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PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/mortalidad , Anciano , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano de 80 o más Años , Temozolomida/uso terapéutico , Adulto , Antineoplásicos Alquilantes/uso terapéutico , Factores de Edad , Terapia Combinada , Resultado del Tratamiento , Manejo de la EnfermedadRESUMEN
PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Estudios Prospectivos , Dacarbazina/efectos adversos , Supervivencia sin Enfermedad , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Antineoplásicos Alquilantes/efectos adversosRESUMEN
Background There is growing evidence that the subventricular zone (SVZ) may be involved in both the initiation and progression of glioblastoma (GB). We aimed to assess tumor proximity to the SVZ as a potential prognostic factor in GB. Method Retrospective study of 133 patients diagnosed with primary GB who underwent surgery followed by temozolomide-based chemoradiation between 2010 and 2016. All lesions were classified according to their anatomic relation with the SVZ. We determined the effect of tumor contact with the SVZ on progression-free survival (PFS), overall survival (OS), type, and patterns of recurrence. Results At a median follow-up of 18.6 months (95% CI 15.921.2), PFS and OS were 7.5 (95% CI 6.78.3) and 13.9 (95% CI 10.916.9) months, respectively. On the univariate analyses, initial contact with the SVZ was a factor for poor prognosis for both PFS (6.1 vs. 8.7 months; p = 0.006) and OS (10.6 vs. 17.9 months; p = 0.037). On the multivariate analysis, tumor contact with the SVZ remained statistically significant for PFS, but not OS. Patients with SVZ-contacting tumors presented a higher rate of aggressive clinical progression (30.9% vs. 11.3%; p = 0.007) and contralateral relapse patterns (23.4% vs. 9.1%; p = 0.048). Conclusions Our results suggest that glioblastoma contact with the SVZ appears to be an independent prognostic factor for poor PFS. The presence of an SVZ-contacting tumor was associated with more aggressive recurrences and a higher rate of contralateral relapses. These findings suggest that this variable may be a new prognostic factor in glioblastoma (AU)
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Humanos , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Glioblastoma/mortalidad , Glioblastoma/patología , Ventrículos Laterales/patología , Invasividad Neoplásica , Antineoplásicos Alquilantes/uso terapéutico , Estudios Retrospectivos , Supervivencia sin Progresión , Pronóstico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Recurrencia Local de NeoplasiaRESUMEN
BACKGROUND: There is growing evidence that the subventricular zone (SVZ) may be involved in both the initiation and progression of glioblastoma (GB). We aimed to assess tumor proximity to the SVZ as a potential prognostic factor in GB. METHOD: Retrospective study of 133 patients diagnosed with primary GB who underwent surgery followed by temozolomide-based chemoradiation between 2010 and 2016. All lesions were classified according to their anatomic relation with the SVZ. We determined the effect of tumor contact with the SVZ on progression-free survival (PFS), overall survival (OS), type, and patterns of recurrence. RESULTS: At a median follow-up of 18.6 months (95% CI 15.9-21.2), PFS and OS were 7.5 (95% CI 6.7-8.3) and 13.9 (95% CI 10.9-16.9) months, respectively. On the univariate analyses, initial contact with the SVZ was a factor for poor prognosis for both PFS (6.1 vs. 8.7 months; p = 0.006) and OS (10.6 vs. 17.9 months; p = 0.037). On the multivariate analysis, tumor contact with the SVZ remained statistically significant for PFS, but not OS. Patients with SVZ-contacting tumors presented a higher rate of aggressive clinical progression (30.9% vs. 11.3%; p = 0.007) and contralateral relapse patterns (23.4% vs. 9.1%; p = 0.048). CONCLUSIONS: Our results suggest that glioblastoma contact with the SVZ appears to be an independent prognostic factor for poor PFS. The presence of an SVZ-contacting tumor was associated with more aggressive recurrences and a higher rate of contralateral relapses. These findings suggest that this variable may be a new prognostic factor in glioblastoma.
