Treatment of Pediatric Adrenocortical Carcinoma With Surgery, Retroperitoneal Lymph Node Dissection, and Chemotherapy: The Children's Oncology Group ARAR0332 Protocol.

Autor:	Rodriguez-Galindo C; Department of Oncology, St Jude Children's Research Hospital, Memphis, TN.; Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN., Krailo MD; Statistics and Data Center, Children's Oncology Group, Monrovia, CA.; Department of Preventive Medicine, University of Southern California, Los Angeles, CA., Pinto EM; Department of Pathology, St Jude Children's Research Hospital, Memphis, TN., Pashankar F; Department of Pediatrics, Yale University School of Medicine, New Haven, CT., Weldon CB; Department of Surgery, Boston Children's Hospital, Boston, MA., Huang L; Statistics and Data Center, Children's Oncology Group, Monrovia, CA., Caran EM; Department of Oncology, Instituto de Oncologia Pediatrica, São Paulo, Brazil., Hicks J; Department of Pathology, Texas Children's Hospital, Houston, TX., McCarville MB; Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, TN., Malkin D; Division of Hematology-Oncology, Hospital for Sick Children and Department of Pediatrics, University of Toronto, Toronto, ON, Canada., Wasserman JD; Division of Endocrinology, Hospital for Sick Children, Toronto, ON., de Oliveira Filho AG; Department of Surgery, Centro Infantil Boldrini, São Paulo, Brazil., LaQuaglia MP; Department of Pediatric Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Ward DA; Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN., Zambetti G; Department of Pathology, St Jude Children's Research Hospital, Memphis, TN., Mastellaro MJ; Department of Oncology, Centro Infantil Boldrini, São Paulo, Brazil., Pappo AS; Department of Oncology, St Jude Children's Research Hospital, Memphis, TN., Ribeiro RC; Department of Oncology, St Jude Children's Research Hospital, Memphis, TN.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2021 Aug 01; Vol. 39 (22), pp. 2463-2473. Date of Electronic Publication: 2021 Apr 06.
DOI:	10.1200/JCO.20.02871
Abstrakt:	Purpose: Adrenocortical carcinoma (ACC) is a rare aggressive pediatric malignancy with distinct biology. Its treatment follows the principles developed for adults; pediatric-specific studies are scarce. Patients and Methods: Prospective single-arm risk-stratified interventional study. Study objectives were (1) to describe the outcome of patients with stage I ACC treated with adrenalectomy alone; (2) to describe the outcome of stage II patients (completely resected > 200 cc or > 100 g) treated with adrenalectomy and retroperitoneal lymph node dissection; and (3) to describe the outcome of patients with stage III or IV treated with mitotane and chemotherapy. Results: Between September 2006 and May 2013, 78 patients (77 eligible, 51 females) were enrolled. The 5-year event-free survival estimates for stages I (24 patients), II (15 patients), III (24 patients), and IV (14 patients) were 86.2%, 53.3%, 81%, and 7.1%, respectively. The corresponding 5-year overall survival estimates were 95.2%, 78.8%, 94.7%, and 15.6%, respectively. On univariate analysis, age, stage, presence of virilization, Cushing syndrome, or hypertension, germline TP53 status, and presence of a somatic ATRX mutation were associated with outcome. On multivariable analysis, only stage and age were significantly associated with outcome. The probabilities of mitotane and chemotherapy feasibility events were 10.5% and 31.6%, respectively. Conclusion: Outcome for children with stage I ACC is excellent with surgery. Outcome for patients with stage II disease is inferior despite retroperitoneal lymph node dissection. Patients with stage III ACC have an excellent outcome combining surgery and chemotherapy. Patients with stage IV ACC are older and have a poor outcome; new treatments should be explored for this high-risk group. The combination of mitotane and chemotherapy as prescribed in ARAR0332 resulted in significant toxicity; one third of patients with advanced disease could not complete the scheduled treatment. Competing Interests: Mark D. KrailoConsulting or Advisory Role: Merck Sharp & DohmeTravel, Accommodations, Expenses: Merck Sharp & Dohme Emilia M. PintoPatents, Royalties, Other Intellectual Property: Genotyping assays to identify mutations in XAF1 pending to St Jude Children's Research Hospital Farzana PashankarConsulting or Advisory Role: Novartis David MalkinConsulting or Advisory Role: Bayer Jonathan D. WassermanConsulting or Advisory Role: Bayer Gerard ZambettiResearch Funding: Johnson & JohnsonPatents, Royalties, Other Intellectual Property: MCL1 antibody license (Rockland Labs) to St Jude Children's Research Hospital. I receive small royalty on an annual basis, Patent pending for Genotyping assays to identify mutations in XAF1 Provisional application #62/659,427; Foreign filing April 18, 2019 Alberto S. PappoHonoraria: Bayer, RocheConsulting or Advisory Role: Merck, Loxo/Bayer, EUSA Pharma, DebbioNo other potential conflicts of interest were reported.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu