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Published in: Strahlentherapie und Onkologie 6/2015

01-06-2015 | Original Article

Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases

Local tumour control and survival

Authors: Dr. med. Dr. rer. nat. Oliver Oehlke, MD, PhD, David Wucherpfennig, Dr. med. Franziska Fels, MD, Dr. phil. Lars Frings, PhD, Dr. med. Karl Egger, MD, PD Dr. med. Astrid Weyerbrock, MD, PD Dr. rer. nat. Vesna Prokic, PhD, Prof. Dr. med. Carsten Nieder, MD, Prof. Dr. med. Anca-Ligia Grosu, MD

Published in: Strahlentherapie und Onkologie | Issue 6/2015

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Abstract

Purpose

Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique.

Methods and materials

Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D98 % to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2–13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2–4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI.

Results

Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. Dmean to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance.

Conclusion

HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration.
Literature
1.
go back to reference Cairncross JG, Kim JH, Posner JB (1980) Radiation therapy for brain metastases. Ann Neurol 7:529–541CrossRefPubMed Cairncross JG, Kim JH, Posner JB (1980) Radiation therapy for brain metastases. Ann Neurol 7:529–541CrossRefPubMed
2.
go back to reference Weissman DE (1988) Glucocorticoid treatment for brain metastases and epidural spinal cord compression: a review. J Clin Oncol 6:543–551PubMed Weissman DE (1988) Glucocorticoid treatment for brain metastases and epidural spinal cord compression: a review. J Clin Oncol 6:543–551PubMed
3.
go back to reference Diener-West M, Dobbins TW, Phillips TL, Nelson DF (1989) Identification of an optimal subgroup for treatment evaluation of patients with brain metastases using RTOG study 7916. Int J Radiat Oncol Biol Phys 16:669–673CrossRefPubMed Diener-West M, Dobbins TW, Phillips TL, Nelson DF (1989) Identification of an optimal subgroup for treatment evaluation of patients with brain metastases using RTOG study 7916. Int J Radiat Oncol Biol Phys 16:669–673CrossRefPubMed
4.
go back to reference Kondziolka D, Patel A, Lunsford LD et al (1999) Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 45:427–434CrossRefPubMed Kondziolka D, Patel A, Lunsford LD et al (1999) Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 45:427–434CrossRefPubMed
5.
go back to reference Kocher M, Soffietti R, Abacioglu U et al (2011) Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952–26001 study. J Clin Oncol 29:134–141CrossRefPubMedCentralPubMed Kocher M, Soffietti R, Abacioglu U et al (2011) Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952–26001 study. J Clin Oncol 29:134–141CrossRefPubMedCentralPubMed
6.
go back to reference Li J, Bentzen SM, Li J, Renschler M, Mehta MP (2008) Relationship between neurocognitive function and quality of life after whole-brain radiotherapy in patients with brain metastasis. Int J Radiat Oncol Biol Phys 71:64–70CrossRefPubMed Li J, Bentzen SM, Li J, Renschler M, Mehta MP (2008) Relationship between neurocognitive function and quality of life after whole-brain radiotherapy in patients with brain metastasis. Int J Radiat Oncol Biol Phys 71:64–70CrossRefPubMed
7.
go back to reference Soffietti R, Kocher M, Abacioglu UM et al (2013) A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol 31:65–72CrossRefPubMed Soffietti R, Kocher M, Abacioglu UM et al (2013) A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol 31:65–72CrossRefPubMed
8.
go back to reference Roman DD, Sperduto PW (1995) Neuropsychological effects of cranial radiation: current knowledge and future directions. Int J Radiat Oncol Biol Phys 31:983–998CrossRefPubMed Roman DD, Sperduto PW (1995) Neuropsychological effects of cranial radiation: current knowledge and future directions. Int J Radiat Oncol Biol Phys 31:983–998CrossRefPubMed
9.
go back to reference Welzel G, Fleckenstein K, Schaefer J et al (2008) Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys 72:1311–1318CrossRefPubMed Welzel G, Fleckenstein K, Schaefer J et al (2008) Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys 72:1311–1318CrossRefPubMed
10.
go back to reference Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:1037–1044CrossRefPubMed Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:1037–1044CrossRefPubMed
11.
