110Phase II study of denileukin diftitox (Ontak) in the treatement of steroid resistant acute graft versus host disease (AGVHD)

Diagnosis and staging of cancer during pregnancy may be difficult due to overlap in physical signs, uncertainties on safety and accuracy of diagnostic tests and histopathology in pregnant women. Tumour markers should be used with caution due to pregnancy-induced elevation. Ionizing imaging and staging techniques such as computed tomography (CT) or positron emission tomography (PET) scans and sentinel node procedures are safe during pregnancy when fetal radiation threshold of 100 mGy is maintained. Ionizing imaging techniques can increasingly be avoided with the technical devolvement of non-ionizing techniques such as magnetic resonance imaging (MRI), including whole body MRI and diffusion-weighted imaging, which hold potentially great opportunities for the diagnostic management of pregnant cancer patients. Pathological evaluation and establishing a diagnosis of malignancy can be difficult in pregnant women, and a note to the pathologist of the pregnant status is essential for accurate diagnosis. This chapter will give an overview of possibilities and difficulties in diagnosing pregnant women with cancer.publisher: Elsevier articletitle: Difficulties with diagnosis of malignancies in pregnancy journaltitle: Best Practice & Research Clinical Obstetrics & Gynaecology articlelink: http://dx.doi.org/10.1016/j.bpobgyn.2015.10.005 content_type: article copyright: © 2015 Elsevier Ltd. All rights reserved.status: publishe

Tumor Volume as an Alternative Response Measurement for Imatinib Treated GIST Patients

Background: Assessment of tumor size changes is crucial in clinical trials and patient care. We compared imatinib-induced volume changes of liver metastases (LM) from gastro-intestinal stromal tumors (GIST) to RECIST and Choi criteria and their association with overall survival (OS). Methods: LM from 84 GIST p

Prognostic value of baseline imaging and clinical features in patients with advanced hepatocellular carcinoma

AIMS To investigate the prognostic value of baseline imaging features for overall survival (OS) and liver decompensation (LD) in patients with hepatocellular carcinoma (HCC). DESIGN Patients with advanced HCC from the SORAMIC trial were evaluated in this post hoc analysis. Several radiological imaging features were collected from baseline computed tomography (CT) and magnetic resonance imaging (MRI) imaging, besides clinical values. The prognostic value of these features for OS and LD (grade 2 bilirubin increase) was quantified with univariate Cox proportional hazard models and multivariate Least Absolute Shrinkage and Selection Operator (LASSO) regression. RESULTS Three hundred and seventy-six patients were included in this study. The treatment arm was not correlated with OS. LASSO showed satellite lesions, atypical HCC, peritumoral arterial enhancement, larger tumour size, higher albumin-bilirubin (ALBI) score, liver-spleen ratio <1.5, ascites, pleural effusion and higher bilirubin values were predictors of worse OS, and higher relative liver enhancement, smooth margin and capsule were associated with better OS. LASSO analysis for LD showed satellite lesions, peritumoral hypointensity in hepatobiliary phase, high ALBI score, higher bilirubin values and ascites were predictors of LD, while randomisation to sorafenib arm was associated with lower LD. CONCLUSIONS Imaging features showing aggressive tumour biology and poor liver function, in addition to clinical parameters, can serve as imaging biomarkers for OS and LD in patients receiving sorafenib and selective internal radiation therapy for HCC

Early tumor shrinkage and response assessment according to mRECIST predict overall survival in hepatocellular carcinoma patients under sorafenib.

BACKGROUND: The aim of this study was to explore the relationship between follow-up imaging characteristics and overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients under sorafenib treatment. METHODS: Associations between OS and objective response (OR) by mRECIST or early tumor shrinkage (ETS; ≥20% reduction in enhancing tumor diameter at the first follow-up imaging) were analyzed in HCC patients treated with sorafenib within a multicenter phase II trial (SORAMIC). 115 patients were included in this substudy. The relationship between survival and OR or ETS were explored. Landmark analyses were performed according to OR at fixed time points. Cox proportional hazards models with OR and ETS as a time-dependent covariate were used to compare survival with factors known to influence OS. RESULTS: The OR rate was 29.5%. Responders had significantly better OS than non-responders (median 30.3 vs. 11.4 months; HR, 0.38 [95% CI, 0.22-0.63], p < 0.001), and longer progression-free survival (PFS; median 10.1 vs. 4.3 months, p = 0.015). Patients with ETS ≥ 20% had longer OS (median 22.1 vs. 11.4 months, p = 0.002) and PFS (median 8.0 vs. 4.3 months, p = 0.034) than patients with ETS < 20%. Besides OR and ETS, male gender, lower bilirubin and ALBI grade were associated with improved OS in univariate analysis. Separate models of multivariable analysis confirmed OR and ETS as independent predictors of OS. CONCLUSION: OR according to mRECIST and ETS in patients receiving sorafenib treatment are independent prognostic factors for OS. These parameters can be used for assessment of treatment benefit and optimal treatment sequencing in patients with advanced HCC

Correlation of liver enhancement in gadoxetic acid-enhanced MRI with liver functions: a multicenter-multivendor analysis of hepatocellular carcinoma patients from SORAMIC trial

