Diagnosis and treatment of lymphoma of the primary central nervous system

Primary central nervous system (CNS) lymphoma refers to the absence of systemic lymphoma, the pervasive large B-cell lymph nodes of the brain, eyes, soft meninges or spinal cord, malignant non-Hodgkin's lymphoma;the incidence of primary CNS lymphoma continued to rise in the 1980s and 1990s, and epidemiological data from high-income countries showed a decline in incidence, especially among young AIDS patientsBy contrast, the incidence of primary CNS lymphoma continued to rise in most immune-functioning older populationsits treatment is controversial due to the complexity of the disease and the low number of existing control studiesbest treatment recommendations come primarily from retrospective or single-arm 2 studies, and as of 2015, only three completed randomized trials were available for primary CNS lymphoma, one phase III and two Phase II clinical trials2013 the European Neurocancer Association established a multidisciplinary working group to establish evidence-based guidelines for adult patients with normal immune function, and to provide clinicians with evidence-based advice and expert consensus to improve the diagnosis and treatment of the disease;the results of the studythe guidelines provide specific recommendations and consensus on the diagnosis, evaluation, staging and treatment of primary CNS lymphoma, including surgery, systemic and intrauterine chemotherapy, immune stem cell transplant ation chemotherapy, radiotherapy, manifestations and treatment of intra-eye lymphoma, and management of elderly patientsthe level of evidence
Class I evidence comes from randomized Phase 3 clinical trials; IIa evidence from Randomized Phase 2 trials; IIb evidence from Phase 2 trials; Category IIA evidence from prospective studies, including observational studies, cohort studies, and case control studies; iiIb evidence from retrospective studies; and Class IV evidence from non-control case series, case reports, and expert opinionrecommended levelrecommended level using the following criteria: A-level requires at least one Class I study or two consistent IIa studies; Pathology, genetics, clinical features and neuroimaging examinations are not gradedWhen there is insufficient evidence to be classified as A-C, the Expert Group recommends good practice recommendations, provided that they need unanimous approval from all members of the Working Groupspecific recommendations are as follows
the diagnosis, staging, prognosis and treatment response assessment recommendations for patients with this type of disease are detailed in topic I;topic series, diagnostic1Diagnostic and follow-up examination methods preferred to use cranial MRI before and after injection of enhanced contrast agent liquid attenuation reversal recovery and T1-weighted sequence imagingDispersion, dynamic magnetic sensitivity comparison, proton spectral MRI and fluorogenide glucose-PET can be used for differential diagnosis, but lack specificity (good practice recommendations)2Prior to treatment, the diagnosis of primary CNS lymphoma must be confirmed by histopathology;3If clinically permitted, the use of steroids should be avoided prior to biopsies, which may hinder histopathological diagnosisFor patients who have had steroid pretreatment, a biopsy (good practice recommendation) is recommended if tissue biopsies show remission or nonspecific inflammation, and continuous MRI close follow-up indicates further tumor growth4For the diagnosis of primary CNS lymphoma according to the WHO classification, an immunohistomy test (good practice recommendations) is required5Immune hetle markers, including pan-B cell markers (CD19, CD20, PAX5), BCL6, MUM1/IRF4 and CD10 (good practice recommendations)6PCR analysis of the immunoglobulin gene family contributes to the diagnosis of difficult cases, such as corticosteroid pre-treated in patients with primary CNS lymphoma (good practice recommendations) 7 If primary CNS lymphoma is suspected, including tests for patients with no eye symptoms, at least one HIV blood test, lumbar punctures (if there is no contraindication) and an eye assessment (using a subcutanigo and a fissure) (good practice recommendations) 8 There are lymphoma cells in cerebrospinal fluid or glass fluid plus clinical and imaging highly suspected primary CNS lymphoma do not require a stereotactic brain biopsy to confirm diagnosis When there are difficulties in cytological diagnosis, it is recommended to ask