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Title: Consolidation Radiotherapy in Primary Central Nervous System Lymphomas: Impact on Outcome of Different Fields and Doses in Patients in Complete Remission After Upfront Chemotherapy

Abstract

Purpose: Avoidance radiotherapy or reduction of irradiation doses in patients with primary central nervous system lymphoma (PCNSL) in complete remission (CR) after high-dose methotrexate (HD-MTX)-based chemotherapy has been proposed to minimize the neurotoxicity risk. Nevertheless, no study has focused on the survival impact of radiation parameters, as far as we know, and the optimal radiation schedule remains to be defined. Methods and Materials: The impact on outcome and neurologic performance of different radiation fields and doses was assessed in 33 patients with PCNSL who achieved CR after MTX-containing chemotherapy and were referred to consolidation whole-brain irradiation (WBRT). Patterns of relapse were analyzed on computed tomography-guided treatment planning, and neurologic impairment was assessed by the Mini Mental Status Examination. Results: At a median follow-up of 50 months, 21 patients are relapse-free (5-year failure-free survival [FFS], 51%). WBRT doses {>=}40 Gy were not associated with improved disease control in comparison with a WBRT dose of 30 to 36 Gy (relapse rate, 46% vs. 30%; 5-year FFS, 51% vs. 50%; p = 0.26). Disease control was not significantly different between patients irradiated to the tumor bed with 45 to 54 Gy or with 36 to 44 Gy, with a 5-year FFS of 35%more » and 44% (p = 0.43), respectively. Twenty patients are alive (5-year overall survival, 54%); WB and tumor bed doses did not have an impact on survival. Impairment as assessed by the Mini Mental Status Examination was significantly more common in patients treated with a WBRT dose {>=}40 Gy. Conclusion: Consolidation with WBRT 36 Gy is advisable in patients with PCNSL in CR after HD-MTX-based chemotherapy. Higher doses do not change the outcome and could increase the risk of neurotoxicity.« less

Authors:
 [1];  [2];  [1];  [2];  [3];  [4];  [5]; ;  [6]
  1. Unit of Lymphoid Malignancies, Department of Oncology, San Raffaele Scientific Institute, Milan (Italy)
  2. (Italy)
  3. Neuroradiology Unit, Department of Oncology, San Raffaele Scientific Institute, Milan (Italy)
  4. Unit of Radiotherapy and Tomotherapy, Department of Oncology, San Raffaele Scientific Institute, Milan (Italy)
  5. Medical Physics Unit, Department of Oncology, San Raffaele Scientific Institute, Milan (Italy)
  6. Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute, Milan (Italy)
Publication Date:
OSTI Identifier:
21491713
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 80; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2010.01.066; PII: S0360-3016(10)00269-5; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BRAIN; CHEMOTHERAPY; COMPUTERIZED TOMOGRAPHY; LYMPHOMAS; METHOTREXATE; MINIMIZATION; RADIATION DOSES; RADIOTHERAPY; ANTIMETABOLITES; BODY; CENTRAL NERVOUS SYSTEM; DIAGNOSTIC TECHNIQUES; DISEASES; DOSES; DRUGS; IMMUNE SYSTEM DISEASES; MEDICINE; NEOPLASMS; NERVOUS SYSTEM; NUCLEAR MEDICINE; OPTIMIZATION; ORGANS; RADIOLOGY; THERAPY; TOMOGRAPHY

