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Chromosome 1q gain linked to shorter survival in favorable-histology Wilms' tumor
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Children with favorable-histology Wilms’ tumor who harbored chromosome 1q gain appeared less likely to achieve 8-year EFS, according to research from the Children’s Oncology Group.
Although OS for patients with Wilms’ tumor is around 90%, subsets of patients, including those with favorable histology, experience shorter survival. Clinical prognostic factors used to stratify patients include tumor histology, disease stage, patient age, tumor weight and completeness of lung nodule response after chemotherapy.
“The only molecular prognostic factor that has been used in clinical studies for the risk stratification for Wilms’ tumor is the combined loss of heterozygosity of chromosomes 1q and 16q,” Eric J. Gratias, MD, associate professor of pediatrics at University of Tennessee College of Medicine in Chattanooga, Tennessee, and colleagues wrote. “Gain of chromosome 1q is one of the most common cryptogenic abnormalities in Wilms’ tumor, observed in approximately 30% of tumors.”
Research from the Children’s Cancer and Leukemia Group confirmed retrospective studies that suggested 1q gain was independently associated with inferior EFS and OS. Further, the National Wilms’ Tumor Study-4 demonstrated shorter 8-year EFS and OS for patients with 1q gain; however, these data did not account for survival differences in disease stages.
Gratias and colleagues sought to examine the prognostic significance of 1q gain for patients with favorable-histology Wilms’ tumor in relation to other established prognostic factors, such as stage and loss of heterozygosity.
Researchers conducted multiplex ligation-dependent probe amplification on 1q gain, 1p loss and 16q loss on 1,114 patients with favorable-histology disease from the National Wilms Tumor Study-5. In the total population, 8-year EFS was 85% and 8-year OS was 94%.
Twenty-eight percent of patients (n = 317) had tumors that harbored 1q gain. These patients were older than patients without 1q gain (median age, 51.1 months vs. 36.5 months), and a smaller proportion achieved 8-year EFS (77% vs. 90%).
Results of a subgroup analysis showed patients with 1q gain were less likely to achieve 8-year EFS across disease stages; however, the difference for stage II disease did not reach statistical significance:
- Stage I: 20% with 1q gain (8-year EFS, 85% vs. 95%; P = .0052);
- Stage II: 26% with 1q gain (81% vs. 87%);
- Stage III: 32% with 1q gain (79% vs. 89%; P = .01); and
- Stage IV: 44% with 1q gain (64% vs. 91%; P = .0004).
Eight-year OS also appeared inferior among patients with 1q gain (88% vs. 96%; P < .001). Subgroup analyses showed 1q gain was associated with a lower rate of 8-year OS for patients with stage I (90% vs. 98%; P = .0015) and stage IV (74% vs. 92%; P = .011) disease.
Further, multivariate analysis indicated that relative risk for relapse increased among patients who harbored 1q gain (RR = 2.4; P < .001), even in analyses adjusted for disease stage (RR = 2.2; P < .001). After adjusting for 1q gain, neither 1p loss or 16q loss were significantly associated with EFS.
Researchers observed that more patients with than without 1q gain also had loss of 1p (23% vs. 4%; P < .001) and loss of 16q (26% vs. 8%; P < .001). There was no difference in relapse risk among patients with 1q gain according to 1p and 16q status; however, among patients without gain of 1q, 8-year EFS was higher among those without than with 1p or 16q loss (91% vs. 84%; P = .03).
“These findings validate the strong association between outcome and 1q gain that affects all stages to some degree, providing support for the use of 1q gain to stratify therapy in future favorable-histology Wilms’ tumor therapeutic trials in a stage-specific manner,” Gratias and colleagues wrote. “The addition of 1q gain to the existing prognostic framework of risk factors has the potential to refine the selection of patients as candidates for either therapy intensification or reduction.”– by Nick Andrews
Disclosure: Gratias reports previous employment with Evicore Healthcare. Other researchers report royalties for patents from Immunochemicals/St. Jude Children’s Research Hospital; employment with and stock ownership in Merck; and consultant/advisory roles with Advanced Medical, Amgen, Merck and SFD Pharma.
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