M. Lin1, S. Shaaban2, J. J. Chen3, R. Bagatell4, B. J. Lerman5, S. G. Dubois6, S. Shusterman1, M. Ioakeim-Ioannidou7, T. I. Yock8, H. Elhalawani9, K. E. Dusenbery10, K. T. Vo11, L. R. Diller1, K. J. Marcus12, S. M. MacDonald8, S. A. Terezakis10, S. E. Braunstein3, C. E. Hill-Kayser13, D. A. Haas-Kogan14, and K. X. Liu15; 1Dana-Farber Cancer Institute, Boston, MA, 2Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Washington, DC, 3Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 4Department of Oncology, Childrens Hospital of Philadelphia, Philadelphia, PA, 5University of California, San Francisco, San Francisco, CA, 6Dana-Farber/Boston Childrens Cancer and Blood Disorders Center, Boston, MA, 7Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 8Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 9Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, 10University of Minnesota: Department of Radiation Oncology, Minneapolis, MN, 11Department of Pediatrics, UCSF Benioff Childrens Hospital, San Francisco, CA, 12Department of Radiation Oncology, Brigham and Womens Hospital/Dana-Farber Cancer Institute, Boston, MA, 13Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 14Brigham and Womens Hospital and Dana-Farber Cancer Institute/ Harvard, Boston, MA, Boston, MA, 15Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
Purpose/Objective(s): Despite advancements in the treatment of high-risk neuroblastoma, overall survival (OS) remains poor in patients who experience relapse after multimodal upfront therapy. Few studies have investigated outcomes in this cohort. Our study aims to characterize clinical outcomes for patients with relapsed high-risk neuroblastoma following definitive upfront treatment and identify factors that are associated with OS. Materials/
Methods: This study was a multi-institutional retrospective cohort analysis of patients who had relapsed high-risk neuroblastoma after definitive upfront treatment, including =1 autologous stem cell transplant and external beam radiation therapy. Follow-up time was defined as time from the end of radiotherapy. Kaplan-Meier methods and log-rank test were used to assess OS. Cox proportional hazards models were used for univariate (UVA) and multivariable (MVA) analyses. All continuous variables were dichotomized at the median of the cohort for UVA and MVA. Results: We identified 87 patients with relapsed high-risk neuroblastoma after upfront definitive treatment with 25 experiencing local or local and distant relapse (LLDR) and 62 experiencing distant-only relapse. The median age at diagnosis for the LLDR cohort was 3.54 years (range: 0.56-15.18) and 3.75 years for the distant-only cohort (range: 0.62-19.73). Patients with LLDR had higher rates of MYCN amplification compared to patients with distant-only relapse (66.7% vs. 34.5%, p=0.038), with no differences in other variables. The median time to first relapse was 1.74 years (range: 0.61-4.38) for the LLDR cohort and 2.03 years (0.71-10.05) for the distant-only relapse cohort. At time of relapse, similar proportions of LLDR and distant-only relapse patients received chemotherapy (88.0% vs. 91.2%, p=0.684), but the receipt of radiotherapy (33.3% vs. 61.7%, p=0.049) and surgery (28.0% vs. 5.1%, p=0.005) was significantly different between the two groups. Patients with LLDR had decreased median OS with a trend to significance (1.05 vs. 1.68 years, p=0.056). On UVA, age at first recurrence (HR: 0.59, 95% CI: 0.36-0.98, p<0.05) and time to relapse (HR: 0.48, 95% CI: 0.29-0.81, p<0.05) were significant predictors of OS. On MVA, time relapse was a significant predictor of OS (HR: 0.53, 95% CI: 0.31-0.92, p<0.05) when controlling for recurrence type (LLDR vs. distant-only) and age at diagnosis. Conclusion: Longer time to first relapse is associated with improved OS in patients with relapsed high-risk neuroblastoma. There is a trend for patients with local relapse to have decreased OS. Future prospective studies are needed to confirm these findings and identify novel therapies to improve outcomes for patients with relapsed high-risk neuroblastoma.
