Krishnan R Patel, Esther Mena, Lindsay S Rowe, Holly Ning, Jason Cheng, Kilian Salerno, Erica Schott, Debbie-Ann Nathan, Erich P Huang, Liza Lindenberg, Peter Choyke, Baris Turkbey, Deborah E Citrin
{"title":"前列腺切除术后图像引导、风险量适应性放疗的一期试验","authors":"Krishnan R Patel, Esther Mena, Lindsay S Rowe, Holly Ning, Jason Cheng, Kilian Salerno, Erica Schott, Debbie-Ann Nathan, Erich P Huang, Liza Lindenberg, Peter Choyke, Baris Turkbey, Deborah E Citrin","doi":"10.1016/j.ijrobp.2024.09.048","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This is a phase I trial with the primary objective of identifying the most compressed dose schedule (DS) tolerable using risk-volume-adapted, hypofractionated, post-operative radiotherapy (PORT) for biochemically recurrent prostate cancer. Secondary endpoints included biochemical progression free survival (bPFS) and quality of life (QOL).</p><p><strong>Methods: </strong>Patients were treated with one of 3 isoeffective dose schedules (DS1: 20 fractions, DS2: 15 fractions, DS3: 10 fractions) that escalated dose to the imaging-defined local recurrence (73Gy<sub>3</sub> EQD2) and de-escalated dose to the remainder of the prostate bed (48Gy<sub>3</sub> EQD2). Escalation followed a standard 3+3 design with a 6-patient expansion at the maximally tolerated hypofractionated dose schedule (MTHDS). Dose limiting toxicity (DLT) was defined as CTCAE v.4.0 grade (G) 3 toxicity lasting >4 days within 21 days of PORT completion or grade 4 gastrointestinal (GI) or genitourinary (GU) toxicities thereafter. QOL was assessed longitudinally through 24 months with the EPIC-26.</p><p><strong>Results: </strong>Between 01/2018 and 12/2023, 15 patients were treated (3 with DS1, 3 with DS2, and 9 with DS3). The median follow-up was 48 months. No DLTs were observed on any DS, and, thus, expansion occurred at DS3. The cumulative incidence of G3 GI and GU toxicity was 7% and 9% at 24 months, respectively, with no G4 events observed. Transient, acute G2+ GI toxicity was most common. QOL worsened transiently during study follow-up in urinary incontinence, GI, and sexual subdomains but was similar to baseline by 24 months. The bPFS was 91% at both 24- and 60-months.</p><p><strong>Conclusions: </strong>The maximally tolerated hypofractionated dose schedule for hypofractionated, risk-volume-adapted PORT was determined to be DS3 (36.4Gy to the prostate bed and 47.1Gy to the imaging-defined recurrence in 10 daily fractions). No >G3 events were observed. Transient declines in QOL did not persist through 24 months.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Phase I Trial of Image-Guided, Risk-Volume-Adapted Post-Prostatectomy Radiotherapy.\",\"authors\":\"Krishnan R Patel, Esther Mena, Lindsay S Rowe, Holly Ning, Jason Cheng, Kilian Salerno, Erica Schott, Debbie-Ann Nathan, Erich P Huang, Liza Lindenberg, Peter Choyke, Baris Turkbey, Deborah E Citrin\",\"doi\":\"10.1016/j.ijrobp.2024.09.048\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>This is a phase I trial with the primary objective of identifying the most compressed dose schedule (DS) tolerable using risk-volume-adapted, hypofractionated, post-operative radiotherapy (PORT) for biochemically recurrent prostate cancer. Secondary endpoints included biochemical progression free survival (bPFS) and quality of life (QOL).</p><p><strong>Methods: </strong>Patients were treated with one of 3 isoeffective dose schedules (DS1: 20 fractions, DS2: 15 fractions, DS3: 10 fractions) that escalated dose to the imaging-defined local recurrence (73Gy<sub>3</sub> EQD2) and de-escalated dose to the remainder of the prostate bed (48Gy<sub>3</sub> EQD2). Escalation followed a standard 3+3 design with a 6-patient expansion at the maximally tolerated hypofractionated dose schedule (MTHDS). Dose limiting toxicity (DLT) was defined as CTCAE v.4.0 grade (G) 3 toxicity lasting >4 days within 21 days of PORT completion or grade 4 gastrointestinal (GI) or genitourinary (GU) toxicities thereafter. QOL was assessed longitudinally through 24 months with the EPIC-26.