Prospective cognitive follow-up in primary CNS lymphoma patients treated with chemotherapy and reduced-dose radiotherapy

Correa, Denise D.; Rocco-Donovan, Mary; DeAngelis, Lisa M.; Dolgoff-Kaspar, Rima; Iwamoto, Fábio M.; Yahalom, Joachim; Abrey, Lauren E.

doi:10.1007/s11060-008-9716-0

Cited by 104 publications

(63 citation statements)

References 29 publications

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“…33 Follow-up of a small number of patients indicates no significant cognitive decline up to 24 months after reduced-dose WBRT; however, difficulties in verbal memory and motor speed have persisted during ongoing follow-up. 34 In our report, there were no differences among the 3 non-WBRT groups in any outcome measure. Of interest, 8 (12%) of 65 survivors treated with chemotherapy without WBRT showed cognitive impairment in multiple domains even after complete disease remission.…”

Section: Statistical Analysis Clinical and Demographic Characteristicscontrasting

confidence: 48%

Long-term cognitive function, neuroimaging, and quality of life in primary CNS lymphoma

et al. 2013

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Objective: To describe and correlate neurotoxicity indicators in long-term primary CNS lymphoma (PCNSL) survivors who were treated with high-dose methotrexate-based regimens with or without whole-brain radiotherapy (WBRT).Methods: Eighty PCNSL survivors from 4 treatment groups (1 with WBRT and 3 without WBRT) who were a minimum of 2 years after diagnosis and in complete remission underwent prospective neuropsychological, quality-of-life (QOL), and brain MRI evaluation. Clinical characteristics were compared among treatments by using the x 2 test and analysis of variance. The association among neuroimaging, neuropsychological, and QOL outcomes was assessed by using the Pearson correlation coefficient. Results:The median interval from diagnosis to evaluation was 5.5 years (minimum, 2 years; maximum, 26 years). Survivors treated with WBRT had lower mean scores in attention/executive function (p 5 0.0011), motor skills (p 5 0.0023), and neuropsychological composite score (p 5 0.0051) compared with those treated without WBRT. Verbal memory was better in survivors with longer intervals from diagnosis to evaluation (p 5 0.0045). On brain imaging, mean areas of total T2 abnormalities were different among treatments (p 5 0.0006). Total T2 abnormalities after WBRT were more than twice the mean of any non-WBRT group and were associated with poorer neuropsychological and QOL outcomes.Conclusions: Our results suggest that in patients treated for PCNSL achieving complete remission and surviving at least 2 years, the addition of WBRT to methotrexate-based chemotherapy increases the risk of treatment-related neurotoxicity. Verbal memory may improve over time. Classification of evidence:This study provides Class III evidence that in patients treated for PCNSL achieving complete remission and surviving at least 2 years, the addition of WBRT to methotrexatebased chemotherapy increases the risk of treatment-related neurotoxicity. High-dose methotrexate is the most widely used drug for primary CNS lymphoma (PCNSL). In combination with whole-brain radiotherapy (WBRT), high-dose methotrexate improved survival rates over WBRT alone. However, delayed treatment-related neurotoxicity emerged as a significant disabling complication of the combined treatment.1-9 Single-drug and multidrug high-dose methotrexate-based regimens without WBRT have been used in an effort to increase survival while avoiding the risk of delayed neurotoxicity. [10][11][12][13][14][15] In patients older than 60 years treated with WBRT, virtually all long-term survivors develop this complication. In patients younger than 60 years, neurotoxicity rates ranging from 26% to 63% have been reported. 2,6 However, the true risk ofFrom the Oregon Health

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Section: Statistical Analysis Clinical and Demographic Characteristicscontrasting

confidence: 48%

Long-term cognitive function, neuroimaging, and quality of life in primary CNS lymphoma

et al. 2013

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“…Two recent studies suggested that WBRT dose reduction to 23-30 Gy in patients in CR after chemotherapy is associated with similar outcomes to receiving higher radiation doses, with better neurotolerability. 83,84 These observations deserve to be addressed in multicenter prospective trials, with standardized neuropsychologic assessment.…”

Section: Is Consolidation Radiotherapy Really Needed?mentioning

confidence: 99%

How I treat primary CNS lymphoma

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2011

Blood

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Primary CNS lymphoma (PCNSL) is a rare malignancy with peculiar clinical and biologic features, aggressive course, and unsatisfactory outcome. It represents a challenge for multidisciplinary clinicians and scientists as therapeutic progress is inhibited by several issues. Molecular and biologic knowledge is incomplete, limiting the identification of new therapeutic targets, and the particular microenvironment of this malignancy, and sanctuary sites where tumor cells grow undisturbed, strongly affects treatment efficacy. Moreover, active treatments are known to be associated with disabling neurotoxicity, posing the dilemma of whether to intensify therapy to improve the cure rate or to de-escalate treatment to avoid sequels. The execution of prospective trials is also difficult because of the rarity of the tumor and the impaired general condition and poor performance status of patients. Thus, level of evidence is low, with consequent uncertainties in therapeutic decisions and lack of consensus on primary endpoints for future trials.Despite this unfavorable background, laboratory and clinical researchers are coordinating efforts to develop new ideas, resulting in the recent publication of studies on PCNSL's biology and molecular mechanisms and of the first international randomized trials. Herein, these important contributions are analyzed to provide recommendations for everyday practice and the rationale for future trials. (Blood. 2011;118(3):510-522) IntroductionPrimary CNS lymphoma (PCNSL) is an aggressive malignancy arising exclusively in the CNS, that is, the brain parenchyma, spinal cord, eyes, cranial nerves, and/or meninges. 1 This lymphoma represents 4% of intracranial neoplasms and 4%-6% of all extranodal lymphomas but some registry studies suggest that its incidence in immunocompetent patients is progressively increasing. 2 PCNSL exhibits peculiar clinical and biologic features and constitutes a diagnostic and therapeutic challenge for multidisciplinary clinicians and scientists. Its outcome remains unsatisfactory if compared with that of patients with extra-CNS lymphomas of a similar stage and histotype, and several factors prevent therapeutic progress. First, molecular and biologic knowledge is insignificant compared with other lymphomas, which limits the identification of new therapeutic targets. Second, patients with PCNSL usually exhibit impaired general condition and poor performance status (PS) more often than subjects with other lymphomas. 1 This usually interferes with the enrollment of patients in prospective trials. In fact, current therapeutic knowledge is only based on 3 randomized trials, some single-arm phase 2 trials, anecdotal meta-analyses, and a few multicenter retrospective studies. Thus, available level of evidence is low, with consequent uncertainties in therapeutic decisions and lack of consensus on primary endpoints for future trials.In this manuscript, I discuss available clinical and biologic data on PCNSL in immunocompetent patients and provide recommendations for everyday pract...

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“…Correa and colleagues investigated a modified treatment regimen consisting of methotrexate-based chemotherapy incorporating rituximab, a chimeric monoclonal antibody, and reduced-dose WBRT aimed at improving efficacy and decreasing neurotoxicity in primary CNS lymphoma patients in a prospective, uncontrolled study [50]. Of the 19 patients with primary CNS lymphoma, 12 completed neuropsychological assessments at diagnosis, after induction chemotherapy and prior to reduced-dose WBRT and consolidation chemotherapy, and approximately 6 and 12 months after treatment.…”

Section: Reviewmentioning

confidence: 99%