Citation Formats

Ferreri, Andres Jose Maria, E-mail: andres.ferreri@hsr.i, Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute, Milan, Verona, Chiara, Internal Medicine Unit, Department of Oncology, San Raffaele Scientific Institute, Milan, Politi, Letterio Salvatore, Chiara, Anna, Perna, Lucia, Villa, Eugenio, and Reni, Michele. Consolidation Radiotherapy in Primary Central Nervous System Lymphomas: Impact on Outcome of Different Fields and Doses in Patients in Complete Remission After Upfront Chemotherapy. United States: N. p., 2011. Web. doi:10.1016/j.ijrobp.2010.01.066.
Ferreri, Andres Jose Maria, E-mail: andres.ferreri@hsr.i, Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute, Milan, Verona, Chiara, Internal Medicine Unit, Department of Oncology, San Raffaele Scientific Institute, Milan, Politi, Letterio Salvatore, Chiara, Anna, Perna, Lucia, Villa, Eugenio, & Reni, Michele. Consolidation Radiotherapy in Primary Central Nervous System Lymphomas: Impact on Outcome of Different Fields and Doses in Patients in Complete Remission After Upfront Chemotherapy. United States. doi:10.1016/j.ijrobp.2010.01.066.
Ferreri, Andres Jose Maria, E-mail: andres.ferreri@hsr.i, Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute, Milan, Verona, Chiara, Internal Medicine Unit, Department of Oncology, San Raffaele Scientific Institute, Milan, Politi, Letterio Salvatore, Chiara, Anna, Perna, Lucia, Villa, Eugenio, and Reni, Michele. 2011. "Consolidation Radiotherapy in Primary Central Nervous System Lymphomas: Impact on Outcome of Different Fields and Doses in Patients in Complete Remission After Upfront Chemotherapy". United States. doi:10.1016/j.ijrobp.2010.01.066.
@article{osti_21491713,
title = {Consolidation Radiotherapy in Primary Central Nervous System Lymphomas: Impact on Outcome of Different Fields and Doses in Patients in Complete Remission After Upfront Chemotherapy},
author = {Ferreri, Andres Jose Maria, E-mail: andres.ferreri@hsr.i and Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute, Milan and Verona, Chiara and Internal Medicine Unit, Department of Oncology, San Raffaele Scientific Institute, Milan and Politi, Letterio Salvatore and Chiara, Anna and Perna, Lucia and Villa, Eugenio and Reni, Michele},
abstractNote = {Purpose: Avoidance radiotherapy or reduction of irradiation doses in patients with primary central nervous system lymphoma (PCNSL) in complete remission (CR) after high-dose methotrexate (HD-MTX)-based chemotherapy has been proposed to minimize the neurotoxicity risk. Nevertheless, no study has focused on the survival impact of radiation parameters, as far as we know, and the optimal radiation schedule remains to be defined. Methods and Materials: The impact on outcome and neurologic performance of different radiation fields and doses was assessed in 33 patients with PCNSL who achieved CR after MTX-containing chemotherapy and were referred to consolidation whole-brain irradiation (WBRT). Patterns of relapse were analyzed on computed tomography-guided treatment planning, and neurologic impairment was assessed by the Mini Mental Status Examination. Results: At a median follow-up of 50 months, 21 patients are relapse-free (5-year failure-free survival [FFS], 51%). WBRT doses {>=}40 Gy were not associated with improved disease control in comparison with a WBRT dose of 30 to 36 Gy (relapse rate, 46% vs. 30%; 5-year FFS, 51% vs. 50%; p = 0.26). Disease control was not significantly different between patients irradiated to the tumor bed with 45 to 54 Gy or with 36 to 44 Gy, with a 5-year FFS of 35% and 44% (p = 0.43), respectively. Twenty patients are alive (5-year overall survival, 54%); WB and tumor bed doses did not have an impact on survival. Impairment as assessed by the Mini Mental Status Examination was significantly more common in patients treated with a WBRT dose {>=}40 Gy. Conclusion: Consolidation with WBRT 36 Gy is advisable in patients with PCNSL in CR after HD-MTX-based chemotherapy. Higher doses do not change the outcome and could increase the risk of neurotoxicity.},
doi = {10.1016/j.ijrobp.2010.01.066},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 80,
place = {United States},
year = 2011,
month = 5
}
