Optimization of Brain and Head & Neck Radiotherapy

TitleOptimization of Brain and Head & Neck Radiotherapy
Publication TypeThesis
Year of Publication2018
AuthorsEekers, DBP
Academic DepartmentGROW - School for Oncology and Developmental Biology
Number of Pages201
Date Published10/2018
UniversityMaastricht University
Publication Languageeng
ISBN Number978-94-6380-036-5
Keywordsbrain, dissertation, EPTN, H&N, proton therapy, ROCOCO

The aim of this thesis is to further optimise radiation therapy of Brain and Head & Neck by reducing the dose to the healthy surrounding tissue, so called organs at risk (OARs), leading to a reduction in side effects.

The first objective of this doctoral thesis was to assess the value of proton therapy in reducing the dose to the OARs, in particular for re-irradiation in head and neck squamous cell carcinoma and primary irradiation of low-grade glioma. Chapters 2 and 3 report on two in silico trials conducted within the international Radiation Oncology Collaborative Comparison (ROCOCO) consortium, comparing different radiotherapy modalities including proton therapy, to assess the potential gains for individual patients due to the dosimetric characteristics of particle therapy. The first trial compared intensity-modulated proton therapy (IMPT) and carbon-ion therapy (IMIT) with the golden standard volumetric modulated arc therapy (VMAT) when re-irradiating patients with head and neck squamous cell carcinoma. The second trial compared intensity- modulated radiation therapy (IMRT), IMPT and helical tomotherapy (TOMO) with the golden standard VMAT in patients with a low-grade glioma. Both trials demonstrated that particle therapy can significantly reduce the dose to OARs whilst maintaining the prescription dose. Whether this translates into a clinically relevant benefit, is the subject of future research. In order to predict such a benefit, normal tissue complication probability (NTCP) models are needed. Validated NTCP models are currently lacking for head and neck re-irradiation as well as for the primary treatment of the central nervous system (CNS).

In Chapter 4, the posterior cerebellum is introduced as a new, potentially relevant OAR for the future development of an NTCP model that is focused on cognition, based on the growing evidence from structural and functional imaging studies that the cerebellum plays a role in neurocognition.

Delineation of the relevant OARs on computed tomography (CT) and magnetic resonance imaging (MRI) is needed to optimise the treatment plan before administering the corresponding dose to the patient. This manual delineation is a time- consuming process and a well-known source of error within the planning process, due to inter- and intra-observer variability1.

Reducing this CNS OAR delineation variability is the second objective of this thesis, as described in Chapter 5. An international group of expert radiation oncologists in the field of neuro-oncology reached agreement on the European Particle Therapy Network (EPTN) consensus-based CNS delineation atlas, in order to decrease the variation in CNS delineation. This CNS atlas is presented online (www.cancerdata.org) and encompasses delineation instructions for 15 CNS OARs, including the posterior cerebellum. It includes one CT-scan at two different brightness and contrast settings and two MR scans (3 and 7 Tesla) showing the OARs in three directions (axial, coronal and sagittal view). In Chapter 6, an EPTN consensus-based normal tissue tolerance table, including all currently known and deemed relevant CNS OARs, reports the tolerance dose in equivalent dose (EQD2), which enables a uniform comparison of different treatment modalities in the future (www.cancerdata.org). The use of the consensus-based EPTN CNS atlas and tolerance table is recommended for the Dutch model-based approach comparing photon and proton beam irradiation as well as for future prospective clinical trials including novel radiation techniques and/or modalities2.

The third objective of this thesis was determining the role of radiotherapy in the treatment of epilepsy. Chapter 7 contains a systematic review about the evidence on the efficacy of primary radiosurgery or stereotactic radiotherapy for drug-resistant non- neoplastic focal epilepsy in adults. After treatment, an average of 58% of the patients reported no or rare seizures (defined as radiotherapy-adapted Engel class [RAEC] I and II). A dose-effect model was fitted to the available response data to derive a relationship between prescribed dose and RAEC frequency of this, in the Netherlands, new indication for radiotherapy. In Chapter 8, the results of the previous mentioned chapters of this thesis are being discussed and future perspectives are presented. Additional research needs to be conducted to gain further knowledge to fully understand the potential of particle therapy. Thanks to solid collaborations throughout the radiotherapy community and beyond, with all our colleagues in the medical field, there is a unique possibility to further optimise the treatment of Brain and Head & Neck together.


  1. Vinod SK, Jameson MG, Min M, Holloway LC. Uncertainties in volume delineation in radiation oncology: A systematic review and recommendations for future studies. Radiother. Oncol 2016;121:169–79.

  2. Widder J, Schaaf van der A, Lambin P, et al. The quest for evidence for proton therapy: the model-based approach and precision medicine. Int J Radiat Oncol Biol Phys 2015. pii: S0360-3016:26569-8. 

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