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Research progress on mechanism and dosimetry of brainstem injury induced by intensity-modulated radiotherapy, proton therapy, and heavy ion radiotherapy

  • Oncology
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Abstract

Radiotherapy (RT) is an effective method for treating head and neck cancer (HNC). However, RT may cause side effects during and after treatment. Radiation-induced brainstem injury (BSI) is often neglected due to its low incidence and short survival time and because it is indistinguishable from intracranial tumor progression. It is currently believed that the possible mechanism of radiation-induced BSI includes increased expression of vascular endothelial growth factor and damage of vascular endothelial cells, neurons, and glial cells as well as an inflammatory response and oxidative stress. At present, it is still difficult to avoid BSI even with several advanced RT techniques. Intensity-modulated radiotherapy (IMRT) is the most commonly used therapeutic technique in the field of RT. Compared with early conformal therapy, it has greatly reduced the injury to normal tissues. Proton beam radiotherapy (PBT) and heavy ion radiotherapy (HIT) have good dose distribution due to the presence of a Bragg peak, which not only results in better control of the tumor but also minimizes the dose to the surrounding normal tissues. There are many clinical studies on BSI caused by IMRT, PBT, and HIT. In this paper, we review the mechanism, dosimetry, and other aspects of BSI caused by IMRT, PBT, and HIT.

Key Points

• Enhanced MRI imaging can better detect radiation-induced BSI early.

• This article summarized the dose constraints of brainstem toxicity in clinical studies using different techniques including IMRT, PBT, and HIT and recommended better dose constraints pattern to clinicians.

• The latest pathological mechanism of radiation-induced BSI and the corresponding advanced treatment methods will be discussed.

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Abbreviations

aVXX:

Absolute volume at dose XXGy

BBB:

Blood-brain barrier

BSI:

Brainstem injury

CGE:

Cobalt gray equivalent

CNS:

Central nervous system

COXs:

Cyclooxygenases

CT:

Computed tomography

Dmax:

The maximum point dose of brainstem

HIT:

Heavy ion radiotherapy

HNC:

Head and neck cancer

IL:

Interleukin

IMRT:

Intensity-modulated radiotherapy

LOXs:

Lipoxygenases

MRI:

Magnetic resonance imaging

NADPH:

Nicotinamide adenine dinucleotide phosphate

NOS:

Nitric oxide synthase

NPC:

Nasopharyngeal carcinoma

OAR:

Organs at risk

OS:

Reactive oxygen species

PBT:

Proton beam therapy

RBE:

Relative biologic effectiveness

RNS:

Reactive nitrogen species

RT:

Radiotherapy

SVZ:

Subependymal ventricular zone

T1WI:

T1-weighted image

T2WI:

T2-weighted image

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Funding

This study has received funding from the National Natural Science Foundation of China (81570344 to Ying Xin), the Norman Bethune Program of Jilin University (2015225 to Ying Xin and 2015203 to Xin Jiang), and the Jilin Provincial Science and Technology Foundations (20180414039GH to Ying Xin and 20190201200JC to Xin Jiang).

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Author notes

  1. Jinlong Wei and Zhiming Shen contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, The First Hospital, Jilin University, 71 Xinmin Street, Changchun, 130021, China

    Jinlong Wei, Huanhuan Wang, Qin Zhao, Bin Wang & Xin Jiang

  2. Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230000, China

    Zhiming Shen

  3. Department of Biology, Valencia College, Orlando, FL, 32825, USA

    Rui Ji

  4. Key Laboratory of Pathobiology, Ministry of Education, Jilin University, 126 Xinmin Street, Changchun, 130021, China

    Ying Xin

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  1. Jinlong Wei
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Wei, J., Shen, Z., Wang, H. et al. Research progress on mechanism and dosimetry of brainstem injury induced by intensity-modulated radiotherapy, proton therapy, and heavy ion radiotherapy. Eur Radiol 30, 5011–5020 (2020). https://doi.org/10.1007/s00330-020-06843-4

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