correspondence

Regarding the Children’s Oncology Group ARAR0332 Protocol for Pediatric Adrenocortical Carcinoma

TO THE EDITOR:

Rodriguez-Galindo et al1 reported the long-awaited results of the Children’s Oncology Group ARAR0332 Protocol, which showed patients with stage II disease treated with adrenalectomy and retroperitoneal lymph node dissection resulting in worse outcomes of 5-year event-free survival (53.3% v 81%) and 5-year overall survival (78.8% v 94.7%) compared to patients with stage III disease treated with combining surgery and chemotherapy in children with adrenocortical carci- noma (ACC). Despite amazing results, we would like to give some comments.

First, we are confused about the staging for patients with pediatric ACC. According to the staging criteria in ARAR0332 (Table 1), patients with stage III included those with retroperitoneal lymph node involvement. However, one of the 15 stage II patients had seven positive lymph nodes, but this patient was not regarded as with stage III disease. Moreover, among the 15 stage II patients, two patients had not undergone a retroperito- neal lymph node dissection (one patient refused, and the reason in the second case was unknown) and did not receive chemotherapy. Because all the 15 patients were included in the final survival analysis and the number of patients was small, these three patients may cause a great impact on the evaluation of outcomes in this group.

Second, the staging criteria in ARAR0332 was modi- fied from Sandrini et al,2 who proposed a set of staging classifications of childhood adrenocortical tumor in 1997. However, because of the low incidence rate of childhood adrenocortical tumors, this staging system was established based on a very small sample size, which was different from the American Joint Committee on Cancer/International Union against Cancer staging criteria for adults. Moreover, Sandrini et al2 found that their staging criteria were highly predictive of outcome among patients with either stage I or stage IV disease, whereas predicting outcome for patients with inter- mediate stages (stages II and III) of disease was much more difficult (only four patients included in stage III group). Thus, what we suggest is that the limitations in current staging criterion may probably affect the evaluation of outcomes for children with ACC.

Third, stage and age were proved to be significantly associated with outcome in adult patients with ACC. In 2014, Asare et al3 reported that using a novel TNM- A staging system (stage |: T1/T2NOMO, age ≤ 55 years; stage II: T1/T2NOMO, age > 55 years; stage III: T1/T2N1M0 or T3/T4N0-N1M0, any age; stage IV: any T, any NM1, any age) could better predict 5-year overall survival among patients with stages I/II ACC. Similar to adults, Rodriguez-Galindo et al1 reported that only age and tumor stage were significantly as- sociated with outcome on multivariable analysis in pediatric ACC, and younger children showed better outcome compared with the olders. These results suggest that using age in staging for pediatric ACC should be feasible, and staging system given to in- cluding age may be more predictive of outcome if in- depth analysis can be performed.

Finally, we congratulate Rodriguez-Galindo et al1 on their valuable study to provide treatment guidance and present risk factors to predict outcomes for ACC. The evidence of their findings may hopefully benefit pa- tients with pediatric ACC.

Ji-Gan Wang, MD

Pediatrics Department, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China

Dun-Chang Mo, MD

Radiotherapy Department, The Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Disclosures provided by the authors are available with this article at DOI https://doi.org/10.1200/JCO.21.00918.

REFERENCES

1. Rodriguez-Galindo C, Krailo MD, Pinto EM, et al: Treatment of pediatric adrenocortical carcinoma with surgery, retroperito- neal lymph node dissection, and chemotherapy: The Children’s Oncology Group ARAR0332 Protocol. J Clin Oncol 39: 2463-2473, 2021

2. Sandrini R, Ribeiro RC, DeLacerda L: Childhood adrenocortical tu- mors. J Clin Endocrinol Metab 82:2027-2031, 1997

3. Asare EA, Wang TS, Winchester DP, et al: A novel staging system for adrenocortical carcinoma better predicts survival in patients with stage I/II disease. Surgery 156:1378-1385, 2014; discussion 1385-1386

DOI: https://doi.org/10.1200/JCO.21.00918; Published at ascopubs.org/ journal/jco on July 6, 2021.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST