Sanjeev A Vasudevan1, Rebecka L Meyers2, Milton J Finegold1, Dolores López-Terrada1, Sarangarajan Ranganathan3, Stephen P Dunn4, Max R Langham5, Eugene D McGahren6, Greg M Tiao3, Christopher B Weldon7, Marcio H Malogolowkin8, Mark D Krailo9, Jin Piao9, Jessica Randazzo10, Alexander J Towbin3, M BethMcCarville5, Allison F O'Neill7, Wayne L Furman5, Carlos Rodriguez-Galindo5, Howard M Katzenstein11. 1. Baylor College of Medicine, Texas Children's Hospital, 6701 Fannin, Houston, TX 77030, United States. 2. Primary Children's Hospital, University of Utah, 100N. Mario Capecchi Dr., Salt Lake City, UT 84113, United States. 3. Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, United States. 4. AI Dupont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19803, United States. 5. St Jude Children's Research Hospital and University of Tennessee Health Science Center, 262 Danny Thomas Place, Memphis, TN 38015, United States. 6. University of Virginia Hospital, 1215 Lee St., Charlottesville, VA 22903, United States. 7. Dana-Farber Cancer Institute and Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, United States. 8. University of California Davis Comprehensive Cancer Center, 2279 45th St., Sacramento, CA 95817, United States. 9. University of Southern California Keck School of Medicine, 1975 Zonal Ave., Los Angeles, CA 90033, United States. 10. Children's Oncology Group, 800 Royal Oaks Dr., Suite 210, Monrovia, CA 91016, United States. 11. Nemours Children's Hospital, 1600 Rockland Road, Wilmington DE 19803, United States. Electronic address: savasude@texaschildrens.org.
Abstract
BACKGROUND: Hepatoblastoma (HB) requires surgical resection for cure, but only 20-30% of patients have resectable disease at diagnosis. Patients who undergo partial hepatectomy at diagnosis have historically received 4-6 cycles of adjuvant chemotherapy; however, those with 100% well-differentiated fetal histology (WDF) have been observed to have excellent outcomes when treated with surgery alone. PATIENTS AND METHODS: Patients on the Children's Oncology Group non randomized, multicenter phase III study, AHEP0731, were stratified based on Evan's stage, tumor histology, and serum alpha-fetoprotein level at diagnosis. Patients were eligible for the very low risk stratum of surgery and observation if they had a complete resection at diagnosis and rapid central histologic review demonstrated HB with 100% WDF histology. RESULTS: A total of 8 eligible patients were enrolled on study between September 14, 2009 and May 28, 2014. Outcome current to 06/30/2020 was used in this analysis. The median age at enrollment was 22.5 months (range: 8-84 months) and the median AFP at enrollment was 714 ng/ml (range: 18-77,747 ng/mL). With a median follow-up of 6.6 years (range: 3.6-9.8 years), the 5-year event-free (EFS) and overall survival (OS) were both 100%. CONCLUSION: This report supports that HB with 100% WDF histology completely resected at diagnosis is curable with surgery only. The development of evidence-based surgical guidelines utilizing criteria based on PRETEXT group, vascular involvement (annotation factors), tumor-specific histology and corresponding biology will be crucial for optimizing which patients are candidates for resection at diagnosis followed by observation. LEVEL OF EVIDENCE: Prognosis study, Level I evidence.
BACKGROUND: Hepatoblastoma (HB) requires surgical resection for cure, but only 20-30% of patients have resectable disease at diagnosis. Patients who undergo partial hepatectomy at diagnosis have historically received 4-6 cycles of adjuvant chemotherapy; however, those with 100% well-differentiated fetal histology (WDF) have been observed to have excellent outcomes when treated with surgery alone. PATIENTS AND METHODS: Patients on the Children's Oncology Group non randomized, multicenter phase III study, AHEP0731, were stratified based on Evan's stage, tumor histology, and serum alpha-fetoprotein level at diagnosis. Patients were eligible for the very low risk stratum of surgery and observation if they had a complete resection at diagnosis and rapid central histologic review demonstrated HB with 100% WDF histology. RESULTS: A total of 8 eligible patients were enrolled on study between September 14, 2009 and May 28, 2014. Outcome current to 06/30/2020 was used in this analysis. The median age at enrollment was 22.5 months (range: 8-84 months) and the median AFP at enrollment was 714 ng/ml (range: 18-77,747 ng/mL). With a median follow-up of 6.6 years (range: 3.6-9.8 years), the 5-year event-free (EFS) and overall survival (OS) were both 100%. CONCLUSION: This report supports that HB with 100% WDF histology completely resected at diagnosis is curable with surgery only. The development of evidence-based surgical guidelines utilizing criteria based on PRETEXT group, vascular involvement (annotation factors), tumor-specific histology and corresponding biology will be crucial for optimizing which patients are candidates for resection at diagnosis followed by observation. LEVEL OF EVIDENCE: Prognosis study, Level I evidence.
Authors: Howard M Katzenstein; Max R Langham; Marcio H Malogolowkin; Mark D Krailo; Alexander J Towbin; Mary Beth McCarville; Milton J Finegold; Sarangarajan Ranganathan; Stephen Dunn; Eugene D McGahren; Gregory M Tiao; Allison F O'Neill; Muna Qayed; Wayne L Furman; Caihong Xia; Carlos Rodriguez-Galindo; Rebecka L Meyers Journal: Lancet Oncol Date: 2019-04-08 Impact factor: 41.316
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Authors: J A Ortega; E C Douglass; J H Feusner; M Reynolds; J J Quinn; M J Finegold; J E Haas; D R King; W Liu-Mares; M G Sensel; M D Krailo Journal: J Clin Oncol Date: 2000-07 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: G Perilongo; E Shafford; R Maibach; D Aronson; L Brugières; P Brock; M Childs; P Czauderna; G MacKinlay; J B Otte; J Pritchard; R Rondelli; M Scopinaro; C Staalman; J Plaschkes Journal: Eur J Cancer Date: 2004-02 Impact factor: 9.162