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Title: Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma

Abstract

Purpose/Objectives: Despite recent improvements in outcomes, 40% of children with high-risk neuroblastoma will experience relapse, facing a guarded prognosis for long-term cure. Whether recurrences are at new sites or sites of original disease may guide decision making during initial therapy. Methods and Materials: Eligible patients were retrospectively identified from institutional databases at first metastatic relapse of high-risk neuroblastoma. Included patients had disease involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and first relapse, achieved a complete or partial response with no more than one residual MIBG-avid site before first relapse, and received no total body irradiation or therapy with {sup 131}I-MIBG before first relapse. Anatomically defined metastatic sites were tracked from diagnosis through first relapse to determine tendency of disease to recur at previously involved versus uninvolved sites and to assess whether this pattern was influenced by site irradiation. Results: Of 159 MIBG-avid metastatic sites identified among 43 patients at first relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at diagnosis. This distribution was similar for bone sites, but patterns of relapse were more varied for the smaller subset of soft tissue metastases. Among all metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3more » of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%) unirradiated sites. Conclusions: Metastatic bone relapse in neuroblastoma usually occurs at anatomic sites of previous disease. Metastatic sites identified at diagnosis that did not receive radiation during frontline therapy appeared to have a higher risk of involvement at first relapse relative to previously irradiated metastatic sites. These observations support the current paradigm of irradiating metastases that persist after induction chemotherapy in high-risk patients. Furthermore, they raise the hypothesis that metastatic sites appearing to clear with induction chemotherapy may also benefit from radiotherapeutic treatment modalities (external beam radiation or {sup 131}I-MIBG)« less

Authors:
 [1];  [2];  [3];  [4];  [5]; ;  [1];  [6];  [7];  [8];  [1]; ;  [9];
  1. Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California (United States)
  2. Division of Radiation Oncology, Dana Farber/Boston Children's Cancer and Blood Disorders Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (United States)
  3. Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (United States)
  4. Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (United States)
  5. Department of Radiology, University of California at San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California (United States)
  6. Division of Hematology/Oncology, Children's Hospital of Los Angeles, Los Angeles, California (United States)
  7. Division of Hematology and Oncology, Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia (Canada)
  8. Division of Pediatric Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, Utah (United States)
  9. Department of Pediatrics, University of California at San Francisco School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California (United States)
Publication Date:
OSTI Identifier:
22420370
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 89; Journal Issue: 4; Other Information: Copyright (c) 2014 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; CHEMOTHERAPY; COMPARATIVE EVALUATIONS; DECISION MAKING; DIAGNOSIS; DISEASES; IODINE 131; METASTASES; MIBG; PATIENTS; SKELETON; WHOLE-BODY IRRADIATION

