How I treat How I treat primary CNS lymphoma

Primary CNS lymphoma (PCNSL) is a rare malignancy with peculiar clinical and bio-logic 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, limit-ing the identification of new therapeutic targets, and the particular microenviron-ment of this malignancy, and sanctuary sites where tumor cells grow undis-turbed, strongly affects treatment effi-cacy. 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 pro-spective 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 consen-sus on primary endpoints for future trials. Despite this unfavorable background, lab-oratory and clinical researchers are coor-dinating efforts to develop new ideas, resulting in the recent publication of stud-ies on PCNSL’s biology and molecular mechanisms and of the first international randomized trials. Herein, these impor-tant contributions are analyzed to provide recommendations for everyday practice and the rationale for future trials. (Blood. 2011;118(3):510-522