that should be compared to standard SRT planning in an ad hoc trial design.