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Head and neck cancers include malignancies originating in the oral cavity, nasopharynx, oropharynx, hypopharynx and larynx. In Belgium, more than 90 % of head and neck cancers are squamous cell carcinomas (HNSCC), and more than 2500 patients were diagnosed with HNSCC in the year 2016. (Belgium Cancer Registry) The use of alcohol and tobacco, with a substantial synergistic effect, induces most HNSCC except for oropharyngeal (OPC) and nasopharyngeal cancer. These HNSCC subsites often have a viral aetiology, Human Papillomavirus (HPV) and Epstein Barr virus, respectively. In the Western world, the incidence of HPV positive OPC is rapidly increasing.The treatment of HNSCC depends mainly on the tumour subsite, tumour size, lymph node involvement and the presence of distant metastases, summarised in the TNM classification. Most early-stage HNSCC can be cured by surgery or radiotherapy (RT), which have similar locoregional control rates. The selection of treatment modality in early disease depends on patient characteristics, the expected post-treatment organ functionality and cosmesis. Unfortunately, the majority of patients with HNSCC have locally advanced disease at diagnosis and should, therefore, be treated with chemoradiotherapy (CRT) or with radical surgery followed by adjuvant (C)RT. Thus, RT is one of the cornerstones of the treatment of HNSCC. Since RT damages both normal and neoplastic cells, the clinical challenge in radical RT is to attain a high therapeutic ratio, which is the highest probability of cure with the least toxicity to surrounding healthy structures.Technical evolutions have made it possible to design high precision three dimensional (3D) conformal and intensity-modulated radiotherapy (IMRT) in which the high dose region is better sculpted around the target volumes, which made it possible to spare the healthy organs at risk (OAR) better. IMRT has become the prefered RT technique in the treatment of HNSCC since the randomised controlled PARSPORT trial has shown the ability and advantage of sparing the parotid salivary glands with IMRT. Despite the improved RT dose distribution on the OAR, acute and late toxicity such as dysphagia, remains a major problem. The risk of dysphagia is correlated with the dose to the swallowing muscles. With the current standard RT dose and fractionation, it is difficult to lower the dose on the swallowing muscles because of the proximity of the target volumes (tumour, nodes and elective neck). Therefore, the current RT procedure and protocol should be optimised in order to reduce treatment-related toxicity.We hypothesised that dose-de-escalation to the elective nodal neck (PTVelect) could lower the RT related toxicity such as dysphagia and lead to better QoL without compromising the oncological outcome. Therefore, a multicentre randomised controlled trial was set up comparing a lower dose to the PTVelect, EQD2 40 Gy, against the standard dose, EQD2 50 Gy. In previous publications, the dosimetric comparison, the effect on acute and late toxicity and the two-year tumour outcome were published showing a significant reduction in dose on several swallowing structures resulting in a substantial reduction in grade ≥3 dysphagia three months after radiotherapy. At later time points, only a trend toward less dysphagia was found. Regarding survival and tumour control, no statistically significant differences were found at two years. We assessed the long term oncological outcome with a special interest in the regional recurrence rate in the PTVelect and investigated the differences in QoL between the 40 Gy and 50 Gy arm.Since in this prospective randomised trial reduction of the dose to PTVelect did not result in a clear benefit in terms of decrease in late dysphagia, other factors may contribute to the development of severe dysphagia. We examined the role of patient and treatment characteristics on dysphagia scored on swallowing videofluoroscopy (VFS) as well as patient and physician scored dysphagia. Next, we evaluated if an existing prediction model for dysphagia, the total dysphagia risk score (TDRS), was also valid in our patient cohort.Besides efforts to reduce the treatment-related toxicity, we should also strive to tailor the treatment to the individual risk profile of the patient. Presently, all patients treated with curative RT receive a standard high dose of 70 Gy (in 35 fractions of 2 Gy), even though some tumours are more radiosensitive than others. The difference in radiosensitivity and prognosis is particularly proven in OPC. In general, HPV positive OPC have a better prognosis than HPV negative OPC. Treatment intensification, e.g. by dose escalation or hypoxia modification, may improve the oncological outcome for patients with poor prognosis while for others with excellent prognosis who might be overtreated, dose reduction could prevent long term toxicity. Good prognostic models are needed to individualise the patients' treatment. At the moment, these models are mostly based on the TNM classification in combination with patient characteristics such as smoking. We examined the prognostic impact of a few models and the new TNM classification in our patient population. Although the new TNM classification (8th edition) provides better OS stratification than the 7th edition, we are convinced that in the future genetic and radiologic information must be integrated to better select patients for de-escalation or escalation of the treatment. First, we examined the prognostic value of a 15-gene hypoxia classifier in OPC. Next, the role of diffusion-weighted (DW) MRI in OPC was investigated. We compared the DW-MRI first-order histogram and radiomic features between HPV positive and negative OPC.Thus, the objectives of this research project are twofold. The first aim is to reduce the treatment-related toxicity in HNSCC with particular focus on dysphagia. The second aim is to predict the prognosis for patients with OPC to tailor the treatment to the individual risk profile.

