TY - JOUR
T1 - SAbR for High-Risk Prostate Cancer—A Prospective Multilevel MRI-Based Dose Escalation Trial
AU - Hannan, Raquibul
AU - Salamekh, Samer
AU - Desai, Neil B.
AU - Garant, Aurelie
AU - Folkert, Michael R
AU - Costa, Daniel N.
AU - Mannala, Samantha
AU - Ahn, Chul
AU - Mohamad, Osama
AU - Laine, Aaron M
AU - Kim, Dong W.Nathan
AU - Dickinson, Tamara
AU - Raj, Ganesh V.
AU - Shah, Rajal B.
AU - Wang, Jing
AU - Jia, Xun
AU - Choy, Hak
AU - Roehrborn, Claus G.
AU - Lotan, Yair
AU - Timmerman, Robert D.
N1 - Funding Information:
Sources of support: The trial was funded by the Department of Radiation Oncology, UT Southwestern Medical Center. Boston Scientific provided the peri-rectal hydrogel spacers. R.H. and J.W. are supported by NIH R01 EB027898. Disclosures: R.D.T. reports research funding from Varian Medical Systems, Elekta Oncology, and Accuray, outside the submitted work. R.H. reports nonfinancial funding from Boston Scientific, who provided hydrogel spacer for the trial. N.B.D. reports consultation and research funding from Boston Scientific, outside the submitted work. M.R.F. reports research funding and travel reimbursement from Boston Scientific and travel reimbursement from Varian Medical Systems, unrelated to submitted work. Y.L. reports grants from GENOMEDX and mdxhealth, unrelated to submitted work. D.N.C. reports an institutional grant from Bayer, consultation fees from Profound, and scientific review honoraria from NIH, unrelated to submitted work.
Funding Information:
Disclosures: R.D.T. reports research funding from Varian Medical Systems, Elekta Oncology, and Accuray, outside the submitted work. R.H. reports nonfinancial funding from Boston Scientific, who provided hydrogel spacer for the trial. N.B.D. reports consultation and research funding from Boston Scientific, outside the submitted work. M.R.F. reports research funding and travel reimbursement from Boston Scientific and travel reimbursement from Varian Medical Systems, unrelated to submitted work. Y.L. reports grants from GENOMEDX and mdxhealth, unrelated to submitted work. D.N.C. reports an institutional grant from Bayer, consultation fees from Profound, and scientific review honoraria from NIH, unrelated to submitted work.
Funding Information:
Sources of support: The trial was funded by the Department of Radiation Oncology , UT Southwestern Medical Center . Boston Scientific provided the peri-rectal hydrogel spacers. R.H. and J.W. are supported by NIH R01 EB027898 .
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021
Y1 - 2021
N2 - Purpose: Radiation dose intensification improves outcome in men with high-risk prostate cancer (HR-PCa). A prospective trial was conducted to determine safety, feasibility, and maximal tolerated dose of multilevel magnetic resonance imaging (MRI)–based 5-fraction SAbR in patients with HR-PCa. Methods and Materials: This phase I clinical trial enrolled patients with HR-PCa with grade group ≥4, prostate-specific antigen (PSA) ≥20 ng/mL, or radiographic ≥T3, and well-defined prostatic lesions on multiparametric MRI (mpMRI) into 4 dose-escalation cohorts. The initial cohort received 47.5 Gy to the prostate, 50 Gy to mpMRI-defined intraprostatic lesion(s), and 22.5 Gy to pelvic lymph nodes in 5 fractions. Radiation doses were escalated for pelvic nodes to 25 Gy and mpMRI lesion(s) to 52.5 Gy and then 55 Gy. Escalation was performed sequentially according to rule-based trial design with 7 to 15 patients per cohort and a 90-day observation period. All men received peri-rectal hydrogel spacer, intraprostatic fiducial placement, and 2 years of androgen deprivation. The primary endpoint was maximal tolerated dose according to a 90-day acute dose-limiting toxicity (DLT) rate <33%. DLT was defined as National Cancer Institute Common Toxicity Criteria for Adverse Events ≥grade 3 treatment-related toxicity. Secondary outcomes included acute and delayed gastrointestinal (GI)/genitourinary (GU) toxicity graded with Common Toxicity Criteria for Adverse Events. Results: Fifty-five of the 62 enrolled patients were included in the analysis. Dose was escalated through all 4 cohorts without observing any DLTs. Median overall follow-up was 18 months, with a median follow-up of 42, 24, 12, and 7.5 months for cohorts 1 to 4 respectively. Acute and late grade 2 GU toxicities were 25% and 20%, while GI were 13% and 7%, respectively. Late grade 3 GU and GI toxicities were 2% and 0%, respectively. Conclusions: SAbR dose for HR-PCa was safely escalated with multilevel dose painting of 47.5 Gy to prostate, 55 Gy to mpMRI-defined intraprostatic lesions, and 25 Gy to pelvic nodal region in 5 fractions. Longer and ongoing follow-up will be required to assess late toxicity.
AB - Purpose: Radiation dose intensification improves outcome in men with high-risk prostate cancer (HR-PCa). A prospective trial was conducted to determine safety, feasibility, and maximal tolerated dose of multilevel magnetic resonance imaging (MRI)–based 5-fraction SAbR in patients with HR-PCa. Methods and Materials: This phase I clinical trial enrolled patients with HR-PCa with grade group ≥4, prostate-specific antigen (PSA) ≥20 ng/mL, or radiographic ≥T3, and well-defined prostatic lesions on multiparametric MRI (mpMRI) into 4 dose-escalation cohorts. The initial cohort received 47.5 Gy to the prostate, 50 Gy to mpMRI-defined intraprostatic lesion(s), and 22.5 Gy to pelvic lymph nodes in 5 fractions. Radiation doses were escalated for pelvic nodes to 25 Gy and mpMRI lesion(s) to 52.5 Gy and then 55 Gy. Escalation was performed sequentially according to rule-based trial design with 7 to 15 patients per cohort and a 90-day observation period. All men received peri-rectal hydrogel spacer, intraprostatic fiducial placement, and 2 years of androgen deprivation. The primary endpoint was maximal tolerated dose according to a 90-day acute dose-limiting toxicity (DLT) rate <33%. DLT was defined as National Cancer Institute Common Toxicity Criteria for Adverse Events ≥grade 3 treatment-related toxicity. Secondary outcomes included acute and delayed gastrointestinal (GI)/genitourinary (GU) toxicity graded with Common Toxicity Criteria for Adverse Events. Results: Fifty-five of the 62 enrolled patients were included in the analysis. Dose was escalated through all 4 cohorts without observing any DLTs. Median overall follow-up was 18 months, with a median follow-up of 42, 24, 12, and 7.5 months for cohorts 1 to 4 respectively. Acute and late grade 2 GU toxicities were 25% and 20%, while GI were 13% and 7%, respectively. Late grade 3 GU and GI toxicities were 2% and 0%, respectively. Conclusions: SAbR dose for HR-PCa was safely escalated with multilevel dose painting of 47.5 Gy to prostate, 55 Gy to mpMRI-defined intraprostatic lesions, and 25 Gy to pelvic nodal region in 5 fractions. Longer and ongoing follow-up will be required to assess late toxicity.
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U2 - 10.1016/j.ijrobp.2021.10.137
DO - 10.1016/j.ijrobp.2021.10.137
M3 - Article
C2 - 34774676
AN - SCOPUS:85121913792
SN - 0360-3016
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
ER -