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Title: Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement

Abstract

Purpose: To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. Methods and Materials: We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. Results: At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gy with respect to local relapse–free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse–free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. Conclusions: Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated formore » gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.« less

Authors:
 [1];  [2];  [1];  [2];  [3];  [2];  [1];  [2]; ; ; ;  [4]; ; ;  [1];  [2]
  1. Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States)
  2. (United States)
  3. Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)
  4. Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia (United States)
Publication Date:
OSTI Identifier:
22649870
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 97; Journal Issue: 4; 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; DISEASES; GY RANGE 10-100; LYMPH NODES; PATHOLOGY; PATIENTS; RADIATION DOSES; RADIATION HAZARDS; RADIOTHERAPY; SURGERY; SURVIVAL TIME

Citation Formats

Ferris, Matthew J., E-mail: mjferri@emory.edu, Winship Cancer Institute, Emory University, Atlanta, Georgia, Danish, Hasan, Winship Cancer Institute, Emory University, Atlanta, Georgia, Switchenko, Jeffrey M., Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia, Deng, Claudia, Winship Cancer Institute, Emory University, Atlanta, Georgia, George, Bradley A., Goldsmith, Kelly C., Wasilewski, Karen J., Cash, W. Thomas, Khan, Mohammad K., Eaton, Bree R., Esiashvili, Natia, and Winship Cancer Institute, Emory University, Atlanta, Georgia. Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement. United States: N. p., 2017. Web. doi:10.1016/J.IJROBP.2016.11.043.
Ferris, Matthew J., E-mail: mjferri@emory.edu, Winship Cancer Institute, Emory University, Atlanta, Georgia, Danish, Hasan, Winship Cancer Institute, Emory University, Atlanta, Georgia, Switchenko, Jeffrey M., Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia, Deng, Claudia, Winship Cancer Institute, Emory University, Atlanta, Georgia, George, Bradley A., Goldsmith, Kelly C., Wasilewski, Karen J., Cash, W. Thomas, Khan, Mohammad K., Eaton, Bree R., Esiashvili, Natia, & Winship Cancer Institute, Emory University, Atlanta, Georgia. Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement. United States. doi:10.1016/J.IJROBP.2016.11.043.
Ferris, Matthew J., E-mail: mjferri@emory.edu, Winship Cancer Institute, Emory University, Atlanta, Georgia, Danish, Hasan, Winship Cancer Institute, Emory University, Atlanta, Georgia, Switchenko, Jeffrey M., Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia, Deng, Claudia, Winship Cancer Institute, Emory University, Atlanta, Georgia, George, Bradley A., Goldsmith, Kelly C., Wasilewski, Karen J., Cash, W. Thomas, Khan, Mohammad K., Eaton, Bree R., Esiashvili, Natia, and Winship Cancer Institute, Emory University, Atlanta, Georgia. Wed . "Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement". United States. doi:10.1016/J.IJROBP.2016.11.043.
@article{osti_22649870,
title = {Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement},
author = {Ferris, Matthew J., E-mail: mjferri@emory.edu and Winship Cancer Institute, Emory University, Atlanta, Georgia and Danish, Hasan and Winship Cancer Institute, Emory University, Atlanta, Georgia and Switchenko, Jeffrey M. and Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia and Deng, Claudia and Winship Cancer Institute, Emory University, Atlanta, Georgia and George, Bradley A. and Goldsmith, Kelly C. and Wasilewski, Karen J. and Cash, W. Thomas and Khan, Mohammad K. and Eaton, Bree R. and Esiashvili, Natia and Winship Cancer Institute, Emory University, Atlanta, Georgia},
abstractNote = {Purpose: To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. Methods and Materials: We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. Results: At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gy with respect to local relapse–free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse–free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. Conclusions: Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.},
doi = {10.1016/J.IJROBP.2016.11.043},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 97,
place = {United States},
year = {Wed Mar 15 00:00:00 EDT 2017},
month = {Wed Mar 15 00:00:00 EDT 2017}
}
  • Purpose: Local recurrence has been demonstrated in previous studies to be one of the obstacles to cure in neuroblastoma. Radiation therapy indications, optimal dose, and technique are still evolving. Here we report our experience of high-risk neuroblastoma patients who received local radiation therapy as part of their cancer management. Methods and Materials: We conducted a retrospective study of 34 high-risk neuroblastoma patients who received radiation therapy to local sites of disease from March 2001 until February 2007 at our institution as part of their multimodality therapy. Results: At a median follow-up of 33.6 months, 6 patients died of disease, 7more » patients were alive with disease, and 21 patients were in clinical remission. Eleven patients relapsed, all distantly. Two patients failed locally in addition to distant sites. Both of these patients had persistent gross disease after induction chemotherapy and surgery. Our 3-year local control, event-free survival, overall survival were 94%, 66%, and 86%, respectively. Conclusion: Patients with high-risk neuroblastoma in our series achieved excellent local control. Doses of 21-24 Gy to the primary tumor site appear to be adequate for local control for patients in the setting of minimal residual disease after induction chemotherapy and surgery. Patients with significant residual disease may benefit from radiation dose escalation, and this should be evaluated in a prospective clinical trial.« less