  • Purpose: To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients 70 years old and younger with newly diagnosed, biopsy-proven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint wasmore » 1-year survival. Results: Thirty-six patients (19 men, 17 women) enrolled between 1995 and 2000. Median age was 60.5 years (range, 34 to 69 years). Thirty (83%) patients had baseline Eastern Cooperative Oncology Group performance scores of 0 to 1. All 36 patients were eligible for survival and response evaluations. Median time to progression was 12.3 months, and median survival was 18.5 months. The percentages of patients alive at 1, 2, and 3 years were 64%, 36%, and 33%, respectively. The best response was complete response in 10 patients and immediate progression in 7 patients. Ten (28%) patients had at least one grade 3 or higher neurologic toxicity. Conclusions: This regimen did improve the survival of PCNSL patients but also caused substantial toxicity. The improvement in survival is less than that reported with high-dose methotrexate-based therapies.« less
  • Purpose: The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radiotherapy-treated (WBRT) and high-dose methylprednisolone (HDMP)-treated in elderly patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients with PCNSL who were 70 years and older received 1 g of methylprednisolone daily for 5 days, 30 days after WBRT. Patients then received 1 g of methylprednisolone every 28 days until progression. The primary endpoint was overall survival (OS) at 6 months. Results were compared with those in patients on the previous North Central Cancer Treatment Group (NCCTG) trial who received pre-WBRT cytoxan,more » adriamycin, vincristine, prednisone (CHOP) and high-dose cytarabine (CHOP-WBRT). A planned interim analysis was performed. The current regimen would be considered inactive if survival was not improved from patients treated with CHOP-WBRT. Results: Nineteen patients were accrued between 1998 and 2003. Median age was 76 years. Interim analysis revealed a 6-month survival of 33%, resulting in closure of the trial. Toxicity, OS, and event-free survival (EFS) were similar to those in patients more than 70 years of age who received CHOP-WBRT. The subgroup of patients who received HDMP had longer OS (12.1 vs. 7.0 months, p = 0.76) and EFS (11.7 vs. 4.0 months, p = 0.04) compared with the CHOP-WBRT patients alive 60 days after the start of treatment. Conclusions: Patients on-study long enough to receive HDMP had prolongation of OS and EFS compared to patients receiving CHOP-WBRT. Although the numbers of patients are too small for statistical conclusions, the HDMP regimen deserves further study.« less
  • Purpose: The use of radiotherapy in patients with advanced Hodgkin's lymphoma (HL) is controversial. The purpose of this study was to describe the role of radiotherapy in patients with advanced HL who were in partial remission (PR) after chemotherapy. Methods: In a prospective randomized trial, patients <70 years old with previously untreated Stage III-IV HL were treated with six to eight cycles of mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycine, vinblastine hybrid chemotherapy. Patients in complete remission (CR) after chemotherapy were randomized between no further treatment and involved-field radiotherapy (IF-RT). Those in PR after six cycles received IF-RT (30 Gy to originallymore » involved nodal areas and 18-24 Gy to extranodal sites with or without a boost). Results: Of 739 enrolled patients, 57% were in CR and 33% in PR after chemotherapy. The median follow-up was 7.8 years. Patients in PR had bulky mediastinal involvement significantly more often than did those in CR after chemotherapy. The 8-year event-free survival and overall survival rate for the 227 patients in PR who received IF-RT was 76% and 84%, respectively. These rates were not significantly different from those for CR patients who received IF-RT (73% and 78%) or for those in CR who did not receive IF-RT (77% and 85%). The incidence of second malignancies in patients in PR who were treated with IF-RT was similar to that in nonirradiated patients. Conclusion: Patients in PR after six cycles of mechlorethamine, vincristine, procarbazine, prednisone/doxorubicine, bleomycine, vinblastine treated with IF-RT had 8-year event-free survival and overall survival rates similar to those of patients in CR, suggesting a definite role for RT in these patients.« less
  • Primary lymphomas of the CNS are rare tumors accounting for less than 2% of all extranodal non-Hodgkin's lymphomas. The treatment for this disease has been disappointing. Radiation therapy and surgery have produced consistently poor control of this disease, with a median survival of 15 months. A review of ten cases of primary lymphoma of the CNS treated at the Joint Center for Radiation Therapy or Dana-Farber Cancer Institute (Boston) from 1968 to 1981 is presented. All patients had biopsy- proven CNS lymphomas without systemic disease at presentation. In this series, control of CNS lymphoma was seen only in patients receivingmore » craniospinal radiation or CNS-penetrating chemotherapy.« less