Citation Formats

Polishchuk, Alexei L., Li, Richard, Hill-Kayser, Christine, Little, Anthony, Hawkins, Randall A., Hamilton, Jeffrey, Lau, Michael, Tran, Hung Chi, Strahlendorf, Caron, Lemons, Richard S., Weinberg, Vivian, Matthay, Katherine K., DuBois, Steven G., and and others. Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma. United States: N. p., 2014. Web. doi:10.1016/J.IJROBP.2014.04.004.
Polishchuk, Alexei L., Li, Richard, Hill-Kayser, Christine, Little, Anthony, Hawkins, Randall A., Hamilton, Jeffrey, Lau, Michael, Tran, Hung Chi, Strahlendorf, Caron, Lemons, Richard S., Weinberg, Vivian, Matthay, Katherine K., DuBois, Steven G., & and others. Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma. United States. doi:10.1016/J.IJROBP.2014.04.004.
Polishchuk, Alexei L., Li, Richard, Hill-Kayser, Christine, Little, Anthony, Hawkins, Randall A., Hamilton, Jeffrey, Lau, Michael, Tran, Hung Chi, Strahlendorf, Caron, Lemons, Richard S., Weinberg, Vivian, Matthay, Katherine K., DuBois, Steven G., and and others. Tue . "Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma". United States. doi:10.1016/J.IJROBP.2014.04.004.
@article{osti_22420370,
title = {Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma},
author = {Polishchuk, Alexei L. and Li, Richard and Hill-Kayser, Christine and Little, Anthony and Hawkins, Randall A. and Hamilton, Jeffrey and Lau, Michael and Tran, Hung Chi and Strahlendorf, Caron and Lemons, Richard S. and Weinberg, Vivian and Matthay, Katherine K. and DuBois, Steven G. and and others},
abstractNote = {Purpose/Objectives: Despite recent improvements in outcomes, 40% of children with high-risk neuroblastoma will experience relapse, facing a guarded prognosis for long-term cure. Whether recurrences are at new sites or sites of original disease may guide decision making during initial therapy. Methods and Materials: Eligible patients were retrospectively identified from institutional databases at first metastatic relapse of high-risk neuroblastoma. Included patients had disease involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and first relapse, achieved a complete or partial response with no more than one residual MIBG-avid site before first relapse, and received no total body irradiation or therapy with {sup 131}I-MIBG before first relapse. Anatomically defined metastatic sites were tracked from diagnosis through first relapse to determine tendency of disease to recur at previously involved versus uninvolved sites and to assess whether this pattern was influenced by site irradiation. Results: Of 159 MIBG-avid metastatic sites identified among 43 patients at first relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at diagnosis. This distribution was similar for bone sites, but patterns of relapse were more varied for the smaller subset of soft tissue metastases. Among all metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3 of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%) unirradiated sites. Conclusions: Metastatic bone relapse in neuroblastoma usually occurs at anatomic sites of previous disease. Metastatic sites identified at diagnosis that did not receive radiation during frontline therapy appeared to have a higher risk of involvement at first relapse relative to previously irradiated metastatic sites. These observations support the current paradigm of irradiating metastases that persist after induction chemotherapy in high-risk patients. Furthermore, they raise the hypothesis that metastatic sites appearing to clear with induction chemotherapy may also benefit from radiotherapeutic treatment modalities (external beam radiation or {sup 131}I-MIBG)},
doi = {10.1016/J.IJROBP.2014.04.004},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 89,
place = {United States},
year = {Tue Jul 15 00:00:00 EDT 2014},
month = {Tue Jul 15 00:00:00 EDT 2014}
}
  • Purpose: To examine the power of the nodal ratio (NR) of positive/excised nodes in predicting postmastectomy locoregional recurrence (LRR) in patients with 1-3 positive nodes (N+) and in identifying cohorts at similar risk across independent data sets. Methods and Materials: Data from 82 patients with 1-3 N+ treated without postmastectomy radiotherapy (PMRT) in the British Columbia (BC) randomized trial were compared with data from 462 patients treated without PMRT in prospective chemotherapy trials at the M. D. Anderson Cancer Center (MDACC). Kaplan-Meier LRR curves were compared between centers using the absolute number of N+ and nodal ratios. Results: The medianmore » number of excised nodes was 10 in BC and 16 in MDACC (p < 0.001). Examining LRR by number of N+, the 10-year LRR rate for patients with 1-3 N+ was higher in BC compared with MDACC (21.5% vs. 12.6%; p = 0.02). However, when examining LRR using NR, no differences were found between institutions. In patients with NR {<=} 0.20, the 10-year LRR rate was 17.7% BC vs. 10.9% MDACC (p = 0.27). In patients with NR {>=} 0.20, the 10-year LRR rate was 28.7% BC vs. 22.7% MDACC (p = 0.32). On Cox regression analysis, NR was a stronger prognostic factor compared with number of N +. Conclusions: In patients with 1-3 N+, evaluating nodal positivity using NR reduced inter-institutional differences in LRR estimates that may exist due to variations in numbers of nodes excised. Nodal ratio >0.20 was associated with LRR >20%, warranting PMRT consideration. Nodal ratio may be useful for extrapolating data from prospective trials to clinical practices in which axillary staging extent vary.« less
  • Purpose: To present a large experience (73 patients) using a standard radiotherapy (RT) protocol to prevent relapse in cranial sites where measurable metastatic neuroblastoma (NB), an adverse prognostic marker, is common. Methods and Materials: High-risk NB patients with measurable cranial disease at diagnosis or residual cranial disease after induction therapy had those sites irradiated with hyperfractionated 21 Gy; a brain-sparing technique was used for an extensive field. The patients were grouped according to the response to systemic therapy. Thus, when irradiated, Group 1 patients were in complete remission and Group 2 patients had primary refractory disease. Follow-up was from themore » start of cranial RT. Results: At 3 years, the 39 Group 1 patients had a progression-free survival rate of 51%; control of cranial disease was 79%. Two relapses involved irradiated cranial sites. Two other patients relapsed in the irradiated cranial sites 6 and 12 months after a systemic relapse. At 3 years, the 34 Group 2 patients had a progression-free survival rate of 33%; control of cranial disease was 52%. Group 2 included 19 patients who had residual cranial (with or without extracranial) disease. The cranial sites showed major (n = 13), minor (n = 2), or no response (n = 4) to RT. Five patients had progression in the cranial RT field at 10-27 months. Group 2 also included 15 patients who had persistent NB in extracranial, but not cranial, sites. Of these 15 patients, 2 relapsed in the irradiated cranial sites and elsewhere at 8 and 14 months. Cranial RT was well tolerated, with no Grade 2 or greater toxicity. Conclusion: Hyperfractionated 21-Gy cranial RT might help control NB and is feasible without significant toxicity in children.« less
  • 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 inmore » 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.« less
  • Purpose: Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach. Methods and Materials: Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dosemore » chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid. Results: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001). Conclusions: RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.« less
  • Purpose: To evaluate genitourinary (GU) and gastrointestinal (GI) morbidity and biochemical control of disease in patients with localized prostate adenocarcinoma treated with escalating doses per fraction of high-dose rate brachytherapy alone. Methods and Materials: A total of 197 patients were treated with 34 Gy in four fractions, 36 Gy in four fractions, 31.5 Gy in three fractions, or 26 Gy in two fractions. Median follow-up times were 60, 54, 36, and 6 months, respectively. Results: Incidence of early Grade {>=} 3 GU morbidity was 3% to 7%, and Grade 4 was 0% to 4%. During the first 12 weeks, themore » highest mean International Prostate Symptom Score (IPSS) value was 14, and between 6 months and 5 years it was 8. Grade 3 or 4 early GI morbidity was not observed. The 3-year actuarial rate of Grade 3 GU was 3% to 16%, and was 3% to 7% for strictures requiring surgery (4-year rate). An incidence of 1% Grade 3 GI events was seen at 3 years. Late Grade 4 GU or GI events were not observed. At 3 years, 99% of patients with intermediate-risk and 91% with high-risk disease were free of biochemical relapse (log-rank p = 0.02). Conclusions: There was no significant difference in urinary and rectal morbidity between schedules. Biochemical control of disease in patients with intermediate and high risk of relapse was good.« less