Staging and Following Common Pediatric Malignancies: MRI vs CT vs Func onal Imaging
Stephan D. Voss, MD, PhD Department of Radiology Boston Children’s Hospital Harvard Medical School
Disclosure Statement
No Disclosure Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Imaging in Childhood Cancer • Detec ng, Characterizing and Staging Disease - Genera ng Differen al Diagnosis • Guiding Surgical Planning - Biopsy, resec on • Evalua ng Treatment Response - Anatomic and Func onal Imaging - Acute and Late • Predic ng Outcome • Diagnosing & Managing Complica ons • Monitoring for Recurrence - Early and Late Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging The “Big Three” • Neuroblastoma • Hepatoblastoma • Wilm’s Tumor • Others: - Rhabdomyosarcoma - Germ Cell Tumors - Neurofibromatosis - Other liver, renal tumors Cases Intro NeuroblastomaNeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging NBL: Previous Staging & Risk Classifica on • Major prognos c factors • Poor prognos c features • INSS stage of the disease include • Age, Histology and • Age >18 months molecular pathology • N-MYC gene amplifica on • 3 different risk categories • Diploid DNA content • Low, Intermediate, High • Poorly differen ated/ undifferen ated histology Cases Intro NeuroblastomaNeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging Image Defined Risk Factors – IDRF’s • Surgical risk factors • L1: IDFR = 0 • Iden fied by imaging, at • L2: IDRF ≥ 1 Dx, before treatment • M: Metasta c disease • Based on imaging criteria • MS: 4S criteria, now age 18 mo • Interna onal consensus Ellsworth, Carroll • Goal: • Uniform repor ng • Prognos c factors
Monclair T, et al. JCO 2009, Brisse H, et al. Radiology 2011
Page: 99 of 186 IM:IM: 9999 SE:SE: 400400 cmcm Page: 42 of 165 IM:IM: 4242 SE:SE: 22 cmcm Cases Intro NeuroblastomaNeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging Neuroblastoma Diagnosis and Staging: MRI, CT and MIBG Cases Intro NeuroblastomaNeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging Neuroblastoma Staging: MRI, CT & MIBG Cases Intro NeuroblastomaNeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging Staging, IDRF’s and MRI vs CT Cases Intro NeuroblastomaNeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging MRI vs sub-sec CT: decreased exposure and reduc on in seda on
~6 mSv Cases Intro NeuroblastomaNeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging 18F-FDG PET/CT vs MIBG in NBL • MIBG: standard of care - Superior for stage 4 Dz - Superior for relapse - No quan ta ve role currently (no SUV) • FDG: - Useful in MIBG (-) pts - False + BM recovery - Accurate where MIBG and CIM are discrepant MIBG - / FDG + MIBG + / FDG - Sharp S. et al. J. Nucl Med, 2009 Taggart et al. JCO, 2001 Melzer et al, EJNMMI, 2011 Intro NeuroblastomaNeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Response Assessment: Primary site criteria • 229 HR NBL pa ents • Interna onal group • Compared volumetric measurement with RECIST - 30% decrease in LD (RECIST) - 50% (INRC) or 65% decrease in volume • Conclusion: None of the methods of primary site assessment predicted outcome.