OBJECTIVES To evaluate the correlation between liver enhancement on hepatobiliary phase and liver function parameters in a multicenter, multivendor study. METHODS A total of 359 patients who underwent gadoxetic acid-enhanced MRI using a standardized protocol with various scanners within a prospective multicenter phase II trial (SORAMIC) were evaluated. The correlation between liver enhancement on hepatobiliary phase normalized to the spleen (liver-to-spleen ratio, LSR) and biochemical laboratory parameters, clinical findings related to liver functions, liver function grading systems (Child-Pugh and Albumin-Bilirubin ALBI), and scanner characteristics were analyzed using uni- and multivariate analyses. RESULTS There was a significant positive correlation between LSR and albumin (rho = 0.193; p < 0.001), platelet counts (rho = 0.148; p = 0.004), and sodium (rho = 0.161; p = 0.002); and a negative correlation between LSR and total bilirubin (rho = -0.215; p < 0.001) and AST (rho = -0.191; p < 0.001). Multivariate analysis confirmed independent significance for each of albumin (p = 0.022), total bilirubin (p = 0.045), AST (p = 0.031), platelet counts (p = 0.012), and sodium (p = 0.006). The presence of ascites (1.47 vs. 1.69, p < 0.001) and varices (1.55 vs. 1.69, p = 0.006) was related to significantly lower LSR. Similarly, patients with ALBI grade 1 had significantly higher LSR than patients with grade 2 (1.74 ± 0.447 vs. 1.56 ± 0.408, p < 0.001); and Child-Pugh A patients had a significantly higher LSR than Child-Pugh B (1.67 ± 0.44 vs. 1.49 ± 0.33, p = 0.021). Also, LSR was negatively correlated with MELD-Na scores (rho = -0.137; p = 0.013). However, one scanner brand was significantly associated with lower LSR (p < 0.001). CONCLUSIONS The liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI is correlated with biomarkers of liver functions in a multicenter cohort. However, this correlation shows variations between scanner brands. KEY POINTS • The correlation between liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI and liver function is consistent in a multicenter-multivendor cohort. • Signal intensity-based indices (liver-to-spleen ratio) can be used as an imaging biomarker of liver function. • However, absolute values might change between vendors

Diffusion-Weighted MRI for Selection of Complete Responders After Chemoradiation for Locally Advanced Rectal Cancer: A Multicenter Study

PURPOSE: In 10-24% of patients with rectal cancer who are treated with neoadjuvant chemoradiation, no residual tumor is found after surgery (ypT0). When accurately selected, these complete responders might be considered for less invasive treatments instead of standard surgery. So far, no imaging method has proven reliable. This study was designed to assess the accuracy of diffusion-weighted MRI (DWI) in addition to standard rectal MRI for selection of complete responders after chemoradiation. METHODS: A total of 120 patients with locally advanced rectal cancer from three university hospitals underwent chemoradiation followed by a restaging MRI (1.5T), consisting of standard T2W-MRI and DWI (b0-1000). Three independent readers first scored the standard MRI only for the likelihood of a complete response using a 5-point confidence score, after which the DWI images were added and the scoring was repeated. Histology (ypT0 vs. ypT1-4) was the standard reference. Diagnostic performance for selection of complete responders and interobserver agreement were compared for the two readings. RESULTS: Twenty-five of 120 patients had a complete response (ypT0). Areas under the ROC-curve for the three readers improved from 0.76, 0.68, and 0.58, using only standard MRI, to 0.8, 0.8, and 0.78 after addition of DWI (P = 0.39, 0.02, and 0.002). Sensitivity for selection of complete responders ranged from 0-40% on standard MRI versus 52-64% after addition of DWI. Specificity was equally high (89-98%) for both reading sessions. Interobserver agreement improved from kappa 0.2-0.32 on standard MRI to 0.51-0.55 after addition of DWI. CONCLUSIONS: Addition of DWI to standard rectal MRI improves the selection of complete responders after chemoradiation

Evaluation of T2-W MR imaging and diffusion-weighted imaging for the early post-treatment local response assessment of patients treated conservatively for cervical cancer: a multicentre study

Objectives: To compare MR imaging with or without DWI and clinical response evaluation (CRE) in the local control evaluation of cervical carcinoma after radiotherapy. Methods: In a multicentre university setting, we prospectively included 107 patients with primary cervical cancer treated with radiotherapy. Sensitivity and specificity for CRE and MR imaging (with pre-therapy MR imaging as reference) (2 readers) were evaluated using cautious and strict criteria for identifying residual tumour. Nested logistic regression models were constructed for CRE, subsequently adding MR imaging with and without DWI as independent variables, as well as the pre- to post-treatment change in apparent diffusion coefficient (delta ADC). Results: Using cautious criteria, CRE and MR imaging with DWI (reader 1/reader 2) have comparable high specificity (83% and 89%/95%, respectively), whereas MR imaging without DWI showed significantly lower specificity (63%/53%) than CRE. Using strict criteria, CRE and MR imaging with DWI both showed very high specificity (99% and 92%/95%, respectively), whereas MR imaging without DWI showed significantly lower specificity (89%/77%) than CRE. All sensitivities were not significantly different. Addition of MR imaging with DWI to CRE has statistically significant incremental value in identifying residual tumour (reader 1: estimate, 1.06; p = 0.001) (reader 2: estimate, 0.62; p = 0.02). Adding the delta ADC did not have significant incremental value in detecting residual tumour. Conclusions: DWI significantly increases the specificity of MR imaging in the detection of local residual tumour. Furthermore, MR imaging with DWI has significant incremental diagnostic value over CRE, whereas adding the delta ADC has no incremental diagnostic value. Key Points: • If MR imaging is used for response evaluation, DWI should be incorporated• MR imaging with DWI has diagnostic value comparable/complementary to clinical response evaluation• Inter-reader agreement is moderate to fair for two experienced radiologist readers• Quantitative measurements of ADC early post-therapy have limited diagnostic valu

