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Title: Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation

Abstract

Purpose: External beam radiation therapy to initial sites of disease may influence relapse patterns in high-risk neuroblastoma. However, the effect of systemic irradiation by use of total body irradiation (TBI) on anatomic patterns of relapse has not previously been investigated. Methods and Materials: We retrospectively analyzed patients receiving definitive treatment of high-risk neuroblastoma with subsequent relapse in bony metastatic sites, with a date of relapse between January 1, 1997, and December 31, 2012. Anatomic sites of disease, defined by metaiodobenzylguanidine (MIBG) avidity, were compared at diagnosis and at first relapse. The Fisher exact test was performed to compare relapse in initially involved sites between patients treated with and without TBI. Results: Seventy-four patients with a median age at diagnosis of 3.5 years (range, 0.3-15.3 years) had relapse in 227 sites of MIBG-avid metastatic disease, with a median time to relapse of 1.8 years. Of the 227 sites of first relapse, 154 sites (68%) were involved at diagnosis. When we compared relapse patterns in patients treated with and without TBI, 12 of 23 patients (52%) treated with TBI had relapse in ≥1 previously MIBG-avid site of disease whereas 40 of 51 patients (78%) treated without TBI had relapse in ≥1 previously MIBG-avid site ofmore » disease (P=.03). Conclusions: Patients treated with systemic irradiation in the form of TBI were significantly less likely to have relapse in prior sites of disease. These findings support further investigation into the role of radiopharmaceutical therapies in curative multimodality therapy.« less

Authors:
 [1];  [2];  [3];  [1];  [2];  [3];  [4];  [5];  [1];  [2];  [6];  [4];  [2];  [1];  [2];  [1];  [2];  [2];  [3];  [1] more »;  [2]; « less
  1. Harvard Medical School, Boston, Massachusetts (United States)
  2. (United States)
  3. School of Medicine, University of California San Francisco, San Francisco, California (United States)
  4. Brigham and Women's Hospital, Boston, Massachusetts (United States)
  5. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (United States)
  6. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States)
Publication Date:
OSTI Identifier:
22645763
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 97; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; DIAGNOSIS; EXTERNAL BEAM RADIATION THERAPY; NEOPLASMS; PATIENTS; RADIATION HAZARDS; WHOLE-BODY IRRADIATION