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Neoplasias Encefálicas/patología , Glioblastoma/patología , Ventrículos Laterales/patología , Recurrencia Local de Neoplasia , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/etiología , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/terapia , Quimioradioterapia , Intervalos de Confianza , Femenino , Estudios de Seguimiento , Glioblastoma/etiología , Glioblastoma/mortalidad , Glioblastoma/terapia , Humanos , Imagen por Resonancia Magnética , Masculino , Recurrencia Local de Neoplasia/diagnóstico por imagen , Pronóstico , Supervivencia sin Progresión , Dosificación Radioterapéutica , Estudios Retrospectivos , Temozolomida/uso terapéuticoRESUMEN
PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.
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Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Carmustina/uso terapéutico , Glioblastoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Antígeno AC133/genética , Antígeno AC133/metabolismo , Adulto , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Bevacizumab/efectos adversos , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Carmustina/efectos adversos , Proteína 1 Similar a Quitinasa-3/genética , Colombia , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Esquema de Medicación , Femenino , Genes erbB-1 , Genes p53 , Glioblastoma/irrigación sanguínea , Glioblastoma/genética , Glioblastoma/mortalidad , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Metilación , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia/irrigación sanguínea , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/mortalidad , Supervivencia sin Progresión , ARN Mensajero/metabolismo , Receptores del Factor de Crecimiento Derivado de Plaquetas/genética , Análisis de Supervivencia , Proteínas Supresoras de Tumor/metabolismo , Adulto JovenRESUMEN
Purpose: We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients. Patients and methods: We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy. Results: OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P = 0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor. Conclusion: In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy
No disponible
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Humanos , Glioblastoma/terapia , Radioterapia/métodos , Terapia Neoadyuvante/métodos , Tiempo de Tratamiento/estadística & datos numéricos , Resultado del Tratamiento , Tasa de Supervivencia , Estudios RetrospectivosRESUMEN
Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed
No disponible
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Humanos , Neoplasias Primarias Desconocidas/diagnóstico , Metástasis de la Neoplasia/patología , Neoplasias/clasificación , Neoplasias Primarias Desconocidas/terapia , Pautas de la Práctica en Medicina , Consenso , Inmunohistoquímica , Biopsia , Biomarcadores de Tumor/análisisRESUMEN
The SEOM/GEINO clinical guidelines provide recommendations for radiological, and molecular diagnosis, treatment and follow-up of adult patients with anaplastic gliomas (AG). We followed the 2016 WHO classification which specifies the major diagnostic/prognostic and predictive value of IDH1/IDH2 missense mutations and 1p/19q codeletions in AG. The diagnosis of anaplastic oligoastrocytoma is discouraged. Surgery, radiotherapy and chemotherapy with PCV or TMZ are the first-line standard of care for AG with slight modifications according to molecular variables. A multidisciplinary team is highly recommended in the management of these tumors.
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PURPOSE: We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients. PATIENTS AND METHODS: We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy. RESULTS: OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P = 0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor. CONCLUSION: In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy.
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Neoplasias Encefálicas/terapia , Quimioterapia Adyuvante/métodos , Glioblastoma/terapia , Radioterapia/métodos , Tiempo de Tratamiento , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/mortalidad , Quimioradioterapia/métodos , Femenino , Glioblastoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.
