Quality Rectal Hydrogel Placement Allows for Gel-Enabled Dose-Escalated EBRT (GEDE-EBRT) Without Rectal Interference in Prostate Cancer - Beyond the Abstract
The FLAME trial specifically showed that a focal external beam boost can improve bPFS without increasing the risk of toxicity. However, a persistent challenge in the pursuit of higher radiation doses has been the limitation imposed by rectal constraints, especially since 70% of dominant intraprostatic lesions lie in the peripheral zone near the rectum. In the FLAME trial, most lesions received less than full dose due to rectal proximity. While dose escalation with brachytherapy has also been proven to have a significant bPFS benefit, these procedures are time-consuming and provide both technical and logistical challenges. In this dose-escalation study, investigators at the University of Michigan at Providence explored the potential of strategically placed rectal hydrogel (RH) to surmount these limitations, ultimately allowing for escalated doses while preserving target coverage.
The study featured patients with high-quality RH (1cm depth from base to apex) and the development of treatment plans both with and without the use of RH. These plans were prescribed a standard dose of 70 Gy in 28 fractions to the prostate and proximal seminal vesicles (PSV), with an additional peripheral zone (PZ) boost or focal boost to 84 Gy, 98 Gy, or 112 Gy. To assess the impact of RH, plans with and without RH were compared.
In the analysis of the 18 plans incorporating a whole PZ boost, the study observed that the planning target volume for the boost (PTV_boost) received improved coverage in RH plans compared to non-RH plans (median 98.5 Gy vs 75.53 Gy, p < 0.01). For the 32 plans targeting simulated DILs with a prescribed dose of 112 Gy, the PTV_boost coverage (median D95% 112.48 Gy vs 102.63 Gy, p < 0.01) and rectal metrics demonstrated marked improvements in the presence of RH. Importantly, all rectal metrics showed significant enhancements with the inclusion of RH, confirming the potential for reducing rectal toxicity in dose-escalated treatments.
Notably, four non-RH plans, which maintained a minimum 4 mm rectal-PTV_boost gap, achieved D95% values exceeding 98% of the prescription dose for the PTV_boost. This suggests that there is a population for whom a less than ideal RH or no RH may be reasonable.
Lastly, another advantage of GEDE-EBRT explored in this study is error tolerance. A critical concern in radiation therapy is ensuring the radiation plan created in a planning system is truly delivered in the clinic. Many studies have used MRI linear accelerators or Calpyso to decrease the PTV margin on the prostate, which can have significant intra-fraction motion. However, these strategies are not available at all institutions, are costly, and are limited by overcorrection and delays between observed motion and correction. With a high-quality RH, we demonstrated that the dose fall-off posteriorly from the GTV can be more generous, which made these plans less susceptible to common patient shifts when compared to non-RH plans. Thus, the use of RH could be a more cost-effective way to address intra-fraction motion when delivering focal boosts.
This study underscores the necessity for placing high quality RH. Quality standards have been lacking but recent publications on technique support the possibility of defining and meeting quality standards for the majority of patients. (Grossman Adv Radiat Oncol 2023, Cousins Brachytherapy 2022). Given the clear dosimetric advantage of a well-placed RH, further work on technical improvements is ongoing including placement of RH under sedation, extensive water dissection, using moldable RH products, and developing more detailed, individualized techniques for placement. In practice, there are also concerns about tumor dissemination or displacement of posteriorly located tumors by RH insertion, though this remains a theoretical concern with no published evidence. Some strategies to mitigate this concern include neoadjuvant ADT, which improves radiographic and pathologic extracapsular extension, or low dose radiation prior to gel placement to decrease tumor viability.
In conclusion, this study details the concept that the placement of a high-quality RH enables the administration of high-dose radiation, up to 112 Gy, in 28 fractions (EQD2 160 Gy with α/β = 2.5), which we’ve termed gel-enabled dose escalation (GEDE-EBRT). This re-purposes gel placement for rectal protection to extreme dose escalation. GEDE-EBRT provides several advantages: dose-escalation to doses similar to brachytherapy, no compromise by rectal constraints, and improved tolerance to intra-fraction motion. This technique should be further investigated prospectively.
Written by: Jamie Takayesu, MD, Resident Physician, Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
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