Dynamic risk stratification accurately predicts risk in pediatric thyroid cancer
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The use of dynamic risk stratification can predict long-term outcomes for most children with differentiated thyroid cancer, according to a study published in The Journal of Clinical Endocrinology & Metabolism.
“Like adults, dynamic risk stratification correctly predicts long-term outcomes in pediatric differentiated thyroid cancers by identifying patients with increased risk of recurrences and persistent disease,” Chandrasekhar Bal, MD, DSc, professor and head of the department of nuclear medicine at All India Institute of Medical Sciences in New Delhi, told Healio. “In addition to American Thyroid Association initial risk stratification, which is static and rigid, dynamic risk stratification further refines risk in pediatric differentiated thyroid cancer and helps in planning more personalized treatment and follow-up strategies.”
Bal and colleagues conducted an observational study of 176 children aged 18 years or younger who were treated for differentiated thyroid cancer from 1981 to 2016 at the All India Institute of Medical Sciences and who had a minimum follow-up of 5 years after diagnosis. All patients underwent surgery followed by radioactive iodine therapy if needed. A whole-body scan was conducted after surgery. Children attended a follow-up visit after 4 to 8 months. Those who achieved remission continued regular follow-up, whereas those who did not achieve remission continued with further radioactive iodine therapy or surgery until remission was achieved.
Dynamic risk stratification was performed during the first 2 years of follow-up and the last recorded follow-up visit. Those who had a stimulated thyroglobulin level of 1 ng/mL or less along with no disease on whole-body scan and a 24-hour radioactive iodine uptake of 0.2% or less were defined as excellent responders. Children were deemed to be structural-incomplete responders if any persistent disease in imaging was detected, whereas those with thyroglobulin levels of more than 10 ng/mL with no evidence of persistent disease were defined as biochemical-incomplete responders. Disease recurrence was defined as the reappearance of disease at least 12 months after remission.
Recurrence lowest among excellent responders
Of the cohort, 59% underwent a total thyroidectomy, 30.7% had a near-total or subtotal thyroidectomy, 8% underwent a hemithyroidectomy and 2.3% underwent a nodulectomy. Papillary thyroid cancer was found in 94.9% of tumors.
At follow-up, 46.6% of children were excellent responders, 31.8% were biochemical incomplete responders and 21.6% were structural incomplete responders. Of the excellent responders, 3.7% had disease recurrence, with two children having local recurrence and one having lung metastasis. The two patients with local recurrence became disease-free after reexploration surgery, whereas the child with lung metastasis had biochemical incomplete disease at final follow-up.
Of the biochemical incomplete responders, 83.9% achieved remission without additional intervention, 10.7% developed local recurrence and 5.4% developed distant metastases. Of those with recurrence, all but two became excellent responders at final follow-up.
Of those who were structural incomplete responders at 2 years, 34 responded to further treatment while four had persistent disease. Of the 34 who responded to further treatment, seven later developed cancer recurrence. At final follow-up, 79% of the structural incomplete responders were disease-free.
“One surprising finding was the high proportion of patients remaining disease-free at final follow-up, even in the structural incomplete response category,” Bal said. “This could be explained by the fact that many patients presented late with a higher initial disease burden. While these patients continued to have the structural disease at 2 years, they subsequently responded to radioiodine treatment and remained disease-free on long-term follow-up.”
Dynamic risk stratification predicts recurrence
Using the ATA initial risk stratification system, 29% of the cohort was classified as low risk, 40.9% as intermediate risk and 30.1% as high risk. The proportion of participants who were excellent responders was 75% in the low-risk group, 39% in the intermediate-risk group and 30% in the high-risk group. The proportion of those who were structural incomplete responders was 16.7% in the intermediate-risk group and 49.1% in the high-risk group.
All children in the low-risk group, 94.4% of the intermediate-risk group and 86.8% of the high-risk group were disease-free at final follow-up, and no one who was an excellent responder at 2 years had persistent disease at final follow-up. Of those in either of the incomplete responder groups, 6.8% of those with intermediate risk and 15.8% of those with high risk had persistent disease at final follow-up.
In multivariable analysis, dynamic risk stratification at 2 years was the only independent prognostic factor predicting disease-free survival. Children who were biochemical-incomplete responders (HR = 5.1; 95% CI, 1.4-18.9; P = .016) or structural-incomplete responders (HR = 7.3; 95% CI, 1.8-29.4; P = .005) had a higher risk for recurrence or persistent disease at final follow-up than excellent responders. The excellent responder group had a 10-year disease-free survival rate of 98.8% compared with an 84.6% rate for biochemical incomplete responders and 72.4% for structural incomplete responders.
“Our study validated the use of dynamic risk stratification in one of the largest retrospective cohorts of pediatric differentiated thyroid cancer patients,” Bal said. “Nevertheless, future prospective studies are still required.”
For more information:
Chandrasekhar Bal, MD, DSc, can be reached at csbal@hotmail.com.
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