RESUMEN
Primary central nervous system lymphomas (PCNSLs) classically remain confined within the CNS throughout their evolution for unknown reasons. Our objective was to analyse the rare extracerebral relapses of PCNSL in a nationwide population-based study. We retrospectively selected PCNSL patients who experienced extracerebral relapse during their follow-up from the French LOC database. Of the 1968 PCNSL included in the database from 2011, 30 (1.5%, median age 71 years, median KPS 70) presented an extracerebral relapse, either pure (n = 20) or mixed (both extracerebral and in the CNS) (n = 10), with a histological confirmation in 20 cases. The median delay between initial diagnosis and systemic relapse was 15.5 months [2-121 months]. We found visceral (n = 23, 77%), including testis in 5 (28%) men and breast in 3 (27%) women, lymph node (n = 12, 40%), and peripheral nervous system (PNS) (n = 7, 23%) involvement. Twenty-seven patients were treated with chemotherapy, either with only systemic targets (n = 7) or mixed systemic and CNS targets (n = 20), 4 were consolidated by HCT-ASCT. After systemic relapse, the median progression-free survival and overall survival (OS) were 7 and 12 months, respectively. KPS > 70 and pure systemic relapses were significantly associated with higher OS. Extracerebral PCNSL relapses are rare, mainly extranodal, and frequently involve the testis, breast, and PNS. The prognosis was worse in mixed relapses. Early relapses raise the question of misdiagnosed occult extracerebral lymphoma at diagnostic workup that should systematically include a PET-CT. Paired tumour analysis at diagnosis/relapse would provide a better understanding of the underlying molecular mechanisms.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma , Masculino , Humanos , Femenino , Anciano , Estudios Retrospectivos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Recurrencia Local de Neoplasia/tratamiento farmacológico , Linfoma/diagnóstico , Linfoma/epidemiología , Linfoma/terapia , Pronóstico , Neoplasias del Sistema Nervioso Central/terapia , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity. PATIENTS AND METHODS: To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data. RESULTS: Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue. CONCLUSIONS: The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma de Células B Grandes Difuso , Humanos , Fosfatidilinositol 3-Quinasas/genética , Linfoma de Células B Grandes Difuso/patología , Mutación , Complejo Represivo Polycomb 2/genética , Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patologíaRESUMEN
PCNSL is a non-Hodgkin lymphoma (NHL) affecting brain, spinal cord, eyes and leptomeninges. In the past two decades, its prognosis significantly improved due to therapeutic advances but it remains a highly aggressive tumor and early diagnosis is necessary for optimal management. Diagnosis relies on the identification of lymphoma cells in brain tissue obtained by stereotactic biopsy. Alternatively, lymphoma cells may be found in CSF through lumbar puncture (LP) or by a vitrectomy. For several reasons, the diagnosis of PCNSL may be challenging. Misleading radiological presentations are frequent. Dramatic response to steroids may bias histological analysis and deep brain location or frail health status can contraindicate brain biopsy. In the follow-up of patients who have been previously treated, differential diagnosis between tumor relapse and post-treatment may be also difficult. Therefore, the development of complementary reliable diagnostic tools is needed. This review will summarize several diagnostic or prognostic CSF biomarkers which have been proposed in PCNSL, their interests and limits.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma no Hodgkin , Humanos , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/patología , Recurrencia Local de Neoplasia , Biomarcadores , PronósticoRESUMEN
BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL PATIENTS AND METHODS: This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. The primary outcome was the disease control (DC) rate after two months of treatment (P0 < 10%; P1 > 30%). RESULTS: Fifty-two patients were recruited. Forty-four patients were evaluable for response. After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5 stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7-30.5), the median progression-free and overall survivals were 4.8 months (95% confidence interval [CI]; 2.8-12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of the gene mutations in the BCR pathway. CONCLUSION: Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base induction chemotherapy will be further evaluated in the first-line treatment. CLINICAL TRIAL NUMBER: NCT02542514.
