RESUMEN
A male patient started PCV chemotherapy (a combination of procarbazine, lomustine and vincristine) for a recurrent oligodendroglioma grade 2. Unfortunately, our patient took an unintended overdose of lomustine during the first PCV course: instead of 160 mg absolute dose of lomustine on day 1 only, he consumed 160 mg absolute dose of lomustine for seven consecutive days to a total dose of 1120 mg. Pancytopenia became evident after 24 days, and several months of severe myelosuppression, infections, reduced general condition, and nutrition difficulties followed. Fortunately, our patient with time recovered his bone marrow function. However, the patient's quality of life was reduced for a long time and several lessons were learnt: oral and written information on chemotherapy is essential, but not always sufficient to ensure the correct dosing of patient-administered chemotherapy. Oral chemotherapeutics should be delivered as a single-dose supply or be administered by experienced health personnel.
Asunto(s)
Neoplasias Encefálicas , Sobredosis de Droga , Lomustina , Oligodendroglioma , Humanos , Lomustina/administración & dosificación , Masculino , Neoplasias Encefálicas/tratamiento farmacológico , Oligodendroglioma/tratamiento farmacológico , Pancitopenia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Glioma/tratamiento farmacológico , Calidad de Vida , Persona de Mediana EdadRESUMEN
A subset of patients with IDH-mutant glioma respond to inhibitors of mutant IDH (IDHi), yet the molecular underpinnings of such responses are not understood. Here, we profiled by single-cell or single-nucleus RNA-sequencing three IDH-mutant oligodendrogliomas from patients who derived clinical benefit from IDHi. Importantly, the tissues were sampled on-drug, four weeks from treatment initiation. We further integrate our findings with analysis of single-cell and bulk transcriptomes from independent cohorts and experimental models. We find that IDHi treatment induces a robust differentiation toward the astrocytic lineage, accompanied by a depletion of stem-like cells and a reduction of cell proliferation. Furthermore, mutations in NOTCH1 are associated with decreased astrocytic differentiation and may limit the response to IDHi. Our study highlights the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas and suggests a genetic modifier that may improve patient stratification.
Asunto(s)
Neoplasias Encefálicas , Diferenciación Celular , Isocitrato Deshidrogenasa , Mutación , Oligodendroglioma , Oligodendroglioma/genética , Oligodendroglioma/patología , Oligodendroglioma/tratamiento farmacológico , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/antagonistas & inhibidores , Humanos , Diferenciación Celular/efectos de los fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/tratamiento farmacológico , Linaje de la Célula/efectos de los fármacos , Receptor Notch1/genética , Receptor Notch1/metabolismo , Proliferación Celular/efectos de los fármacos , Animales , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/patología , Ratones , Análisis de la Célula Individual/métodosRESUMEN
Oligodendrogliomas characterized and defined by 1p/19q co-deletion are slowly growing tumors showing better prognosis than astrocytomas. TP53 mutation is rare in oligodendrogliomas while the vast majority of astrocytomas harbor the mutation, making TP53 mutation mutually exclusive with 1p/19q codeletion in lower grade gliomas virtually. We report a case of 51-year-old woman with a left fronto-temporal oligodendroglioma that contained a small portion with a TP53 mutation, R248Q, at the initial surgery. On a first, slow-growing recurrence 29 months after radiation and nitrosourea-based chemotherapy, the patient underwent TMZ chemotherapy. The recurrent tumor responded well to TMZ but developed a rapid progression after 6 cycles as a malignant hypermutator tumor with a MSH6 mutation. Most of the recurrent tumor lacked typical oligodendroglioma morphology that was observed in the primary tumor, while it retained the IDH1 mutation and 1p/19q co-deletion. The identical TP53 mutation observed in the small portion of the primary tumor was universal in the recurrence. This case embodied the theoretically understandable clonal expansion of the TP53 mutation with additional mismatch repair gene dysfunction leading to hypermutator phenotype. It thus indicated that TP53 mutation in oligodendroglioma, although not common, may play a critical role in the development of hypermutator after TMZ treatment.
Asunto(s)
Antineoplásicos Alquilantes , Neoplasias Encefálicas , Mutación , Recurrencia Local de Neoplasia , Oligodendroglioma , Temozolomida , Proteína p53 Supresora de Tumor , Femenino , Humanos , Persona de Mediana Edad , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/tratamiento farmacológico , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 19/genética , Dacarbazina/uso terapéutico , Dacarbazina/análogos & derivados , Isocitrato Deshidrogenasa/genética , Recurrencia Local de Neoplasia/genética , Oligodendroglioma/genética , Oligodendroglioma/patología , Oligodendroglioma/tratamiento farmacológico , Fenotipo , Temozolomida/uso terapéutico , Proteína p53 Supresora de Tumor/genéticaRESUMEN
INTRODUCTION: Procarbazine is an oral chemotherapeutic agent used in the treatment of brain malignancies and is associated with hypersensitivity reactions. In case of grade 4 reactions, rechallenge should be avoided, and the agent should be replaced, unless the treatment is curative, in which case the application of a desensitization protocol should be considered. We present a successful case of desensitization in procarbazine anaphylaxis. CASE REPORT: A 53-year-old male patient was diagnosed with recurrent anaplastic oligodendroglioblastoma. The patient received three cycles of procarbazine, lomustine, and vincristine chemotherapy for malignancy recurrence. In the fourth cycle, on the 12th day of procarbazine treatment, the patient developed anaphylaxis. Procarbazine was given together with premedication as part of the 12-step desensitization process, and the fourth cycle was successfully completed. MANAGEMENT AND OUTCOME: Procarbazine hypersensitivity reactions are observed less frequently than reactions to other chemotherapeutics. We presented a case of procarbazine-associated severe anaphylaxis that was able to continue procarbazine chemotherapy with successful desensitization. This case is important in terms of confirming the procarbazine desensitization protocol. DISCUSSION: In literature there is only one protocol developed was successfully applied in one patient with procarbazine anaphylaxis. In the current case, we took this protocol into consideration in the management of our patient. Following the use of this protocol, the patient was able to continue procarbazine chemotherapy successfully. Procarbazine anaphylaxis is rare, and more cases are needed to be reported to confirm the desensitization protocol and when to continue procarbazine treatment.
