Pediatric Cancer

PD 04 - Pediatrics 1 - Poster Discussion

1030 - Incidence, Severity, and Duration of Sinusoidal Obstruction Syndrome in High-Risk Neuroblastoma: Contributors, Management, and Outcomes in a Modern Multi-Institutional Cohort

Sunday, October 21
5:03 PM - 5:09 PM
Location: Room 217 C/D

Incidence, Severity, and Duration of Sinusoidal Obstruction Syndrome in High-Risk Neuroblastoma: Contributors, Management, and Outcomes in a Modern Multi-Institutional Cohort
C. A. Devine1, K. X. Liu1, A. Sunkara2, G. Kang2, E. Burghen2, S. Cross2, L. T. Orlina3, C. Zaslowe-Dude4, R. Goldsby5, C. C. Dvorak5, V. P. Tolbert5, M. Krasin2, K. J. Marcus6, S. G. Dubois7, S. Shusterman8, L. R. Diller8, L. E. Lehmann8, K. K. Matthay5, S. P. Margossian8, D. A. Haas-Kogan3, S. M. Federico9, V. M. Santana2, W. L. Furman2, L. Cunningham2, S. E. Braunstein10, and J. T. Lucas Jr2; 1Harvard Medical School, Boston, MA, 2St. Jude Children's Research Hospital, Memphis, TN, 3Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA, 4Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, 5University of California San Francisco Benioff Children's Hospital, San Francisco, CA, 6Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, 7Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, 8Dana-Farber Cancer Institute, Boston, MA, 9St. Jude Children's Research Hospital, M, TN, 10University of California, San Francisco, San Francisco, CA

Purpose/Objective(s): Sinusoidal obstruction syndrome (SOS) is a significant contributor to morbidity and mortality in children with high risk neuroblastoma (HRNB) and is associated with inferior outcomes. Risk factors include external beam radiation therapy (EBRT), lack of prophylaxis, and various chemotherapy regimens. We evaluated the impact of type of therapy, pre-transplant characteristics, and laboratory findings on the incidence, duration, and severity of SOS.

Materials/Methods: HRNB patients treated from 1996-2015 at three institutions were retrospectively reviewed. Disease and treatment parameters, including MYCN, stage, primary site, chemotherapy regimen, transplant product and type, pre-transplant therapeutic MIBG, SOS prophylaxis and treatment, and EBRT dose and volume were collected. Laboratory values and percent weight gain were noted post-consolidation and at 0, 30, 60, and 100 days after transplant. Incidence, duration, and complications of SOS were documented. Predictors of SOS and SOS-related mortality were evaluated using Wilcoxon rank sum test or t-test for continuous data and chi-square test or Fisher’s exact test for categorical data. The associations between duration and incidence of SOS were assessed using generalized linear regression models. Time to progression and death were described using the Kaplan-Meier estimator and compared using the log-rank test.

Results: Of the 191 patients with HRNB, 24 patients met criteria (Seattle/Baltimore) for SOS, with a median time to SOS from transplant of 22 days (range: 3-130). Median time to SOS resolution was 14 days (range: 2-63). Patients with SOS had comparable OS and PFS relative to those without SOS (p=0.14, p=0.67). Most SOS cases (N=15, 62.5%) occurred prior to EBRT, resulting in a significant increase in the median time from transplant to EBRT (8.9 weeks (5.1-20.7) vs. 6.4 weeks (2.4-59) (p=0.001)). EBRT dose to the liver (Dmean, D75, D50, D25) did not differ significantly between the SOS vs. non-SOS patients (p=0.09, 0.97, 0.89, 0.72) and did not contribute to duration or severity of SOS. The incidence of SOS was 23.1%, 14.3%, 3.8%, and 7.0% in patients consolidated with BuMel, Cy-THIO/mCEM, CEM, and other, respectively (p=0.014). The duration and severity of SOS were not associated with tandem transplant, therapeutic MIBG, or time between EBRT and SOS. ICU admission due to respiratory and/or multi-organ failure was required in 4 of 24 (16.7%) patients and resulted in death in 2 patients. Univariate analysis showed that duration of SOS decreases as age increases (β= -0.11; p=0.02) and is less likely to resolve in INSS stage 4 (β= -0.88, p=0.04) patients.

Conclusion: SOS primarily occurred prior to EBRT and resulted in EBRT delay. BuMel was a significant contributor to the incidence SOS. EBRT dose, volume, and timing did not contribute to SOS morbidity.

Author Disclosure: C.A. Devine: None. K.X. Liu: None. A. Sunkara: None. G. Kang: None. C. Zaslowe-Dude: None. V.P. Tolbert: None. M. Krasin: None. K.J. Marcus: Editorial Board Member; PDQ. S. Shusterman: None. D. Haas-Kogan: Research Grant; Novartis. Clinical Advisory Board; Cellworks. S.E. Braunstein: Advisory Board; Radiation Oncology Questions, LLC. J.T. Lucas: Employee; University of Memphis.

Christopher Devine, MPhil

Disclosure:
Employment
Harvard Medical School: Employee: Employee

Biography:
Chris Devine is a joint MD/MBA candidate at Harvard Medical School and Harvard Business School working at the Dana-Farber/Brigham and Women's Cancer Center. He holds an MPhil from the University of Cambridge and an AB from Harvard College, and is expected to graduate from medical school in 2019. His research is focused on outcomes in pediatric radiation oncology, and his primary mentor is Professor Daphne Haas-Kogan.

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1030 - Incidence, Severity, and Duration of Sinusoidal Obstruction Syndrome in High-Risk Neuroblastoma: Contributors, Management, and Outcomes in a Modern Multi-Institutional Cohort



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