Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) – a phase II prospective randomized multicenter trial (NOA-14, ARO 2015–3, DKTK-ROG)
Abstract Background Whole brain radiation therapy (WBRT) is the standard therapy for multiple brain metastases. However, WBRT has a poor local tumor control and is associated with a decline in neurocognitive function (NCF). Aim of this trial is to assess the efficacy and safety of a new treatment me...
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2020-06-01
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Online Access: | http://link.springer.com/article/10.1186/s12885-020-07011-z |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anca-Ligia Grosu Lars Frings Iryna Bentsalo Oliver Oehlke Franziska Brenner Angelika Bilger Jamina Tara Fennell Thomas Rothe Sabine Schneider-Fuchs Erika Graf Claudia Schmoor Jürgen Beck Gerhild Becker Michael Bock Karl Egger Horst Urbach Claas Lahmann Ilinca Popp |
spellingShingle |
Anca-Ligia Grosu Lars Frings Iryna Bentsalo Oliver Oehlke Franziska Brenner Angelika Bilger Jamina Tara Fennell Thomas Rothe Sabine Schneider-Fuchs Erika Graf Claudia Schmoor Jürgen Beck Gerhild Becker Michael Bock Karl Egger Horst Urbach Claas Lahmann Ilinca Popp Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) – a phase II prospective randomized multicenter trial (NOA-14, ARO 2015–3, DKTK-ROG) BMC Cancer Brain metastases Hippocampus avoidance Whole brain radiation therapy Neurocognitive function |
author_facet |
Anca-Ligia Grosu Lars Frings Iryna Bentsalo Oliver Oehlke Franziska Brenner Angelika Bilger Jamina Tara Fennell Thomas Rothe Sabine Schneider-Fuchs Erika Graf Claudia Schmoor Jürgen Beck Gerhild Becker Michael Bock Karl Egger Horst Urbach Claas Lahmann Ilinca Popp |
author_sort |
Anca-Ligia Grosu |
title |
Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) – a phase II prospective randomized multicenter trial (NOA-14, ARO 2015–3, DKTK-ROG) |
title_short |
Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) – a phase II prospective randomized multicenter trial (NOA-14, ARO 2015–3, DKTK-ROG) |
title_full |
Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) – a phase II prospective randomized multicenter trial (NOA-14, ARO 2015–3, DKTK-ROG) |
title_fullStr |
Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) – a phase II prospective randomized multicenter trial (NOA-14, ARO 2015–3, DKTK-ROG) |
title_full_unstemmed |
Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) – a phase II prospective randomized multicenter trial (NOA-14, ARO 2015–3, DKTK-ROG) |
title_sort |
whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (hipporad) – a phase ii prospective randomized multicenter trial (noa-14, aro 2015–3, dktk-rog) |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2020-06-01 |
description |
Abstract Background Whole brain radiation therapy (WBRT) is the standard therapy for multiple brain metastases. However, WBRT has a poor local tumor control and is associated with a decline in neurocognitive function (NCF). Aim of this trial is to assess the efficacy and safety of a new treatment method, the WBRT with hippocampus avoidance (HA) combined with the simultaneous integrated boost (SIB) on metastases/resection cavities (HA-WBRT+SIB). Methods This is a prospective, randomized, two-arm phase II multicenter trial comparing the impact of HA on NCF after HA-WBRT+SIB versus WBRT+SIB in patients with multiple brain metastases. The study design is double-blinded. One hundred thirty two patients are to be randomized with a 1:1 allocation ratio. Patients between 18 and 80 years old are recruited, with at least 4 brain metastases of solid tumors and at least one, but not exceeding 10 metastases ≥5 mm. Patients must be in good physical condition and have no metastases/resection cavities in or within 7 mm of the hippocampus. Patients with dementia, meningeal disease, cerebral lymphomas, germ cell tumors, or small cell carcinomas are excluded. Previous irradiation and resection of metastases, as well as the number and size of metastases to be boosted have to comply with certain restrictions. Patients are randomized between the two treatment arms: HA-WBRT+SIB and WBRT+SIB. WBRT is to be performed with 30 Gy in 12 daily fractions and the SIB with 51 Gy/42 Gy in 12 daily fractions on 95% of volume for metastases/resection cavities. In the experimental arm, the dose to the hippocampi is restricted to 9 Gy in 98% of the volume and 17Gy in 2% of the volume. NCF testing is scheduled before WBRT, after 3 (primary endpoint), 9, 18 months and yearly thereafter. Clinical and imaging follow-ups are performed 6 and 12 weeks after WBRT, after 3, 9, 18 months and yearly thereafter. Discussion This is a protocol of a randomized phase II trial designed to test a new strategy of WBRT for preventing cognitive decline and increasing tumor control in patients with multiple brain metastases. Trial registration The HIPPORAD trial is registered with the German Clinical Trials Registry ( DRKS00004598 , registered 2 June 2016). |
