Rosa Nguyen1, M Beth McCarville2, April Sykes3, Shenghua Mao3, Jianrong Wu3, Max R Langham4, Wayne L Furman5. 1. Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA. 2. Department of Diagnostic Imaging, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA. 3. Department of Biostatistics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA. 4. Department of Surgery, University of Tennessee Health Science Center, Le Bonheur Children's Hospital, 50 N Dunlap St, Memphis, TN, 38105, USA. 5. Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA. wayne.furman@stjude.org.
Abstract
BACKGROUND: Neoadjuvant chemotherapy is given to children with unresectable hepatoblastoma to increase the rate and safety of curative complete surgical resection. Elevated levels of serum alpha-fetoprotein (sAFP) decline with tumor shrinkage. In this single-institution retrospective study, we determined early dynamic changes of sAFP levels and tumor volume in children during therapy for unresectable hepatoblastoma. METHODS: We correlated early dynamic changes of sAFP levels and tumor volume and the sum of the longest primary tumor and measurable metastatic disease diameters as per RECIST 1.1 criteria with patient outcome. RESULTS: There were 34 patients, 7 of whom died of disease. Patients with ≥ 90% (≥ 1 log10) decrease in sAFP levels after two chemotherapy courses had a better event-free survival (P = 0.039) and overall survival (OS; P = 0.045) than those with < 90% decrease. During this treatment interval, average tumor volume decreased from 481 mL (± 254 mL) to 268 mL (± 258 mL; P < 0.001) which was associated with OS (P = 0.029). Relative change in sAFP levels or tumor volume in between course 2 and pre-surgery or response as per RECIST 1.1 was not associated with OS. CONCLUSION: Early decline of sAFP levels and tumor volume, but not response as per RECIST 1.1 may predict survival in children with unresectable hepatoblastoma. This finding could be useful to identify therapy non-responders for whom alternative interventions may be required for cure. Confirmation of the finding using larger patient cohorts will be necessary before this strategy is incorporated into prospective trials.
BACKGROUND: Neoadjuvant chemotherapy is given to children with unresectable hepatoblastoma to increase the rate and safety of curative complete surgical resection. Elevated levels of serum alpha-fetoprotein (sAFP) decline with tumor shrinkage. In this single-institution retrospective study, we determined early dynamic changes of sAFP levels and tumor volume in children during therapy for unresectable hepatoblastoma. METHODS: We correlated early dynamic changes of sAFP levels and tumor volume and the sum of the longest primary tumor and measurable metastatic disease diameters as per RECIST 1.1 criteria with patient outcome. RESULTS: There were 34 patients, 7 of whom died of disease. Patients with ≥ 90% (≥ 1 log10) decrease in sAFP levels after two chemotherapy courses had a better event-free survival (P = 0.039) and overall survival (OS; P = 0.045) than those with < 90% decrease. During this treatment interval, average tumor volume decreased from 481 mL (± 254 mL) to 268 mL (± 258 mL; P < 0.001) which was associated with OS (P = 0.029). Relative change in sAFP levels or tumor volume in between course 2 and pre-surgery or response as per RECIST 1.1 was not associated with OS. CONCLUSION: Early decline of sAFP levels and tumor volume, but not response as per RECIST 1.1 may predict survival in children with unresectable hepatoblastoma. This finding could be useful to identify therapy non-responders for whom alternative interventions may be required for cure. Confirmation of the finding using larger patient cohorts will be necessary before this strategy is incorporated into prospective trials.
Authors: Piotr Czauderna; Jean Bernard Otte; Daniel C Aronson; Frederic Gauthier; Gordon Mackinlay; Derek Roebuck; Jack Plaschkes; Giorgio Perilongo Journal: Eur J Cancer Date: 2005-05 Impact factor: 9.162
Authors: J M Van Tornout; J D Buckley; J J Quinn; J H Feusner; M D Krailo; D R King; G D Hammond; J A Ortega Journal: J Clin Oncol Date: 1997-03 Impact factor: 44.544
Authors: J Pritchard; J Brown; E Shafford; G Perilongo; P Brock; C Dicks-Mireaux; J Keeling; A Phillips; A Vos; J Plaschkes Journal: J Clin Oncol Date: 2000-11-15 Impact factor: 44.544
Authors: Giorgio Perilongo; Rudolf Maibach; Elisabeth Shafford; Laurence Brugieres; Penelope Brock; Bruce Morland; Beatriz de Camargo; Jozsef Zsiros; Derek Roebuck; Arthur Zimmermann; Daniel Aronson; Margaret Childs; Eva Widing; Veronique Laithier; Jack Plaschkes; Jon Pritchard; Marcello Scopinaro; Gordon MacKinlay; Piotr Czauderna Journal: N Engl J Med Date: 2009-10-22 Impact factor: 91.245
Authors: J B Otte; J Pritchard; D C Aronson; J Brown; P Czauderna; R Maibach; G Perilongo; E Shafford; J Plaschkes Journal: Pediatr Blood Cancer Date: 2004-01 Impact factor: 3.167
Authors: József Zsiros; Laurence Brugieres; Penelope Brock; Derek Roebuck; Rudolf Maibach; Arthur Zimmermann; Margaret Childs; Daniele Pariente; Veronique Laithier; Jean-Bernard Otte; Sophie Branchereau; Daniel Aronson; Arun Rangaswami; Milind Ronghe; Michela Casanova; Michael Sullivan; Bruce Morland; Piotr Czauderna; Giorgio Perilongo Journal: Lancet Oncol Date: 2013-07-04 Impact factor: 41.316