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Objective: To obtain the diagnostic performance of a short MRI protocol of the liver that includes diffusion weighted imaging combined with conventional T2 and in-phase/out-phase sequences in the detection of liver metastases. Methods: A retrospective consecutive case series of 124 patients with a known primary malignancy was reviewed by two independent readers. All focal liver lesions were graded on a 5-point scale from definitely benign to definitely metastasis. Results: Histopathology and serial imaging showed that 38 patients had one or more liver metastases and 86 had no liver metastases. Reader 1 had a sensitivity of 97.1% and reader 2 of 81.1% in the detection of liver metastases. However, more experienced reader 2 reported 98.4% of cases as conclusive to diagnose metastases, versus 83.9% of less experienced reader 1. False negative diagnosis was due to misinterpretation of a lesion as haemangioma or due to a non-detected lesion. The specificity of both readers was similar, respectively 90.0% and 94.1%. False positive diagnosis was due mischaracterizing a haemangioma, FNH or adenoma as metastasis. Conclusion: There is a clinical need for a short MRI protocol to screen patients with a known primary malignancy for liver metastases, and to replace other less accurate and currently used screening modalities. Our proposed MRI protocol is a possible time-efficient and thereby accessible alternative, without the need for contrast agents and their associated disadvantages. Our results show reasonable accuracies and confidence levels to detect liver metastases.

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Purpose: To compare the diagnostic performance of intra-arterial dual phase cone-beam computed tomography (DP-CBCT) and contrast-enhanced computed tomography (CE-CT) in accurately characterizing tumor burden in patients with metastatic liver cancer. Materials & Methods: This retrospective study included patients with liver metastases, referred for catheter-directed liver intervention. Demographic and radiological data were gathered, including type of tumor, number, maximum size, type and degree of contrast enhancement of liver metastases. Results: 29 patients with colorectal (n=10), breast (n=9) and neuroendocrine (n=10) liver metastases were included. DP-CBCT and CE-CT were in agreement on number and distribution of liver metastases in 18 out of 29 patients (62%). In the remaining 9 out of 11 patients DP-CBCT and CE-CT identified a mean of 10 and 7.2 metastases, respectively (p=0.025); in 2 out of 11 patients DP-CBCT identified fewer metastases than CE-CT. Metastases were larger in diameter on DP-CBCT than on CE-CT regardless of origin: colorectal: 57 +/- 9.5 mm vs 43 +/- 8.3 mm, p=0.02; breast: 57 +/- 10 mm vs 43 +/- 8.5 mm, p=0.03 and neuroendocrine: 56 +/- 6.3 mm vs 51 +/- 5.8 mm, p=0.01. In colorectal metastases, rim enhancement appeared in 100% of cases on DP-CBCT, but was variable on CE-CT. In breast metastases, DP-CBCT displayed thick, hyper-dense rims while CE-CT did not, or had rims of variable thickness and density. Neuroendocrine tumors had variable rim enhancement within the same patient and differed between DP-CBCT and CE-CT in 40% of patients. Conclusions: DP-CBCT appears to identify the vast majority of liver metastases, demonstrates a larger diameter and a peripherally enhancing tumoral rim compared to CE-CT. DP-CBCT substantially improved the visibility of liver metastases during IAT

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Objective To determine the diagnostic value of whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) to predict resectable disease at the time of secondary cytoreductive surgery (SCS) for relapsed epithelial ovarian cancer (EOC) with a platinum-free interval (PFI) of at least 6 months. Methods A retrospective cohort study between January 2012 and December 2021 in a tertiary referral hospital. Inclusion criteria were: (a) first recurrence of EOC; (b) PFI of ≥6 months; (c) intent to perform SCS with complete macroscopic resection; and (d) WB-DWI/MRI was performed. Diagnostic tests of WB-DWI/MRI for predicting complete resection during SCS are calculated as well as the progression-free (PFS) and overall survival (OS) of the patients with a WB-DWI/MRI that showed resectable disease or not. Results In total, 238 patients could be identified, of which 123 (51.7%) underwent an SCS. WB-DWI/MRI predicted resectable disease with a sensitivity of 93.6% (95% confidence interval [CI] 87.3 – 96.9%), specificity of 93.0% (95%CI 87.3 – 96.3%), and an accuracy of 93.3% (95%CI 89.3 – 96.1%). The positive predictive value was 91.9% (95%CI 85.3 – 95.7%). Prediction of resectable disease by WB-DWI/MRI correlated with improved PFS (median 19 months vs. 9 months; hazard ratio [HR] for progression 0.36; 95%CI 0.26 – 0.50) and OS (median 75 months vs. 28 months; HR for death 0.33; 95%CI 0.23 – 0.47). Conclusion WB-DWI/MRI accurately predicts resectable disease in patients with a PFI ≥6 months at the time of SCS and could be of complementary value to the currently used models.

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Objectives To examine if intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced MRI (DCE-MRI) can be used as new and supplemental MRI technique to differentiate hepatocellular adenomas (HCAs) from focal nodular hyperplasias (FNHs) and analyse if diffusion parameter ADC and IVIM parameter D differ in doing so. Methods This prospective study included 21 patients (8 HCAs and 13 FNHs) who underwent a specifically designed MRI scanning protocol, including series for analysis of IVIM (4 b-values 0, 10, 150 and 800 s/mm²) and DCE-MRI. On a dedicated workstation, identical regions of interest were placed in parametric maps of Ktrans, Ve, D, and ADC in each lesion for quantification. Diagnostic accuracy was assessed using receiver operating characteristics analysis. Time-intensity curves (TICs) were classified in different types. Results HCAs had significantly lower values for Ktrans (mean 1.45 min-1 vs 2.68 min-1; p=0.029) and D (mean 1.02 x 10-3 mm²/s vs 1.22 x 10-3 mm²/s; p=0.033). Both parameters showed good diagnostic accuracy of 76%. TIC analysis could not differentiate between HCAs and FNHs. Conclusions In this exploratory study, Ktrans and D were able to differentiate HCAs from FNHs in most cases while Ve, ADC, and TIC analysis were not. Advances in knowledge Histological differences between HCAs and FNHs can be quantified on MRI using Ktrans and D.