"PET Imaging of a Wilms Tumor"
St. Jude Solid Tumor Board St. Jude Solid Tumor Board 27 February 2009 27 February 2009 PET Imaging PET Imaging of a Wilms Tumor of a Wilms Tumor Shulkin, Barry Shulkin, MD Jesse Jenkins, III, MD Andrew Davidoff, MD Pai-Panandiker, Atmaram Pai-Panandiker, MD Shulkin, Barry L. Shulkin, MD, MBA • 4-year-old girl • Physical exam – large right sided • May 2006 – 1 week constipation and abdominal mass crossing midline abdominal enlargement • PH – unremarkable • Physical exam – abdominal mass • FH – nothing particularly informative • Referred to LBCMC – CT confirmed • SH – lives with parents and 21 y/o brother abdominal mass • Sent to SJCRH 1 Jeffrey S. Dome MD JD Main Considerations • Clear cell variant of Wilms • Anaplastic Wilms • Less likely – ACC – Primary hepatic tumor (HCC) – Epithelioid sarcoma http://www.childrensnational.org/research/faculty/bios/ccir/Dome_j.aspx St. Jude Solid Tumor Board 27 February 2009 Needle biopsy • 5/26/06 Needle Biopsy of Right Kidney and Omentum • Interventional radiology 5/26/06 Jesse J. Jenkins, III, MD 2 WT1 Immunohistochemistry St. Jude Solid Tumor Board 27 February 2009 FDG PET CT Scan PET Imaging of a Wilms Tumor • 5/30/06 Shulkin, Barry L. Shulkin, MD, MBA 3 Therapy • ICE – Ifosfamide – Carboplatin – Etoposide Alternating with • VDC – Vincristine – Doxorubicin – Cyclophosphamide 4 St. Jude Solid Tumor Board 27 February 2009 National Wilms Tumor Study Pre- or Postoperative Therapy Pre- Group (NWTSG) for Wilms tumor? • immediate nephrectomy • post-operative chemotherapy and radiation therapy administered based on the surgical pathologic Andrew Davidoff, MD stage International Society of Pediatric Primary Nephrectomy Oncology (SIOP) • Benefits – accurate histology • pre-nephrectomy chemotherapy • no influence of treatment effect • benign v. malignant • delayed surgery – congenital lesions, mesoblastic nephroma, angiolipoma – anaplastic Wilms, rhabdoid, clear cell sarcoma, renal cell – accurate stage • post-nephrectomy adjuvant therapy • particularly lymph node involvement as dictated by histology, stage, • Disadvantages response – higher incidence of tumor rupture • similar incidence in single-institution review – Hall et al, J Pediatr Surg, 2006 (Hospital for Sick Children, Toronto) Pre-nephrectomy Chemotherapy COG indications for • Advantages pre-nephrectomy chemotherapy – Fewer complications (SIOP-93-01 vs NWTS-5) • Overall: 6.4% vs 9.8% (p=0.12) • Intravenous tumor thrombus extending above the level of the • lower incidence of tumor rupture hepatic veins – 2.2% vs 15.3% (p<0.001) – risk of tumor embolus – Assess tumor response → change therapy – need for cardiopulmonary bypass – “downstaging” of patients • Unable to tolerate surgery • Stage III: 14.2% vs 30.4% (p<0.001) • lower the use of XRT – general condition (e.g. nutrition) – extensive pulmonary metastases→respiratory insufficiency • Disadvantages – 5% diagnostic error rate • Bilateral Wilms tumor • benign tumors or non-Wilms malignant tumors – tumor in solitary, horseshoe kidney – “Downstaging” • “Evidence” of pre-operative rupture • SIOP-6, stage II +/- XRT • “Unresectable” – more local recurrence when not given XRT – now give adriamycin for stage II – Size alone is NOT an indication 5 St. Jude Solid Tumor Board 27 February 2009 Pre- or Postoperative Right Nephrectomy with Sampling of therapy for Lymph Nodes, Peritoneal Nodules & Paraduodenal Mass Wilms tumor? 7/14/06 Remains an unresolved controversy Jesse J. Jenkins, III, MD Right Kidney Right Kidney ? Questions and Answers Peritoneal Nodules Some questions were asked without Paraduodenal Mass a microphone nearby and may be difficult to hear. 6 St. Jude Solid Tumor Board 27 February 2009 Historical data Radiation Therapy • Now 7 y/o (dx at 4) with hemi-hypertrophy and FH Stage IV (lung) Wilms’ tumor of the right kidney 8/30/06 • Pre-operative chemotherapy initiated 5/2006 Sup/ant di ti l t diagnosis • S / t mediastinal LAD at di i • Pre-operative (7/14/06) diffuse tumor spillage noted (prior biopsy on 5/26/06) • Peri-nephric and aorto-caval LN negative Pai-Panandiker, Atmaram Pai-Panandiker, MD – LN chains negative by PET, primary heterogeneous uptake Association with 3 congenital NWTSG RT dose data syndromes • Denys-Drash point mutation WT-1 NWTS-1 – Intersexual disorder (ambiguous genitalia, • Group I pseudohermaphrodism, streak gonads) – Arm 1 = AMD + RT (18-40Gy by stage/age) – Nephropathy – Arm 2 = AMD alone – >90% incidence of Wilms’ Tumor • < 2 y/o RT made no diff when added to AMD • WAGR • ≥ 2 y/o RT + AMD adds benefit – Wilms, Aniridia, GU malformation, Mental Retardation • Groups II/III – 33% develop Wilms’ Tumor – VCN vs AMD vs VA • For VCN or AMD alone, no difference @ 4yrs ~70% OS • Beckwith-Wiedemann linked to WT-2 • VA – OS significantly ~ 80-90% @ 4yrs – Overgrowth complex –hemihypertrophy, organomegaly, • Group IV macroglossia, omphalocoele, predilection for embryonal tumors – Pre-operative VCN, then VA post-op vs – <5% incidence of Wilms’ Tumor, but synch/metach bilateral – Post-op RT + VA disease rates are higher • Pre-op VCN not helpful ALL NWTS studies showed decrement to OS if post-op RT delayed > post-op day 9 NWTS – 3 (added staging and NWTS - 2 histology to stratification) • Gp I: post-op VA (no RT) • Stage I: post-op, no RT – 6 months VA vs 15 months VA – No diff between 10 wks vs 6 months VA – No diff, 6 months standard (OS~90%) • Stage II: post-op, 4 arms (no RT vs 20 Gy) • Gp II-IV: post-op RT (same age dependent scale – Chemo = VAA x 15 months vs Intensive VAA x 15 months • No benefit to adding Doxo or RT from NWTS 1) & chemo • Stage III: post-op, RT (RND 10 vs 20 Gy) – 15 months VA vs 15 months VAA – Intensive VA x 15 months vs VAA x 15 months – FH II/III = 3 yr OS ~80-90% • RT to 10 Gy for St III FH suffices, Doxo adds OS benefit • Doxo adds significant survival benefit~10% • Stage IV(all UH/any St): post-op, RT to 20 Gy – Improved 82% OS to 92 % OS with doxo – RND VAA vs VAA + CYT x 15 months • CYT no benefit to St IV FH, helps focally anaplastic and CCSK, not • Gp IV VAA = 3 yr OS ~ 60% vs 44% w/o doxo RTK • VAA + WLI/WAI had 4 yr OS ~ 81% Lung mets initially got 14 Gy, but 10% developed pneumonitis: dropped dose to 12 Gy 7 Stage FH Anaplastic CCK/Rhabdoid NWTS - 4 I-II •No RT •Stage I: no RT •All receive flank or •Stage II: flank RT abdomen RT • Minimization of therapy and toxicity III •Flank RT: If involving renal hilar •The same as FH •The same as FH – Economic assessment nodes, gross or microscopic disease stage III stage III confined to the flank, or PA nodes • For St III/IV FH, St I-IV CCSK •WART: peritoneal seeding, gross – VAA vs pulsed/intense VAA residual abdominal disease, intra- p p p y peritoneal spill or rupture. 10.8Gy in Chemotx was RND 26 vs 65 weeks • Ch t k 6 fx, boost tumor >3cm to an • FH got 10.8 Gy abdominal RT additional 10.8Gy. • 12 Gy WLI for St IV – No diff, between risk groups, P/I vs non-P/I or length IV •Treat abdomen as per the intra- •The same as FH • The same as FH of chemotherapy abdominal stage (ie for local stage Stage IV stage IV except stage I • Risk of relapse increased for: I/II, no RT) and II abdominal – Higher stage, aggressive histologies, + margins, + nodes, older •Whole lung: resect or 12Gy, boost disease is also children, incomplete resection, spillage or tumor rupture persistent mets to 19.5Gy irradiated. •Irradiate liver in certain circumstances Wilms’ Tumor – Low and Standard Wilm’s Tumor – High Risk Therapy Risk Therapy (AREN 0532) (AREN 0533) • No RT for FH Stage I/II – Relapsed disease treated at primary or met site as indicated • Focal anaplasia now treated (incl. Stage I) • Radiotherapy starts by post-op day 9 • Stage III FH: flank vs WAI • By nature, planning commonly 2-dimensional – Local vs diffuse • Patient age and under-development toxicities disease – Bone growth, renal, bowel, lung and secondary cancers Wilm’s Tumor – High Risk Therapy Wilms Tumor – High Risk Therapy (AREN 0533) (AREN 0533) 8 Toxicities • Orthopedic • Hepatic • Renal • Pregnancy • Cardiac • Secondary Malignancy 9 St. Jude Solid Tumor Board 27 February 2009 PET Scanning of Wilms Tumors PET Scanning • Shulkin BL, Chang E, Strouse PJ et al. PET FDG studies of Wilms tumors. J Pediatr Hematol Oncol. 