a specialist pathologist for the examination If in doubt, a biopsy of the brain lesions (good practice recommendations) is required 9 Immune phenotype analysis of cells collected from cerebrospinal fluid or glass fluid swashes through multi-parameter flow cell detection; 10 In samples of atypical or suspicious cells, pcR analysis of immunoglobulin genes in cerebrospinal fluid may result in false positive results, if b cell monoclonal is present Therefore, with the exception of patients with clinically highly suspected primary CNS lymphoma, lymphocyte population cloning is not sufficient to diagnose primary CNS lymphoma (good practice recommendations) , phased indicators of systemic staging, including physical examination, bone marrow biopsy, testicular ultrasound, and CT scans of the chest, abdomen and pelvis Full-body fluorine deoxyglucose-PET is a good alternative to full body CT scans and testicular ultrasound (good practice recommendations) three, prognosis
1 Consistently determine the age and general status of the measurements of various scales as prognostic factors unrelated to treatment Prior to treatment, patients should be assessed for existing prognostic scores and individual risks (good practice recommendations) 2 Older patients are those over 60-65 years of age (good practice recommendations) IV, evaluation and follow-up of therapeutic responses
1 Evaluate the therapeutic response (good practice recommendations) in combination with MRI, ophthalmology, cerebrospinal fluid analysis and steroid use dose sympathise (2005 edition) of the International Collaboration Group Standard for Primary CNS Lymphoma (2005 Edition) 2 Cerebral fluoro-deoxyglucose-PET has been used to evaluate the therapeutic response of other types of lymphoma, but there is no evidence that it can be used to assess the therapeutic response of patients with primary CNS lymphoma (good practice recommendations) 3 Formal prospective neuropsychological tests (good practice recommendations) are recommended during follow-up treatment in patients with primary CNS lymphoma in clinical trials topic 2 , surgery 1 For patients with large lesions and acute symptoms of cerebral palsy, surgical removal of tumors can be performed to rapidly reduce intracranial pressure (good practice recommendations) 2 In patients with single-pre-primary CNS lymphoma, the Group did not reach a consensus on whether the tumor should be surgically removed or whether a tissue biopsy was required II, chemotherapy
1 It is not recommended to use cyclophosphamide, amycin, changchun neonicotinoids and punisepine (CHOP) to treat primary CNS lymphoma (Class B) with a co-use scheme and derivatives 2 Chemotherapy should include a large dose of methotrexate (at least 3g/m2) so that the drug can pass through the blood-brain barrier and reach cytotoxic levels in cerebrospinal fluid Methotrexate intravenous drip sin 2-3h, at least 4-6 injections, interval shorter than 2-3 weeks (good practice recommended) 3 Large doses of methotrexate combined with other chemotherapy drugs can improve efficacy compared to single-use high-dose methotrexate (Class B) 4 Chemotherapy drugs used in combination with high doses of methotrexate should be selected from active drugs that can pass through the blood-brain barrier, such as high doses of alysatorine (Class B) 5 High doses of methotrexate chemotherapy (Class B) can be used in elderly patients with general clinical and renal function 6 After the destruction of the blood-brain barrier, methotrexate injection in the arteries is an alternative implementation method, and the selected patient group can only be treated by a high-level team of professionals (B-grade) 7 The value of preventive intrauterine chemotherapy is unclear When the meninges are affected and intravenous chemotherapy for high doses of methotrexate (at least 3 g/m2) is not effective, intrauterine chemotherapy (injected through the Ommaya reservoir brain chamber or by waist) may be recommended (good practice recommendations) The rituximam-combination chemotherapy programme is recommended only as an embodiment in clinical trials (Class C) , radiotherapy
