PROGNOSTIC IMPACT OF MINIMAL DISSEMINATION DETECTION IN NON-METASTATIC RETINOBLASTOMA WITH HIGH-RISK PATHOLOGY FEATURES

VIVIANA LAURENT; VALERIA VAZQUEZ; RAMIREZ MARCO; JORGE ROSSI; SAMPOR CLAUDIA; GABRI MARIANO; ALONSO CRISTINA; CHANTADA GUILLERMO; ANA VANESA TORBIDONI; OTTAVIANI DANIELA; GARCIA DE DAVILA MARIA TERESA; ALONSO DANIEL

Congreso; III international Congress in translational medicine; 2016

Introduction: Metastatic relapse may occur inchildren with retinoblastoma and high-risk pathology features (HRPF) and it isa major cause of mortality worldwide. The detection of minimal dissemination(MD) may be a tool for risk estimation. We previously reported the use of CRXmRNA for MD determination in metastatic retinoblastoma but no data innon-metastatic children with retinoblastoma and HRPF are available. Objectives: To evaluate whether MD isdetectable in children with non-metastatic retinoblastoma who have HRPF and toassess the prognostic impact of MD on disease-free survival (DFS).Material and methods: It was a prospectivestudy carry on from 05-2007 to 10-2013. Median follow up was 38 month (range 8to 89). We studied 84 patients with non-metastatic retinoblastoma and HRPF(isolated massive choroidal invasion in 14, post laminar optic nerve invasion(PLONI) in 51 (26 with concomitant massive choroidal and 13 with scleralinvasion), 12 with scleral invasion without PLONI and 7 with tumor at theresection margin of the optic nerve) were evaluated at the time of primary orsecondary enucleation. CRX mRNA was evaluated by RT-qPCR in bone marrow(BM) and cerebrospinal fluid (CSF) at diagnosis and during follow-up. In 14cases, GD2 synthase was used instead of CRX for CSF evaluation. Patients weretreated under uniform guidelines. The main outcome measure was the metastaticrelapse.   Results: MD was detected in 9 cases (BM=7,CSF=2). MD was significantly associated with tumor extension beyond theresection margin of the optic nerve (p=0.0005) and sclera involvement(p=0.002). MD occurred in 18.6% of the group E eyes with glaucoma and in 8/80and 1/16 of initially and secondarily enucleated children, respectively.Children with MD had a significantly lower 3-year DFS (0.78 (95% CI= 0.37-0.94)versus 0.98 (95% CI= 0.93-1) p=0.004).Conclusions: We identified a very high-riskpopulation of children with retinoblastoma and HRPF who have MD in whom DFS issignificantly lower despite intensive adjuvant therapy. Children with group Eretinoblastoma and glaucoma have a significantly higher risk of MD atdiagnosis.