Rectal Sparing Via Hydrogel Spacer For Dose-Escalated Hypofractionated Radiation Course In High Risk Localized Prostate Cancer: Analysis Of Dosimetric and Toxicity Outcomes
Radiation dose-escalation is a major issue in prostate cancer, since there is growing evidence that cure rates indicated by biochemical disease-free survival and prostate cancer-specific survival depend on the radiation dose to the target . However, increased radiation dose to the rectum results in dose – limiting toxicity . The aim of this study is to evaluate the contribution of an injection of an absorbable synthetic polyethylene glycol (PEG) hydrogel for temporarily separating the rectum and prostate during a dose-escalated hypofractionated course of radiotherapy (RT) for high – risk prostate cancer (PCa) in order to decrease the rectal radiation-induced toxicity.
Methods and results
Eight patients with high risk, localized PCa underwent a dose-escalated hypofractionated radiation schedule of 16 fractions of 3.5 Gy for a total dose of 56 Gy to prostate and seminal vesicles, considered isoeffective to 80 Gy with conventional fractionation with regard to tumor control (a/b value of 1.5 Gy) and administered with Helical Tomotherapy (HT). All patients were simulated before and after a transperineal injection of a spacer in order to increase the distance between the prostate and the rectal wall. MRI scans were used for anatomical assessment of rectal separation. HT plans were generated on both scans for dosimetric comparisons. Procedure adverse events and acute GI toxicity according to RTOG were documented. The hydrogel placement in the Denonvillier space was successfully obtained in all patients without complications, with a median gel thickness at midgland of 11 mm (range, 6-16 mm). Dosimetric comparisons between preinjection and postinjection plans showed a statistically significant reductions (p<0.005) in rectal dose across high dose levels, resulting in a maximum reduction in rectal volume receiving 90% and 75% of the prescription dose of 19.6 Gy (35%) and 15.68 Gy (28%), respectively. No significant dose reductions were seen at low rectal dose levels. After a median follow up of 6 months (range 3 to 12 months), no patients experienced RTOG grade ≥ 2 rectal toxicity and two patients were classified as having RTOG grade 1 rectal toxicity in the last week of radiotherapy, completely resolved within 40 days.
Despite advanced treatment delivery and a more favourable therapeutic ratio, that can be exploited by a hypofractionated approach, dose escalation leads to increased side effects [3-5]. As a consequence up to 20% of the patients develop acute and chronic grade ≥ 2 rectal toxicity after dose-escalated RT, either normo or hypofractionated [6-8]. A method of reducing the amount of rectum treated to higher dose levels would be expected to result in reduction of the rate of rectal toxicity. The current study shows that the decrease in high rectal dose levels obtained by the use of a hydrogel spacer is associated with negligible acute GI toxicity and allows dose-escalated hypofractionated radiotherapy. Longer follow-up is warranted to assess late toxicity and define which patients might benefit from this approach.
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