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Oncología Médica/normas , Neoplasias Primarias Desconocidas/diagnóstico , Neoplasias Primarias Desconocidas/terapia , Patología Clínica/normas , Anciano , Consenso , Humanos , Oncología Médica/organización & administración , Persona de Mediana Edad , Patología Clínica/organización & administración , Sociedades Médicas/organización & administración , Sociedades Médicas/normas , EspañaRESUMEN
INTRODUCTION: The European Organisation for Research and Treatment of Cancer (EORTC) 22033-26033 clinical trial (NCT00182819) investigated whether initial temozolomide (TMZ) chemotherapy confers survival advantage compared with radiotherapy (RT) in low-grade glioma (LGG) patients. In this study, we performed gene expression profiling on tissues from this trial to identify markers associated with progression-free survival (PFS) and treatment response. METHODS: Gene expression profiling, performed on 195 samples, was used to assign tumours to one of six intrinsic glioma subtypes (IGSs; molecularly similar tumours as previously defined using unsupervised expression analysis) and to determine the composition of immune infiltrate. DNA copy number changes were determined using OncoScan arrays. RESULTS: We confirm that IGSs are prognostic in the EORTC22033-26033 clinical trial. Specific genetic changes segregate in distinct IGSs: most samples assigned to IGS-9 have IDH-mutations and 1p19q codeletion, samples assigned to IGS-17 have IDH-mutations without 1p19q codeletion and samples assigned to other intrinsic subtypes often are IDH-wildtype. A trend towards benefit from RT was observed for samples assigned to IGS-9 (hazard ratio [HR] for TMZ is 1.90, P = 0.065) but not for samples assigned to IGS-17 (HR 0.87, P = 0.62). We did not identify genes significantly associated with PFS within intrinsic subtypes, although follow-up time is limited. We also show that LGGs and glioblastomas differ in their immune infiltrate, which suggests that LGGs are less amenable to checkpoint inhibitor-type immune therapies. Gene expression analysis also allows identification of relatively rare subtypes. Indeed, one patient with a pilocytic astrocytoma was identified. CONCLUSION: IGSs are prognostic for PFS in EORTC22033-26033 clinical trial samples.
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Biomarcadores de Tumor/genética , Neoplasias Encefálicas/patología , Glioma/patología , Transcriptoma , Adulto , Anciano , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Femenino , Glioma/genética , Glioma/terapia , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Temozolomida/uso terapéutico , Resultado del TratamientoRESUMEN
The SEOM/GEINO clinical guidelines provide recommendations for radiological, and molecular diagnosis, treatment and follow-up of adult patients with anaplastic gliomas (AG). We followed the 2016 WHO classification which specifies the major diagnostic/prognostic and predictive value of IDH1/IDH2 missense mutations and 1p/19q codeletions in AG. The diagnosis of anaplastic oligoastrocytoma is discouraged. Surgery, radiotherapy and chemotherapy with PCV or TMZ are the first-line standard of care for AG with slight modifications according to molecular variables. A multidisciplinary team is highly recommended in the management of these tumors (AU)
No disponible
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Humanos , Glioma/diagnóstico , Glioma/terapia , Anaplasia/patología , Guías de Práctica Clínica como Asunto , Astrocitoma/patología , Oligodendroglioma/patología , Neoplasias del Sistema Nervioso Central/patologíaRESUMEN
The SEOM/GEINO clinical guidelines provide recommendations for radiological, and molecular diagnosis, treatment and follow-up of adult patients with anaplastic gliomas (AG). We followed the 2016 WHO classification which specifies the major diagnostic/prognostic and predictive value of IDH1/IDH2 missense mutations and 1p/19q codeletions in AG. The diagnosis of anaplastic oligoastrocytoma is discouraged. Surgery, radiotherapy and chemotherapy with PCV or TMZ are the first-line standard of care for AG with slight modifications according to molecular variables. A multidisciplinary team is highly recommended in the management of these tumors.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Glioma/diagnóstico , Glioma/terapia , HumanosRESUMEN
