Oral Presentation Advances in Neuroblastoma Research Congress 2016

Did we improve results in infants with MYCN Amplified Neuroblastoma? Comparison of treatment strategy and outcomes in INES 99.4 and HR-NBL1/ SIOPEN. A SIOPEN Study   (#86)

Adela Cañete 1 , Ulrike Poetschger 2 , Peter Ambros 3 , Domonique Valteau-Couanet 4 , Martin Elliot 5 , Roberto Luksch 6 , Victoria Castel 1 , Walentyna Balwierz 7 , Isaac Yaniv 8 , Ellen Ruud 9 , Per Kogner 10 , Anne O´Meara 11 , Genevieve Laureys 12 , Vassilios Papadakis 13 , Henrik Shroeder 14 , Josef Malis 15 , Ana Forjaz de Lacerda 16 , Maia Beck-Popovic 17 , Pavel Bician 18 , Miklos Garami 19 , Toby Trahair 20 , Keith Holmes 21 , Guenter Schreier 22 , Mark Gaze 23 , Andrew Pearson 24 , Ruth Ladenstein 25
  1. La Fe, Valencia, Spain
  2. Studies and Statistics on Integrated Research and Projects, St. Anna Kinderkrebsforschung, Vienna, Austria
  3. Tumor Biology, St. Anna Kinderkrebsforschung, Vienna, Austria
  4. Dept Paediatric Oncology, Institut Gustave Roussy, Villejuif, France
  5. Pediatric Haematology / Oncology, Leeds Teaching Hospital NHS Trust, Leeds, United Kingdom
  6. Paediatric Haematology / Oncology, Istituto Nacionale TUmore di Milano, Milano, Italy
  7. Paediatric Haematology / Oncology, Jagiellonia University Medical College, Krakow, Poland
  8. Paediatric Haematology / Oncology, Schneider Children´s Medical Center of Israel, Petah Tikva, Israel
  9. Paediatric Haematology / Oncology, Rikshospitalet, Oslo, Norway
  10. Pediatric Haematology / Oncology, Karolinska Institute, Stockholm, Sweden
  11. Paediatric Haematology / Oncology, Our Ladys Children´s Hospital, Crumlin, Ireland
  12. Paediatric Haematology / Oncology, University Hospital Gent, Gent, Belgium
  13. Paediatric Haematology / Oncology, Agia Sofia Children´s Hospital, Athenx, Greece
  14. Department of Paediatrics, University Hospital of Aarhus, Skejby, Denmarck
  15. Paediatric Haematology / Oncology, University Hospital Motol, Prague, Czech Republica
  16. Paediatric Haematology / Oncology, Portuguese Institute of Oncology, Lisboa, Portugal
  17. Dept. of Paediatrics, University Hospital (CHUV), Lausanne, Switzerland
  18. Paediatric Haematology / Oncology, University Children´s Hospital, Banska Bystrica, Slovakia
  19. Paediatric Haematology / Oncology, Semmelweis University, Budapest, Hungary
  20. Centre for Children’s Cancer & Blood Disorders, Sydney Children’s Hospital, Sydney, Australia
  21. Pediatric Surgery, St. George´s Hospital, London, United Kingdom
  22. AIT, Austrian Institut of Technology, Graz, Austria
  23. Pediatric Haematology / Oncology, University College of London, London, United Kingdom
  24. Paediatric Department, Institute of Cancer Research/ Royal Marsden Hospital, London, United Kingdom
  25. CCRI, St. Anna Kinderkrebsforschung, Vienna, Austria

Background/Introduction:

Infants with MYCN amplified (MYCN-A) neuroblastoma treated in INES 99.4 (Canete et al, JCO 2009) showed a very dismal prognosis. Therefore, SIOPEN decided to submit these infants to the HR-NBL1/SIOPEN intensified treatment .

 

Methods and population:

94 MYCN-A infants (58 males, 36 females) were considered eligible, (75% stage 4; 13% stage 2-3, 12% 4s) with a median age of 8.5 months. All received induction chemotherapy (IC: Rapid-Cojec ± TVD) followed by BuMel/SCT, primary site surgery, radiation (21Gy) and 13-cisRA as maintenance. 35 received antiGD2 ch14.18/CHO treatment since 2010. Median follow up time is 3.9 years. In 99.4 trial, 35 patients (20 males, 15 females; median age 7,6 months) were analyzed (69% stage 4, 28% stage 4s and 3% stage 3). Treatment consisted in standard IC (carboplatin&etoposide-CADO), surgery, BuMel/SCT, local radiotherapy, 13-cisRA maintenance (JCO 2009).

 

Results: For HR-NBL1, 85% of evaluable cases (n=80) achieved CR/VGPR/PR following IC. Six infants went off treatment, one had PD whilst five had less than PR. The EFS and OS rates are 0.44±0.06 and 0.48±0.06 for all 94 MYCN-A infants. The 5 yr EFS and OS rates were 0.4 and 0.45 for stage 4; 0.51 and 0.51 for stage 2&3, 0.58 and 0.65 for stage 4s (NS). The main cause of death remained progression/relapse, while only 4 cases were due to toxicity. For 99.4 population, 30% of patients progressed/did not respond to IC, with median time to progression of 4 months. The 2y-OS was 28% (SD: 0.15), 2y-EFS 24% (SD:0,11) , 12 months median survival time.

 

Conclusions: Rapid-Cojec resulted in less disease progressions and better response rate than 99.4 IC. Although OS and EFS improved in HR-NBL1/ SIOPEN as compared to 99.4, it is below 50% with lack of disease control being the main cause of death. The number of infants treated with ch14.18/CHO is too small to conclude currently and will be further addressed.