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Title: Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia

Abstract

Purpose: To determine the benefit of radiation therapy (RT) in resolution of neurologic symptoms and deficits and whether the type of RT fields influences central nervous system (CNS) control in adults with CNS leukemia. Methods and Materials: A total of 163 adults from 1996 to 2012 were retrospectively analyzed. Potential associations between use of radiation and outcome were investigated by univariate and multivariate analysis. Results: The median survival time was 3.8 months after RT. Common presenting symptoms were headache in 79 patients (49%), cranial nerve VII deficit in 46 (28%), and cranial nerve II deficit in 44 (27%). RT was delivered to the base of skull in 48 patients (29%), to the whole brain (WB) in 67 (41%), and to the craniospinal axis (CS) in 48 (29%). Among 149 patients with a total of 233 deficits, resolution was observed in 34 deficits (15%), improvement in 126 deficits (54%), stability in 34 deficits (15%), and progression in 39 deficits (17%). The 12-month CNS progression-free survival was 77% among those receiving CS/WB and 51% among those receiving base of skull RT (P=.02). On multivariate analysis, patients who did not undergo stem cell transplantation after RT and base of skull RT were associated withmore » worse CNS progression-free survival. Conclusions: Improvement or resolution of symptoms occurred in two thirds of deficits after RT. Comprehensive radiation to the WB or CS seems to offer a better outcome, especially in isolated CNS involvement.« less

Authors:
;  [1];  [2];  [1]; ;  [3];  [2]; ; ;  [1];  [2];  [4]; ; ;  [1];  [1]
  1. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  2. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  3. Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  4. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
Publication Date:
OSTI Identifier:
22420504
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 90; Journal Issue: 5; 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; ADULTS; CENTRAL NERVOUS SYSTEM; LEUKEMIA; MULTIVARIATE ANALYSIS; PATIENTS; RADIOTHERAPY; SKULL; STEM CELLS; SURVIVAL TIME

