1. Herron-Cologna, Romi

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Less than half of children with high-risk neuroblastoma live 5 or more years after diagnosis. A National Cancer Institute-funded phase III trial performed by the Children's Oncology Group determined a second autologous stem cell transplant to standard therapy improves outcomes for these patients. The data was presented at the 2016 American Society of Clinical Oncology Annual Meeting (Abstract LBA3). It was one of four abstracts determined to have the greatest potential impact for patient care.

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"The finding will change the way we treat children with high-risk neuroblastoma in North America, which still claims many young lives and is in urgent need of better treatment," said lead study author Julie R. Park, MD, an attending physician at Seattle Children's Hospital and Professor in Pediatrics at the University of Washington School of Medicine. "The regimen we use for high-risk neuroblastoma is also the most aggressive and toxic regimen we give to children with cancer. For that reason, future research needs to focus both exploring possible effects of current therapy and developing newer less toxic therapies."


In the trial, 61.4 percent of patients who received a double transplant were alive and cancer-free at 3 years, compared to 48.4 percent of those who received a single transplant. Side effects were similar in both sets.


Neuroblastoma Treatments

Enrolled were children newly diagnosed with high-risk neuroblastoma, at a median age of 3.1 years. Eighty-eight percent of patients had stage 4 disease and 38.2 percent had a tumor high-risk genetic abnormality called MYCN application.


All patients received six cycles of a multi-agent chemotherapy regimen including an initial two cycles of high-dose cyclophosphamide/topotecan. A collection of stem cells from the blood followed, to be used for subsequent transplantation. With the completion of the induction therapy, patients were randomly assigned to receive a single ASCT with carboplatin-etoposide-melphalan (CEM) chemotherapy or a double (tandem) ASCT with thiotepa-cyclophosphamide prior to the first ASCT. Then, a modified CEM chemotherapy followed, prior to second ASCT. In the double ASCT group, patients received two transplants in the span of 6-8 weeks.


In the ASCT group with single treatment, 129 of 179 patients were then enrolled onto a trial delivering anti-GD2 (dinutuximab) plus cytokine immunotherapy after single transplant consolidation therapy. A similar proportion of patients, 121 out of 176, received the immunotherapy after the tandem transplant consolidation therapy.


The end of the study was the 3-year event-free survival (EFS) or the percentage of patients who have not had an "event" at 3 years after randomization. An "event" was defined as recurring of cancer, diagnosis of a second cancer, or death from any cause.


Long-Term Survival

"We know that most neuroblastoma recurrences occur within 2-3 years from diagnosis and that patients who have not had a recurrence at 3 years have a better chance of long-term survival. The study was not designed to observe a difference in overall survival, as this would take many years and cannot be adequately controlled for additional therapies received after an initial disease recurrence," said Park.


Considering all patients on the study, the 3-year EFS from enrollment was 51 percent and 3-year overall survival was 68.3 percent. Among patients randomized, the 3-year EFS rate from time of randomization was higher following tandem transplant (61.4%). Single transplant EFS was 48.4 percent. The 3-year overall survival rate was slightly higher in the tandem transplant group than the single transplant group (74% vs 69.1%).


Outcomes were generally better among patients who enrolled onto the immunotherapy trial that included anti-GD2 antibody plus cytokines after the transplant. The 3-year EFS rate was significantly higher for those who had were assigned to tandem transplant (73.2%) compared to those assigned to a single transplant (55.5%) among those patients.


The 3-year overall survival rate was significantly higher with a tandem transplant than with a single transplant (85.6% vs. 75.8%).


Fewer treatment-related deaths occurred among patients who received a tandem transplant than among those who received a single transplant (2 vs. 8). The rates of severe toxicities were similar between treatment groups.


The use of potent therapies has been the focus of progress against childhood cancers, according to Stephen P. Hunger, MD, ASCO expert. "This is yet another example of how commitment to clinical research delivers potentially lifesaving results," he said. "Still, this is a more aggressive approach and these children will need to be closely followed throughout their lives for long-term side effects."


Romi Herron-Cologna is a contributing writer.