go back to reference Taphoorn MJ, Klein M (2004) Cognitive deficits in adult patients with brain tumours. Lancet Neurol 3:159–168CrossRefPubMed Taphoorn MJ, Klein M (2004) Cognitive deficits in adult patients with brain tumours. Lancet Neurol 3:159–168CrossRefPubMed
12.
go back to reference Milner B, Squire LR, Kandel ER (1998) Cognitive neuroscience and the study of memory. Neuron 20:445–468CrossRefPubMed Milner B, Squire LR, Kandel ER (1998) Cognitive neuroscience and the study of memory. Neuron 20:445–468CrossRefPubMed
15.
go back to reference Shors TJ, Miesegaes G, Beylin A et al (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 410:372–376CrossRefPubMed Shors TJ, Miesegaes G, Beylin A et al (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 410:372–376CrossRefPubMed
16.
go back to reference Deng W, Aimone JB, Gage FH (2010) New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 11:339–350CrossRefPubMedCentralPubMed Deng W, Aimone JB, Gage FH (2010) New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 11:339–350CrossRefPubMedCentralPubMed
17.
go back to reference Small SA, Schobel SA, Buxton RB et al (2011) A pathophysiological framework of hippocampal dysfunction in ageing and disease. Nat Rev Neurosci 12:585–601CrossRefPubMedCentralPubMed Small SA, Schobel SA, Buxton RB et al (2011) A pathophysiological framework of hippocampal dysfunction in ageing and disease. Nat Rev Neurosci 12:585–601CrossRefPubMedCentralPubMed
18.
go back to reference Gondi V, Tome WA, Marsh J et al (2010) Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: safety profile for RTOG 0933. Radiother Oncol 95:327–331CrossRefPubMedCentralPubMed Gondi V, Tome WA, Marsh J et al (2010) Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: safety profile for RTOG 0933. Radiother Oncol 95:327–331CrossRefPubMedCentralPubMed
19.
go back to reference Oskan F, Ganswindt U, Schwarz SB et al (2014) Hippocampus sparing in whole-brain radiotherapy. A review. Strahlenther Onkol 190:337–341CrossRefPubMed Oskan F, Ganswindt U, Schwarz SB et al (2014) Hippocampus sparing in whole-brain radiotherapy. A review. Strahlenther Onkol 190:337–341CrossRefPubMed
20.
go back to reference Assouline A, Levy A, Chargari C et al (2011) Whole brain radiotherapy: prognostic factors and results of a radiation boost delivered through a conventional linear accelerator. Radiother Oncol 99:214–217CrossRefPubMed Assouline A, Levy A, Chargari C et al (2011) Whole brain radiotherapy: prognostic factors and results of a radiation boost delivered through a conventional linear accelerator. Radiother Oncol 99:214–217CrossRefPubMed
21.
go back to reference Casanova N, Mazouni Z, Bieri S et al (2010) Whole brain radiotherapy with a conformational external beam radiation boost for lung cancer patients with 1–3 brain metastasis: a multi institutional study. Radiat Oncol 5:13CrossRefPubMedCentralPubMed Casanova N, Mazouni Z, Bieri S et al (2010) Whole brain radiotherapy with a conformational external beam radiation boost for lung cancer patients with 1–3 brain metastasis: a multi institutional study. Radiat Oncol 5:13CrossRefPubMedCentralPubMed
22.
go back to reference Prokic V, Wiedenmann N, Fels F et al (2013) Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases: a planning study on treatment concepts. Int J Radiat Oncol Biol Phys 85:264-270 Prokic V, Wiedenmann N, Fels F et al (2013) Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases: a planning study on treatment concepts. Int J Radiat Oncol Biol Phys 85:264-270
23.
go back to reference Broemme J, Abu-Isa J, Kottke R et al (2013) Adjuvant therapy after resection of brain metastases. Frameless image-guided LINAC-based radiosurgery and stereotactic hypofractionated radiotherapy. Strahlenther Onkol 189:765–770CrossRefPubMed Broemme J, Abu-Isa J, Kottke R et al (2013) Adjuvant therapy after resection of brain metastases. Frameless image-guided LINAC-based radiosurgery and stereotactic hypofractionated radiotherapy. Strahlenther Onkol 189:765–770CrossRefPubMed
24.
go back to reference Brant-Zawadzki M, Gillan GD, Nitz WR (1992) MP RAGE: a three-dimensional, T1-weighted, gradient-echo sequence–initial experience in the brain. Radiology 182:769–775CrossRefPubMed Brant-Zawadzki M, Gillan GD, Nitz WR (1992) MP RAGE: a three-dimensional, T1-weighted, gradient-echo sequence–initial experience in the brain. Radiology 182:769–775CrossRefPubMed
25.
go back to reference Lin NU, Lee EQ, Aoyama H et al (2013) Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression. A report from the RANO group. Lancet Oncol 14:e396–e406CrossRefPubMed Lin NU, Lee EQ, Aoyama H et al (2013) Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression. A report from the RANO group. Lancet Oncol 14:e396–e406CrossRefPubMed
