We enrolled 254 pediatric adrenocortical tumor (ACT) cases in the first phase of the IPACTR. We report a brief summary of the clinical and laboratory data from phase 1.
Demographics and Clinical Findings
- Most of the study patients (79.5%) were from Brazil; 13% were from the US, and 7.5% were from 9 other countries.
- There were 156 girls and 98 boys. The overall female-male ratio was 1.6:1.
- The median age was 3.2 years (range, 0 to 19 years).
- Approximately 90% of the children had clinical evidence of an endocrine syndrome. Virilization, alone or in combination with signs of overproduction of other adrenal hormones, was the most common clinical presentation (84.3%).
- The median interval between the first symptoms and diagnosis was 5 months, with a range from 0 years to 90 months.
Pathologic Findings and Disease Stage
- Using histology, we classified 228 as carcinomas and 26 as adenomas.
- We considered stage I and II as limited disease – these cases accounted for about two thirds of the total. Of these, 112 patients (44.1%) had stage I disease, and 80 patients (31.5%) had stage II disease.
- Among patients with advanced disease (stages III and IV), 25 patients (9.8%) had stage III and 37 patients (14.6%) had stage IV disease.
- Among those with stage IV disease, we found that there were sites of metastasis in 34 of these 37 patients (pulmonary or lung metastasis).
- In cases in which tumor spillage during surgery was reported, 18 of 86 patients (21%) had stage I or II disease, whereas intravenous tumor thrombus was found in 9 of 64 such patients (14%).
- In addition to surgery, 7 of 116 patients with stage I disease received adjuvant treatment (5 patients received mitotane, 1 patient received local radiotherapy, and 1 patient received combination chemotherapy).
- Of 80 patients with stage II disease, 16 received adjuvant treatment (13 patients received mitotane; 2 patients received combination chemotherapy; and 1 patient received local radiation).
- All patients with stage III or IV disease received intensive chemotherapy.
Follow-up and Outcomes
- At a median follow-up of 2 years and 5 months, with a range from 5 days to 22 years:
- 157 patients (61.8%) remained alive.
- 97 patients (38.2%) had died. In 92 cases, death was associated with disease progression (including 22 patients who had active disease at the time of the last follow-up visit). Five patients died from causes unrelated to tumor progression.
- The 5-year EFS was 54.2%.
- The overall survival estimate was 54.7%.
- We examined several clinical features for association with outcome. Features we looked at included age, sex, clinical syndrome, interval between first symptoms and diagnosis, blood pressure, disease stage, tumor spillage during surgery, intravenous tumor thrombus, and tumor weight. Please note that histologic criteria were not consistently used to classify pediatric ACTs as benign (adenoma) or malignant (carcinoma); therefore, we did not evaluate these data as prognostic factors.
- Among 26 patients reported to have adrenocortical adenoma, only 1 experienced relapse.
- In patients between 0 and 3 years old with localized disease, we found the following factors were associated with a greater probability of EFS: virilization alone, normal blood pressure, disease stage I, absence of spillage during surgery, and tumor weight ≥200 grams.
- A Cox regression model analysis showed the following factors were independently associated with a greater probability of EFS: disease stage I, virilization alone, and age 0 to 3 years. This remained the case even when patients with adenoma were excluded.
- We were unable to do a factor analysis for patients with stages III and IV disease because of the small number and dismal outcome of such patients.