Value of MRI and diffusion-weighted MRI for the diagnosis of locally recurrent rectal cancer

OBJECTIVES: To evaluate the accuracy of standard MRI, diffusion-weighted MRI (DWI) and fusion images for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence. METHODS: Forty-two patients with a clinical suspicion of recurrence underwent 1.5-T MRI consisting of standard T2-weighted FSE (3 planes) and an axial DWI (b0,500,1000). Two readers (R1,R2) independently scored the likelihood of recurrence; [1] on standard MRI, [2] on standard MRI+DWI, and [3] on T2-weighted+DWI fusion images. RESULTS: 19/42 patients had a local recurrence. R1 achieved an area under the ROC-curve (AUC) of 0.99, sensitivity 100% and specificity 83% on standard MRI versus 0.98, 100% and 91% after addition of DWI (p = 0.78). For R2 these figures were 0.87, 84% and 74% on standard MRI and 0.91, 89% and 83% with DWI (p = 0.09). Fusion images did not significantly improve the performance. Interobserver agreement was kappa0.69 for standard MRI, kappa0.82 for standard MRI+DWI and kappa0.84 for the fusion images. CONCLUSIONS: MRI is accurate for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence. Addition of DWI does not significantly improve its performance. However, with DWI specificity and interobserver agreement increase. Fusion images do not improve accuracy

Proceedings of the International Cancer Imaging Society (ICIS) 16th Annual Teaching Course

