Safety and outcome of stereotactic body radiation therapy (SBRT) with rectal hydrogel spacer for prostate cancer.

Abstract

76 Background: Ultra-hypofractionated radiotherapy delivered using stereotactic body radiotherapy (SBRT) is a cost-effective treatment for localized prostate cancer. Optimal dosing remains unclear, as commonly used 30-40Gy/5fx regimens appear to overestimate hypofractionation’s control benefits. Here, we report the largest experience of 45Gy/5Fx of SBRT for prostate cancer patients treated with hydrogel peri-rectal spacer (‘hydrogel’). Methods: An IRB-approved retrospective protocol was used to conduct a registry search identifying all patients with prostate cancer who received 45Gy/5Fx between 2015-2019 with hydrogel. Genitourinary (GU) and gastrointestinal (GI) toxicities were defined using the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0. The ASTRO-Phoenix failure definition of Nadir+2 ng/mL was used for biochemical failure. Results: We analyzed 250 low (9.2%), intermediate (85.2%), and high-risk (5.6%) prostate cancer patients with a median follow-up of 9.9 months (range: 0-45.7 months). Acute GU and GI grade ≥ II toxicities were noted in 15.2% and 7.2% of patients, respectively. Late GU grade II and III toxicities occurred in 24.0% and 1.2% of patients, respectively, while late GI grade II and III toxicities occurred in 4.0% and 0.4% of patients, respectively. In patients (N=44) with follow-up >2 years, late GU and GI grade III toxicities occurred in 4.55% and 2.27% of patients, respectively. A significant correlation was noted for acute GI and GU toxicity predicting the respective late GI and GU toxicity (p-value < 0.001 for both). Physician-reported Grade ≥ II new onset erectile dysfunction was 17.2%. A gradual decline in prostate-specific antigen with a mean nadir of 0.04 (95% CI: [0.018, 0.067]) at 36 months was noted. The actuarial freedom from biochemical failure was 96.33% at 3 years. Overall survival was 94.09% at 3 years with no deaths attributed to prostate cancer. Conclusions: SBRT treatment of 45Gy/5Fx with hydrogel is well tolerated with GU/GI toxicities comparable to those reported for conventional fractionation. Although short, the 3-year biochemical control rate is encouraging. Longer follow-up and prospective evaluation are warranted.

Hydrogel Spacer Rectal Wall Infiltration Associated With Severe Rectal Injury and Related Complications After Dose Intensified Prostate Cancer Stereotactic Ablative Radiation Therapy

“…16,17 Second, while infrequent but severe rectal toxicity has been observed with high dose SAbR in early studies without spacer gel, as reported by our group, 10,15 the patient's rectal dosimetry fell well within institutional constraints developed based on those experiences 15 and largely met constraints of lower SAbR dose regimens (Table 1). Notably, in our own institution's prospective 13 and retrospective 11 experiences because initiation of rectal hydrogel spacer placement with high dose SAbR across all risk groups (n = 250), no other single case of grade >2 rectal toxicity has been noted. 11 Third, rectal wall infiltration in retrospect was of substantial depth and resulted in an area of delamination of deep rectal wall muscle layers, best approximated on sagittal sequences.…”

“…Notably, in our own institution's prospective 13 and retrospective 11 experiences because initiation of rectal hydrogel spacer placement with high dose SAbR across all risk groups (n = 250), no other single case of grade >2 rectal toxicity has been noted. 11 Third, rectal wall infiltration in retrospect was of substantial depth and resulted in an area of delamination of deep rectal wall muscle layers, best approximated on sagittal sequences.…”

“…Indeed, our elected institutional SAbR dose (45 Gy in 5 fractions) exceeds that endorsed by other practitioners (36.25-40 Gy in 5 fractions) 19 and relies upon the demonstrated ability of rectal hydrogel spacer to facilitate rectal doses normally achieved by those latter regimens. 11 However, in the setting of delamination of muscle layers, we speculate that portions of vascular supply containing rectal wall may be displaced toward the high dose regions, creating the potential for an occult ischemic injury revealed upon dissolution of the hydrogel. This possibility would argue for conservative organ-at-risk delineation of rectum to include gel in areas of infiltration.…”

“…First, the timing of rapid and new symptom onset at~5 months after spacer gel insertion approximates the expected time of its resorption, whereas severe late radiation proctitis typically occurs later and is often preceded by acute/subacute symptoms, 16 particularly in the setting of high dose SBRT related injuries in our prior trial experience. 11,17 Classically, acute proctitis develops within 3 months of treatment, although late proctitis typically develops >9 months after treatment and is commonly associated with prior acute symptoms. 16,17 Second, while infrequent but severe rectal toxicity has been observed with high dose SAbR in early studies without spacer gel, as reported by our group, 10,15 the patient's rectal dosimetry fell well within institutional constraints developed based on those experiences 15 and largely met constraints of lower SAbR dose regimens (Table 1).…”

“…1). SAbR was prescribed to an escalated dose of 45 Gy in 5 fractions, delivered on nonconsecutive days over 3 weeks using volumetric modulated arc therapy, after treatment delivery and institutional constraints based upon data from successive phase 2 to 3 trials of SAbR at our institution, 10,11 including a trial specifically focused on use of rectal spacer and modified rectal constraints to reduce associated toxicity. Notably, rectal dosimetry (V24 Gy was~33% of rectal circumference vs 50% limit, V39 Gy was~10% of rectal circumference vs 35% limit, max dose to 0.035 mL volume was 43.8 Gy) was well within these limits.…”