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Journal of Clinical Oncology, Vol 22, No 6 (March 15), 2004: pp. 1167-1168 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.99.307
In Reply:Federation of Neurology, Division Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris, France Evaluating the role of consolidation radiotherapy (RT) in older patients (over 60 years) suffering from primary CNS lymphoma in remission after initial methotrexate- (MTX) based chemotherapy in a randomized trial, as proposed by Drs Reni and Ferreri, would expose the patients to an unacceptable risk of delayed neurotoxicity and raises ethical concern. Indeed there is evidence that combined treatment with MTX-based chemotherapy followed by RT exposes the elderly to a high rate of delayed neurotoxicity. Whole brain irradiation and high-dose MTX, especially when associated, may cause severe leukoencephalopathy and brain atrophy. This complication occurs as early as 3 months after the treatment and is characterized by attention deficit, memory impairment, ataxia, urine incontinence, ultimately leading to dementia with a disastrous consequence on the quality of life of the patients. In multicenter trials [1-3], a 19%, 48%, and 62% rate of dementia have been reported respectively in patients over 60 years. Moreover, these studies should be considered as conservative, since no prospective neuropsychological testing was proposed. Therefore, it is likely that only the most severe cognitive dysfunction was recorded by the investigators. Consistently, most of these neurotoxicities were fatal. Abrey et al [4,5] reported a 10-year experience at the Memorial Sloan-Kettering Cancer Center in a neurological setting with a higher rate of delayed neurotoxicity occurring in more than 80% of the older patients. This also corresponds to our own experience in our institution. Conversely, we and others have showed that MTX-based chemotherapy as initial treatment allows a substantial proportion of patients to reach prolonged remission without the need of consolidation RT, and with an excellent tolerance. A careful review [6] of the specific results of the elderly subgroup in prospective trials showed comparable results in term of survival between both approaches (median survival was 14-34 months with MTX-based chemotherapy alone [4,7-9] v 18 to 32 months with combined treatment [1-4,12]). Prospective follow-up of cognitive functions (Mini Mental Status Examination and/or psychometric testing) and/or quality of life was performed in most of the studies evaluating the chemotherapy-alone approach. All converge to demonstrate an excellent preservation of the cognitive functions and good quality of life with a rate of delayed neurotoxicity ranging from 0% to 8% [4,7-11]. If a randomized study evaluating the role of consolidation RT is really needed for young patients (< 60 years), who are much less exposed to delayed neurotoxicity, defending this question in the elderly patients in remission after primary chemotherapy appears as a pointless, risky exercise in "rearguard fighting." Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. DeAngelis LM, Seiferheld W, Schold SC, et al: Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 20:4643-4648, 2002 2. Desablens B, Gardembas M, Haie-Meder C, et al: Primary central nervous system lymphoma: Long term results of the GOELAMS LCP 88 trial with a focus on neurological complications among 152 patients. Ann Oncol 10:14, 1999 (abstr 40) 3. Bessell EM, Graus F, Lopez-Guillermo A, et al: CHOD/BVAM regimen plus radiotherapy in patients with primary CNS non-Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys 50:457-464, 2001[CrossRef][Medline]
4. Abrey LE, Yahalom J, DeAngelis LM: Treatment for primary CNS lymphoma: The next step. J Clin Oncol 18:3144-3150, 2000 5. Abrey LE, DeAngelis LM, Yahalom J: Long-term survival in primary CNS lymphoma. J Clin Oncol 16:859-863, 1998[Abstract] 6. Hoang-Xuan K, Chinot O, Taillandier L. Treatment of primary central nervous system lymphoma in the elderly. Semin Oncol 30:53-57, 2003 (suppl 19)[CrossRef][Medline] 7. McAllister LD, Doolittle ND, Guastadisegni PE, et al: Cognitive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma. Neurosurgery 46:51-60, 2000[CrossRef][Medline]
8. Hoang-Xuan K, Taillandier L, Chinot O, et al: Chemotherapy alone as initial treatment for primary CNS lymphoma in patients older than 60 years: A multicenter phase II study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group. J Clin Oncol 21:2726-2731, 2003
9. Pels H, Schmidt-Wolf IG, Glasmacher A, et al: Primary central nervous system lymphoma: Results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy. J Clin Oncol 21:4489-4495, 2003 10. Guha-Thakurta N, Damek D, Pollack C, et al: Intravenous methotrexate as initial treatment for primary central nervous system lymphoma: Response to therapy and quality of life of patients. J Neurooncol 43:259-268, 1999[CrossRef][Medline]
11. Fliessbach K, Urbach H, Helmstaedter C, et al: Cognitive performance and magnetic resonance imaging findings after high-dose systemic and intraventricular chemotherapy for primary central nervous system lymphoma. Arch Neurol 60:563-568, 2003 12. Desablens B, Francois S, Rodier JM, et al: Prognostic factors in HIV-negative primary CNS NHL: Analysis from 135 patients treated by the LCP 88 trial. Blood 90:587a, 1997 (suppl 1; abstr 2609)
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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