C hoeffel imaging of gastroenteropancreatic neuroendocrine tumors jfim hanoi 2015
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This document discusses imaging of gastroenteropancreatic neuroendocrine tumors. It covers pathology, diagnosis and staging of tumors in the pancreas and small bowel using various imaging modalities like CT, MRI, EUS. Tumors are classified based on grade and stage. Characteristic features on CT and MRI include arterial phase enhancement and appearance on T2-weighted MRI sequences. Imaging helps in local staging, detecting metastases, and monitoring response to treatment. A multidisciplinary approach is important for management.
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C hoeffel imaging of gastroenteropancreatic neuroendocrine tumors jfim hanoi 2015
- 1. Imaging of gastroenteropancrea0c neuroendocrine tumors C.HOEFFEL CHU REIMS Hanoi, nov 2015
- 2. Learning Objec0ves • Pathology • Diagnosis and Local staging – Pancreas – Small bowel • Distant staging • Follow-‐up/Therapy monitoring • Perspec0ves
- 3. General Considera0ons • Epithelial neoplasms with neuroendocrine differen0a0on expressing – general markers such as chromogranin A and synaptophysin – and neurone specific markers • Rare but incidence increasing over the past two decades • Heterogeneous group of diseases with various clinical presenta0ons – Inherited disorders (MEN, NF, VHL): small size and mul0ple-‐ 10 % – Vague or aspecific symptoms ( 2/3) – Func0onal symptoms – Unknown primary tumor in 15 % of cases Lawrence B. Endoc Metab Clin N Am 2011
- 4. Treatment Op0ons • Surgery – Primary – Liver metastases (if no extrahepa0c disease) • Interven0onal Radiology and abla0ve therapies • Medical treatment – Somatosta0n Analogues-‐ Interferon alpha – Pep0de receptor targeted terapy/Novel targeted drugs – Systemic chemotherapy (for higher grade) • Mul0disciplinary approach=> role of radiologist
- 5. • Pathology – High cellularity – Hypervascular stroma but MVD variable from one tumor to another, even in same pa0ent – Liver metastases common, biopsied • Before medical treatment • Unknown Primary • In pa0ents who have been resected from primary and for whom adapta0on of the treatment is necessary-‐changing or growing tumor – Histological grade assessment reliable en case of liver metastasis biopsy but less reliable with fine neddle cytology under EUS guidance Pathology Singh S. Eur J Surg Oncol. 2014
- 6. Pathology WHO 2000 WHO 2010 1. Well differen0ated endocrine tumor Neuro endocrine tumor Grade 1 2. Well differen0ated endocrine carcinoma Neuroendocrine tumor Grade 2 3. Poorly differen0ated endocrine carcinoma/ small cel neuroendocrine carcinoma (PDEC) Neuroendocrine carcinoma Grade 3 (large or small cell type) 4. Mixed exocrine-‐endocrine carcinoma (MEEC) Tumor like lesions Mixed adenoneuroendocrine carcinoma (MANEC) Hyperplas0c and preneoplas0c lesions Grading Mitosis 10 HPF KI67 index (%) Grade 1 <2 ≤2 Grade 2 2-‐20 >2-‐20 Grade 3 >20 >20
- 7. Pathology –T stage Pancreas • Classifica0on UICC • T0 No visible tumor • T1 : T limited to p and < 2 cm • T2 :T limited to p and > 2 cm • T3: T extending beyond pancreas but without extension to caeliac axis nor the superior mesenteric artery • T4 :T extending to caeliac axis or to superior mesenteric artery • Classifica0on ENETS • T1: T limited to p and < 2 cm • T2: T limited to p and from 2 to 4 cm • T3: T invading duodenum or biliary tract or T > 4 cm • T4: T invading vessels, stomach, spleen, colon, adrenal
