Development of an isotoxic decision support system integrating genetic markers of toxicity for the implantation of a rectum spacer

Introduction: Previous studies revealed that dose escalated radiotherapy for prostate cancer patients leads to higher tumor control probabilities (TCP) but also to higher rectal toxicities. An isotoxic model was developed to maximize the given dose while controlling the toxicity level. This was applied to analyze the effect of an implantable rectum spacer (IRS) and extended with a genetic test of normal tissue radio-sensitivity. A virtual IRS (V-IRS) was tested using this method. We hypothesized that the patients with increased risk of toxicity would benefit more from an IRS.

Material and methods: Sixteen localized prostate cancer patients implanted with an IRS were included in the study. Treatment planning was performed on computed tomography (CT) images before and after the placement of the IRS and with a V-IRS. The normal tissue complication probability (NTCP) was calculated using a QUANTEC reviewed model for Grade > =2 late rectal bleeding and the number of fractions of the plans were adjusted until the NTCP value was under 5%. The resulting treatment plans were used to calculate the TCP before and after placement of an IRS. This was extended by adding the effect of two published genetic single nucleotide polymorphisms (SNP’s) for late rectal bleeding.

Results: The median TCP resulting from the optimized plans in patients before the IRS was 75.1% [32.6–90.5%]. With IRS, the median TCP is significantly higher: 98.9% [80.8–99.9%] (p < .01). The difference in TCP between the V-IRS and the real IRS was 1.8% [0.0–18.0%]. Placing an IRS in the patients with SNP’s improved the TCP from 49.0% [16.1–80.8%] and 48.9% [16.0–72.8%] to 96.3% [67.0–99.5%] and 90.1% [49.0–99.5%] (p < .01) respectively for either SNP.

Conclusion: This study was a proof-of-concept for an isotoxic model with genetic biomarkers with a V-IRS as a multifactorial decision support system for the decision of a placement of an IRS.