Bagatell R. et al. JCO 2016 Intro NeuroblastomaNeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Response Assessment: MIBG & Curie scoring • MIBG scoring: predicts outcome for pa ents with MIBG-avid, stage 4 neuroblastoma • No correla on between Curie score at diagnosis and subsequent treatment outcome • Post-induc on Curie scores > 2: – poor prognosis – alterna ve therapeu c op ons Yanik G, et al. J Nucl Med 2013 Intro NeuroblastomaNeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Neuroblastoma: Predictors of Outcome
• High Stage at Dx • IDRF > 2, impac ng surgical resectability • Presence of MIBG avid disease - Independent predictor of outcome (Dubois, 2017) - MIBG (-) pts have fewer mets and increased EFS • Extent of surgical resec on: gross total > 90% (La Quaglia et al, JCO 2017; Fischer et al, BMC Cancer 2017) • MIBG+ residual disease a er induc on Rx Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Hepatoblastoma: Imaging • Establishing the presence of a liver lesion • Characterizing the lesion (focal vs mul -focal) - Primary vs metastasis from elsewhere - Local / regional spread (lymph nodes, adjacent structures) • Determining surgical resectability (PRETEXT) • Contraindica ons to surgery or transplant • Presence of metasta c disease (lungs): CT Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Goals of Imaging and Therapy • Surgical resec on mainstay of cura ve Rx - Only ⅓ - ½ are resectable at diagnosis - Complete resec on of primary: 90% EFS • Un-resectable tumors: neoadjuvant chemoRx - Large, PRETEXT III and IV - Portal or HV invasion - Lung metastases at Dx • OLTX for pa ents unresponsive to chemoRx - POSTTEXT IV (III with major vascular invasion) - Should have drop in AFP and response to ChemoRx Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging PRETEXT Staging System • I One sec on involved; three adjoining sec ons are free • II One or two sec ons involved, two adjoining sec ons are free • III Two or three sec ons involved; no two adjoining sec ons are free • IV All four sec ons are involved • Addi onal considera ons - Mets, vascular invasion, rupture
Roebuck et al. Pediatr Radiol. 2007 17 Intro Neuroblastoma Hepatoblastoma Wilms Tumor Surveillance Imaging
• PRETEXT Stage and Risk Determina on • Accurate preopera ve imaging is cri cal to management - Low risk vs High Risk
Aronson & Meyers (2016) Seminars in Ped Surg 25: 265-75 Cases Intro NeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging Hepatoblastoma and EOVIST: Upstaging Cases Intro NeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging Hepatoblastoma and EOVIST: Characterizing Indeterminate Lesions 5 yo with incidental mass on appy CT
CT: reported c/w FNH
MRI/EOVIST: No uptake on hepatocyte phase
Bx: HBL, PRETEXT III Intro Neuroblastoma Hepatoblastoma Wilms Tumor Surveillance Imaging Hepatoblastoma: Other Modali es/Strategies • No role for rou ne FDG PET/CT in HBL - May be useful for detec ng relapse • MRI of lungs not yet accepted for assessing pulmonary mets • TACE, HIFU: Exploratory to reduce tumor size Small nodules ≤ 5 mm: CT Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging
Hepatoblastoma: Predictors of Outcome
• High Stage at Dx (PRETEXT III, IV) • Residual disease a er induc on Rx • Surgical Resectability • Metasta c disease (pulmonary) - Response of mets to induc on chemoRx Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Wilm’s Tumor Imaging • Establish the stage of tumor - Local, locoregional, or metasta c • MRI and CT comparable for tumor rupture • Vascular invasion: renal vein, IVC • MRI: superior for detec ng bilateral disease • Chest CT for pulmonary metasta c disease • Treatment response: - USA: upfront surgical resec on, unless bilateral - Europe: induc on chemoRx, response eval, surgery Cases Intro NeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging Wilm’s Tumor – NWTS Staging I Limited to kidney and completely excised. No rupture II Extends through renal capsule but completely excised. May be local vascular invasion and/or local spillage/rupture. III Unresectable primary tumor. Residual local disease. Lymph node metastasis. Extension beyond surgical margins. IV Hematogenous metastasis: lung, brain, liver V Bilateral
Prognosis: 4 years DFS > 90% Cases Intro NeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging
Wilm’s Tumor: Predictors of Outcome Stage, Histology, LOH Intro Neuroblastoma Hepatoblastoma Wilms Tumor Surveillance Imaging Wilms: US vs CT vs MRI • US screening for syndromes - Abnormali es -> MRI • CT: o en the ini al study - If unilateral, localized -> OR • MRI: Bilateral Disease - Response assessment - Characterize lesions in each kidney (20% different path) • CT: pulmonary metastases - Debate re: CT only lung mets • MRI: surveillance, with US Intro Neuroblastoma Hepatoblastoma Wilms Tumor Surveillance Imaging Wilms: CT vs MRI • MRI: - Mul -sequence/mul -plane - Superior to CT for subtle lesions in contrateral kidney - Vascular invasion • Not contrast phase dependent • MRI/DWI: - Improved sensi vity for malignant lesions - ADC change correlates with histopathology post chemo Servaes et al. (2016) • MRI ≈ CT Pediatr Radiol. 45:166-72
- Lymph node invasion Li ooij et al. (2017) - Capsular penetra on Pediatr Radiol. July 1
• MRI: pulmonary metastases Olsen et al. (2017) - CT remains standard JMRI. 45: 1316-24 Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Wilm’s Imaging : High Impact Opportuni es • Chest CT - Improve specificity of lung nodule characteriza on - Reduce unnecessary surgery, chemo, lung XRT - DECT • Pre-surgical lesion characteriza on - MRI, DWI/ADC, spectroscopy • Targeted therapies/nephron sparing: RFA Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Surveillance Imaging Rou ne imaging surveillance • End of therapy; free of disease or stable abnormalites • Issues: - Time, cost - Repeat exposure to ionising radia on - Repeat contrast administra on (Gd) - Cumula ve anesthesia risks - False posi ves & false nega ves • ‘li le if any improvement in salvage rates between relapse detected by imaging and by clinical suspicions’ Kaste SC. Oncological imaging: tumor surveillance in children. Pediatr Radiol 2011: 41; S505-508 Cases Intro NeuroblastomaCancer Hepatoblastoma WilmsImaging & Tumor Surveillance Imaging Survivorship Radia on Risk Surveillance Imaging Surveillance Imaging in HD – What is the Impact on Survival?
