TUMOR BOARD 2/18/2004

History  This patient is a 4 month old male with a 2 month history on a palpable mass on the back. It was being followed at the pediatrician’s office. About 1 month prior to presentation, he had a cough and fever and a CXR obtained by the PMD. It was initially read as a pneumonia and then a possible solid mass and he was referred for a chest CT.  No change in the size of the mass during this time

 No pain, no redness of the mass  No respiratory symptoms  Always an active child, with good weight gain. BHx : Born full term, NSVD, FHx: Not significant

Physical  Vitals: Alert, playful, in no distress HEENT: AF soft, flat, PERRL, EOMI Chest/Back: Posteriorly in the region of the 8 ICS,5 x 5 cm hard mass, non-tender, intact overlying skin. Good AE b/l Abdomen: soft, non-distended, no organomegaly Neuro: Moving 4 extremities symmetrically, DTR’s intact

Labs  WBC: 7.3, Hb: 13.3, Plts: 308  Electrolytes: WNL  AST: 65, ALT: 29  Alk Phos: 346  Urine HVA: 124, VMA: 146

 Stage 3 Neuroblastoma  N-MYC non-amplified, Diploid  Intermediate risk  On the A 3961

COG A 3961  Based on the previous POG data : intermediate risk NBL- estimated 3 year survival %  Favourable biology: Course 1 only  Unfavourable biology : Course 1 and 2  Radiation only if clinical deterioration despite chemo/surgery, viable tumor after 8 cycles in unfavourable biology.

NEJM 1984 Cellular DNA content as a predictor of response to chemotherapy in infants with unresectable NBL  23 pts  4 stages of unresectable NBL  Response to Cytoxan/Dox assessed  17 were hyperdiploid, 6 diploid  17: 15 CR, 2 PR  6 Diploid : NR

J Clin Oncol,Look et al Clinical relevance of tumor cell ploidy and N-myc amplification in childhood NBL  Influence of DNA ploidy and N-myc expression on clinical outcomes  298 children  34 %: Diploid, 65 % Hyperdiploid  Nmyc amplification more common in diploid  Highly predictive of outcome in 2 groups: - Stage D ( Stg 4): > 90 % PFS in hyperdiploid vs 0 % diploid) - - Children mths: 50-60% PFS vs 0% in diploid) - Not predictive for loco-regional disease POG A,B and C.

Cancer Res 1991 Combined analysis of DNA ploidy index and Nmyc in NBL  To assess the prognostic value of Nmyc and DNA ploidy accounting for the confounding factors of age and stage.  59 pts studied: 26 were diploid, 33 were aneuploid  More aneuploid tumors in Stg 1, 2, 4S And in children < 1 0/28 near-triploid were Nmyc +, 9/31 : diploid, near-diploid Nmyc +

Cancer Res 1991  Multivariate analysis: NMYC and Ploidy were associated with relapse  2 yr DFS: 94 %( 77-98%) with near triploid NBL  2 yr DFS: Diploid, – NMYC amplified: 45% (32-70% ) Diploid, +NMYC :11 %( 4-23%)

 Ploidy in this study only for stratifying for Course 1 vs Course 1 and 2: each course with 4 cycles  Cisplatinum/VP16/ Cytoxan/Dox in various combinations  Catecholamines prior to every other cycle, reeval at end of course 1 Will start cycle 3 next week

J Clin Oncol,Look et al Clinical relevance of tumor cell ploidy and N-mc amplification in childhood NBL  Influence of DNA ploidy and N-myc expression on clinical outcomes  298 children  34 %: Diploid, 65 % Hyperdiploid  Nmyc amplification more common in diploid  Highly predictive of outcome in 2 groups: - Stage D ( Stg 4): > 90 % PFS in hyperdiploid vs 0 % diploid) - - Children mths: 50-60% PFS vs 0% in diploid) - Not predictive for loco-regional disease POG A,B and C.