Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Aug 1;39(22):2463-2473.
doi: 10.1200/JCO.20.02871. Epub 2021 Apr 6.

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

Carlos Rodriguez-Galindo  1   2 , Mark D Krailo  3   4 , Emilia M Pinto  5 , Farzana Pashankar  6 , Christopher B Weldon  7 , Li Huang  3 , Eliana M Caran  8 , John Hicks  9 , M Beth McCarville  10 , David Malkin  11 , Jonathan D Wasserman  12 , Antonio G de Oliveira Filho  13 , Michael P LaQuaglia  14 , Deborah A Ward  15 , Gerard Zambetti  5 , Maria J Mastellaro  16 , Alberto S Pappo  1 , Raul C Ribeiro  1
Affiliations
Clinical Trial

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

Carlos Rodriguez-Galindo et al. J Clin Oncol. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

FIG 1.
FIG 1.
Patient flow diagram of ARAR0332.
FIG 2.
FIG 2.
(A) EFS and (B) OS probabilities for 78 patients enrolled on ARAR0332. EFS, event-free survival; OS, overall survival.
See this image and copyright information in PMC

Comment in

References

    1. Siegel DA, King J, Tai E, et al. Cancer incidence rates and trends among children and adolescents in the United States, 2001–2009 Pediatrics 134e945–e9552014 - PMC - PubMed
    1. Michalkiewicz E, Sandrini R, Figueiredo B, et al. Clinical and outcome characteristics of children with adrenocortical tumors. An analysis of 254 cases from the International Pediatric Adrenocortical Tumor Registry J Clin Oncol 22838–8452004 - PubMed
    1. Ribeiro RC, Pinto EM, Zambetti GP, et al. The International Pediatric Adrenocortical Tumor Registry initiative: Contributions to clinical, biological, and treatment advances in pediatric adrenocortical tumors Mol Cell Endocrinol 35137–432012 - PubMed
    1. Wasserman JD, Novokmet A, Eichler-Jonsson C, et al. Prevalence and functional consequence of TP53 mutations in pediatric adrenocortical carcinoma: A Children's Oncology Group study J Clin Oncol 33602–6092015 - PMC - PubMed
    1. Clay MR, Pinto EM, Cline C, et al. DNA methylation profiling reveals prognostically significant groups in pediatric adrenocortical tumors: A report from the International Pediatric Adrenocortical Tumor Registry. JCO Precis Oncol. 2019 - PMC - PubMed

Publication types

MeSH terms

Supplementary concepts