Update on RECIST and Staging of Common Pediatric Tumors Ethan A. Smith, MD

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1 Update on RECIST and Staging of Common Pediatric Tumors Ethan A. Smith, MD Section of Pediatric Radiology C.S. Mott Children s Hospital University of Michigan ethans@med.umich.edu

2 Disclosures No relevant financial disclosures

3 Objectives Discuss the need for objective response criteria Discuss RECIST and RECIST 1.1 Review staging for common abdominal tumors Neuroblastoma, Wilms, hepatoblastoma

4 Tumor Response Criteria Why? Objective Reproducible Standardized measurement for clinical trials 2 year old with Wilms tumor.

5 History and Development Response Evaluation Criteria In Solid Tumors Initially published in 2000 Tumor shrinkage correlates with Overall survival Progression free survival Updated in 2009 RECIST 1.1 Eisenhauer EA, et al. Eur J Cancer 2009; 45:

6 RECIST vs. RECIST 1.1 RECIST 1.1 Revised the number of lesions measured 10 5 lesions Progression criteria vs. response Newer imaging technologies MRI, FDG-PET Assessment of lymph nodes Use of targeted (non-cytotoxic) drugs Eisenhauer EA, et al. Eur J Cancer 2009; 45:

7 RECIST 1.1: Target Lesions Assessment methods Imaging CT and MRI preferred Ultrasound not permitted Clinical Endoscopy/laparoscopy Tumor markers Pathology 4 year old with Wilms tumor.

8 RECIST 1.1: Target Lesions Target lesions: Types Soft tissue lesions Must be well defined, easily measurable Bone lesions Must have identifiable soft tissue component Bone scan, FDG-PET, plain film not included Cystic lesions Simple cysts are not included Cystic metastases can be included Solid lesions preferred Eisenhauer EA, et al. Eur J Cancer 2009; 45:

9 RECIST 1.1: Target Lesions Target lesions: Size Must be accurately measured in at least 1 plane >10 mm by CT >10 mm by physical exam >20 mm by chest radiograph Lymph nodes > 15 mm in short axis dimension Eisenhauer EA, et al. Eur J Cancer 2009; 45:

10 RECIST 1.1: Assessment Baseline tumor burden Summation of maximum diameters of lesions Up to 5 lesions, maximum 2 per organ Short axis diameter for lymph node target lesions Response assessment Compared to baseline Eisenhauer EA, et al. Eur J Cancer 2009; 45:

11 RECIST 1.1: Response Complete Response (CR) Disappearance of all target lesions Normalization of lymph nodes Partial Response (PR) At least 30% decrease in sum of diameters Progressive Disease (PD) At least 20% increase in sum of diameters (over 5 mm) Stable Disease (SD) Eisenhauer EA, et al. Eur J Cancer 2009; 45:

12 RECIST 1.1: Non-Target Lesions Other sites of disease Non-pathologically enlarged lymph nodes Bone lesions Multiple lesions Above the 5 lesions counted as target lesions Assessed qualitatively Disappearance, persistence, unequivocal progression Eisenhauer EA, et al. Eur J Cancer 2009; 45:

13 RECIST 1.1: Pitfalls Lymph nodes Normalization of size = response Lesions that become to small to measure Do your best! Lesions that split or coalesce with treatment Add together diameters of fragments Use the diameter of coalesced lesions Sum of the two original lesions Eisenhauer EA, et al. Eur J Cancer 2009; 45:

14 Staging of Common Abdominal Tumors

15 Neuroblastoma Most widely used staging system = INSS International neuroblastoma staging system Newer system = INRG (2011) International neuroblastoma risk group Depends on imaged defined risk factors (IRDF s) Brisse HJ, et al. Radiology 2011; 261:

16 Neuroblastoma: INSS Stage 1 = localized disease, resected Stage 2 = incomplete resection, unilateral disease Stage 3 = unresectable, crosses midline Stage 4 = metastatic disease 50% of patients present as stage 4 Stage 4S = < 1 year of age, localized primary tumor Liver, skin, bone marrow metastases Brisse HJ, et al. Radiology 2011; 261:

17 Neuroblastoma: INRG Staging Staging depends on imaged defined risk factors (IDRF s) Multiple body compartments Vessel encasement Infiltrating solid organs Intra-spinal extension 3 year old with neuroblastoma. Brisse HJ, et al. Radiology 2011; 261:

18 Neuroblastoma: INRG Staging Stage L1 Localized tumor, no IDRF s Stage L2 Localized tumor, 1 or more IDRF Stage M Metastatic disease Stage MS Under 18 months of age Skin, bone marrow, liver metastases Neuroblastoma with vascular encasement (stage L2). Brisse HJ, et al. Radiology 2011; 261:

19 Wilms Tumor Stage 1 (40-45%) Confined to kidney, intact capsule Stage 2 (20-25%) Invades adjacent fat/vessels Completely resected Stage 3 (20-25%) + retroperitoneal nodes Residual disease Disrupted capsule (pre-op biopsy?) 4 year old with Wilms tumor and vascular invasion (arrow).

20 Wilms Tumor Stage 4 (10%) Distant metastasis Stage 5 (5%) Bilateral tumors After resection, each kidney staged individually Treatment depends on the highest stage 3 year old with bilateral Wilms tumors. T2W Hamilton TE, et al. Ann Surg 2011: 253;

21 PRETEXT staging Based on liver segments Hepatoblastoma Left lateral section (2, 3) Left medial section (4a, 4b) Right anterior section (5,8) Right posterior section (6,7) procedures/liver-transplantation.aspx Roebuck DJ, et al. Pediatr Radiol 2007: 37;

22 Hepatoblastoma: Pretext Pretext I = 1 section involved 3 adjoining sections free of tumor Pretext II = 1 or 2 sections involved 2 adjoining sections free of tumor Pretext III = 2 or 3 sections involved No 2 adjoining sections free of tumor Pretext IV = all 4 sections involved Roebuck DJ, et al. Pediatr Radiol 2007: 37;

23 Hepatoblastoma: Pretext Additional criteria Cuadate lobe involvement (C1) Extrahepatic abdominal disease Tumor rupture Lymph nodes Distant metastases Vascular involvement Portal vein, hepatic veins, IVC 3 month old with hepatoblastoma. T2W Roebuck DJ, et al. Pediatr Radiol 2007: 37;

24 Summary RECIST criteria (1.1) Up to 5 lesions Well defined, measureable, over 1 cm (1.5 cm for lymph nodes) Neuroblastoma staging systems Newer INRG system uses IDRF s (Image Defined Risk Factors) Wilm s tumor Stages 1-5 (5 = bilateral Wilm s tumors) Hepatoblastoma PRETEXT staging for treatment planning

25 Thank You

26 References 1. Eisenhauer EA, et al. New response evaluation criteria in solid tumors: Revised RECIST guideline (v1.1). Eur J Cancer 2009; 45: Brisse HJ, et al. Guidelines for imaging and staging neuroblastic tumours: Consensus report from the international neuroblastoma risk group project. Radiology 2011; 261: Hamilton TE, et al. The management of synchronous bilateral Wilms tumor: A report from the national Wilms tumor study group. Ann Surg 2011: 253; Roebuck DJ, et al PRETEXT: a revised staging system for primary malignant tumours of childhood developed by the SIOPEL group. Pediatr Radiol 2007: 37;

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