26.
go back to reference Monje ML, Mizumatsu S, Fike JR, Palmer TD (2002) Irradiation induces neural precursor-cell dysfunction. Nat Med 8:955–962CrossRefPubMed Monje ML, Mizumatsu S, Fike JR, Palmer TD (2002) Irradiation induces neural precursor-cell dysfunction. Nat Med 8:955–962CrossRefPubMed
27.
go back to reference Dietrich J, Monje M, Wefel J, Meyers C (2008) Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist 13:1285–1295CrossRefPubMed Dietrich J, Monje M, Wefel J, Meyers C (2008) Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist 13:1285–1295CrossRefPubMed
28.
go back to reference Gondi V, Pugh SL, Tome WA et al (2014) Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol 32:3810–3816CrossRefPubMed Gondi V, Pugh SL, Tome WA et al (2014) Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol 32:3810–3816CrossRefPubMed
29.
go back to reference Harth S, Abo-Madyan Y, Zheng L et al (2013) Estimation of intracranial failure risk following hippocampal-sparing whole brain radiotherapy. Radiother Oncol 109:152–158CrossRefPubMed Harth S, Abo-Madyan Y, Zheng L et al (2013) Estimation of intracranial failure risk following hippocampal-sparing whole brain radiotherapy. Radiother Oncol 109:152–158CrossRefPubMed
30.
go back to reference Gondi V, Hermann BP, Mehta MP, Tomé WA (2013) Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys 85:348–354CrossRefPubMed Gondi V, Hermann BP, Mehta MP, Tomé WA (2013) Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys 85:348–354CrossRefPubMed
31.
go back to reference Rades D, Pluemer A, Veninga T et al (2007) A boost in addition to whole-brain radiotherapy improves patient outcome after resection of 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients. Cancer 110:1551–1559CrossRefPubMed Rades D, Pluemer A, Veninga T et al (2007) A boost in addition to whole-brain radiotherapy improves patient outcome after resection of 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients. Cancer 110:1551–1559CrossRefPubMed
32.
go back to reference Andrews DW, Scott CB, Sperduto PW et al (2004) Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 363:1665–1672CrossRefPubMed Andrews DW, Scott CB, Sperduto PW et al (2004) Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 363:1665–1672CrossRefPubMed
33.
go back to reference Yamamoto M, Serizawa T, Shuto T et al (2014) Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 15:387–395CrossRefPubMed Yamamoto M, Serizawa T, Shuto T et al (2014) Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 15:387–395CrossRefPubMed
34.
go back to reference Wiggenraad R, Verbeek-de Kanter A, Mast M et al (2012) Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases. A single centre study. Strahlenther Onkol 188:696–701CrossRefPubMed Wiggenraad R, Verbeek-de Kanter A, Mast M et al (2012) Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases. A single centre study. Strahlenther Onkol 188:696–701CrossRefPubMed
36.
go back to reference Awad R, Fogarty G, Hong A et al (2013) Hippocampal avoidance with volumetric modulated arc therapy in melanoma brain metastases—the first Australian experience. Radiat Oncol 8:62CrossRefPubMedCentralPubMed Awad R, Fogarty G, Hong A et al (2013) Hippocampal avoidance with volumetric modulated arc therapy in melanoma brain metastases—the first Australian experience. Radiat Oncol 8:62CrossRefPubMedCentralPubMed
37.
go back to reference Rades D, Gerdan L, Segedin B et al (2013) Brain metastasis. Prognostic value of the number of involved extracranial organs. Strahlenther Onkol 189:996–1000CrossRefPubMed Rades D, Gerdan L, Segedin B et al (2013) Brain metastasis. Prognostic value of the number of involved extracranial organs. Strahlenther Onkol 189:996–1000CrossRefPubMed
38.
go back to reference Gaspar L, Scott C, Rotman M et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751CrossRefPubMed Gaspar L, Scott C, Rotman M et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751CrossRefPubMed
Metadata
Title
Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases
Local tumour control and survival
Authors
Dr. med. Dr. rer. nat. Oliver Oehlke, MD, PhD
David Wucherpfennig
Dr. med. Franziska Fels, MD
Dr. phil. Lars Frings, PhD
Dr. med. Karl Egger, MD
PD Dr. med. Astrid Weyerbrock, MD
PD Dr. rer. nat. Vesna Prokic, PhD
Prof. Dr. med. Carsten Nieder, MD
Prof. Dr. med. Anca-Ligia Grosu, MD
Publication date
01-06-2015
Publisher
Springer Berlin Heidelberg
Published in
Strahlentherapie und Onkologie / Issue 6/2015
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-014-0808-9

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