1 The combination of whole brain radiotherapy (WBRT) and large doses of methotrexate has a significant neurotoxicity risk (Class A) 2 After chemotherapy based on high doses of methotrexate, consolidation of whole-brain radiotherapy is still controversial The optimal dose of radiotherapy has not yet been determined and should be selected according to the response to initial chemotherapy (good practice recommendations) 3 For those who progress or remain in the lesions after initial chemotherapy, the recommended total dose of radiotherapy is 40-45Gy, with a dose of 1.8-2.0Gy per split When using the above dose, there is no evidence of a lesions fortification (good practice recommendation) in MRI-enhanced contrast scans 4 For patients younger than 60 years of age who have been fully relieved by induced chemotherapy, it should be discussed with the patient immediate full-brain radiotherapy (40-45Gy, sub-dose 1.8-2.0Gy) or omitted full-brain radiotherapy Reduced dose of solideniday whole brain radiotherapy (23.4-30.0Gy, sub-1.8-2.0Gy) should be the option of treatment and need to be studied in clinical trials (good practice recommendations) 5 Patients older than 60 years of age have an excessive risk of late neurotoxicity after full brain radiotherapy (total dose greater than 30Gy, sub-dose 1.8-2.0Gy), especially after treatment with high doses of methotrexate; 4, high-dose chemotherapy combined autologous stem cell transplantation (High-dose chemotherapy with autologous stem-cell transplantation, HDC-ASCT) 1.HDC-ASCT is an effective treatment for recurrent or refractory primary CNS lymphoma (Class B) 2.HDC-ASCT is used in patients younger than 60-65 years of age (good practice recommendations) 3 Pre-treatment chemotherapy (class C) based on high doses of pyridine should be preferred compared to the carmostine, etopolysine, aglycine and metapolifazole (BEAM) co-use programmes 4.HDC-ASCT as a first-line consolidation therapy for primary CNS lymphoma is experimental and is limited to fully trained clinical centers (good practice recommendations) Five, save the treatment
1 Patients with recurrent or refractory primary CNS lymphoma should be included in Phases 1 and 2 trials (good practice recommendations) 2 The most appropriate rescue treatment should be selected according to the patient's age, general clinical state, comorbidities, relapse site, past treatment and duration of remission The expected side effects of the selected drug (good practice recommendations) should also be carefully evaluated 3 Rescued whole-brain radiotherapy can be performed prior to induced chemotherapy and may be given to patients who have not received radiation therapy (good practice recommendations) 4.HDC-ASCT is an effective treatment option (Class B) for patients younger than 60-65 years of age and sensitive to chemotherapy recurrent primary CNS lymphoma 5 Resuscent chemotherapy can be used as an induction therapy before WBRT or HDC-ASCT, or as the only treatment option (B) for patients who are not suitable for WBRT or HDC-ASCT 6 Patients with effective relapsed primary CNS lymphoma treated with high doses of methotrexate should consider the redoofment of methotrexate (Class C) 7 Patients with relapses outside of isolated CNS should use chemotherapy, combined or not combined with HDC-ASCT (good practice recommendations) 6, primary eye lymphoma
1 Primary intra-eye lymphoma can be performed with high doses of methotrexate chemotherapy (may have or without full brain radiotherapy) or local therapy (glass in vivo chemotherapy or eye radiotherapy) (good practice recommendations) 2 Local therapy (glass in vivo chemotherapy or eye radiotherapy) is an effective treatment for patients with systemic chemotherapy contraindications or elderly patients with recurrent intra-eye disease (good practice recommendations) 3 Patients with both intra-ophalmme and CNS lymphoma are treated in the same way as patients with primary CNS lymphoma (good practice recommendations) 4 If a solid whole brain radiotherapy is carried out, the scope of eye exposure should be included (good practice recommendations) 5 The treatment of refractory and recurrent intra-eye lymphoma should be carried out according to the characteristics of the patient and the previous treatment history Treatments include injections of methotrexate in the glass body, metastatherapy, whole brain radiotherapy, systemic chemotherapy and HDC-ASCT (good practice recommendations) conclusions the European Neurocancer Association's 2015 guidelines on primary CNS lymphoma to facilitate clinicians' daily clinical practice and decision-making choices and can serve as the basis for future neuro-oncology research It is worth noting, however, that the guide reflects only the level of awareness at the time of writing Specific updates are available on the European Neurocancer Society website.