NEW YORK (Reuters Health) – Combined lymph node and loss of heterozygosity (LOH) status are highly predictive of event-free survival (EFS) in certain young patients with Wilms tumor (WT), according to researchers in the U.S. and Canada.
Dr. Conrad V. Fernandez told Reuters Health by email, “The paper describes the excellent outcome of patients with stage III favorable histology WT and builds on previously published work showing that lymph node involvement by WT confers a poorer prognosis, especially if combined with a tumor biomarker called loss of heterozygosity. Conversely, the absence of these risk factors portends an excellent outcome.”
In a December 6 online article in the Journal of Clinical Oncology, Dr. Fernandez of Dalhousie University, Halifax, and colleagues note that although EFS and overall survival (OS) are often very good for patients with favorable-histology WT, this may not be the case for certain subgroups.
The National Wilms Tumor Study Group and the Children’s Oncology Group (COG), they go on to say, “have adopted an approach of upfront nephrectomy when feasible, followed by stage and biology-directed treatment.”
To investigate further, the researchers studied 535 patients (median age, 3.7 years) with favorable-histology stage III WT. They had been treated, under the auspices of COG, with vincristine, doxorubicin, and dactinomycin – plus radiation. Median follow-up was 5.2 years.
For the cohort as a whole, estimated four-year EFS was 88% and OS was 97%. The 419 patients who underwent upfront nephrectomy and the 116 who had delayed nephrectomy after preoperative chemotherapy did not differ significantly in EPS or OS.
Of 66 relapses, 58 (88%) occurred in the first two years; 36 were pulmonary. Fourteen of 18 patient deaths were secondary to WT.
Better EFS was significantly associated with negative lymph node status and with absence of LOH 1p or 16q – but not with gross residual disease or peritoneal implants.
Patients with combined positive lymph node status and LOH 1p or 16q had a 4-year EFS rate of 74%, significantly worse than patients without that status. This subgroup also had a trend toward poorer 4-year OS, but it was not statistically significant.
The researchers observe, “Some of these patients may have had local stage I or II disease and were converted to stage III by virtue of biopsy and delay in nephrectomy. Despite these limitations that could be considered stage migration, we are able, with these analyses, to identify particular subgroups that may be tested for therapy intensification or reduction.”
“These findings,” concluded Dr. Fernandez, “allow the prospect of studying the impact of omitting the chemotherapy agent, doxorubicin (known to have cardiac toxicity), in patients with expected very good outcomes. They also, with another known biomarker (1q gain) that confers poor risk, allow for the opportunity to potentially improve the outcome of stage III favorable histology WT patients by intensifying therapy for patients identified with biomarkers to have a higher risk of relapse.”
Pediatric hematologist-oncologist Dr. Daniel Green of St. Jude Children’s Research Hospital, Memphis, Tennessee, emphasized the role of stage migration, telling Reuters Health by email that the work “is in essence a confirmatory study in which stage migration almost certainly is responsible for the minimally superior outcome observed when the current data are compared to those from the National Wilms Tumor Study.”
SOURCE: http://bit.ly/2D5zEFF
J Clin Oncol 2017.
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