Table of contents O1 Tumour heterogeneity: what does it mean? Dow-Mu Koh O2 Skeletal sequelae in adult survivors of childhood cancer Sue Creviston Kaste O3 Locoregional effects of breast cancer treatment Sarah J Vinnicombe O4 Imaging of cancer therapy-induced CNS toxicity Giovanni Morana, Andrea Rossi O5 Screening for lung cancer Christian J. Herold O6Risk stratification of lung nodules Theresa C. McLoud O7 PET imaging of pulmonary nodules Kirk A Frey O8 Transarterial tumour therapy Bernhard Gebauer O9 Interventional radiology in paediatric oncology Derek Roebuck O10 Image guided prostate interventions Jurgen J. Fütterer O11 Imaging cancer predisposition syndromes Alexander J. Towbin O12Chest and chest wall masses Thierry AG Huisman O13 Abdominal masses: good or bad? Anne MJB Smets O14 Hepatobiliary MR contrast: enhanced liver MRI for HCC diagnosis and management Giovanni Morana O15 Role of US elastography and multimodality fusion for managing patients with chronic liver disease and HCC Jeong Min Lee O16 Opportunities and challenges in imaging metastatic disease Hersh Chandarana O17 Diagnosis, treatment monitoring, and follow-up of lymphoma Marius E. Mayerhoefer, Markus Raderer, Alexander Haug O18 Managing high-risk and advanced prostate cancer Matthias Eiber O19 Immunotherapy: imaging challenges Bernhard Gebauer O20 RECIST and RECIST 1.1 Andrea Rockall O21 Challenges of RECIST in oncology imaging basics for the trainee and novice Aslam Sohaib O22 Lymphoma: PET for interim and end of treatment response assessment: a users’ guide to the Deauville Score Victoria S Warbey O23 Available resources Hebert Alberto Vargas O24 ICIS e-portal and the online learning community Dow-Mu Koh O25 Benign lesions that mimic pancreatic cancer Jay P Heiken O26 Staging and reporting pancreatic malignancies Isaac R Francis, Mahmoud, M Al-Hawary, Ravi K Kaza O27 Intraductal papillary mucinous neoplasm Giovanni Morana O28 Cystic pancreatic tumours Mirko D’Onofrio O29 Diffusion-weighted imaging of head and neck tumours Harriet C. Thoeny O30 Radiation injury in the head and neck Ann D King O31 PET/MR of paediatric brain tumours Giovanni Morana, Arnoldo Piccardo, Maria Luisa Garrè, Andrea Rossi O32 Structured reporting and beyond Hebert Alberto Vargas O33 Massachusetts General Hospital experience with structured reporting Theresa C. McLoud O34 The oncologist’s perspective: what the oncologist needs to know Nick Reed O35 Towards the cure of all children with cancer: global initiatives in pediatric oncology Carlos Rodriguez-Galindo O36 Multiparametric imaging of renal cancers Hersh Chandarana O37 Linking imaging features of renal disease and their impact on management strategies Hebert Alberto Vargas O38 Adrenals, retroperitoneum and peritoneum Isaac R Francis, Ashish P Wasnik O39 Lung and pleura Stefan Diederich O40 Advances in MRI Jurgen J. Fütterer O41 Advances in molecular imaging Wim J.G. Oyen O42 Incorporating advanced imaging, impact on treatment selection and patient outcome Cheng Lee Chaw, Nicholas van As S1 Combining ADC-histogram features improves performance of MR diffusion-weighted imaging for Lymph node characterisation in cervical cancer Igor Vieira, Frederik De Keyzer, Elleke Dresen, Sileny Han, Ignace Vergote, Philippe Moerman, Frederic Amant, Michel Koole, Vincent Vandecaveye S2 Whole-body diffusion-weighted MRI for surgical planning in patients with colorectal cancer and peritoneal metastases R Dresen, S De Vuysere, F De Keyzer, E Van Cutsem, A D’Hoore, A Wolthuis, V Vandecaveye S3 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extra capsular extension of prostate cancer. P. Pricolo ([email protected]), S. Alessi, P. Summers, E. Tagliabue, G. Petralia S4 Generating evidence for clinical benefit of PET/CT – are management studies sufficient as surrogate for patient outcome? C. Pfannenberg, B. Gückel, SC Schüle, AC Müller, S. Kaufmann, N. Schwenzer, M. Reimold,C. la Fougere, K. Nikolaou, P. Martus S5 Heterogeneity of treatment response in skeletal metastases from breast cancer with 18F-fluoride and 18F-FDG PET GJ Cook, GK Azad, BP Taylor, M Siddique, J John, J Mansi, M Harries, V Goh S6 Accuracy of suspicious breast imaging—can we tell the patient? S Seth, R Burgul, A Seth S7 Measurement method of tumour volume changes during neoadjuvant chemotherapy affects ability to predict pathological response S Waugh, N Muhammad Gowdh, C Purdie, A Evans, E Crowe, A Thompson, S Vinnicombe S8 Diagnostic yield of CT IVU in haematuria screening F. Arfeen, T. Campion, E. Goldstraw S9 Percutaneous radiofrequency ablation of unresectable locally advanced pancreatic cancer: preliminary results D’Onofrio M, Ciaravino V, Crosara S, De Robertis R, Pozzi Mucelli R S10 Iodine maps from dual energy CT improve detection of metastases in staging examinations of melanoma patients M. Uhrig, D. Simons, H. Schlemmer S11Can contrast enhanced CT predict pelvic nodal status in