Imaging for Target Delineation in Head and Neck Cancer Radiotherapy

doi:10.1053/j.semnuclmed.2020.07.010

Seminars in Nuclear Medicine

Volume 51, Issue 1, January 2021, Pages 59-67

https://doi.org/10.1053/j.semnuclmed.2020.07.010 Get rights and content

The definition of tumor involved volumes in patients with head and neck cancer poses great challenges with the increasing use of highly conformal radiotherapy techniques eg, volumetric modulated arc therapy and intensity modulated proton therapy. The risk of underdosing the tumor might increase unless great care is taken in the process. The information gained from imaging is increasing with both PET and MRI becoming readily available for the definition of targets. The information gained from these techniques is indeed multidimensional as one often acquire data on eg, metabolism, diffusion, and hypoxia together with anatomical and structural information. Nevertheless, much work remains to fully exploit the available information on a patient-specific level.

Multimodality target definition in radiotherapy is a chain of processes that must be individually scrutinized, optimized and quality assured. Any uncertainties or errors in image acquisition, reconstruction, interpretation, and delineation are systematic errors and hence will potentially have a detrimental effect on the entire radiotherapy treatment and hence; the chance of cure or the risk of unnecessary side effects.

Common guidelines and procedures create a common minimum standard and ground for evaluation and development. In Denmark, the treatment of head and neck cancer is organized within the multidisciplinary Danish Head and Neck Cancer Group (DAHANCA). The radiotherapy quality assurance group of DAHANCA organized a workshop in January 2020 with participants from oncology, radiology, and nuclear medicine from all centers in Denmark, treating patients with head and neck cancer. The participants agreed on a national guideline on imaging for target delineation in head and neck cancer radiotherapy, which has been approved by the DAHANCA group. The guidelines are available in the Supplementary.

The use of multimodality imaging is being recommended for the planning of all radical treatments with a macroscopic tumor. 2-[¹⁸F]FDG-PET/CT should be available, preferable in the treatment position. The recommended MRI sequences are T1, T2 with and without fat suppression, and T1 with contrast enhancement, preferable in the treatment position. The interpretation of clinical information, including thorough physical examination as well as imaging, should be done in a multidisciplinary setting with an oncologist, radiologist, and nuclear medicine specialist.

Section snippets

Background

Radiotherapy is used for a large number of head and neck cancer cases, either as a radical treatment or postoperatively. As radiotherapy is a localized treatment the extent of the primary tumor and any regional metastasis, needs to be well known, for it to be efficient. The area chosen to be irradiated is called the target. The target is subdivided, by International Commission on Radiation Units and Measurements, into gross tumor volume (GTV), the gross extent and location of the tumor

Basic requirements for imaging in head and neck radiotherapy planning

A CT scan in treatment position ie, with the patient immobilized serves as the reference model of the patient for target definition and dose planning. The CT image serves as a direct source of data for dose calculation with X-rays, but can only serve as an indirect source of information for proton radiotherapy as the stopping power of protons and hence, dose calculation, can only be estimated from the CT number. Anatomic imaging needs to be geometrically accurate since not only the presence of

MRI for target delineation in head and neck cancer

Various studies on head-and-neck cancers report large variation in target contouring, even with the use of multiple imaging modalities²¹^,²⁷:

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Differentiation between the tumor and the surrounding healthy tissues on imaging studies ie, soft tissue contrast (expansion/shrinkage of volume).
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Disagreement between observers on tumor extensions such as perineural spread, (more or less “independent” localization).
•
Lack of delineation protocols and guidelines.

The superior soft-tissue contrast of MRI in

PET/CT for target delineation in head and neck cancer

The developments of functional and structural imaging, including hybrid positron emission tomography and computed tomography scanner (PET/CT), has led to a paradigm shift in staging, treatment, target volume definition and response evaluation of patients with head and neck cancers.³⁶^,³⁷ The most widely used and studied radiotracer for PET/CT in patients with head and neck squamous cell carcinoma (HNSCC) is the glucose analog ¹⁸F-Fluorodeoxyglucose (2-[¹⁸F]FDG) which depicts tumor metabolism. It

Multimodality approach in GTV delineation

Until recently, CT has been the most common imaging modality to delineate the tumor in radiation oncology. However, in this era of high precision RT there is increased interest in the role of MR and/or PET/CT (or PET/MRI) in GTV delineation. The use of these newer modalities may lead to better local control and improved quality of life due to dose intensification to the GTV and lesser dose to the surrounding normal tissues. The advantages of MRI over CT include superior soft-tissue contrast and

Future developments

The need for standardization of the tumor delineation has been widely confirmed.⁵⁵ Furthermore, in radiation oncology, GTV delineation is one of the most important and time-consuming processes. Implementation of an automatic GTV delineation tool, which should be fast, accurate, robust, and flexible, would be a great improvement.⁶⁶ Progress may also be expected from artificial intelligence. Yang et al. developed an automated multimodality segmentation framework for automatic target delineation

Conclusion

Radiation therapy planning in head and neck cancer is a complex process that requires a close multidisciplinary collaboration in which imaging, together with the clinical information, plays a crucial part in target selection and delineation of tumor volumes.