</p><p><strong>Results: </strong>Between 01/2018 and 12/2023, 15 patients were treated (3 with DS1, 3 with DS2, and 9 with DS3). The median follow-up was 48 months. No DLTs were observed on any DS, and, thus, expansion occurred at DS3. The cumulative incidence of G3 GI and GU toxicity was 7% and 9% at 24 months, respectively, with no G4 events observed. Transient, acute G2+ GI toxicity was most common. QOL worsened transiently during study follow-up in urinary incontinence, GI, and sexual subdomains but was similar to baseline by 24 months. The bPFS was 91% at both 24- and 60-months.</p><p><strong>Conclusions: </strong>The maximally tolerated hypofractionated dose schedule for hypofractionated, risk-volume-adapted PORT was determined to be DS3 (36.4Gy to the prostate bed and 47.1Gy to the imaging-defined recurrence in 10 daily fractions). No >G3 events were observed. 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A Phase I Trial of Image-Guided, Risk-Volume-Adapted Post-Prostatectomy Radiotherapy.
Purpose: This is a phase I trial with the primary objective of identifying the most compressed dose schedule (DS) tolerable using risk-volume-adapted, hypofractionated, post-operative radiotherapy (PORT) for biochemically recurrent prostate cancer. Secondary endpoints included biochemical progression free survival (bPFS) and quality of life (QOL).
Methods: Patients were treated with one of 3 isoeffective dose schedules (DS1: 20 fractions, DS2: 15 fractions, DS3: 10 fractions) that escalated dose to the imaging-defined local recurrence (73Gy3 EQD2) and de-escalated dose to the remainder of the prostate bed (48Gy3 EQD2). Escalation followed a standard 3+3 design with a 6-patient expansion at the maximally tolerated hypofractionated dose schedule (MTHDS). Dose limiting toxicity (DLT) was defined as CTCAE v.4.0 grade (G) 3 toxicity lasting >4 days within 21 days of PORT completion or grade 4 gastrointestinal (GI) or genitourinary (GU) toxicities thereafter. QOL was assessed longitudinally through 24 months with the EPIC-26.
Results: Between 01/2018 and 12/2023, 15 patients were treated (3 with DS1, 3 with DS2, and 9 with DS3). The median follow-up was 48 months. No DLTs were observed on any DS, and, thus, expansion occurred at DS3. The cumulative incidence of G3 GI and GU toxicity was 7% and 9% at 24 months, respectively, with no G4 events observed. Transient, acute G2+ GI toxicity was most common. QOL worsened transiently during study follow-up in urinary incontinence, GI, and sexual subdomains but was similar to baseline by 24 months. The bPFS was 91% at both 24- and 60-months.
Conclusions: The maximally tolerated hypofractionated dose schedule for hypofractionated, risk-volume-adapted PORT was determined to be DS3 (36.4Gy to the prostate bed and 47.1Gy to the imaging-defined recurrence in 10 daily fractions). No >G3 events were observed. Transient declines in QOL did not persist through 24 months.
期刊介绍:
International Journal of Radiation Oncology • Biology • Physics (IJROBP), known in the field as the Red Journal, publishes original laboratory and clinical investigations related to radiation oncology, radiation biology, medical physics, and both education and health policy as it relates to the field.
This journal has a particular interest in original contributions of the following types: prospective clinical trials, outcomes research, and large database interrogation. In addition, it seeks reports of high-impact innovations in single or combined modality treatment, tumor sensitization, normal tissue protection (including both precision avoidance and pharmacologic means), brachytherapy, particle irradiation, and cancer imaging. Technical advances related to dosimetry and conformal radiation treatment planning are of interest, as are basic science studies investigating tumor physiology and the molecular biology underlying cancer and normal tissue radiation response.