Citation Formats

Li, Richard, Brigham and Women's Hospital, Boston, Massachusetts, Polishchuk, Alexei, DuBois, Steven, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Hawkins, Randall, Lee, Stephanie W., Bagatell, Rochelle, Shusterman, Suzanne, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Hill-Kayser, Christine, Al-Sayegh, Hasan, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Diller, Lisa, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Haas-Kogan, Daphne A., Brigham and Women's Hospital, Boston, Massachusetts, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Matthay, Katherine K., London, Wendy B., Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, and and others. Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation. United States: N. p., 2017. Web. doi:10.1016/J.IJROBP.2016.10.047.
Li, Richard, Brigham and Women's Hospital, Boston, Massachusetts, Polishchuk, Alexei, DuBois, Steven, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Hawkins, Randall, Lee, Stephanie W., Bagatell, Rochelle, Shusterman, Suzanne, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Hill-Kayser, Christine, Al-Sayegh, Hasan, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Diller, Lisa, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Haas-Kogan, Daphne A., Brigham and Women's Hospital, Boston, Massachusetts, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Matthay, Katherine K., London, Wendy B., Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, & and others. Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation. United States. doi:10.1016/J.IJROBP.2016.10.047.
Li, Richard, Brigham and Women's Hospital, Boston, Massachusetts, Polishchuk, Alexei, DuBois, Steven, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Hawkins, Randall, Lee, Stephanie W., Bagatell, Rochelle, Shusterman, Suzanne, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Hill-Kayser, Christine, Al-Sayegh, Hasan, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Diller, Lisa, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Haas-Kogan, Daphne A., Brigham and Women's Hospital, Boston, Massachusetts, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, Matthay, Katherine K., London, Wendy B., Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, and and others. Wed . "Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation". United States. doi:10.1016/J.IJROBP.2016.10.047.
@article{osti_22645763,
title = {Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation},
author = {Li, Richard and Brigham and Women's Hospital, Boston, Massachusetts and Polishchuk, Alexei and DuBois, Steven and Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts and Hawkins, Randall and Lee, Stephanie W. and Bagatell, Rochelle and Shusterman, Suzanne and Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts and Hill-Kayser, Christine and Al-Sayegh, Hasan and Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts and Diller, Lisa and Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts and Haas-Kogan, Daphne A. and Brigham and Women's Hospital, Boston, Massachusetts and Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts and Matthay, Katherine K. and London, Wendy B. and Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts and and others},
abstractNote = {Purpose: External beam radiation therapy to initial sites of disease may influence relapse patterns in high-risk neuroblastoma. However, the effect of systemic irradiation by use of total body irradiation (TBI) on anatomic patterns of relapse has not previously been investigated. Methods and Materials: We retrospectively analyzed patients receiving definitive treatment of high-risk neuroblastoma with subsequent relapse in bony metastatic sites, with a date of relapse between January 1, 1997, and December 31, 2012. Anatomic sites of disease, defined by metaiodobenzylguanidine (MIBG) avidity, were compared at diagnosis and at first relapse. The Fisher exact test was performed to compare relapse in initially involved sites between patients treated with and without TBI. Results: Seventy-four patients with a median age at diagnosis of 3.5 years (range, 0.3-15.3 years) had relapse in 227 sites of MIBG-avid metastatic disease, with a median time to relapse of 1.8 years. Of the 227 sites of first relapse, 154 sites (68%) were involved at diagnosis. When we compared relapse patterns in patients treated with and without TBI, 12 of 23 patients (52%) treated with TBI had relapse in ≥1 previously MIBG-avid site of disease whereas 40 of 51 patients (78%) treated without TBI had relapse in ≥1 previously MIBG-avid site of disease (P=.03). Conclusions: Patients treated with systemic irradiation in the form of TBI were significantly less likely to have relapse in prior sites of disease. These findings support further investigation into the role of radiopharmaceutical therapies in curative multimodality therapy.},
doi = {10.1016/J.IJROBP.2016.10.047},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 97,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2017},
month = {Wed Feb 01 00:00:00 EST 2017}
}
  • Background: As systemic control of high-risk neuroblastoma (NB) has improved, relapse in the central nervous system (CNS) is an increasingly recognized entity that carries a grim prognosis. This study describes the use of craniospinal irradiation (CSI) for CNS relapse and compares outcomes to patients who received focal radiotherapy (RT). Methods: A retrospective query identified 29 children with NB treated at Memorial Sloan-Kettering Cancer Center since 1987 who received RT for CNS relapse. At CNS relapse, 16 patients received CSI (median dose, 2160cGy), and 13 received focal RT. Of those who underwent CSI, 14 (88%) received intra-Ommaya (IO) radioimmunotherapy (RIT); onemore » patient in the non-CSI cohort received IO-RIT. Results: Patient characteristics were similar between the groups. Time to CNS relapse was 20 and 17 months for the CSI and non-CSI cohorts, respectively. At a median follow-up of 28 months, 12 patients (75%) in the CSI group are alive without CNS disease, including two patients with isolated skeletal relapse. Another patient is alive without disease after a brain relapse was retreated with RT. Three patients died-one with no NB at autopsy, one of CNS disease, and one of systemic disease. The two patients who died of NB did not receive IO-RIT. All 13 patients in the non-CSI cohort died at a median of 8.8 months. Conclusions: Low-dose CSI together with IO-RIT provides durable CNS remissions and improved survival compared with focal RT and conventional therapies. Further evaluation of long-term NB survivors after CSI is warranted to determine the treatment consequences for this cohort.« less
  • Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses atmore » the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.« less
  • Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC; forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC; carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and inflammatory breast cancer (3 patients) treated with sequential high-dose therapy comprising the following phases over approximately 2 months: (a) cyclophosphamide (7 g/m2); (b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120 mg/m2) or etoposide (2 g/m2); (c) total body irradiation (TBI; 12.5 gy, 5 fractions overmore » 48 hours), intravenous melphalan (120-180 mg/m2), and transplantation of autologous peripheral blood and/or bone marrow hematopoietic stem cells. Within 2 months after transplantation, 12 patients also received 25 Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry evaluations of fractionated TBI treatments showed that mean radiation dose absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO. The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients receiving radiotherapy boost. All parameters progressively recovered to normal values within 2 years after transplantation. In contrast, FEV1/FVC remained within normal limits in all patients, thus demonstrating the absence of obstructive ventilatory changes. In addition, no interstitial pneumonia was observed.« less
  • We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the bloodmore » by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.« less
  • Purpose: To identify prognostic factors and patterns of relapse for patients with Ewing sarcoma who underwent chemotherapy and R0 resection without radiation therapy (RT). Methods and Materials: We reviewed the medical records of patients who underwent surgical resection at our institution between 2000 and 2013 for an initial diagnosis of Ewing sarcoma. The associations of demographic and clinical factors with local control (LC) and patient outcome were determined by Cox regression. Time to events was measured from the time of surgery. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: A total of 66more » patients (median age 19 years, range 4-55 years) met the study criteria. The median follow-up was 5.6 years for living patients. In 43 patients (65%) for whom imaging studies were available, the median tumor volume reduction was 73%, and at least partial response by Response Evaluation Criteria in Solid Tumors was achieved in 17 patients (40%). At 5 years, LC was 78%, progression-free survival (PFS) was 59%, and overall survival (OS) was 65%. Poor histologic response (necrosis ≤95%) was an independent predictor of LC (hazard ratio [HR] 6.8, P=.004), PFS (HR 5.2, P=.008), and OS (HR 5.0, P=.008). Metastasis on presentation was also an independent predictor of LC (HR 6.3, P=.011), PFS (HR 6.8, P=.002), and OS (HR 6.7, P=.002). Radiologic partial response was a predictor of PFS (HR 0.26, P=.012), and postchemotherapy tumor volume was associated with OS (HR 1.06, P=.015). All deaths were preceded by distant relapse. Of the 8 initial local-only relapses, 5 (63%) were soon followed by distant relapse. Predictors of poor postrecurrence survival were time to recurrence <1 year (HR 11.5, P=.002) and simultaneous local and distant relapse (HR 16.8, P=.001). Conclusions: Histologic and radiologic response to chemotherapy were independent predictors of outcome. Additional study is needed to determine the role of adjuvant radiation therapy for patients who have poor histologic response after R0 resection.« less