Five-Year Outcomes of a Phase 1 Dose-Escalation Study Using Stereotactic Body Radiosurgery for Patients With Low-Risk and Intermediate-Risk Prostate Cancer

Zeléfsky, Michael J.; Kollmeier, Marisa A.; McBride, Sean; Varghese, Melissa; Mychalczak, Borys; Gewanter, Richard M.; Garg, Madhur; Happersett, Laura; Goldman, Debra A.; Pei, Xin; Lin, Mingjie; Zhang, Zhigang; Cox, Brett

doi:10.1016/j.ijrobp.2018.12.045

Cited by 98 publications

(86 citation statements)

References 15 publications

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“…IPSS scores were dichotomized into <15 and 15. The IPSS constraint was recommended only for our prior phase 1 study, but subsequently treated patients were deemed eligible for SBRT even at higher IPSS scores [8]. PSA failure was estimated from the start of RT until biochemical relapse.…”

Section: Discussionmentioning

confidence: 99%

“…The treatment planning approach for these patients has been described previously [8,11]. In brief, all patients underwent either electromagnetic transponder or fiducial marker placement under transrectal ultrasound guidance.…”

Section: Treatment Protocolmentioning

confidence: 99%

“…Nearly 90% of those who underwent biopsies after treatment did not demonstrate residual active disease. Dose-volume constraints for target and normal tissue structures used in treatment planning have been described previously [8]. The standard PTV D95 was 90-100% of the prescription dose; the maximum PTV dose did not exceed 112% of the prescription dose, and the mean dose to the PTV was 99-104% of the prescription, while meeting normal tissue constraints.…”

Section: Treatment Protocolmentioning

confidence: 99%

“…Ultrahypofractionated stereotactic body radiotherapy (SBRT) regimens have increasingly been used to treat clinically localized prostate cancer [1][2][3][4][5][6][7]. We conducted a phase 1 dose escalation study in low-and intermediate-risk prostate cancer patients and demonstrated improved tumor control outcomes in patients who received 40 Gy prescription doses based on 2-yr post-treatment biopsies [8]. Favorable tolerance profiles may be attributed to the use of image guidance to track inter-and intrafraction motion and tight planning target volume (PTV) margins with magnetic resonance imaging (MRI)-computed tomography (CT) fusion for target delineation and normal tissue contouring.…”

Section: Introductionmentioning

confidence: 99%

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Early Tolerance and Tumor Control Outcomes with High-dose Ultrahypofractionated Radiation Therapy for Prostate Cancer

Zeléfsky

Pinitpatcharalert

Goldman

et al. 2020

European Urology Oncology

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Section: Discussionmentioning

confidence: 99%

Section: Treatment Protocolmentioning

confidence: 99%

Section: Treatment Protocolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Early Tolerance and Tumor Control Outcomes with High-dose Ultrahypofractionated Radiation Therapy for Prostate Cancer

Zeléfsky

Pinitpatcharalert

Goldman

et al. 2020

European Urology Oncology

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“…Thus far, reports of toxicity outcomes after SBRT have been encouraging. Comparable rates of genitourinary and bowel toxicities to IMRT have been reported in preliminary trials and multi-institutional experiences (1,(4)(5)(6)13). Recently, a Phase III noninferiority clinical trial comparing conventional prostate EBRT to a seven-fraction prostate SBRT regimen (4270 cGy) revealed a comparable acute end-of-treatment urinary and bowel toxicity outcomes, as well as at ve-year follow-up (7).…”

Section: Introductionmentioning

confidence: 91%

Strict bladder filling and rectal emptying during prostate SBRT - does it make a dosimetric or clinical difference?

Byun

Gorovets

Jacobs

et al. 2020

Preprint

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Abstract Background: To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences. Methods: Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to maintain a full bladder and empty rectum prior to simulation and each treatment. A single reviewer delineated organs at risk (OARs) on the simulation (Sim-CT) and Cone Beam CTs (CBCT) for analyses. Results: Bladder and rectum volume reductions were observed throughout the course of SBRT, with largest mean reductions of 86.9 mL (19.0%) for bladder and 6.4 mL (8.7%) for rectum noted at fraction #5 compared to Sim-CT (P<0.01). Higher initial Sim-CT bladder volumes were predictive for greater reduction in absolute bladder volume during treatment (ρ=-0.69; P<0.01). Over the course of SBRT, there was a small but significant increase in bladder mean dose (+4.5±12.8%; P<0.01) but no significant change in the D2cc (+0.8±4.0%; P=0.28). The mean bladder trigone displacement was in the anterior direction (+4.02±6.59 mm) with a corresponding decrease in mean trigone dose (-3.6±9.6%; P<0.01) and D2cc (-6.2±15.6%; P<0.01). There was a small but significant increase in mean rectal dose (+7.0±12.9%, P<0.01) but a decrease in rectal D2cc (-2.2±10.1%; P=0.04). No significant correlations were found between relative bladder volume changes, bladder trigone displacements, or rectum volume changes with rates of genitourinary or rectal toxicities. Conclusions: Despite smaller than expected bladder and rectal volumes at the time of treatment compared to the planning scans, dosimetric impact was minimal and not predictive of detrimental clinical outcomes. These results cast doubt on the need for excessively strict bladder filling and rectal emptying protocols in the context of image guided prostate SBRT and prospective studies are needed to determine its necessity.