  • Purpose: (1) To examine the effect of surgical margin status on local recurrence (LR) and survival following breast-conserving therapy; (2) To identify subsets with close or positive margins with high LR risk despite whole breast radiotherapy (RT) plus boost. Methods and Materials: Subjects were 2,264 women with pT1-3, any N, M0 invasive breast cancer, treated with breast-conserving surgery and whole breast {+-} boost RT. Five-year Kaplan-Meier (KM) LR, breast cancer-specific and overall survival (BCSS and OS) were compared between cohorts with negative (n = 1,980), close (n = 222), and positive (n = 62) margins. LR rates were analyzed accordingmore » to clinicopathologic characteristics. Multivariable Cox regression modeling and matched analysis of close/positive margin cases and negative margin controls were performed. Results: Median follow-up was 5.2 years. Boost RT was used in 92% of patients with close or positive margins. Five-year KM LR rates in the negative, close and positive margin cohorts were 1.3%, 4.0%, and 5.2%, respectively (p = 0.001). BCSS and OS were similar in the three margin subgroups. In the close/positive margin cohort, LR rates were 10.2% with age <45 years, 11.8% with Grade III, 11.3% with lymphovascular invasion (LVI), and 26.3% with {>=}4 positive nodes. Corresponding rates in the negative margin cohort were 2.3%, 2.4%, 1.0%, and 2.4%, respectively. On Cox regression analysis of the entire cohort, close or positive margin, Grade III histology, {>=}4 positive nodes, and lack of systemic therapy were significantly associated with higher LR risk. When close/positive margin cases were matched to negative margin controls, the difference in 5-year LR remained significant (4.25% vs. 0.7%, p < 0.001). Conclusions: On univariable analysis, subsets with close or positive margins, in combination with age <45 years, Grade III, LVI, and {>=}4 positive nodes, have 5-year LR >10% despite whole breast plus boost RT. These patients should be considered for more definitive surgery.« less
  • Seventy-nine patients with supraglottic carcinoma treated between 1966 and 1985 are reviewed. All patients were treated with surgery and postoperative radiation therapy. Thirty-five percent of the patients had positive margins at the site of resection of the primary tumor. Of the 25 patients who had positive nodal disease, 13 patients (52%) had either extracapsular extension or soft-tissue or adjacent organ invasion, referred to in composite as grave signs. The median follow-up of the patients was 4.9 years and all patients were followed for a minimum of 3 years. The disease-free survival for all patients was 76% at 2 years andmore » 71% at 3 years. The locoregional control rate for all patients was 70%. This study demonstrates that there is no difference in local recurrence or disease-free survival, or time to recurrence relative to the status of the surgical margins, which may be a benefit of the postoperative radiation therapy. This study also demonstrates that there is an increase in the number of patients with grave signs with increasing nodal stage. The rate of neck recurrence in patients with grave signs was substantially higher (54%) than in patients without grave signs (8%), even though these patients also had positive lymph nodes. Interestingly, there was also a higher rate of local recurrence among patients who had grave signs. Patients receiving doses higher than 6000 cGy to the primary site had fewer local failures, although within each group of patients with positive or negative surgical margins the differences in survival were minimal.« less
  • Purpose: To evaluate local control after 21-Gy radiation therapy (RT) to the primary site in patients with high-risk neuroblastoma. Methods and Materials: After receiving dose-intensive chemotherapy and gross total resection (GTR), 246 patients (aged 1.2-17.9 years, median 4.0 years) with high-risk neuroblastoma underwent RT to the primary site at Memorial Sloan Kettering from 2000 to 2014. Radiation therapy consisted of 21 Gy in twice-daily fractions of 1.5 Gy each. Local failure (LF) was correlated with biologic prognostic factors and clinical findings at the time of diagnosis and start of RT. Results: Median follow-up of surviving patients was 6.4 years. Cumulative incidence of LF was 7.1%more » at 2 years after RT and 9.8% at 5 years after RT. The isolated LF rate was 3.0%. Eighty-six percent of all local failures were within the RT field. Local control was worse in patients who required more than 1 surgical resection to achieve GTR (22.4% vs 8.3%, P=.01). There was also a trend toward inferior local control with MYCN-amplified tumors or serum lactate dehydrogenase ≥1500 U/L (P=.09 and P=.06, respectively). Conclusion: After intensive chemotherapy and maximal surgical debulking, hyperfractionated RT with 21 Gy in high-risk neuroblastoma results in excellent local control. Given the young patient age, concern for late effects, and local control >90%, dose reduction may be appropriate for patients without MYCN amplification who achieve GTR.« less
  • Purpose: Radiation therapy is important for local control in neuroblastoma. This study reviewed the compliance of plans with the radiation therapy guidelines of the International Society of Paediatric Oncology (Europe) Neuroblastoma Group (SIOPEN) High-Risk Trial protocol. Methods and Materials: The SIOPEN trial central electronic database has sections to record diagnostic imaging and radiation therapy planning data. Individual centers may upload data remotely, but not all centers involved in the trial chose to use this system. A quality scoring system was devised based on how well the radiation therapy plan matched the protocol guidelines, to what extent deviations were justified, andmore » whether adverse effects may result. Central review of radiation therapy planning was undertaken retrospectively in 100 patients for whom complete diagnostic and treatment sets were available. Data were reviewed and compared against protocol guidelines by an international team of radiation oncologists and radiologists. For each patient in the sample, the central review team assigned a quality assurance score. Results: It was found that in 48% of patients there was full compliance with protocol requirements. In 29%, there were deviations for justifiable reasons with no likely long-term adverse effects resulting. In 5%, deviations had occurred for justifiable reasons, but that might result in adverse effects. In 1%, there was a deviation with no discernible justification, which would not lead to long-term adverse events. In 17%, unjustified deviations were noted, with a risk of an adverse outcome resulting. Conclusions: Owing to concern over the proportion of patients in whom unjustified deviations were observed, a protocol amendment has been issued. This offers the opportunity for central review of radiation therapy plans before the start of treatment and the treating clinician a chance to modify plans.« less