malignant melanoma of the lower limb? Kate Downey S12 Current practice in the investigation for suspected Paraneoplastic Neurological Syndromes (PNS) and positive malignancy yield. S Murdoch, AS Al-adhami, S Viswanathan P1 Technical success and efficacy of Pulmonary Radiofrequency ablation: an analysis of 207 ablations S Smith, P Jennings, D Bowers, R Soomal P2 Lesion control and patient outcome: prospective analysis of radiofrequency abaltion in pulmonary colorectal cancer metastatic disease S Smith, P Jennings, D Bowers, R Soomal P3 Hepatocellular carcinoma in a post-TB patient: case of tropical infections and oncologic imaging challenges TM Mutala, AO Odhiambo, N Harish P4 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extracapsular extension of prostate cancer P. Pricolo, S. Alessi, P. Summers, E. Tagliabue, G. Petralia P5 What a difference a decade makes; comparison of lung biopsies in Glasgow 2005 and 2015 M. Hall, M. Sproule, S. Sheridan P6 Solid pseudopapillary tumour of pancreas: imaging features of a rare neoplasm KY Thein, CH Tan, YL Thian, CM Ho P7 MDCT - pathological correlation in colon adenocarcinoma staging: preliminary experience S De Luca, C Carrera, V Blanchet, L Alarcón, E Eyheremnedy P8 Image guided biopsy of thoracic masses and reduction of pneumothorax risk: 25 years experience B K Choudhury, K Bujarbarua, G Barman P9 Tumour heterogeneity analysis of 18F-FDG-PET for characterisation of malignant peripheral nerve sheath tumours in neurofibromatosis-1 GJ Cook, E Lovat, M Siddique, V Goh, R Ferner, VS Warbey P10 Impact of introduction of vacuum assisted excision (VAE) on screen detected high risk breast lesions L Potti, B Kaye, A Beattie, K Dutton P11 Can we reduce prevalent recall rate in breast screening? AA Seth, F Constantinidis, H Dobson P12 How to reduce prevalent recall rate? Identifying mammographic lesions with low Positive Predictive Value (PPV) AA Seth ([email protected]), F Constantinidis, H Dobson P13 Behaviour of untreated pulmonary thrombus in oncology patients diagnosed with incidental pulmonary embolism on CT R. Bradley, G. Bozas, G. Avery, A. Stephens, A. Maraveyas P14 A one-stop lymphoma biopsy service – is it possible? S Bhuva, CA Johnson, M Subesinghe, N Taylor P15 Changes in the new TNM classification for lung cancer (8th edition, effective January 2017) LE Quint, RM Reddy, GP Kalemkerian P16 Cancer immunotherapy: a review of adequate imaging assessment G González Zapico, E Gainza Jauregui, R Álvarez Francisco, S Ibáñez Alonso, I Tavera Bahillo, L Múgica Álvarez P17 Succinate dehydrogenase mutations and their associated tumours O Francies, R Wheeler, L Childs, A Adams, A Sahdev P18 Initial experience in the usefulness of dual energy technique in the abdomen SE De Luca, ME Casalini Vañek, MD Pascuzzi, T Gillanders, PM Ramos, EP Eyheremendy P19 Recognising the serious complication of Richter’s transformation in CLL patients C Stove, M Digby P20 Body diffusion-weighted MRI in oncologic practice: truths, tricks and tips M. Nazar, M. Wirtz, MD. Pascuzzi, F. Troncoso, F. Saguier, EP. Eyheremendy P21 Methotrexate-induced leukoencephalopathy in paediatric ALL Patients D.J. Quint, L. Dang, M. Carlson, S. Leber, F. Silverstein P22 Pitfalls in oncology CT reporting. A pictorial review R Rueben, S Viswanathan P23 Imaging of perineural extension in head and neck tumours B Nazir, TH Teo, JB Khoo P24 MRI findings of molecular subtypes of breast cancer: a pictorial primer K Sharma, N Gupta, B Mathew, T Jeyakumar, K Harkins P25 When cancer can’t wait! A pictorial review of oncological emergencies K Sharma, B Mathew, N Gupta, T Jeyakumar, S Joshua P26 MRI of pancreatic neuroendocrine tumours: an approach to interpretation D Christodoulou, S Gourtsoyianni, A Jacques, N Griffin, V Goh P27 Gynaecological cancers in pregnancy: a review of imaging CA Johnson, J Lee P28 Suspected paraneoplastic neurological syndromes - review of published recommendations to date, with proposed guideline/flowchart JA Goodfellow, AS Al-adhami, S Viswanathan P29 Multi-parametric MRI of the pelvis for suspected local recurrence of prostate cancer after radical prostatectomy R Bradley P30 Utilisation of PI-RADS version 2 in multi-parametric MRI of the prostate; 12-months experience R Bradley P31 Radiological assessment of the post-chemotherapy liver A Yong, S Jenkins, G Joseph P32 Skeletal staging with MRI in breast cancer – what the radiologist needs to know S Bhuva, K Partington P33 Perineural spread of lympoma: an educational review of an unusual distribution of disease CA Johnson, S Bhuva, M Subesinghe, N Taylor P34 Visually isoattenuating pancreatic adenocarcinoma. Diagnostic imaging tools. C Carrera, A Zanfardini, S De Luca, L Alarcón, V Blanchet, EP Eyheremendy P35 Imaging of larynx cancer: when is CT, MRI or FDG PET/CT the best test? K Cavanagh, E Lauhttp://deepblue.lib.umich.edu/bitstream/2027.42/134651/1/40644_2016_Article_79.pd

