Childhood Adrenal Cortical Tumors With High Mitotic Rate Likely to Recur

Jim Kling

October 12, 2010

October 12, 2010 (San Francisco, California) — A new study has revealed tumor and patient characteristics that predict greater likelihood of recurrence and death in pediatric adrenal cortical tumors. These risk factors include older age at onset and tumors with a high mitotic rate and necrosis. The research was presented here at the American Academy of Pediatrics 2010 National Conference and Exhibition.

Histopathology and imaging are often used to generate a prognosis for adult adrenal cortical tumors, but pediatric cases are more difficult to characterize in part because they are very rare and physician experience is more limited, noted Justin Klein, MD, a resident physician at the Detroit Medical Center, in Michigan, who presented the research. The research was conducted while he was at Children's Hospital Boston, Massachusetts.

Dr. Klein and colleagues set out to identify patients at greater risk to determine a subset that could benefit from chemotherapy in addition to surgery. They conducted a retrospective review of children with adrenal cortical neoplasms treated between 1918 and 2009 at Children's Hospital Boston. They reviewed medical records and pathology material and conducted a multivariate analysis to identify prognostic factors associated with outcomes.

The team identified 33 patients, 29 of whom had sufficient records to include in the study. There were 12 boys and 17 girls (median age, 3.7 years; interquartile range, 1 - 9 years). Of these patients, 24 presented with symptoms, with virilization the most common (67%; 16/24). Five tumors were discovered incidentally. Some patients had associated conditions, including hemihypertrophy, Beckwith-Wiedemann syndrome, and Carney complex. Two thirds of the tumors were right sided.

In all, 27 patients were treated with tumor resection, and 22 (81%) were localized to the adrenal gland. Two (9%) of the 22 patients with localized tumors had recurrences and died. Four (15%) of the 27 patients who underwent resection were discovered to have locally advanced disease at the time of operation. These patients received adjuvant therapy, which achieved a cure in 2 patients (50%). Two patients presented with metastatic disease; both died. All recurrences occurred within a year of diagnosis, and all of those patients died.

Overall, tumor-related mortality was 24% (7/29 patients). At 1 year, Kaplan-Meier freedom from recurrence was 83% (95% confidence interval [CI], 70% - 96%). At 5 years, it was 74% (95% CI, 59% - 89%). For patients with no evidence of disease, median follow-up was 4.6 years (interquartile range, 3.1 - 9.5 years). Multivariate Cox regression showed that factors independently associated with tumor-related death were older age, high mitotic rate, and necrosis (all P < .01). Tumor recurrence was predicted by high mitotic rate (P < .01) and necrosis (P < .05). In receiver-operating characteristic curve analysis, mitotic rate and necrosis combined had an area under the curve of 0.95 (95% CI, 0.87 - 1.00; P = .002).

"Our analysis suggests that risk factors for recurrence and death include older age and tumors with high mitotic rate and necrosis. Therefore, patients with these factors may warrant adjuvant chemotherapy, even in the absence of advanced disease," the researchers wrote in the abstract.

"Even with tumors that are localized to the adrenal gland, which we would think would be resectionable by surgery or curable by resection, we're seeing those tumors also behave as malignant. Without adjuvant therapy, these patients with bad tumor characteristics developed recurrence and died from this disease," Dr. Klein told Medscape Medical News.

The difference in predictably between adult and pediatric tumors may be attributable to different cell types responsible for the tumor's origin. "With adults, we think it's probably an epithelial cell precursor, whereas perhaps in pediatric [cases,] it's an embryonic cell origin," Dr. Klein said.

He added that there are prospective trials now being conducted to identify chemotherapy regimens that will be most effective in treating pediatric adrenal cortical tumors.

One conference attendee specifically noted that the 4 patients whose tumors had spread locally had only a 50% survival rate. "That confirms for us that the quality of the surgical resection is critical in the outcome for the patient, and it predicts recurrence or lack thereof," said Andrea Hayes-Jordan, MD, director of pediatric surgery at MD Anderson Cancer Center, in Houston, Texas. "If, for whatever reason, the surgeon cannot remove all of the tumor, then the survival was much worse. That suggests that the surgeon should be aggressive in trying to remove the entire tumor."

Dr. Klein and Dr. Hayes-Jordan have disclosed no relevant financial relationships.

American Academy of Pediatrics 2010 National Conference and Exhibition: Abstract 11217. Presented October 2, 2010.


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