- 8. Diagnosis and Local staging • Pancreas EUS/CT/MR • Small bowel CT/MR
- 9. • Mul0phasic: – Without IV – Late arterial: 35 sec -‐40 sec – Portal venous: 90 sec – Late 3 min • Thin slices • Variable sensi0vity-‐ up to 95 % Manfredi Eur Radiol 2013 Pancrea0c NET-‐MDCT
- 10. – Late arterial enhancement 80 % – dd: kidney mets, intrapancrea0c spleen, pseudosolid serous cystadenoma Cappelli et al. Eur Radiol 2015 Pancrea0c NET-‐MDCT
- 11. – Rare pancrea0c/Biliary duct dilata0on – Mismatch size of tumor and intact MPD – Venous encasement -‐ 1/3 of non func0onal tumors but no arterial involvement Grade 3 Grade 2 Pancrea0c NET-‐MDCT
- 12. • Cys0c changes > 50 % up to 20 % of cases-‐ rim enhancement • Kawamoto AJR 2013 Pancrea0c NET-‐MDCT
- 13. Pancrea0c NET-‐ MRI – Sensi0vity up to 95 % – If CT unconclusive/ Inherited disorders – Same features than CT – Common features: • hyper T2++ 80 %, hyper or iso pancrea0c phase 76 % (dd adk), both 60 % – If enuclea0on • Distance MPD-‐ Tumor • Perop US and preop MR cholangiography Caramella et al. European Radiol 2010 Manfredi Eur Radiol 2013 Brenner EJR 2012 T1 G1 Ki 1.5 % insulinoma-‐ enuclea0on under laparoscopy
- 14. Manfredi Eur Radiol 2013 Atypical appearance most frequently encountered in grade 3 tumors: ill-‐ defined borders, hypovascular in art and venous phases, duct dilata0on Pancrea0c NET-‐ MRI
- 15. DWI-‐MRI • Added value of DWI for Pancreas ? – Increased detec0on on T2+ DWI – ADC correlates well with Ki 67 index but contamina0on by perfusion characteris0cs – Differen0a0on between grade 1 vs 2 or 3 (40 p with pNETs) • When any of the following 2 criteria was used, (a) tumor size smaller than 2.0 cm in diameter and (b) D value greater than 1.2×10(-‐3) mm(2)/s, the sensi0vity, specificity, and posi0ve predic0ve value for diagnosing grade 1 PNETs were 76.92%, 100%, and 100%, respec0vely Brenner EJR 2012 Wang et al JMRI 2011 Hwang EJ Invest Radiol 2014
- 16. 60 year-‐old man. Nega0ve SRS. Grade 2. Ki 4 % B 500
- 17. Pancreas-‐ Endoscopic Ultrasound • Highly sensi0ve/specific – head-‐ isthmic por0on (83-‐100 %) > distal body/tail. • Invasive, observer-‐dependent • Indica0on ++ – Clinical suspicion of pancrea0c NET with normal CT/MRI – Mul0ple endocrine neoplasia – When histology is necessary Caramella et al. Eur Radiol 2010
- 18. • 40 % of tumors are located in last ileal cen0meters ++ • Liver mets 20 % at diagnosis • CT-‐enteroclysis = reference, if not seen at standard CT Se 95-‐100 %, Sp > 95 % • Focal, mul0ple in up to 20 % of cases Woodbridge et al. Radiographics 2014 Kamaoui I AJR 2010 Small Bowel-‐ Local Staging
- 19. MDCT • Small submucosal mass or focal SB wall thickening • Mesenteric mass-‐ calcifica0on, spiculated • Encasement of vessels -‐ arteries or veins • SB Obstruc0on frequent
- 20. Specific assessment of the mesenteric complex Stage I Stage IV Stage II Stage III Lardière-‐Deguelte et al, Neuroendocrinology, in press Iden0fy non or borderline resectable forms (IV and III) TT= resec0on of primary lesion and mesenteric mass, evenif metastases Rela0onship between mesenteric involvement (lymph nodes or/and desmoplas0c mass) and superior mesenteric arteries and jejunal branches.