Minimal invasive imaging of the tumoral micro-environment in squamous cell carcinoma of the head and neck: value of diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging for tumour detection, regional staging and treatment follow-up

Het globale doel van de thesis was om de waarde te evalueren van dynamis che contrast- (DCE-MRI) en diffusiegewogen magnetische resonantie (DWI) in de karakterisatie van lymfeklieren, de differentiatie van post-radiot herapie necrose en inflammatie van tumorrecidief en de vroegtijdige voor spelling van het therapieresultaat in het spinocellulair carcinoom van h et hoofd-halsgebied. Terwijl DWI onderzocht werd voor lymfeklierstadiëring, differentiatie va n het post-radiotherapie tumorrecidief en therapiepredictie, werd voor D CE-MRI de nadruk gelegd op therapie follow-up en -predictie. Voor de pretherapeutische studie met betrekking tot lymfeklierdifferenti atie werden 33 patiënten geïncludeerd, voor wie DWI in de eerste plaats werd vergeleken met conventionele MRI. DWI, gekwantificeerd door de appa rent diffusion coefficient (ADC), toonde een significant hogere sensitiv iteit dan conventionele MRI voor de detectie van lymfeklier-metastasen ( per nekzone: 94% vs. 57%, p<0.0001) met een gelijkaardige specificiteit (per nekzone: 97% vs. 95%). Hierbij maakte conventionele MRI gebruik van lymfeklierdiameter en morfologische klierafwijkingen ter differentiatie . Vergeleken met conventionele MRI veranderde DWI correct de lymfekliers tadiëring in 13 van de 33 patiënten (39%). Het grootste voordeel van DWI lag in de detectie van subcentimetrische lymfekliermetastasen tot een m inimale diameter over de kortste as van 4 mm, waarbij voor DWI een signi ficant hogere sensitiviteit werd bekomen in vergelijking met conventione le MRI (per lymfeklier: 76% vs. 7%). In een kleinere studiepopulatie van 11 patiënten toonde DWI een hogere sensitiviteit dan fluoro-deoxy-gluco se positron emission tomography/computer tomografie (FDG-PET/CT) voor ly mfeklierdifferentiatie (per nekzone: 96% vs. 67%). Hoewel DWI de differe ntiatie van kleine lymfeklieren als belangrijkste voordeel heeft, laat d e spatiële resolutielimiet de detectie van metastatische deposities klei ner dan 4 mm - en dus micrometastasen - niet toe. De belangrijkste toegevoegde waarde van DWI in de pre-operatieve situatie lijkt de stadië ring van de contralaterale nek te zijn in tumoren die over of dicht op d e midlijn uitbreiden en voor de detectie van skip metastasen in de lag ere nekzones bij mondholtetumoren. In geval van radiotherapieplanning ka n de verbeterde karakterisatie van lymfeklieren leiden tot een hogere co nformiteit tussen het doelvolume van de bestraling en de regionale tumor uitbreiding. Dit kan enerzijds leiden tot een verbeterde regionale tumor controle en anderzijds tot een daling van de therapie-geïnduceerde neven werkingen. In een tweede correlatieve studie met histopathologie in 26 patiënten di e chirurgie ondergingen voor een mogelijk recidief na chemoradiotherapie toonde DWI een hogere accuraatheid dan DCE-MRI voor de differentiatie v an tumorrecidief met necrose en inflammatie (primaire tumoursite: 97% vs . 82%; lymfeklieren: 88% vs. 76%). De hogere accuraatheid van DWI t.o.v. DCE-MRI kon teruggebracht worden op lagere vals positieve ratio secunda ir aan inflammatie, en aan de hogere sensitiviteit van DWI als gevolg va n het hogere beeldcontrast dewelke de detectie van kleine letsels toelaa t. DWI leverde complementaire informatie aan CT en conventionele MRI en FDG-PET door de vals positieve ratio te verlagen en persisterende of rec idief tumor uit te sluiten in ulceraties of vergrote adenopathieën meer dan 4 maand na het beëindigen van de chemoradiotherapie. Evenals in de e erste studie, verbeterde DWI de detectie van subcentimetrische lymfeklie rmetastasen. De hoge sensitiviteit en negatieve predictieve waarde van D WI kan behulpzaam zijn om invasieve diagnostische procedures te vermijde n in persisterende letsels en om de locoregionale stadiëring te vervolle digen, meer bepaald de identificatie van lymfeklier-metastasen en dus he t helpen bepalen van de uitbreiding van de geplande nekdissectie. Semi-k wantitatieve analyse van de DCE-MRI was minder accuraat dan DWI, vooral in het uitsluiten van tumoraal weefsel in persisterende letsels. Dit bep erkt de rol van DCE-MRI als diagnostische techniek in de post-chemoradio therapeutische evaluatie van het hoofd-halsgebied. Evenwel kan DCE-MRI n uttig zijn wanneer deze gebruikt wordt in combinatie met andere function ele technieken, zoals DWI. De waarde van functionele MRI-technieken voor vroegtijdige therapie foll ow-up werd arbitrair opgedeeld in beeldvorming gedurende, respectievelij k vroegtijdig na chemo-radiotherapie. Predictieve beeldvorming gedurende chemoradiotherapie zou nuttig kunnen zijn om de therapie aan de individ uele situatie van de patiënt aan te passen, terwijl beeldvorming vroegti jdig na chemoradiotherapie als doel heeft om vroegtijdig patiënten te se lecteren die aanvullende chirurgie nodig hebben na het beëindigen van de chemoradiotherapie. Bij eenendertig patiënten met lokaal gevorderd hoofd-hals