Risk factors associated with metastatic site failure in patients with high-risk neuroblastoma
Purpose: This retrospective study sought to identify predictors of metastatic site failure (MSF) at new and/or original (present at diagnosis) sites in high-risk neuroblastoma patients. Methods and materials: Seventy-six high-risk neuroblastoma patients treated on four institutional prospective tria...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-05-01
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| Series: | Clinical and Translational Radiation Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S240563082200012X |
| _version_ | 1818007063627825152 |
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| author | John Thomas Lucas, Jr. Daniel Victor Wakefield Michael Doubrovin Yimei Li Teresa Santiago Sara Michele Federico Thomas E. Merchant Andrew M. Davidoff Matthew J. Krasin Barry L. Shulkin Victor M. Santana Wayne Lee Furman |
| author_facet | John Thomas Lucas, Jr. Daniel Victor Wakefield Michael Doubrovin Yimei Li Teresa Santiago Sara Michele Federico Thomas E. Merchant Andrew M. Davidoff Matthew J. Krasin Barry L. Shulkin Victor M. Santana Wayne Lee Furman |
| author_sort | John Thomas Lucas, Jr. |
| collection | DOAJ |
| description | Purpose: This retrospective study sought to identify predictors of metastatic site failure (MSF) at new and/or original (present at diagnosis) sites in high-risk neuroblastoma patients. Methods and materials: Seventy-six high-risk neuroblastoma patients treated on four institutional prospective trials from 1997 to 2014 with induction chemotherapy, surgery, myeloablative chemotherapy, stem-cell rescue, and were eligible for consolidative primary and metastatic site (MS) radiotherapy were eligible for study inclusion. Computed-tomography and I123 MIBG scans were used to assess disease response and Curie scores at diagnosis, post-induction, post-transplant, and treatment failure. Outcomes were described using the Kaplan–Meier estimator. Cox proportional hazards frailty (cphfR) and CPH regression (CPHr) were used to identify covariates predictive of MSF at a site identified either at diagnosis or later. Results: MSF occurred in 42 patients (55%). Consolidative MS RT was applied to 30 MSs in 10 patients. Original-MSF occurred in 146 of 383 (38%) nonirradiated and 18 of 30 (60%) irradiated MSs (p = 0.018). Original- MSF occurred in postinduction MIBG-avid MSs in 68 of 81 (84%) nonirradiated and 12 of 14 (85%) radiated MSs (p = 0.867). The median overall and progression-free survival rates were 61 months (95% CI 42.6Not Reached) and 24.1 months (95% CI 16.538.7), respectively. Multivariate CPHr identified inability to undergo transplant (HR 32.4 95%CI 9.396.8, p < 0.001) and/or maintenance chemotherapy (HR 5.2, 95%CI 1.716.2, p = 0.005), and the presence of lung metastases at diagnosis (HR 4.4 95%CI 1.711.1, p = 0.002) as predictors of new MSF. The new MSF-free survival rate at 3 years was 25% and 87% in patients with and without high-risk factors. Conclusions: Incremental improvements in systemic therapy influence the patterns and type of metastatic site failure in neuroblastoma. Persistence of MIBG-avidity following induction chemotherapy and transplant at MSs increased the hazard for MSF. |
| first_indexed | 2024-04-14T05:09:46Z |
| format | Article |
| id | doaj.art-6ade4831c50140b89f8a8b0af0478d55 |
| institution | Directory Open Access Journal |
| issn | 2405-6308 |
| language | English |
| last_indexed | 2024-04-14T05:09:46Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical and Translational Radiation Oncology |