POG 9425 • > 8 years of follow-up • 25/216 relapses • Median me to relapse = 7 months
Voss et al., J. Clin Oncol. 2012 Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging
Cancer Recurrence in Childhood Solid tumors* Type of inves ga on No. performed • Plain radiograph 1029 • Ultrasound 272 • MRI 249 • CT 129 • Bone scan 41 • Renal scan 7 • Total 1727
• 1727 tests to detect 11 recurrences (30%) * n = 186 solid tumors, > 5 years follow-up Howell et al. Cancer (2005) 103: 1274 Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Hepatoblastoma Surveillance • 26 children with hepatoblastoma - mean age 2.4 yrs, mean Dx AFP 132,732 ng/dl • 105 imaging exams post-comple on of Rx - CT (84%), MRI (8%), US (5%), PET/CT (4%) • 5/26 relapses - AFP elevated in all recurrences - No recurrence detected before AFP eleva on - 2 false + AFP; 15 false + imaging exams Rojas et al. Pediatr Radiol. 2014; 44:1275 Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Wilm’s Surveillance Off Therapy Monitoring Low Risk Stage I, II with LOH, Standard Risk Stage III, And Relapsed Very Low Risk Stage 1 Wilm’s
0 3 6 9 12 15 18 21 24 27 30 33 36 48 60 Chest CT x x x x x x x CXR x x x x x x x x US x x x x x x x x CT/MRI x x x x x x x 7 MRI’s and Chest CT’s Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Wilm’s and Pelvic Surveillance • 80 pa ents had 605 CTs • 371 included the pelvis • only 3 pelvic relapses, all symptoma c • all 3 had risk factors (age >48 months, higher disease stage) • all salvaged
• omit pelvic CT from off-therapy surveillance • (use MRI if possible) Kaste et al. Cancer 2012: 119: 182-8 Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging
Neuroblastoma and CT Surveillance • 183 NBL pts: 50 relapses - 41 HR; 4 IR, 5 LR (observa on only post resec on) - Most relapses detected by Sx, Exam, MIBG or Urine catacholamines • 88 High Risk NBL pts: 46 relapses - 5 yr OS = 52%; 5 yr EFS 43% - 46 (59%) with relapse or progression - 11 (14%) with thoracic relapse (8/11 MIBG+; 3/11 Sx - Majority of pa ents with non-thoracic HR NBL do not benefit from rou ne chest CT surveillance
Owens et al. Pediatric Blood and Cancer (2016) Federico et al. Pediatric Blood and Cancer (2015) Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Neuroblastoma Surveillance Off Therapy Monitoring Low/Intermediate Risk Neuroblastoma( COG ANBL1232) High Risk Neuroblastoma (COG ANBL0532, ANBL1531)
0 3 6 9 12 15 18 24 30 36 42 48 60 CT / MRI x x x x x x x x x MIBG x x x x x x x x x Labs/PE x x x x x x x x x x x x x
BUT, NO DATA currently to support: - Reducing surveillance in non-HR pa ents with reduc on in Rx intensity - Reducing surveillance in HR pa ents who are at increased risk of relapse - Is the greater risk from CT or MRI with anesthesia +/ Gd - Consider MIBG alone for surveillance, with CT/MRI for MIBG abnormali es Intro NeuroblastomaCancer Hepatoblastoma Wilms Tumor Surveillance Survivorship Imaging Take Home Points • MRI: Key role for staging for NBL, HBL & Wilms - Stage and disease extent assoc’d with outcome • MRI for response assessment - Neuroblastoma & Hepatoblastoma (PRETEXT 3, 4) - Bilateral Wilms; • Func onal imaging: Neuroblastoma - MIBG, 18F-FDG for MIBG-nega ve disease • Rou ne off therapy surveillance - O en extensive with no impact on overall outcome - New concerns about anesthesia risk for MRI