Elsevier

Clinical Lung Cancer

Volume 18, Issue 2, March 2017, Pages 127-131
Clinical Lung Cancer

Review
Hippocampal-Sparing Whole-Brain Radiotherapy for Lung Cancer

https://doi.org/10.1016/j.cllc.2016.09.007Get rights and content

Abstract

Brain metastases occur in 20% to 40% of lung cancer patients. Whole-brain radiotherapy (WBRT) has long been considered the treatment of choice for many patients with lung cancer, because of its wide availability, ease of delivery, and effectiveness in prolonging survival. However, WBRT is also associated with several side effects, such as decline in memory and other cognitive functions. There exists significant preclinical and clinical evidence that radiation-induced injury to the hippocampus correlates with neurocognitive decline of patients who receive WBRT. Technological advances in treatment planning and delivery facilitate the use of hippocampal-sparing (HS) WBRT as prophylactic cranial irradiation or the primary treatment modality for lung cancer patients with brain metastases. In this review, we provide a detailed and comprehensive discussion of the safety profile, techniques for hippocampus-sparing, and the clinical evidence of HS-WBRT for lung cancer patients.

Introduction

Lung cancer is a major health problem with a generally grim prognosis.1, 2 In patients with non–small-cell lung cancer (NSCLC), 40% to 50% will eventually develop brain metastases (BM).3, 4 For patients with small-cell lung cancer (SCLC), 15% to 20% initially present with BM, and > 80% of patients will eventually develop metastases.5 Whole-brain radiotherapy (WBRT), open resection, stereotactic radiosurgery (SRS), and stereotactic fractionated radiotherapy are available treatment modalities for BM of lung cancer.6 The use of WBRT has been shown to improve many neurological symptoms, allow corticosteroid reduction, enhance quality of life, and prolong survival. Furthermore, WBRT is also used in prophylactic cranial irradiation (PCI) for patients with SCLC.7, 8 However, the same as other treatment modalities, WBRT is also associated with many side effects including consolidation of new memory, poor attention concentration, visual spatial difficulties, difficulty with executive planning, and poor fine motor control.9, 10 There exists significant preclinical and clinical evidence that radiation-induced injury to the hippocampus correlates with neurocognitive decline of patients who received WBRT.11, 12, 13, 14, 15 Reducing radiation dose to the hippocampus during WBRT has been postulated as an approach to mitigate neurocognitive impairment.

Thanks to the development of modern precision radiotherapy technique, such as intensity modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy, it has recently become possible to deliver the hippocampal-sparing (HS) WBRT (HS-WBRT) for patients with lung cancer patients.16, 17, 18 HS-WBRT techniques have been shown to reduce mean dose to the hippocampus by at least 80%, while providing acceptable coverage and dose homogeneity to the remaining whole-brain parenchyma.17 In this review, we focus on HS-WBRT for patients with lung cancer, the safety profile of HS-WBRT, the advances in the HS-WBRT delivery technique, and the clinical results of HS-WBRT studies are discussed.

Section snippets

Search Strategy and Quality Assessment

Searches for original and review articles were conducted in PubMed, Embase, and Web of Science databases. Search terms included brain metastases, lung cancer or lung carcinoma or lung neoplasm or lung malignancy, WBRT or whole-brain radiotherapy, PCI or prophylactic cranial irradiation, hippocampus, HS-WBRT or hippocampus-sparing whole-brain radiotherapy, hippocampal-avoiding WBRT or hippocampal-avoiding whole-brain radiotherapy, conformal avoidance, hippocampal dosimetry, planning study,

Retrospective Imaging Studies

Conformal hippocampal avoidance during WBRT raises the risk of disease relapse within this area. Before initiating HS-WBRT clinically, some retrospective imaging studies had estimated the risk of disease progression within the hippocampal avoidance region first.

Ghia et al19 reviewed the records of 272 intracranial metastases and reported that only 3.3% of lesions were within 5 mm of the hippocampus, whereas 86.4% of lesions were > 15 mm distant from the hippocampus. The percentage of NSCLC

Conclusion

We have some initial data, including the safety profiles of dosimetric capabilities of modern precision radiotherapy techniques to conformally avoid the hippocampus. We also have evidence from prospective clinical trials to support the feasibility of HS-WBRT in the preservation of neurocognitive functions for lung cancer patients. However, some critical questions about HS-WBRT, such as actual threshold dose for the hippocampus, biomarkers, or imaging characteristics to help identify those most

Disclosure

The authors have stated that they have no conflicts of interest.

Acknowledgments

This study was supported by the Key Disciplines Supporting Program of General Hospital of Ningxia Medical University (2016).

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