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Magnetic Resonance Imaging–Guided vs Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer

et al. 2023

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ImportanceMagnetic resonance imaging (MRI) guidance offers multiple theoretical advantages in the context of stereotactic body radiotherapy (SBRT) for prostate cancer. However, to our knowledge, these advantages have yet to be demonstrated in a randomized clinical trial.ObjectiveTo determine whether aggressive margin reduction with MRI guidance significantly reduces acute grade 2 or greater genitourinary (GU) toxic effects after prostate SBRT compared with computed tomography (CT) guidance.Design, Setting, and ParticipantsThis phase 3 randomized clinical trial (MRI-Guided Stereotactic Body Radiotherapy for Prostate Cancer [MIRAGE]) enrolled men aged 18 years or older who were receiving SBRT for clinically localized prostate adenocarcinoma at a single center between May 5, 2020, and October 1, 2021. Data were analyzed from January 15, 2021, through May 15, 2022. All patients had 3 months or more of follow-up.InterventionsPatients were randomized 1:1 to SBRT with CT guidance (control arm) or MRI guidance. Planning margins of 4 mm (CT arm) and 2 mm (MRI arm) were used to deliver 40 Gy in 5 fractions.Main Outcomes and MeasuresThe primary end point was the incidence of acute (≤90 days after SBRT) grade 2 or greater GU toxic effects (using Common Terminology Criteria for Adverse Events, version 4.03 [CTCAE v4.03]). Secondary outcomes included CTCAE v4.03–based gastrointestinal toxic effects and International Prostate Symptom Score (IPSS)–based and Expanded Prostate Cancer Index Composite-26 (EPIC-26)–based outcomes.ResultsBetween May 2020 and October 2021, 156 patients were randomized: 77 to CT (median age, 71 years [IQR, 67-77 years]) and 79 to MRI (median age, 71 years [IQR, 68-75 years]). A prespecified interim futility analysis conducted after 100 patients reached 90 or more days after SBRT was performed October 1, 2021, with the sample size reestimated to 154 patients. Thus, the trial was closed to accrual early. The incidence of acute grade 2 or greater GU toxic effects was significantly lower with MRI vs CT guidance (24.4% [95% CI, 15.4%-35.4%] vs 43.4% [95% CI, 32.1%-55.3%]; P = .01), as was the incidence of acute grade 2 or greater gastrointestinal toxic effects (0.0% [95% CI, 0.0%-4.6%] vs 10.5% [95% CI, 4.7%-19.7%]; P = .003). Magnetic resonance imaging guidance was associated with a significantly smaller percentage of patients with a 15-point or greater increase in IPSS at 1 month (6.8% [5 of 72] vs 19.4% [14 of 74]; P = .01) and a significantly reduced percentage of patients with a clinically significant (≥12-point) decrease in EPIC-26 bowel scores (25.0% [17 of 68] vs 50.0% [34 of 68]; P = .001) at 1 month.Conclusions and RelevanceIn this randomized clinical trial, compared with CT-guidance, MRI-guided SBRT significantly reduced both moderate acute physician-scored toxic effects and decrements in patient-reported quality of life. Longer-term follow-up will confirm whether these notable benefits persist.Trial RegistrationClinicalTrials.gov Identifier: NCT04384770

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Five-Year Outcomes of a Phase 1 Dose-Escalation Study Using Stereotactic Body Radiosurgery for Patients With Low-Risk and Intermediate-Risk Prostate Cancer

Cited by 98 publications

References 15 publications

Early Tolerance and Tumor Control Outcomes with High-dose Ultrahypofractionated Radiation Therapy for Prostate Cancer

Early Tolerance and Tumor Control Outcomes with High-dose Ultrahypofractionated Radiation Therapy for Prostate Cancer

Strict bladder filling and rectal emptying during prostate SBRT - does it make a dosimetric or clinical difference?

Magnetic Resonance Imaging–Guided vs Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer

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