topic |
Brain metastases Hippocampus avoidance Whole brain radiation therapy Neurocognitive function |
url |
http://link.springer.com/article/10.1186/s12885-020-07011-z |
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doaj-d09a5d94cac04a0293a4652e9b3b3cb52020-11-25T03:20:47ZengBMCBMC Cancer1471-24072020-06-0120111310.1186/s12885-020-07011-zWhole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) – a phase II prospective randomized multicenter trial (NOA-14, ARO 2015–3, DKTK-ROG)Anca-Ligia Grosu0Lars Frings1Iryna Bentsalo2Oliver Oehlke3Franziska Brenner4Angelika Bilger5Jamina Tara Fennell6Thomas Rothe7Sabine Schneider-Fuchs8Erika Graf9Claudia Schmoor10Jürgen Beck11Gerhild Becker12Michael Bock13Karl Egger14Horst Urbach15Claas Lahmann16Ilinca Popp17Department of Radiation Oncology, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Psychosomatic Medicine and Psychotherapy, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of FreiburgClinical Trials Unit, Faculty of Medicine, Medical Center – University of FreiburgInstitute of Medical Biometry and Statistics, Faculty of Medicine, Medical Center – University of FreiburgClinical Trials Unit, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Neurosurgery, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Palliative Care, Faculty of Medicine, Medical Center - University of FreiburgGerman Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ)Department of Neuroradiology, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Neuroradiology, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Psychosomatic Medicine and Psychotherapy, Faculty of Medicine, Medical Center – University of FreiburgDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of FreiburgAbstract Background Whole brain radiation therapy (WBRT) is the standard therapy for multiple brain metastases. However, WBRT has a poor local tumor control and is associated with a decline in neurocognitive function (NCF). Aim of this trial is to assess the efficacy and safety of a new treatment method, the WBRT with hippocampus avoidance (HA) combined with the simultaneous integrated boost (SIB) on metastases/resection cavities (HA-WBRT+SIB). Methods This is a prospective, randomized, two-arm phase II multicenter trial comparing the impact of HA on NCF after HA-WBRT+SIB versus WBRT+SIB in patients with multiple brain metastases. The study design is double-blinded. One hundred thirty two patients are to be randomized with a 1:1 allocation ratio. Patients between 18 and 80 years old are recruited, with at least 4 brain metastases of solid tumors and at least one, but not exceeding 10 metastases ≥5 mm. Patients must be in good physical condition and have no metastases/resection cavities in or within 7 mm of the hippocampus. Patients with dementia, meningeal disease, cerebral lymphomas, germ cell tumors, or small cell carcinomas are excluded. Previous irradiation and resection of metastases, as well as the number and size of metastases to be boosted have to comply with certain restrictions. Patients are randomized between the two treatment arms: HA-WBRT+SIB and WBRT+SIB. WBRT is to be performed with 30 Gy in 12 daily fractions and the SIB with 51 Gy/42 Gy in 12 daily fractions on 95% of volume for metastases/resection cavities. In the experimental arm, the dose to the hippocampi is restricted to 9 Gy in 98% of the volume and 17Gy in 2% of the volume. NCF testing is scheduled before WBRT, after 3 (primary endpoint), 9, 18 months and yearly thereafter. Clinical and imaging follow-ups are performed 6 and 12 weeks after WBRT, after 3, 9, 18 months and yearly thereafter. Discussion This is a protocol of a randomized phase II trial designed to test a new strategy of WBRT for preventing cognitive decline and increasing tumor control in patients with multiple brain metastases. Trial registration The HIPPORAD trial is registered with the German Clinical Trials Registry ( DRKS00004598 , registered 2 June 2016).http://link.springer.com/article/10.1186/s12885-020-07011-zBrain metastasesHippocampus avoidanceWhole brain radiation therapyNeurocognitive function |