There is no solid evidence for which modality provides the most accurate illustration of the GTV tumor extension in all head and neck cancers and no modality seems to encompass all tumor involved tissues.⁶⁰ However, a combination and

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Although magnetic resonance imaging (MRI) has become standard diagnostic workup for head and neck malignancies and is currently recommended by most radiological societies for pharyngeal and oral carcinomas, its utilization in radiotherapy has been heterogeneous during the last decades. However, few would argue that implementing MRI for annotation of target volumes and organs at risk provides several advantages, so that implementation of the modality for this purpose is widely accepted. Today, the term MR-guidance has received a much broader meaning, including MRI for adaptive treatments, MR-gating and tracking during radiotherapy application, MR-features as biomarkers and finally MR-only workflows. First studies on treatment of head and neck cancer on commercially available dedicated hybrid-platforms (MR-linacs), with distinct common features but also differences amongst them, have also been recently reported, as well as “biological adaptation” based on evaluation of early treatment response via functional MRI-sequences such as diffusion weighted ones. Yet, all of these approaches towards head and neck treatment remain at their infancy, especially when compared to other radiotherapy indications. Moreover, the lack of standardization for reporting MR-guided radiotherapy is a major obstacle both to further progress in the field and to conduct and compare clinical trials. Goals of this article is to present and explain all different aspects of MR-guidance for radiotherapy of head and neck cancer, summarize evidence, as well as possible advantages and challenges of the method and finally provide a comprehensive reporting guidance for use in clinical routine and trials.
Evaluation of decentralised model-based selection of head and neck cancer patients for a proton treatment study. DAHANCA 35
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Proton treatment can potentially spare patients with H&N cancer for substantial treatment-related toxicities. The current study investigated the reproducibility of a decentralised model-based selection of patients for a proton treatment study when the selection plans were compared to the clinical treatment plans performed at the proton centre.
Sixty-three patients were selected for proton treatment in the six Danish Head and Neck Cancer (DAHANCA) centres. The patients were selected based on normal tissue complication probability (NTCP) estimated from local photon and proton treatment plans, which showed a ΔNTCP greater than 5%-point for either grade 2 + dysphagia or grade 2 + xerostomia at six months. The selection plans were compared to the clinical treatment plans performed at the proton centre.
Of the 63 patients, 49 and 25 were selected based on an estimated benefit in risk of dysphagia and xerostomia, respectively. Eleven patients had a potential gain in both toxicities. The mean ΔNTCP changed from the local selection plan comparison to the clinical comparison from 6.9 to 5.3 %-points (p = 0.01) and 7.3 to 4.9 %-points (p = 0.03) for dysphagia and xerostomia, respectively. Volume differences in both CTV and OAR could add to the loss in ΔNTCP. 61 of the 63 clinical plans had a positive ΔNTCP, and 38 had a ΔNTCP of 5%-points for at least one of the two endpoints.
A local treatment plan comparison can be used to select candidates for proton treatment. The local comparative proton plan overestimates the potential benefit of the clinical proton plan. Continuous quality assurance of the delineation procedures and planning is crucial in the subsequent randomised clinical trial setting.
Response Evaluation Following Radiation Therapy With <sup>18</sup>F-FDG PET/CT: Common Variants of Radiation-Induced Changes and Potential Pitfalls
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Defining target volumes in RT planning is a crucial step and depends on high-quality imaging for specific characterization of tumor location and extent in order to achieve highest level of accuracy. Multimodal imaging is often adopted in RT planning and tumor delineation is ideally a multi-disciplinary task with radiation oncologist, radiologist and nuclear medicine physician working in close collaboration.24 The three volumes to consider in defining the RT target volumes are gross tumor volume (GTV) including involved lymph nodes, clinical target volume (CTV), and planning target volume (PTV).25
Radiation therapy (RT) is one of the cornerstones in cancer treatment and approximately half of all patients will receive some form of RT during the course of their cancer management. Response evaluation after RT and follow-up imaging with ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) can be complicated by RT-induced acute, chronic or consequential effects. There is a general consensus that ¹⁸F-FDG PET/CT for response evaluation should be delayed for 12 weeks after completing RT to minimize the risk of false-positive findings. Radiation-induced late side effects in normal tissue can take years to develop and eventually cause symptoms that on imaging can potentially mimic recurrent disease. Imaging findings in radiation induced injuries depend on the normal tissue included in the irradiated volume and the radiation therapy regime including the total dose delivered, dose per fraction and treatment schedule. The intent for radiation therapy should be taken in consideration when evaluating the response on imaging, that is palliative vs curative or neoadjuvant vs adjuvant RT. Imaging findings can further be distorted by altered anatomy and sequelae following surgery within the radiation field. An awareness of common PET/CT-induced changes/injuries is essential when interpreting ¹⁸F-FDG PET/CT as well as obtaining a complete medical history, as patients are occasionally scanned for an unrelated cause to previously RT treated malignancy. In addition, secondary malignancies due to carcinogenic effects of radiation exposure in long-term cancer survivors should not be overlooked. ¹⁸F-FDG PET/CT can be very useful in response evaluation and follow-up in patients treated with RT, however, variants and pitfalls are common and it is important to remember that radiation-induced injury is often a diagnosis of exclusion.
Co-registration of radiotherapy planning and recurrence scans with different imaging modalities in head and neck cancer
2022, Physics and Imaging in Radiation Oncology
Citation Excerpt :
If a patient is suspected of having a loco-regional recurrence after primary RT, a scan of the suspected area is usually performed. Traditionally, this involves a CT-scan, however, in some instances, MRI is preferred due to the higher contrasts of soft tissues and thus recommended by national guidelines for certain anatomical regions in the head and neck [6]. Co-registration method of planning-CT to recurrence-CT scans have been validated with mean surface distances ranging from 1 to 3 mm for DIR and between 1 and 1.5 mm for re-delineation uncertainty [7].
MRI (magnetic resonance imaging) scans are frequently used in follow-up after radiotherapy for head and neck cancer. With the overall aim of enabling MRI-based pattern of failure analysis, this study evaluated the accuracy of recurrence MRI (rMRI) deformable co-registration with planning CT (computed tomography)-scans (pCT). Uncertainty of anatomical changes between pCT and rMRI was assessed by similarity metric analyses of co-registered image structures from 19 patients. Average mean distance to agreement and Dice similarity coefficient performed adequately. Our findings provide proof of concept for reliable co-registration of pCT and rMRI months to years apart for MRI-based pattern of failure analysis.
Detailed patient-individual reporting of lymph node involvement in oropharyngeal squamous cell carcinoma with an online interface: Patterns of lymphatic progression in 287 oropharyngeal SCC patients
2022, Radiotherapy and Oncology
Whereas the prevalence of lymph node level (LNL) involvement in head & neck squamous cell carcinomas (HNSCC) has been reported, the details of lymphatic progression patterns are insufficiently quantified. In this study, we investigate how the risk of metastases in each LNL depends on the involvement of upstream LNLs, T-category, HPV status and other risk factors.
We retrospectively analyzed patients with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) treated at a single institution, resulting in a dataset of 287 patients. For all patients, involvement of LNLs I-VII was recorded individually based on available diagnostic modalities (PET, MRI, CT, FNA) together with clinicopathological factors. To analyze the dataset, a web-based graphical user interface (GUI) was developed, which allows querying the number of patients with a certain combination of co-involved LNLs and tumor characteristics.
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Unfortunately, the process of target delineation is associated with far greater uncertainties and inter-observer variation than the other steps of radiotherapy.22 Radiation oncology requires dedicated imaging protocols for therapy planning as well as a multidisciplinary collaboration between experts in oncology and medical imaging.23, 24 In our country, radiation oncology is performed in hospital radiotherapy centers by specialists in clinical oncology, that is, oncologists without specialist level training in imaging.
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Some of the unresolved issues in many of the available technical solutions are related to data security and public regulation, for example, GDPR (General Data Protection Regulation) in the EU and HIPAA compliance (Health Insurance Portability and Accountability Act) in the USA. Using a solution that involves a supplier's server in a non-EU country is problematic within the EU.
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Imaging for Target Delineation in Head and Neck Cancer Radiotherapy

