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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Primary CNS lymphoma is a lymphoma confined to the brain, eyes and spinal fluid. Unlike most brain tumours it is chemo-sensitive: high-dose methotrexate-based treatment cures a substantial minority, and consolidation with a stem-cell transplant has replaced whole-brain radiation for the fit.
PCNSL is almost always a diffuse large B-cell lymphoma of activated B-cell type, with near-universal MYD88 L265P and CD79B mutations and 9p24 (PD-L1) gains. It presents with focal deficits or cognitive change; diagnosis needs stereotactic biopsy before steroids, plus eye examination and CSF cytology/flow.
Induction is high-dose methotrexate (≥3 g/m²) combined with cytarabine, thiotepa and rituximab (MATRix, IELSG32) or with temozolomide/procarbazine (R-MPV). Consolidation with high-dose chemotherapy and autologous transplant matches or beats whole-brain radiotherapy with far less neurotoxicity (IELSG32, PRECIS), so radiation is reserved for the unfit or as salvage. Older patients receive methotrexate-based regimens with maintenance (temozolomide, lenalidomide or ibrutinib). Relapsed disease responds to ibrutinib, lenalidomide and PD-1 blockade transiently; CD19 CAR-T crosses into the CNS with responses in small series.
| Setting | Approach | Guideline |
|---|---|---|
| Newly diagnosed, fit (<65-70) | Rituximab + high-dose methotrexate + cytarabine ± thiotepa (MATRix) ×4, then high-dose thiotepa-based chemotherapy with autologous transplant (IELSG32, IELSG43). | NCCN Category 2A |
| Newly diagnosed, older/unfit | High-dose methotrexate with temozolomide, procarbazine or rituximab (e.g. MT-R, R-MP), then maintenance (temozolomide, lenalidomide) or reduced-dose WBRT; ibrutinib-based induction in trials. | not mapped |
| Relapsed/refractory | Re-induction with methotrexate if durable first remission; ibrutinib, lenalidomide-rituximab, high-dose chemotherapy/ASCT if not done, WBRT; CD19 CAR-T and PD-1 inhibitors in trials or off-label. | not mapped |
| Primary CNS lymphoma: why R-CHOP fails, and what is given instead | A diffuse large B-cell lymphoma confined to the brain, spinal cord, eyes or meninges. The drugs that cure it elsewhere do not reach it: cyclophosphamide, doxorubicin and vincristine cross the blood-brain barrier poorly, so R-CHOP produces responses in the body and not in the brain, and trials of it in this disease were abandoned decades ago. Surgery has no therapeutic role beyond biopsy, and debulking does not help. Corticosteroids shrink the tumour dramatically and dissolve the diagnostic material with it, so steroids are withheld until the biopsy is taken wherever the patient is stable enough to wait. Induction is built around high-dose methotrexate at 3 to 3.5 g per square metre or more, given with leucovorin rescue and urinary alkalinisation, every two to three weeks. MATRix adds cytarabine, thiotepa and rituximab: in the first randomisation of IELSG32 the complete remission rate was 49 per cent with MATRix against 23 per cent with methotrexate and cytarabine alone and 30 per cent with methotrexate, cytarabine and rituximab. Six per cent of patients died of toxicity, so it is for patients fit enough to take it. The contribution of rituximab itself is contested: HOVON 105 randomised it into a methotrexate-based regimen and did not show the benefit that IELSG32's arm B against arm A comparison suggested. | not mapped |
| Consolidation after methotrexate-based induction: transplant against whole-brain radiotherapy | Induction alone relapses, so responders are consolidated. The two options are thiotepa-based high-dose chemotherapy with an autologous stem cell transplant, or whole-brain radiotherapy, and the choice is dominated by what each does to thinking. MATRix/IELSG43 randomised consolidation in the largest trial ever run in this disease: three-year progression-free survival was 78 per cent (95 per cent confidence interval 69 to 85) with transplant against 51 per cent (41 to 60) with non-myeloablative R-DeVIC consolidation, hazard ratio 0.43, with overall survival also improved; the cost was more toxicity, a mean of 14.6 against 9.3 adverse events per patient and five against two fatal serious adverse events. In the earlier IELSG32 trial, whole-brain radiotherapy and autologous transplant were similarly effective, and at seven years the difference was cognitive: patients who had whole-brain radiotherapy lost attention and executive function, while those who had transplant improved in those domains, in memory and in quality of life. Seven-year overall survival was 21, 37 and 56 per cent for the three induction arms, and 70 per cent for patients who received MATRix and went on to consolidation. So transplant is preferred for patients fit enough. Whole-brain radiotherapy is reserved for those who are not, usually at a reduced dose, and is increasingly deferred to relapse. | not mapped |
| Primary CNS lymphoma in older or less fit patients, and at relapse | Age is not by itself a reason to withhold methotrexate: reduced-intensity methotrexate-based combinations, usually with rituximab and an alkylating agent such as procarbazine or temozolomide, are given to patients in their seventies and eighties with attention to renal function, and produce durable remissions in a minority. Whole-brain radiotherapy in older patients carries a high risk of progressive cognitive decline and is generally avoided as first consolidation. At relapse the options depend on the interval. Re-treatment with methotrexate is effective in patients who relapse late, and in the seven-year IELSG32 report it was the only salvage that clearly benefited anyone. Other options are high-dose cytarabine with thiotepa and transplant if not already given, whole-brain radiotherapy if not already given, ibrutinib, which crosses into the brain and has single-agent activity, lenalidomide with rituximab, temozolomide, and a clinical trial. Ocular involvement is treated with systemic therapy, often with intravitreal methotrexate or rituximab added. | not mapped |