| spelling | doaj.art-6ade4831c50140b89f8a8b0af0478d552022-12-22T02:10:35ZengElsevierClinical and Translational Radiation Oncology2405-63082022-05-01344250Risk factors associated with metastatic site failure in patients with high-risk neuroblastomaJohn Thomas Lucas, Jr.0Daniel Victor Wakefield1Michael Doubrovin2Yimei Li3Teresa Santiago4Sara Michele Federico5Thomas E. Merchant6Andrew M. Davidoff7Matthew J. Krasin8Barry L. Shulkin9Victor M. Santana10Wayne Lee Furman11Department of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis, TN, United States; Corresponding author at: Department of Radiation Oncology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, MS 210, Memphis TN 38106-3678, United States.Department of Radiation Oncology, University of Tennessee Health Science Center, Memphis, TN, United States; Harvard T.H. Chan School of Public Health, Boston, MA, United StatesDepartment of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, United StatesDepartment of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Surgery, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, United StatesDepartment of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, United StatesPurpose: This retrospective study sought to identify predictors of metastatic site failure (MSF) at new and/or original (present at diagnosis) sites in high-risk neuroblastoma patients. Methods and materials: Seventy-six high-risk neuroblastoma patients treated on four institutional prospective trials from 1997 to 2014 with induction chemotherapy, surgery, myeloablative chemotherapy, stem-cell rescue, and were eligible for consolidative primary and metastatic site (MS) radiotherapy were eligible for study inclusion. Computed-tomography and I123 MIBG scans were used to assess disease response and Curie scores at diagnosis, post-induction, post-transplant, and treatment failure. Outcomes were described using the Kaplan–Meier estimator. Cox proportional hazards frailty (cphfR) and CPH regression (CPHr) were used to identify covariates predictive of MSF at a site identified either at diagnosis or later. Results: MSF occurred in 42 patients (55%). Consolidative MS RT was applied to 30 MSs in 10 patients. Original-MSF occurred in 146 of 383 (38%) nonirradiated and 18 of 30 (60%) irradiated MSs (p = 0.018). Original- MSF occurred in postinduction MIBG-avid MSs in 68 of 81 (84%) nonirradiated and 12 of 14 (85%) radiated MSs (p = 0.867). The median overall and progression-free survival rates were 61 months (95% CI 42.6Not Reached) and 24.1 months (95% CI 16.538.7), respectively. Multivariate CPHr identified inability to undergo transplant (HR 32.4 95%CI 9.396.8, p < 0.001) and/or maintenance chemotherapy (HR 5.2, 95%CI 1.716.2, p = 0.005), and the presence of lung metastases at diagnosis (HR 4.4 95%CI 1.711.1, p = 0.002) as predictors of new MSF. The new MSF-free survival rate at 3 years was 25% and 87% in patients with and without high-risk factors. Conclusions: Incremental improvements in systemic therapy influence the patterns and type of metastatic site failure in neuroblastoma. Persistence of MIBG-avidity following induction chemotherapy and transplant at MSs increased the hazard for MSF.http://www.sciencedirect.com/science/article/pii/S240563082200012X |
| spellingShingle | John Thomas Lucas, Jr. Daniel Victor Wakefield Michael Doubrovin Yimei Li Teresa Santiago Sara Michele Federico Thomas E. Merchant Andrew M. Davidoff Matthew J. Krasin Barry L. Shulkin Victor M. Santana Wayne Lee Furman Risk factors associated with metastatic site failure in patients with high-risk neuroblastoma Clinical and Translational Radiation Oncology |
| title | Risk factors associated with metastatic site failure in patients with high-risk neuroblastoma |
| title_full | Risk factors associated with metastatic site failure in patients with high-risk neuroblastoma |
| title_fullStr | Risk factors associated with metastatic site failure in patients with high-risk neuroblastoma |
| title_full_unstemmed | Risk factors associated with metastatic site failure in patients with high-risk neuroblastoma |
| title_short | Risk factors associated with metastatic site failure in patients with high-risk neuroblastoma |
| title_sort | risk factors associated with metastatic site failure in patients with high risk neuroblastoma |
| url | http://www.sciencedirect.com/science/article/pii/S240563082200012X |
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