spinocellulair carcinoom werd een DWI en DCE-MRI uitgevoerd op 2 en 4 weken gedurende de chemoradiotherapie. DWI was accurater dan seriële volumetrische metin gen en DCE-MRI voor de differentiatie van therapiegevoelige en therapier esistente primaire tumoren en lymfekliermetastasen (primaire tumor 2 wek en: DWI=94% vs. conventionele MRI=65% vs. DCE-MRI=87%; adenopathieën 2 w eken: DWI=87% vs. conventionele MRI=56% vs. DCE-MRI=56%; primaire tumor 4 weken: DWI=94% vs. conventionele MRI=61% vs. DCE-MRI=72%; adenopa thieën: DWI=93% vs. conventionele MRI=63% vs. DCE-MRI=59%). Terwijl volu metrische metingen een relatief hoge negatieve predictieve waarde vertoo nden voor de exclusie van letsels met risico op ziekterecidief, belette de lage positieve waarde de vroegtijdige identificatie van patiënten die baat zouden kunnen hebben bij therapieaanpassing. De belangrijkste toeg evoegde waarde van DWI was terug te brengen op het vroegtijdig herkennen van therapierespons in letsels die geen volumeafname vertoonden en dus het verbeteren van de positief predictieve waarde. Bovendien verbeterde DWI de identificatie van letsels die een onvolledige therapierespons had den en tegelijkertijd toch een belangrijke doch onvolledige volumeafname vertoonden. DCE-MRI leverde geen toegevoegde informatie voor vroe gtijdige evaluatie van therapierespons. Mogelijks is dit gedeeltelijk wi jten aan de radiotherapie-geïnduceerde inflammatie. Multivariaat analyse toonde dat DWI 2 en 4 weken gedurende chemoradiothe rapie een onafhankelijke predictor was voor de 2-jaars locoregionale con trole, terwijl dit niet het geval was voor volumetrie en DCE-MRI. Indien therapiestrategieën zoals dosisescalatie, weefselspecifieke systemische antitumorale geneesmiddelen of radio-sensibele medicatie beschikbaar ko men, dan zou DWI kunnen helpen om patiënten uit te selecteren voor derge lijke bio-adaptieve therapieën. Verder onderzoek in een grotere patiënte ngroep is bezig om de gevonden resultaten te bevestigen. In een studie met 29 patiënten werd een DWI en DCE-MRI uitgevoerd vóór e n 3 weken na het beëindigen van de chemoradiotherapie. De accuraatheid v an beide functionele technieken werd vergeleken met conventionele MRI op 3 weken na het beëindigen van chemo-radiotherapie en met de routinemati g uitgevoerde CT gemiddeld 3 maand na het beëindigen van de therapie. DC E-MRI kon geen significant verschil aantonen tussen letsels die een late r tumorrecidief vertoonden en letsels met volledige remissie 2 jaar na h et beëindigen van de chemoradiotherapie. DWI was accurater dan conventio nele MRI en CT voor therapie-evaluatie van de primaire tumorlokalisatie (DWI=97% vs. TSE-MRI=80% vs. CT= 87%) en lymfekliermetastasen (per nekzi jde: DWI=89% vs. TSE-MRI=67% vs. CT=75%). Voor de primaire tumorlokalisa tie verbeterde DWI vooral de positieve predictieve waarde in vergelijkin g met conventionele MRI en CT. Als dusdanig kan DWI nuttig zijn voor de vroegtijdige selectie van patiënten met verhoogd risico op later tumorre cidief en die dus nood hebben aan bijkomende chirurgie. Tijdige selectie van patiënten voor vroegtijdige chirurgie kan leiden tot een verbeterde lokale controle en patiëntoverleving voor T3-T4 niet-laryngeale tumoren . Voor de evaluatie van lymfekliermetastasen verbeterde DWI zowel de pos itieve als de negatief predictieve waarde in vergelijking met convention ele MRI en CT. DWI toonde een zeer hoge negatieve predictieve waarde dew elke op een betrouwbare wijze de uitsluiting van persisterende tumor toe liet, ook in patiënten met persisterende vergrote adenopathieën. Daardoo r zou DWI nuttig kunnen zijn voor de selectie tussen patiënten die baat kunnen hebben van een bijkomende chirurgische nekdissectie of patiënten bij wie een afwachtende houding gewettigd is. Hoewel de positieve predic tieve waarde van conventionele MRI en CT sterk werd verbeterd door DWI, is verdere oppuntstelling van de techniek nodig teneinde het aantal vals positieven in subcentimetrische lymfeklieren verder te beperken. In een laatste studie werd de inter- en intraobserver variabiliteit van de manuele aflijningen voor ADC-berekening in lymfeklieren vergeleken tu ssen 2 observatoren met ervaring in hoofd-hals DWI. Statistische analyse toonde een hoge correlatie voor zowel de inter- als de intraobserver va riabiliteit (inter-observer: R2 = 0.79, slope=0.84; intraobserver: R2 = 0.88, slope=0.97). Ook werd de directe berekening van de ADC van de uitgemiddelde aflijning en op de natieve diffusiegewogen beelden (NATIVE groep) vergeleken met d e waarden bekomen uit de gecoregistreerde pixelgebaseerde ADC-map (ADCMA P groep), voor variabiliteit tussen de aflijningen in 1 observator. Prel iminaire resultaten duiden aan dat de standaarddeviatie van het verschil tussen de herhaalde metingen 5.9 x 10-5 was voor de NATIVE groep, terwi jl de standaarddeviatie van het verschil tussen de herhaalde metingen in de ADCMAP groep ongeveer 40% hoger was (8.3 x 10-5). Dit suggeree rt dat ADC-berekening van aflijningen op de natieve diffusiegewogen beel den meer reproduceerbaar en betrouwbaar zijn dan deze bekomen van de pix elgebaseerde ADC-map. Hieruit