- 21. MR Enterography • Limited by lower spa0al resolu0on but high contrast resolu0on • In case of contraindica0on of CT • Diffusion= no added value Amzallag-‐Bellenger –Hoeffel C. Eur Radiol 2013 and Eur Radiol 2014
- 22. Distant Staging • Metastases – Liver – Peritoneal carcinomatosis for SB – Lymph nodes-‐medias0num and neck – Bone, Lung only if liver involved KI 3 %
- 23. Distant Staging • WELL DIFFERENTIATED CT TAP Liver: MRI if doubt or if need to resect Search for extrahepa0c mets when liver mets are present SRS or Ga Dota Noc (par0cularly if primary unknown or clinically suspected but invisible or if NET receptor radionuclide therapy) • Metabolic principle is the same but higher resolu0on and sensi0vity for detec0ng mets • POORLY DIFFERENTIATED (KI 67% >10%) CT TAP TEP/CT Dedicated MR examina0on depending on involved site
- 24. Metastases • Liver = major prognosis factor • Assess tumor burden and – Type I = unilobar liver mets/ limited disease – Type II= bilobar or complex liver metastases – Type III= mul0ple or diffuse metastases • MR> CT> SRS • “They are many more than you think” Frilling. Lancet Oncol 2014 Elias Ann Surgery 2010 D’assignies Radiology 2013
- 25. MRI>CT Increased Sensi0vity and berer reproducibility Op0miza0on of protocol ++ Liver metastases
- 26. D’assignies Radiology 2013-‐ 41 p with 162 mets Metastases
- 27. Metastases • Best results= combina0on of sequences D’assignies-Radiology 2013
- 28. DD: Angiome/HNF-‐rôle de l’échographie de contraste? Metastases
- 30. Carcinomatosis • Small bowel • Pancreas 10 % • No specific studies • Arterial phase • Value of MRI
- 31. Follow-‐up • Characteris0cs of GEP-‐NET • Slow evolu0on, numerous lesions, dissociated response • Secre0on • RECIST • Target choice • Compare to nadir ≠ former CT • Use dedicated sowware
- 33. New lesions Janvier 2011 Juillet 2011 : CT _ MS IRM T1Gd + diffusion _ MP (2 nouvelles lésions) • Liver : MRI +++ 15 mm 17 mm T1Gd Diffusion
- 35. Entre 20 et 40 secondes post IV, quatre acquisi0ons
- 36. Janvier 2015 Juin 2015 Everolimus + analogues somatosta0ne Septembre 2015 Follow-‐up
- 37. • Follow-‐up of the ac0ve tumoral volume? January 2015 July 2015 RECIST : Σd 85 mm Σd 107 mm + 26% P m-‐RECIST : Σd 85 mm Σd 53 mm -‐ 38% RP Follow-‐up
- 38. New lesions • Whole body imaging : MRI, PET, Scin0graphy SRS CT MRI T1Gd MRI DWI PET Gallium 68 MRI Gallium PET Schraml. Cancer Imaging. 2013 IRM vs 68Ga-‐DOTATOC, 51 pa0ents Per lesion analysis: TEP-‐Ga/CT = MRI but with differences PET (lung and lymph nodes), MRI (liver and bone)
- 39. Perspec0ves
- 40. EPI Ultrafast imaging with powerful gradients Parrallel imaging Combine signal from numerous elements of coil in phased array Respiratory Ga0ng / trigger or echonavigator Surface coil Mobile table Whole Body DWMR
- 41. • Ax T2 FS • Ax diffusion • Coro T1 Spine • Gadolinium injec0on: Ax T1 EG arterial, portal on liver then pelvis Positionnement des coupes Axiales T2 FS-‐diff Coronales T1 6 overlapping stacks (28 slices with no gap 7mm =19.6 cm) 2 overlapping stacks for spine Protocol: DWI + standard MRI Our Protocol
- 42. • Currently under inves0ga0on • Ongoing study in France-‐ comparison to SRS • So far one study • Etchebehere. J Nuc Med. oct 2014 68Ga-‐ DOTATATE, 19 pa0ents ü TEP/CT > IRM CE, mainly for bone lesions and unknown primary ü Absence of gado Whole Body DWMR
- 46. Prognosis • Diffusion • Perfusion characteris0cs? – CT in 36 pNET – Correla0on between perfusion parameters (BF, MTT) and WHO grades D’assignies G. Radiology 2009
- 47. European Radiology 2015. Capelli et al 19 pNETs 31 % No malignant NET 12 pNETs 20 % malignant 29 pNETs 48 % ½ carcinomas
- 48. Conclusion • CT = ref for diagnosis-‐ first line exam for ini0al staging but role of MRI and EUS for pancreas • Liver MRI for diagnosis of mets and follow-‐up – Include diffusion • Op0mize and standardize protocols • Follow-‐up: be aware of limits of RECIST • Growing role of Diffusion-‐weighted whole-‐body MR imaging