Asunto(s)
Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Linfoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Neoplasias de la Retina/tratamiento farmacológico , Terapia Recuperativa , Adenina/análogos & derivados , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/patología , Femenino , Estudios de Seguimiento , Humanos , Linfoma/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Piperidinas , Pronóstico , Estudios Prospectivos , Neoplasias de la Retina/patología , Tasa de SupervivenciaAsunto(s)
Linfoma Intraocular , Linfoma , Humanos , Lenalidomida , Estudios Prospectivos , RituximabRESUMEN
BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal center B-cell (non-GCB) subtype. This study aimed to determine the efficacy of rituximab plus lenalidomide (R2) in DLBCL-PCNSL. PATIENTS AND METHODS: Patients with refractory/relapsed (R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma (PVRL) were included in this prospective phase II study. The induction treatment consisted of eight 28-day cycles of R2 (rituximab 375/m2 i.v. D1; lenalidomide 20 mg/day, D1-21 for cycle 1; and 25 mg/day, D1-21 for the subsequent cycles); in responding patients, the induction treatment was followed by a maintenance phase comprising 12 28-day cycles of lenalidomide alone (10 mg/day, D1-21). The primary end point was the overall response rate (ORR) at the end of induction (P0 = 10%; P1 = 30%). RESULTS: Fifty patients were included. Forty-five patients (PCNSL, N = 34; PVRL, N = 11) were assessable for response. The ORR at the end of induction was 35.6% (95% CI 21.9-51.2) in assessable patients and 32.0% (95% CI 21.9-51.2) in the intent-to-treat analysis, including 13 complete responses (CR)/unconfirmed CR (uCR; 29%) and 3 partial responses (PR; 7%). The best responses were 18 CR/uCR (40%) and 12 PR (27%) during the induction phase. The maintenance phase was started and completed by 18 and 5 patients, respectively. With a median follow-up of 19.2 months (range 1.5-31), the median progression-free survival (PFS) and overall survival (OS) were 7.8 months (95% CI 3.9-11.3) and 17.7 months (95% CI 12.9 to not reached), respectively. No unexpected toxicity was observed. The peripheral baseline CD4/CD8 ratio impacted PFS [median PFS = 9.5 months (95% CI, 8.1-14.8] for CD4/CD8 ≥ 1.6; median PFS = 2.8 months, [95% CI, 1.1-7.8) for CD4/CD8 < 1.6, P = 0.03). CONCLUSIONS: The R2 regimen showed significant activity in R/R PCNSL and PVRL patients. These results support assessments of the efficacy of R2 combined with methotrexate-based chemotherapy as a first-line treatment of PCNSL. CLINICAL TRIALS NUMBER: NCT01956695.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma Intraocular/tratamiento farmacológico , Lenalidomida/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Rituximab/administración & dosificación , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Sistema Nervioso Central/mortalidad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Análisis de Intención de Tratar , Linfoma Intraocular/mortalidad , Lenalidomida/efectos adversos , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Supervivencia sin Progresión , Prueba de Estudio Conceptual , Estudios Prospectivos , Inducción de Remisión/métodos , Rituximab/efectos adversosRESUMEN
Recurrent primary central nervous system lymphomas (PCNSL) have a very poor prognosis. For young and fit patients, intensive chemotherapy followed by autologous stem cell transplantation could be proposed at relapse. In the other cases (unfit or elderly patients), therapeutic options are limited with no consensual regimen. The poly-chemotherapy by (R)-GEMOX is associated with anti-tumor activity in systemic lymphomas and a favorable toxicity profile. Our objective was to evaluate the activity and tolerance of (R)-GEMOX in PCNSL patients enrolled in the French nation-wide LOC cohort. We retrospectively analyzed all refractory or recurrent patients included in the LOC network who benefited from (R)-GEMOX (rituximab 375 mg/m2, gemcitabine 1000 mg/m2, and oxaliplatine 100 mg/m2). Administration, tolerance, and efficacy data were analyzed. Thirteen patients, treated in five different institutions, benefited from the (R)-GEMOX regimen from February 2013 to August 2017. At the initiation of (R)-GEMOX, median age was 71.4 years old (range, 49.5-82.5) and median Karnofsky performance status (KPS) was 60 (range, 40-80). Seven patients were in second line of treatment whereas the six others were in third line or over. All patients had received methotrexate-based polychemotherapy as first-line treatment except one. Overall response rate was 38% with two complete responses and three partial responses. Median progression-free survival was 3.2 months (95%CI: 0.2-6.2), and median overall survival was 8.2 months (95%CI: 0.6-15.8). Toxicity was mainly hematological including grade ¾ neutropenia (38%), lymphopenia (23%), and thrombopenia (23%). Older age (p = 0.046) and low KPS (p = 0.054) tended to be associated with a worse prognosis. (R)-GEMOX is associated with substantial response rate and favorable toxicity profile in unfit patients with recurrent PCNSL. (R)-GEMOX could be considered to be an additional option in patients with recurrent/refractory PCNSL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Linfoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Rituximab/administración & dosificación , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Sistema Nervioso Central/mortalidad , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
In this retrospective multicentre study, we investigated the outcomes of elderly primary central nervous system lymphoma (PCNSL) patients (⩾65 years) who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) at 11 centres between 2003 and 2016. End points included remission, progression-free survival (PFS), overall survival (OS) and treatment-related mortality. We identified 52 patients (median age 68.5 years, median Karnofsky Performance Status before HDT-ASCT 80%) who all underwent thiotepa-based HDT-ASCT. Fifteen patients (28.8%) received HDT-ASCT as first-line treatment and 37 (71.2%) received it as second or subsequent line. Remission status before HDT-ASCT was: CR 34.6%, PR 51.9%, stable disease 3.8% and progressive disease 9.6%. Following completion of HDT-ASCT, 36 patients (69.2%) achieved CR (21.2% first-line setting and 48.1% second or subsequent line setting) and 9 (17.3%) PR (5.8% first-line setting and 11.5% second or subsequent line setting). With a median follow-up of 22 months after HDT-ASCT, median PFS and OS were reached after 51.1 and 122.3 months, respectively. The 2-year PFS and OS rates were 62.0% and 70.8%, respectively. We observed two HDT-ASCT-associated deaths (3.8%). In selected elderly PCNSL patients, HDT-ASCT, using thiotepa-based conditioning regimes, is feasible and effective. Further prospective and comparative studies are warranted to further evaluate the role of HDT-ASCT in elderly PCNSL patients.