kan worden geconcludeerd dat, hoewel een h oge overeenkomst in observaties kan worden bekomen, strikte standaardisa tie van de beeldinterpretatie nodig is om de toepassing van DWI verder u it te breiden in de hoofd-hals oncologie. Momenteel is voor hoofd-hals D WI training en een minimale expertise noodzakelijk; daardoor blijft het gebruik beperkt tot centra met een hoge doorstroming van hoofd-hals onco logische pathologie. Aangezien het vrij eenvoudig is de techniek te inte greren in het standaard beeldvormingsprotocol zonder belasting van de pa tiënt, zou er een makkelijke toegang voor verder onderzoek moeten zijn. Verdere standaardisatie zou in de toekomst moeten leiden tot een makkeli jker beeldinterpretatie en meer verspreid gebruik van deze niet-invasiev e techniek.List of abbreviations Research team and co-operators Chapter 1: General introduction 1.1 Definition and epidemiology of head and neck cancer 1.2 Histopathology of head and neck squamous cell carcinoma 1.2.1 Primary tumour 1.2.2 Lymph node metastases 1.3 Tumour classification 1.4 Treatment 1.5 Imaging 1.5.1 Pre-treatment phase 1.5.2 Post-treatment phase 1.6 References 1.7 Aims of the study Chapter 2: Rationale for using functional magnetic resonance imaging: probing the tumoral microenvironment 2.1 Diffusion-weighted MRI 2.2 Dynamic contrast-enhanced MRI 2.3 References Chapter 3: Standardized methodological aspects common to the consecutive studies 3.1 Imaging techniques 3.1.1 MRI 3.1.2 CT scan 3.1.3 FDG-PET/CT 3.2 Image analysis 3.2.1 DWI 3.2.2 DCE-MRI 3.2.3 CT scan – conventional MRI 3.2.4 FDG-PET/CT 3.3 Reference standard 3.3.1 Historadiological correlation and histopathological analysis 3.3.2 Follow-up and correlation to long-term treatment outcome 3.4 Estimation of study population size and number of patients included 3.5 References Chapter 4: DWI for differentiation of benign and metastatic lymph nodes in HNSCC 4.1 Introduction 4.2 Materials and Methods 4.2.1 Patient selection and study design 4.2.2 Imaging technique 4.2.3 Image analysis 4.2.4 Topographic correlation and histopathological analysis 4.2.5 Historadiological correlation and comparison of different imaging modalities 4.2.6 Statistical analysis 4.3 Results 4.3.1 Histopathology 4.3.2 Historadiological correlation 4.3.2.1 Conventional MRI 4.3.2.2 DWI 4.3.2.3 FDG-PET 4.3.3 Comparison of DWI and conventional MRI 4.3.3.1 DWI and TSE-MRI per lymph node and per level 4.3.3.2 ADCb0-1000 and TSE-MRI in correlation to nodal diameter 4.3.4 Comparison of DWI, conventional MRI and FDG-PET in patient subgroup 4.4 Discussion 4.5 Conclusion 4.6 References Chapter 5: DWI and DCE-MRI for differentiation of recurrent head and neck squamous cell carcinoma after chemoradiotherapy: a correlative study to histopathology 5.1 Introduction 5.2 Materials and Methods 5.2.1 Patient selection 5.2.2 Imaging technique 5.2.3 Image analysis 5.2.4 Topographic correlation and histopathological analysis 5.2.5 Historadiological correlation and comparison of different imaging modalities 5.2.6 Statistical analysis 5.3 Results 5.3.1 Histopathology 5.3.2 Historadiological correlation 5.3.2.1 DWI 5.3.2.2 DCE-MRI 5.3.3 Comparison of DWI with CT/conventional MRI and FDG-PET 5.3.4 Comparison of DCE-MRI to CT/conventional MRI and FDG-PET 5.4 Discussion 5.5 Conclusion 5.6 References Chapter 6: Value of DWI and DCE-MRI as imaging biomarkers during chemo-radiotherapy of head and neck squamous cell carcinoma 6.1 Introduction 6.2 Materials and Methods 6.2.1 Study design 6.2.2 Imaging technique 6.2.3 Image analysis 6.2.3.1 Lesion identification and correlation 6.2.3.2 Image analysis 6.2.4 Correlation to treatment outcome 6.2.5 Statistical analysis 6.3 Results 6.3.1 Treatment outcome 6.3.2 Clinical variables and volumetric tumour assessment: lesion based assessment and correlation with locoregional control 6.3.3 Tumour diffusion: correlation with locoregional control 6.3.4 Tumour perfusion: correlation with locoregional control 6.3.5 Comparison of different tumour imaging methods 6.4 Discussion 6.5 Conclusion 6.6 References Chapter 7: DWI and DCE-MRI for assessment of early post-treatment tumour response in head and neck squamous cell carcinoma after (chemo)radiotherapy 7.1 Introduction 7.2 Materials and Methods 7.2.1 Study design 7.2.2 Imaging technique 7.2.3 Image analysis 7.2.3.1 Lesion identification and correlation 7.2.3.2 Image analysis 7.2.3.3 Comparison with anatomical imaging criteria 7.2.4 Correlation to treatment outcome 7.2.5 Statistical analysis 7.3 Results 7.3.1 Treatment outcome 7.3.2 Primary tumour 7.3.3 Lymph node metastases 7.4 Discussion 7.5 Conclusion 7.6 References Chapter 8: Challenges in apparent diffusion coefficient-based quantitative analysis: inter- and intra-observer variability of region-of-interest assessment 8.1 Introduction 8.2 Materials and Methods 8.2.1 Study design 8.2.2 Imaging technique 8.2.3 Image analysis 8.2.4 Data analysis 8.3 Results 8.3.1 Inter- and intra-observer agreement 8.3.2 Intra-observer variance in correlation to ADC-methodology 8.4 Discussion 8.5 Conclusion 8.6 References Summary Samenvatting Bibliography-nrpages: 183status: publishe