Citation Formats

Walker, Gary V., Shihadeh, Ferial, Kantarjian, Hagop, Allen, Pamela, Rondon, Gabriela, Kebriaei, Partow, O'Brien, Susan, Kedir, Aziza, Said, Mustefa, Grant, Jonathan D., Thomas, Deborah A., Gidley, Paul W., Arzu, Isidora, Pinnix, Chelsea, Reed, Valerie, and Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org. Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia. United States: N. p., 2014. Web. doi:10.1016/J.IJROBP.2014.08.004.
Walker, Gary V., Shihadeh, Ferial, Kantarjian, Hagop, Allen, Pamela, Rondon, Gabriela, Kebriaei, Partow, O'Brien, Susan, Kedir, Aziza, Said, Mustefa, Grant, Jonathan D., Thomas, Deborah A., Gidley, Paul W., Arzu, Isidora, Pinnix, Chelsea, Reed, Valerie, & Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org. Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia. United States. doi:10.1016/J.IJROBP.2014.08.004.
Walker, Gary V., Shihadeh, Ferial, Kantarjian, Hagop, Allen, Pamela, Rondon, Gabriela, Kebriaei, Partow, O'Brien, Susan, Kedir, Aziza, Said, Mustefa, Grant, Jonathan D., Thomas, Deborah A., Gidley, Paul W., Arzu, Isidora, Pinnix, Chelsea, Reed, Valerie, and Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org. Mon . "Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia". United States. doi:10.1016/J.IJROBP.2014.08.004.
@article{osti_22420504,
title = {Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia},
author = {Walker, Gary V. and Shihadeh, Ferial and Kantarjian, Hagop and Allen, Pamela and Rondon, Gabriela and Kebriaei, Partow and O'Brien, Susan and Kedir, Aziza and Said, Mustefa and Grant, Jonathan D. and Thomas, Deborah A. and Gidley, Paul W. and Arzu, Isidora and Pinnix, Chelsea and Reed, Valerie and Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org},
abstractNote = {Purpose: To determine the benefit of radiation therapy (RT) in resolution of neurologic symptoms and deficits and whether the type of RT fields influences central nervous system (CNS) control in adults with CNS leukemia. Methods and Materials: A total of 163 adults from 1996 to 2012 were retrospectively analyzed. Potential associations between use of radiation and outcome were investigated by univariate and multivariate analysis. Results: The median survival time was 3.8 months after RT. Common presenting symptoms were headache in 79 patients (49%), cranial nerve VII deficit in 46 (28%), and cranial nerve II deficit in 44 (27%). RT was delivered to the base of skull in 48 patients (29%), to the whole brain (WB) in 67 (41%), and to the craniospinal axis (CS) in 48 (29%). Among 149 patients with a total of 233 deficits, resolution was observed in 34 deficits (15%), improvement in 126 deficits (54%), stability in 34 deficits (15%), and progression in 39 deficits (17%). The 12-month CNS progression-free survival was 77% among those receiving CS/WB and 51% among those receiving base of skull RT (P=.02). On multivariate analysis, patients who did not undergo stem cell transplantation after RT and base of skull RT were associated with worse CNS progression-free survival. Conclusions: Improvement or resolution of symptoms occurred in two thirds of deficits after RT. Comprehensive radiation to the WB or CS seems to offer a better outcome, especially in isolated CNS involvement.},
doi = {10.1016/J.IJROBP.2014.08.004},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 90,
place = {United States},
year = {Mon Dec 01 00:00:00 EST 2014},
month = {Mon Dec 01 00:00:00 EST 2014}
}
  • Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methodsmore » with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy of further protocol investigation in children with CNS leukemia.« less
  • In acute lymphoblastic leukemia, central nervous system prophylaxis with irradiation plus intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity was recognized mainly in children as CT scan abnormalities and neuropsychologic alterations. Two questions were analyzed: (1) Will further doses of i.t. methotraxate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse. (2) Is i.t. MTX-DMT given during induction and maintenance as effective as cranium irradiation plus i.t. MTX-DMT. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count < 50,000 and in the untreated groupmore » was 11%. In patients with a WBC count > 50,000, it was 16% in the treated group and 19% in the control group. These patients were compared with patients which had received 3 doses of i.t. MTX-DMT alone during induction, 3 doses weekly during the first month of remission, and quarterly thereafter. The incidence of leukemia at 60 mo in patients with a WBC count < 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. The relapse-free survival at 60 mo was 26% and 41%, respectively, (p < 0.0005). The incidence in patients with a WBC count > 50,000 at 48 mo was 28% and 42% in the irradiated and nonirradiated group respectively. Complete remission remained at 15% and 16% respectively of patients disease-free at 48 mo. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) use of i.t. MTX-DMT alone compares with cranial irradiation plus i.t. MTX-DMT in incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count < 50.000 were significantly longer in those without cranial irradiation.« less
  • The authors report a case of fatal necrotizing leukoencephalopathy following prophylactic therapy of the central nervous system for acute lymphoblastic leukemia. The clinical, CT, and neuropathological findings are described. The CT scan demonstrated symmetrical white-matter enhancement. Histological analysis was consistent with the effects of irradiation and methotrexate. The differential diagnosis of the clinical and CT findings is discussed. Brain biopsy is the diagnostic procedure of choice.
  • Short communication.
  • The results of six different types of central nervous system (CNS) prophylaxis were studied in two successive Children's Cancer Study Group clinical trials of children with acute leukemia. Radiation therapy doses and technical factors were analyzed in relation to survival, relapse-free survival, bone marrow and CNS relapse rates, and the toxicities encountered in 656 study children. They were randomized among: (1) 2400 rad to the craniospinal axis (CS) and 1200 rad to the abdomen and gonad, (2) 2400 rad CS, and (3) 2400 rad to the cranium (Cr) + IT/MTX. Hematologic, gastrointestinal and infectious disease compilations were highest in groupmore » 1. The patients were divided into low and high risk categories, defined as those with initial white blood cell counts below and above 20,000/cu mm for outcome analyses. No statistically significant differences were detected in the five-year rates for relapse-free survival or survival, nor fo CNS or bone marrow relapse among the 5 irradiated groups when equipment variables, total doses, field arrangements, fractionation, and protraction were analyzed. These results should be interpreted in the light of the group 4 children who had the highest CNS relapse rates (e.g., 33% for low risk patients vs 4 to 16% for their counterparts in the other 5 groups), but nonetheless had a generally similar bone marrow and survival experience. Exceptions to the foregoing are the better five-year survival rates of 64 and 73% respectively for group 3 and group 6 high-risk boys, contrasted with 25 to 42% for their counterparts in the other 4 groups.« less