Letters to the editor

Can a mathematical formula help define a radiation target volume using positron emission tomography? In regard to Black et al. (Int J Radiat Oncol Biol Phys 2004;60:1272–1282)

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.

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.

The aim of this work is to evaluate the role of different amount of attenuation and scatter on FDG-PET image volume segmentation using a contrast-oriented method based on the target-to-background (TB) ratio and target dimensions. A phantom study was designed employing 3 phantom sets, which provided a clinical range of attenuation and scatter conditions, equipped with 6 spheres of different volumes (0.5–26.5 ml). The phantoms were: (1) the Hoffman 3-dimensional brain phantom, (2) a modified International Electro technical Commission (IEC) phantom with an annular ring of water bags of 3 cm thickness fit over the IEC phantom, and (3) a modified IEC phantom with an annular ring of water bags of 9 cm. The phantoms cavities were filled with a solution of FDG at 5.4 kBq/ml activity concentration, and the spheres with activity concentration ratios of about 16, 8, and 4 times the background activity concentration. Images were acquired with a Biograph 16 HI-REZ PET/CT scanner. Thresholds (TS) were determined as a percentage of the maximum intensity in the cross section area of the spheres. To reduce statistical fluctuations a nominal maximum value is calculated as the mean from all voxel >95%. To find the TS value that yielded an area A best matching the true value, the cross section were auto-contoured in the attenuation corrected slices varying TS in step of 1%, until the area so determined differed by less than 10 mm² versus its known physical value. Multiple regression methods were used to derive an adaptive thresholding algorithm and to test its dependence on different conditions of attenuation and scatter.

The errors of scatter and attenuation correction increased with increasing amount of attenuation and scatter in the phantoms. Despite these increasing inaccuracies, PET threshold segmentation algorithms resulted not influenced by the different condition of attenuation and scatter. The test of the hypothesis of coincident regression lines for the three phantoms used provided no statistical basis for believing that the three lines are not coincident.

Calibration curves needed to implement contouring algorithms based on adaptive TS segmentation of PET volumes can be devised in different conditions of attenuation and scatter. This opens the possibility of defining a unified contrast-based method for target delineation in different anatomical districts.

Positron Emission Tomography (PET) is a significant advance in cancer imaging with great potential for optimizing radiation therapy (RT) treatment planning and thereby improving outcomes for patients. The use of PET and PET/CT in RT planning was reviewed by an international panel. The International Atomic Energy Agency (IAEA) organized two synchronized and overlapping consultants’ meetings with experts from different regions of the world in Vienna in July 2006. Nine experts and three IAEA staff evaluated the available data on the use of PET in RT planning, and considered practical methods for integrating it into routine practice. For RT planning, ¹⁸F fluorodeoxyglucose (FDG) was the most valuable pharmaceutical. Numerous studies supported the routine use of FDG-PET for RT target volume determination in non-small cell lung cancer (NSCLC). There was also evidence for utility of PET in head and neck cancers, lymphoma and in esophageal cancers, with promising preliminary data in many other cancers. The best available approach employs integrated PET/CT images, acquired on a dual scanner in the radiotherapy treatment position after administration of tracer according to a standardized protocol, with careful optimization of images within the RT planning system and carefully considered rules for contouring tumor volumes. PET scans that are not recent or were acquired without proper patient positioning should be repeated for RT planning. PET will play an increasing valuable role in RT planning for a wide range of cancers. When requesting PET scans, physicians should be aware of their potential role in RT planning.