Asunto(s)
Anafilaxia , Desensibilización Inmunológica , Oligodendroglioma , Procarbazina , Humanos , Masculino , Persona de Mediana Edad , Procarbazina/administración & dosificación , Procarbazina/uso terapéutico , Anafilaxia/inducido químicamente , Oligodendroglioma/tratamiento farmacológico , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/terapia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Encefálicas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
PURPOSE: Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity remains unknown. We analyzed the relationship between the RT dose to the fornix and symptomatic radiation necrosis (SRN). MATERIALS AND METHODS: A total of 67 patients treated between 2009 and 2019 were analyzed. SRN was defined according to the following three criteria: 1) radiographic findings, 2) symptoms attributable to the lesion, and 3) treatment resulting in symptom improvement. Various contours, including the fornix, were delineated. Univariate and multivariate analyses of the relationship between RT dose and SRN, as well as receiver operating characteristic curve analysis for cut-off values, were performed. RESULTS: The most common location was the frontal lobe (n=40, 60%). Gross total resection was performed in 38 patients (57%), and 42 patients (63%) received procarbazine, lomustine, and vincristine chemotherapy. With a median follow-up of 42 months, the median overall and progression-free survival was 74 months. Sixteen patients (24%) developed SRN. In multivariate analysis, age and maximum dose to the fornix were associated with the development of SRN. The cut-off values for the maximum dose to the fornix and age were 59 Gy (equivalent dose delivered in 2 Gy fractions) and 46 years, respectively. The rate of SRN was higher in patients whose maximum dose to the fornix was >59 Gy (13% vs. 43%, p=0.005). CONCLUSION: The maximum dose to the fornix was a significant factor for SRN development. While fornix sparing may help maintain neurocognitive function, additional studies are needed.
Asunto(s)
Neoplasias Encefálicas , Oligodendroglioma , Humanos , Oligodendroglioma/tratamiento farmacológico , Oligodendroglioma/radioterapia , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Vincristina/efectos adversos , Dosis de Radiación , Necrosis/inducido químicamente , Necrosis/tratamiento farmacológicoRESUMEN
The present report describes the case of a male 17-year-old patient who progressively developed a hydrocephalus and polyradiculopathy due to involvement of central nervous system (CNS) by a diffuse leptomeningeal glioneuronal tumor (DLGNT). The tumor had partial remission in response to the treatment with radiotherapy plus procarbazine, lomustine, and vincristine (PCV) chemotherapy, and the patient had improvement in function and pain levels. The current knowledge about DLGNT, including its clinical manifestations, imaging findings, histological characteristics, and treatment are revised and discussed in the present paper.
Asunto(s)
Humanos , Masculino , Adulto Joven , Oligodendroglioma/patología , Oligodendroglioma/tratamiento farmacológico , Oligodendroglioma/radioterapia , Neoplasias Meníngeas , Oligodendroglioma/diagnóstico por imagen , Polirradiculopatía/complicaciones , Derivación Ventriculoperitoneal/métodos , Hidrocefalia/complicacionesRESUMEN
A incidência dos oligodendrogliomas tem aumentado provavelmente em razão do progresso na precisão de diagnóstico. Aproximadamente dois terços dos pacientes com a forma mais agressiva, oligodendroglioma anaplásico, mostram resposta substancial à quimioterapia com a associação procarbazina/lomustina/vincristina (PCV). Entretanto, os resultados da quimuiterapia anaplásica dos oligodendrogliomas resulta em grande número de células com ERK/MAPK ativadas. O monoterpeno álcool perílico demonstra atividades quimiopreventiva e quimioterápica em diversos modelos de tumores e sugere-se que estas possam estar associadas com a capacidade de inibir a farmesilação pós-traducional e a sinalização da Ras, assim como a cascata de sinalização por meio da RAF-MEK-ERK. Estudo do nosso grupo observou que pode estar atuando mediante a inibição da fosforilação da extracellular regulated kinase (ERK), uma proteína envolvida na cascata de transdução de sinal através da membrana e proliferação celular induzida pela proteína Ras. Este artigo discute a redução de oligodendroglioma anaplásico recidivado em paciente tratado durante nove meses com álcool perílico por via intranasal.
Asunto(s)
Humanos , Femenino , Anciano , Monoterpenos/uso terapéutico , Oligodendroglioma/tratamiento farmacológicoRESUMEN
Recidiva intraventricular de oligodendroglioma frontal foi tratada com sucesso através de quimioterapia sistêmica