Phase 2 Multicenter Study of Gantry-Based Stereotactic Radiotherapy Boost for Intermediate and High Risk Prostate Cancer (PROMETHEUS)

Abstract

Objectives: To report feasibility, early toxicity, and PSA kinetics following gantry-based, stereotactic radiotherapy (SBRT) boost within a prospective, phase 2, multicenter study (PROMETHEUS: ACTRN12615000223538). Methods: Patients were treated with gantry-based SBRT, 19–20 Gy in two fractions delivered 1 week apart, followed by conventionally fractionated IMRT (46 Gy in 23 fractions). The study mandated MRI fusion for RT planning, rectal displacement, and intrafraction image guidance. Toxicity was prospectively graded using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4). Results: Between March 2014 and July 2018, 135 patients (76% intermediate, 24% high-risk) with a median age of 70 years (range 53–81) were treated across five centers. Short course (≤6 months) androgen deprivation therapy (ADT) was used in 36% and long course in 18%. Rectal displacement method was SpaceOAR in 59% and Rectafix in 41%. Forty-two and ninety-three patients were treated at the 19 Gy and 20 Gy dose levels, respectively. Median follow-up was 24 months. Acute grade 2 gastrointestinal (GI) and urinary toxicity occurred in 4.4 and 26.6% with no acute grade 3 toxicity. At 6, 12, 18, 24, and 36 months post-treatment the prevalence of late grade ≥2 gastrointestinal toxicity was 1.6, 3.7, 2.2, 0, and 0%, respectively, and the prevalence of late grade ≥2 urinary toxicity was 0.8, 11, 12, 7.1, and 6.3%, respectively. Three patients experienced grade 3 late toxicity at 12 to 18 months which subsequently resolved to grade 2 or less. For patients not receiving ADT the median PSA value pre-treatment was 7.6 ug/L (1.1–20) and at 12, 24, and 36 months post-treatment was 0.86, 0.36, and 0.20 ug/L. Conclusions: Delivery of a gantry-based SBRT boost is feasible in a multicenter setting, is well-tolerated with low rates of early toxicity and is associated with promising PSA responses. A second transient peak in urinary toxicity was observed at 18 months which subsequently resolved. Follow-up is ongoing to document late toxicity, long-term patient reported outcomes, and tumor control with this approach.

Phase I/IIa trial of androgen deprivation therapy, external beam radiotherapy, and stereotactic body radiotherapy boost for high-risk prostate cancer (ADEBAR)

“…According to the IPSS questionnaire, 27% of patients had mild symptoms with an average score of 5 (range, 4-6), and the majority of patients (62%) demonstrated moderate symptoms with an average score of 12.8 (range, [8][9][10][11][12][13][14][15][16][17][18][19]. There was no statistically significant difference between 18 Gy and 21 Gy arms, except in baseline quality of life, which included more patients who answered "delighted" in 18 Gy arm. Figure 2 demonstrates changes in symptom scores at 5-time points (baseline, after WPRT, after CyberKnife boost, 1 month after radiotherapy, and 4 months after radiotherapy) in 25 patients.…”

“…HDRB might be replaced by EBRT while retaining its high-dose-rate effect. Pryor et al [18] evaluated a gantry-based linear accelerator for SBRT boost and reported a 2-year cumulative incidence of grade 2 or more GU toxicities of 24.9%. This result was slightly higher than that reported by other studies, except Anwar et al [9], which reported a rate of 1.4-14% (Table 3).…”

“…Several studies evaluated SBRT boost using various modalities after EBRT, and their results are summarized in Table 3 [ 7 – 12 , 17 , 18 ]. Except for two studies, the majority of studies utilized CyberKnife as a modality for the SBRT boost.…”

What is the quality of hydrogel spacer insertions? and which patients will benefit? A literature review

“…However, several other factors may have also contributed to the low GI toxicity scores, such as the use of coplanar arc therapy 390 Joseph Drabble and Heather Drury-Smith with flattening free filter dose delivery, reduced posterior PTV margins and intra-fraction imaging verification of fiducial markers using exactrac®. 16 Conclusion HS has been shown to reduce rectal planning doses in radical prostate radiotherapy. There is a correlation between placement symmetry and reduced rectal dose.…”

A Brief Review of Low-Dose Rate (LDR) and High-Dose Rate (HDR) Brachytherapy Boost for High-Risk Prostate

“…For patients with high-risk prostate cancer, treatment options most often include surgery or a combination of androgen deprivation therapy (ADT) and radiation therapy. External beam radiation therapy (EBRT) is the most common method to deliver radiotherapy for localized prostate cancer.Multiple studies have demonstrated that dose-escalated external beam radiation therapy (DE-EBRT) improves local control, freedom from biochemical failure, freedom from distance metastases, and decreases the need for salvage therapy (3)(4)(5)(6). DE-EBRT, however, has also been associated with increases in late genitourinary (GU) and gastrointestinal (GI) toxicities (3).…”