Section snippets

Background

Basic requirements for imaging in head and neck radiotherapy planning

MRI for target delineation in head and neck cancer

PET/CT for target delineation in head and neck cancer

Multimodality approach in GTV delineation

Future developments

Conclusion

Am J Surg

Int J Radiat Oncol Biol Phys

Cancer/Radiotherapie

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Radiother Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Phys Imaging Radiat Oncol

Int J Radiat Oncol Biol Phys

Pr Radiat Oncol

Radiother Oncol

Oral Oncol

PET Clin

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol BiolPhys

Radiother Oncol

Radiother Oncol

Comput Biol Med

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Radiother Oncol

Int J Radiat Oncol

Int J Radiat Oncol Biol Phys

Phys Imaging Radiat Oncol

Int J Radiat Oncol Biol Phys

Semin Radiat Oncol

Radiother Oncol

Definition of volumes

J ICRU

Distribution of cervical lymph node metastasis from sqaumous cell carcinoma of the upper respiratory and digestive tract

Cancer1

Definition of locally recurrent head and neck squamous cell carcinoma: A systematic review and proposal for the Odense–Birmingham definition

Eur Arch Oto-Rhino-Laryngol

Local recurrences after curative IMRT for HNSCC: Effect of different GTV to high-dose CTV margins

Radiother Oncol

Analysis of CT-verified loco-regional recurrences after definitive IMRT for HNSCC using site of origin estimation methods

Acta Oncol (Madr)

Assessment and topographic characterization of locoregional recurrences in head and neck tumours

Radiat Oncol