How I treat primary CNS lymphoma

Abstract

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...

The diagnostic role of 18F-FDG PET for primary central nervous system lymphoma

“…Since at presentation patients sometimes have severe neurological deficits and an elevation of intracranial pressure, steroids are frequently prescribed to PCNSL patients before the biopsy. It is recognized that the effects of corticosteroid can interfere with histopathological diagnosis on PCNSLs by lympholytic effect [22]. Unexpectedly, in our series the mean T/N ratio of these tumors was 2.51 with no significant difference from PCNSLs without steroid administration in our series (p = 0.46).…”

Findings at presentation in primary CNS diffuse large B-cell lymphoma of the brain: A comparison of immunocompetent and immunodeficient patients

“…With respect to T2WI, most lesions were hyperintense, in contrast to the results cited by some authors [23] , in which the lesions were mostly iso-hypointense, but in agreement with multiple other studies [9,12,22,24] . Our result may have been influenced by the high percentage of necrosis in our study.…”

Prognosis of patients with primary central nervous system lymphoma after high-dose chemotherapy followed by autologous stem cell transplantation

“…The rate of concurrent meningeal involvement detected by cerebrospinal fluid cytology examination is estimated to be 16%, whereby isolated leptomeningeal lymphoma only represents less than 5% of all PCNSL. 24,25 The high rate of missing values in our cohort may be explained by the fact that spinal tabs to obtain cerebrospinal fluid protein concentration or meningeal involvement are often not collected in routine clinical practice. Patients with PCNSL initially often present with space-consuming intracerebral masses with perifocal edema and presumed increased intracranial pressure.…”