Original contributionFunctional MRI for radiotherapy dose painting
Introduction
In radiation therapy (RT), modern treatment techniques distinguish themselves by an exceptional flexibility in dose delivery. With techniques such as intensity-modulated RT (IMRT) and volumetric-modulated arc therapy (VMAT), complex dose distributions can be realized, so that a tumor can be exposed to a lethal radiation dose, while nearby healthy tissue can be optimally spared. With brachytherapy, radioactive sources are positioned inside (or in close proximity to) the tumor. This again results in a high tumor dose, with minimal exposure of surrounding healthy tissue. A reliable delivery of these complex treatments is ensured with imaging of the patient in the treatment room. For this purpose, cone-beam computed tomography (CT) scanners are attached to the linear accelerator making image-guided radiotherapy (IGRT) feasible [1], [2]. Strategies for precise irradiation of moving tumors (gating/tracking) have been developed. As part of the brachytherapy procedure, patients increasingly receive some form of three-dimensional (3D) imaging [CT or magnetic resonance imaging (MRI)] to verify the application [3], [4]. With these technological innovations in RT, an improvement in tumor control is no longer invariably associated with an increase in radiation-induced toxicity [2], [5].
RT has the capacity for differential treatment, in which a high dose can be delivered to the visible tumor, whereas tissue holding microscopic disease is irradiated with a lower dose. In this way, tumor cells are eradicated while the underlying healthy tissue is allowed to recover. This capacity sets it apart from all-or-nothing therapies, such as surgery. Taking this concept a step further, Ling et al. [6] proposed to use biological imaging to achieve “biological conformality” by escalating the dose to parts of the tumor that are particularly aggressive or radiation resistant, while reducing the dose to less aggressive parts. This new approach is called dose painting [7], [8]. Several theoretical studies showed that treatment plans indeed can be modulated to match the biological properties reflected by functional imaging modalities [8], [9], [10]. Aerts et al. [11], [12] confirmed that certain areas within the gross tumor volume are more therapy resistant. Malinen et al. [13] investigated the potential of dose painting based on dynamic contrast-enhanced MRI in natural nasopharynx tumors in dogs.
For dose painting to be effective, high-quality imaging of the tumor and surrounding tissue is required. In this review, we will describe developments in MRI-guided dose painting and identify the issues that must be addressed when applying MRI in the context of a radiotherapy treatment.
Section snippets
Imaging for radiotherapy
Anatomical and functional MRIs are commonly used in a diagnostic setting. For many tumor sites, the sensitivity and specificity of combinations of techniques for tumor detection and staging have been established.
The purpose of an MRI exam for radiotherapy treatment planning is, however, distinctly different from most diagnostic exams. At the time a patient arrives at a radiation oncology department, the diagnosis of cancer is established and staging of the disease is already finalized. For RT
Radiotherapy-compatible patient position
External-beam RT is mostly delivered in a series of daily irradiation sessions that can last up to 2 months. To achieve a precise dose delivery, it is therefore essential that the patient can be positioned reproducibly from day to day. Obviously, images that form the basis for a treatment plan must be made in the same position. The CT scan used for setting up treatment portals and for dose calculations (planning CT) is usually made in an RT department, where identical setup procedures are
Future prospects
The use of MRI has just started to spread into the daily practice in radiation oncology. Several innovations in this field have a high potential to result in further improvements in the treatment.
Conclusion
In recent years, a considerable research effort has been dedicated to the integration of MRI into the external radiotherapy workflow motivated by the superior soft tissue contrast as compared to CT.
In this review, we have addressed these issues and described clinical developments in MRI-guided dose painting such as improved precision in delivery in RT, use of combinations of functional MR (and PET), MRI-guided radiotherapy (MR-linacs, MR-guided brachytherapy, MR for proton therapy) and dose
Acknowledgments
We acknowledge financial support from the EU IMI program (QuIC-ConCePT), the CTMM framework (AIRFORCE project), EU 7th framework program (Metoxia program) and NIH-QIN (Radiomics of NSCLC U01 CA143062).
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