Abstract
PurposeCancer-associated fibroblasts (CAFs) expressing fibroblast activation protein (FAP) have been associated with the aggressive nature of head and neck cancers (HNCs). These tumours grow diffusely, leading to extremely challenging differentiation between tumour and healthy tissue. This analysis aims to introduce a novel approach of tumour detection, contouring and targeted radiotherapy of HNCs using visualisation of CAFs: PET-CT with 68Ga-radiolabeled inhibitors of FAP (FAPI).MethodsFAPI PET-CT was performed without complications prior to radiotherapy in addition to contrast enhanced CT (CE-CT) and MRI on 14 patients with HNC. First, for tissue biodistribution analysis, volumes of interest were defined to quantify SUVmean and SUVmax in tumour and healthy parenchyma. Secondly, using four thresholds of three-, five-, seven- and tenfold increase of FAPI enhancement in the tumour as compared with normal tissue, four different gross tumour volumes (FAPI-GTV) were created automatically. These were compared with GTVs created conventionally with CE-CT and MRI (CT-GTV).ResultsThe biodistribution analysis revealed high FAPI avidity within tumorous lesions (e.g. primary tumours, SUVmax 14.62 ± 4.44; SUVmean 7.41 ± 2.39). In contrast, low background uptake was measured in healthy tissues of the head and neck region (e.g. salivary glands: SUVmax 1.76 ± 0.31; SUVmean 1.23 ± 0.28). Considering radiation planning, CT-GTV was of 27.3 ml, whereas contouring with FAPI resulted in significantly different GTVs of 67.7 ml (FAPI × 3, p = 0.0134), 22.1 ml (FAPI × 5, p = 0.0419), 7.6 ml (FAPI × 7, p = 0.0001) and 2.3 ml (FAPI × 10, p = 0.0001). Taking these significant disparities between the GTVs into consideration, we merged FAPI-GTVs with CT-GTVs. This resulted in median volumes, that were, as compared to CT-GTVs, significantly larger with FAPI × 3 (54.7 ml, + 200.5% relative increase, p = 0.0005) and FAPI × 5 (15.0 ml, + 54.9%, p = 0.0122). Furthermore, FAPI-GTVs were not covered by CE-CT-based planning target volumes (CT-PTVs) in several cases.ConclusionWe present first evidence of diagnostic and therapeutic potential of FAPI ligands in head and neck cancer. Larger studies with histopathological correlation are required to validate our findings.
Highlights
Head and neck cancers (HNC) are the sixth most common malignancy in the world with over 650,000 cases and 330,000 deaths annually [1]
We present first evidence of diagnostic and therapeutic potential of FAP inhibitors (FAPI) ligands in head and neck cancer
This analysis was done using an existing database of 14 HNC patients with age > 18 years (Table 1). They were referred to our Department of Radiation Oncology of the Heidelberg University Hospital, Heidelberg, Germany between July 2017 and August 2018 by their primary otorhinolaryngologists, oral and maxillofacial surgeons or oncologists due to the challenging complexity of the tumours. This complexity required advanced and experimental diagnostic imaging and treatment planning for which we referred them to our collaborating Department of Nuclear Medicine for the FAPI Positron emission tomography-CT (PET-CT)
Summary
Head and neck cancers (HNC) are the sixth most common malignancy in the world with over 650,000 cases and 330,000 deaths annually [1]. Radiation therapy (RT) is well established as one of the most important modalities of treating HNC and has immensely contributed to improvements in overall survival of HNC patients. The opportunities of precise RT are growing, e.g. intensity-modulated radiation therapy (IMRT) allows steep gradients. There is a growing necessity for higher precision in diagnostics and differentiation between tumour and adjacent healthy tissue [3]. This is directly relevant for target volume definition for RT and decides about tumour recurrence patterns and toxicity to healthy tissue [4]. Tumour recurrence is often observed within the RT target volume or at its margins [5].
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