Risk stratification reduces exposure to radiation with ‘excellent OS’ for metastatic Wilms tumor
Omitting radiation therapy for patients with complete lung nodule response to chemotherapy showed promising OS among patients with favorable-histology Wilms tumor and lung metastases, according to study results published in Journal of Clinical Oncology.
The standard treatment for children with Wilms tumor and lung metastases is combination therapy with vincristine, dactinomycin and doxorubicin, or DD4A, and lung radiation therapy. However, the treatment has been linked with various health problems later in life, such as cardiac dysfunction and second malignancies.
Researchers of the AREN0533 trial evaluated whether patients with complete lung nodule response after 6 weeks of DD4A could avoid lung radiation therapy, and whether patients with an incomplete lung nodule response could benefit from the addition of cyclophosphamide and etoposide.
“These findings will change clinical practice and improve survival for patients with Wilms tumor whose cancer has spread to the lungs,” Jeffrey Dome, MD, PhD, vice president at Center for Cancer and Blood Disorders at Children’s National Health System, said in a press release. “The risk-adapted approach to treatment based on tumor biology and tumor response provides a framework for future studies as we come one step closer to achieving 100% survival without treatment-associated side effects.”
The researchers assessed 292 patients (median age, 50 months; 51.5% female) who received 6 weeks of DD4A. Overall, 133 patients had complete lung nodule response and 159 had an incomplete response.
Patients with complete response continued receiving therapy, and patients with incomplete response or loss of heterozygosity at chromosomes 1p or 16q received four cycles of cyclophosphamide and etoposide in addition to lung radiation therapy and DD4A.
Researchers designed the study to show a 4-year EFS of 85% for patients with complete response and raise 4-year EFS from 75% to 85% for patients with incomplete response.
The estimated 4-year EFS was 79.5% (95% CI, 71.2-87.8) among patients with complete response, with an OS of 96.1% (95% CI, 92.1-100).
The expected event rate was 15% compared with an observed event rate of 20.2% (P = .052).
Patients with an incomplete response had an estimated 4-year EFS of 88.5% (95% CI, 81.8-95.3) and an estimated 4-year OS of 95.4% (95% CI, 90.9-99.8).
In the overall study population, 85.4% (95% CI, 80.5-90.2) of patients achieved 4-year EFS and 95.6% (95% CI, 92.8-98.4) achieved 4-year OS. Researchers found these results to be significantly better than that of the predecessor NWTS-5 study, which showed a 4-year EFS of 72.5% (95% CI, 66.9-78.1) and 4-year OS of 84% (95% CI, 79.4-88.6).
“Patients with isolated lung metastases and complete lung nodule response after 6 weeks of therapy had excellent OS when treated initially without lung radiation therapy in the setting of low cumulative doxorubicin exposure,” the researchers wrote. “Patients with incomplete lung nodule response or loss of heterozygosity at chromosomes 1p or 16q had improved EFS and excellent OS using [DD4A and cyclophosphamide/etoposide] and lung radiation therapy. These results provide a benchmark for future studies.” – by Andy Polhamus
Disclosures: Dome reports patents, royalties or other intellectual property with Rockland Immunochemicals. Please see the study for a list of all other authors’ relevant financial disclosures.