Asunto(s)
Neoplasias del Sistema Nervioso Central/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Tiotepa/administración & dosificación , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/administración & dosificación , Neoplasias del Sistema Nervioso Central/mortalidad , Terapia Combinada , Supervivencia sin Enfermedad , Europa (Continente) , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Inducción de Remisión , Estudios Retrospectivos , Análisis de Supervivencia , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/mortalidad , Trasplante AutólogoAsunto(s)
Anilidas/uso terapéutico , Proteínas Hedgehog/antagonistas & inhibidores , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Piridinas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Anilidas/farmacología , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Linfoma no Hodgkin/diagnóstico , Masculino , Persona de Mediana Edad , Piridinas/farmacologíaRESUMEN
After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS. Patients received LEN alone, 10 mg per day, 21 days per 4 weeks (L arm) or LEN (same schedule) + erythropoietin (EPO) beta, 60,000 U per week (LE arm). In an intent-to-treat (ITT) analysis, erythroid response (HI-E, IWG 2006 criteria) after four treatment cycles (primary end point) was 23.1% (95% CI 13.5-35.2) in the L arm and 39.4% (95% CI 27.6-52.2) in the LE arm (P=0.044), while RBC-TI was reached in 13.8 and 24.2% of the patients in the L and LE arms, respectively (P=0.13). Median response duration was 18.1 and 15.1 months in the L and LE arms, respectively (P=0.47). Side effects were moderate and similar in the two arms. Low baseline serum EPO level and a G polymorphism of CRBN gene predicted HI-E. Combining LEN and EPO significantly improves erythroid response over LEN alone in lower-risk non-del5q MDS patients with anemia resistant to ESA.
Asunto(s)
Transfusión Sanguínea , Deleción Cromosómica , Cromosomas Humanos Par 5/genética , Eritropoyetina/uso terapéutico , Síndromes Mielodisplásicos/tratamiento farmacológico , Talidomida/análogos & derivados , Anciano , Anemia/prevención & control , Inhibidores de la Angiogénesis/uso terapéutico , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Talidomida/uso terapéuticoAsunto(s)
Neoplasias del Sistema Nervioso Central/epidemiología , Virus de la Hepatitis B/patogenicidad , Hepatitis B/epidemiología , Linfoma/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Distribución por Sexo , Adulto JovenRESUMEN
INTRODUCTION: Limited data is available on the feasibility of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) in elderly patients over 70 years of age with non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: In the setting of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) group, we retrospectively analyzed 81 consecutive patients with NHL over 70 years of age who received AHSCT. RESULTS: The median age at AHSCT was 72.3 years [70-80]. Patients' were diagnosed with diffuse large B-cell lymphoma (n=40), follicular lymphoma (n=16), mantle cell lymphoma (n=15), T-cell lymphoma (n=5), and other (n=5). Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) was 0 in 73% of patients. Main conditionings were BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=61) and melphalan alone (n=14). Median delays to reach 0.5×109/L neutrophils and 20 × 10(9)/L platelets were of 12 [9-76] days and 12 [0-143] days, respectively. One hundred day and one year cumulative incidence of NRM was 5.4% and 8.5%, respectively. The main cause of death remains relapse. CONCLUSION: In conclusion, this study revealed that AHSCT seemed to be acceptable in patients over 70 years of age with NHL. Patient age is not a limiting factor if clinical condition is adequate.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma no Hodgkin/terapia , Sociedades Médicas , Anciano , Anciano de 80 o más Años , Trasplante de Médula Ósea , Tratamiento Basado en Trasplante de Células y Tejidos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Incidencia , Linfoma no Hodgkin/epidemiología , Masculino , Prevalencia , Estudios Retrospectivos , Tasa de Supervivencia/tendenciasRESUMEN