1997;19(4):334-338. – Metabolic activity • Misch D, Steffen IG, Schonberger S et al. Use of it i i tomography f staging, preoperative positron emission t h for t i ti response assessment and posttherapeutic evaluation in children with Wilms tumour. Eur J Nucl Med Mol Imaging. 2008;35(9):1642-1650 – 9 patients with newly diagnosed Wilms’ tumor and – perfect concordance between the PET-CT and conventional Barry L. Shulkin, MD, MBA Shulkin, imaging studies – None of the patients had metastatic disease PET Scanning of Wilms Tumors PET Scanning of Wilms Tumors • AKM Moinul Hossain MD PhD • 27 patients • 3 institutions • 58 scans – St. Jude Children’s Research Hospital – 1 at diagnosis Cincinatti Children’s Hospital – Ci i tti Child ’ H it l following – 1 f ll i surgery – Vancouver Children’s Hospital – 56 relapse, progressive disease, monitoring of therapy PET Scanning of Wilms Tumors PET Scanning of Wilms Tumors • 34 scans abnormal • Two of 8 patients with lung metastases – 8 patients (24 scans) had pulmonary metastases larger than 10 mm in diameter had variable uptakes. – 10 patients (12 scans) had hepatic metastases • Lung lesions 10 mm or smaller were not – 11 patients (11 scans) had regional nodal scans. consistently visualized on PET scans involvement – 3 patients (3 scans) had bone metastases • One patient with liver metastasis showed – 1 patient (1 scan) had chest wall involvement no uptake on PET scan after treatment – 2 patients (2 scans) had pancreatic metastasis (size decreased from 45 mm to 15 mm) – 5 patients (5 scans) had abdominal and pelvic soft tissue involvement 10 8-year-old girl with recurrent Wilms’ tumor showing 9-year-old girl with bilateral lung metastases focal uptake in the liver 11 year old 11-year-old girl with recurrent Wilms’ tumor showing focal uptake and sclerotic process in the left proximal tibia; consistent with bony metastatic disease 7-year-old girl with newly diagnosed right sided Wilms’ tumor showing extensive metastatic disease in the chest, abdomen and pelvis PET Scanning of Wilms Tumors • 27 patients • 58 scans – 1 at diagnosis following – 1 f ll i surgery – 56 relapse, progressive disease, monitoring of therapy 10-year-old girl with left sided recurrent Wilms’ tumor showing two liver metastases (yellow arrows) on contrast enhanced CT and three foci on MRI not detectable on PET-CT fusion image (without intravenous contrast). The lesion in the pancreatic tail area (red arrows) is evident in all images. 11 Patient Followup Conclusion • Per Fariba Navid MD • FDG PET CT useful in Wilms tumors – Staging +/- – Recurrent disease – Monitoring during and following therapy – Lung metastases < 1 cm better visualized with CT Thanks ? Jesse Jenkins, MD Andrew Davidoff, MD Atman Pai, MD Moinul Hossain, MD Questions and Answers Najat Daw, MD Some questions were asked without a microphone nearby and may be difficult to hear. End Shulkin, Barry Shulkin, MD Jesse Jenkins, III, MD Andrew Davidoff, MD Pai-Panandiker, Atmaram Pai-Panandiker, MD More medical education materials are available at: Cure4Kids is an initiative of St. Jude Children’s Research Hospital You may print and download content for personal educational use only. All material is copyrighted by the author of the content or St. Jude Children’s Research Hospital. See legal terms and conditions at http://www.Cure4Kids.org 12