BACKGROUND: The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which evaluates the role of rituximab combined with ACVBP (R-ACVBP) in these patients. PATIENTS AND METHODS: Untreated patients younger than 66 years with stage I or II DLBCL and no adverse prognostic factors of the age-adjusted International Prognostic Index were randomly assigned to receive three cycles of ACVBP plus sequential consolidation with or without the addition of four infusions of rituximab. RESULTS: A total of 223 patients were randomly allocated to the study, 110 in the R-ACVBP group and 113 in the ACVBP group. After a median follow-up of 43 months, our 3-year estimate of event-free survival was 93% in the R-ACVBP group and 82% in the ACVBP group (P = 0.0487). Three-year estimate of progression-free survival was increased in the R-ACVBP group (95% versus 83%, P = 0.0205). Overall survival did not differ between the two groups with a 3-year estimates of 98% and 97%, respectively (P = 0.686). CONCLUSION: In young patients with low-risk localized DLBCL, rituximab combined with three cycles of ACVBP plus consolidation is significantly superior to ACVBP plus consolidation alone.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/administración & dosificación , Prednisona/efectos adversos , Rituximab , Resultado del Tratamiento , Vindesina/administración & dosificación , Vindesina/efectos adversosRESUMEN
Primary CNS lymphoma is the malignant brain tumor whose prognosis has improved the most the two past decades. The majority of the patients achieve a complete remission with treatment and a substantial minority may hope to be cured. The treatment includes high-dose methotrexate polychemotherapy combined or not with whole brain radiotherapy (WBRT). Elderly patients who are exposed to a high risk of treatment induced neurotoxicity need a specific management avoiding or defering WBRT. In young patients, the main questions concerning the treatment are the role of consolidation WBRT and intensive chemotherapy with peripheral blood stem cell rescue in the initial treatment of PCNSL. As recently shown, national and international collaborative efforts make now possible randomized trials for this rare disease, which would contribute to better define the treatment strategy. New insights in PCNSL tumorigenesis would help to better understand the heterogeneity of outcome and to develop efficient targeted therapies.
Asunto(s)
Neoplasias del Sistema Nervioso Central/terapia , Linfoma/terapia , Adulto , Anciano , Envejecimiento/fisiología , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/fisiopatología , Terapia Combinada , Humanos , Linfoma/diagnóstico , Linfoma/fisiopatología , Metotrexato/uso terapéutico , PronósticoRESUMEN
Treatment-induced CNS toxicity remains a major cause of morbidity in patients with cancer. Real advances in the design of safer radiation procedures have been counterbalanced by a wider use of combined radiotherapy (RT)-chemotherapy regimens, the development of radiosurgery, and the increasing number of long-term survivors. While classic radionecrosis or chemonecrosis have become less common, more subtle changes such as progressive cognitive dysfunction are increasingly reported after RT (radiation-induced leukoencephalopathy) or chemotherapy (administered alone or in combination). The most important and controversial complications of RT, chemotherapy and combined treatments in the CNS are reviewed here, including new diagnostic tools, practical management and prevention that will influence the future management of cancer patients.
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Antineoplásicos/efectos adversos , Neoplasias/complicaciones , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/terapia , Radioterapia/efectos adversos , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/radioterapia , Trastornos del Conocimiento/etiología , Terapia Combinada/efectos adversos , Humanos , Leucoencefalopatías/inducido químicamente , Leucoencefalopatías/etiología , Imagen por Resonancia Magnética , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Síndromes de Neurotoxicidad/patología , Síndromes de Neurotoxicidad/prevención & controlRESUMEN
Damage to the central nervous system induced by treatment of brain tumors is common and impairs the patient quality-of-life. Neurotoxicity is induced by synergistic effects of different cytotoxic treatments such as radiotherapy and chemotherapies administered concurrently or sequentially. Recent progress in the management of brain tumors has led to new neurotoxicities. The growing concern about the neuropsychological performance of patients has disclosed another type of brain damage which has been largely neglected to date. Neurological toxicity can be acute, requiring dose adaptation or a change of drugs. But it also often occurs late and can be irreversible. To date, treatments have been ineffective. The early diagnosis of neurotoxicity is thus a major challenge. Numerous clinical studies suggest an individual sensitivity which is not only related to age or vascular status, but also to genetic predisposition that remains to be detailed. Understanding the mechanisms of personal susceptibilities would be helpful in designing more tailored treatments. In this review we address the question of adverse effects of brain radiation as well as those of chemotherapy protocols which are particularly toxic for the central nervous system that is, methotrexate, platin and aracytin.