Purpose. We assessed agreement among neurosurgeons on surgical approaches to individual glioblastoma patients and between their approach and those recommended by the topographical staging system described by Shinoda. Methods. Five neurosurgeons were provided with pre-surgical MRIs of 76 patients. They selected the surgical approach [biopsy, partial resection, or gross total resection (GTR)] that they would recommend for each patient. They were blinded to each others response and they were told that patients were younger than 50 years old and without symptoms. Three neuroradiologists classified each case according to the Shinoda staging system. Results. Biopsy was recommended in 35.5-82.9%, partial resection in 6.6-32.9%, and GTR in 3.9-31.6% of cases. Agreement among their responses was fair (global kappa = 0.28). Nineteen patients were classified as stage I, 14 as stage II, and 43 as stage III. Agreement between the neurosurgeons and the recommendations of the staging system was poor for stage I (kappa = 0.14) and stage II (kappa = 0.02) and fair for stage III patients (kappa = 0.29). An individual analysis revealed that in contrast to the Shinoda system, neurosurgeons took into account T2/FLAIR sequences and gave greater weight to the involvement of eloquent areas. Conclusions. The surgical approach to glioblastoma is highly variable. A staging system could be used to examine the impact of extent of resection, monitor post-operative complications, and stratify patients in clinical trials. Our findings suggest that the Shinoda staging system could be improved by including T2/FLAIR sequences and a more adequate weighting of eloquent areas (AU)
No disponible
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Humanos , Glioblastoma/cirugía , Neurocirugia/normas , Biopsia , Estadificación de Neoplasias/métodos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodosRESUMEN
PURPOSE: We assessed agreement among neurosurgeons on surgical approaches to individual glioblastoma patients and between their approach and those recommended by the topographical staging system described by Shinoda. METHODS: Five neurosurgeons were provided with pre-surgical MRIs of 76 patients. They selected the surgical approach [biopsy, partial resection, or gross total resection (GTR)] that they would recommend for each patient. They were blinded to each other's response and they were told that patients were younger than 50 years old and without symptoms. Three neuroradiologists classified each case according to the Shinoda staging system. RESULTS: Biopsy was recommended in 35.5-82.9%, partial resection in 6.6-32.9%, and GTR in 3.9-31.6% of cases. Agreement among their responses was fair (global kappa = 0.28). Nineteen patients were classified as stage I, 14 as stage II, and 43 as stage III. Agreement between the neurosurgeons and the recommendations of the staging system was poor for stage I (kappa = 0.14) and stage II (kappa = 0.02) and fair for stage III patients (kappa = 0.29). An individual analysis revealed that in contrast to the Shinoda system, neurosurgeons took into account T2/FLAIR sequences and gave greater weight to the involvement of eloquent areas. CONCLUSIONS: The surgical approach to glioblastoma is highly variable. A staging system could be used to examine the impact of extent of resection, monitor post-operative complications, and stratify patients in clinical trials. Our findings suggest that the Shinoda staging system could be improved by including T2/FLAIR sequences and a more adequate weighting of eloquent areas.
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Neoplasias Encefálicas/cirugía , Glioblastoma/cirugía , Estadificación de Neoplasias/métodos , Procedimientos Neuroquirúrgicos/normas , Adulto , Neoplasias Encefálicas/patología , Ensayos Clínicos Fase II como Asunto , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Neurocirujanos/normas , Procedimientos Neuroquirúrgicos/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y CuestionariosRESUMEN
Purpose. The aim of this prospective and multicentric phase II study was to evaluate the efficacy and safety of temozolomide (TMZ) and bevacizumab (BV) in patients (pts) with recurrent glioblastoma (GB), previously treated with chemoradiotherapy and at least three cycles of adjuvant TMZ. Patients and methods. Patients with GB at first relapse received BV 10 mg/kg day every 2 weeks and TMZ 150 mg/m2 days 17 and 1521, every 28 days. Patients underwent brain magnetic resonance imaging every 8 weeks. Results. Thirty-two evaluable pts were recruited in 8 sites. Fourteen pts (44 %) had gross total resection. O6-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 12 pts, unmethylated in 6 pts, and missing in 14 pts. The estimated 6-month progression free survival (PFS) rate was 21.9 % (95 % CI 9.340.0 %). The median PFS and overall survival (OS) were 4.2 months (95 % CI 3.65.4 months) and 7.3 months (95 % CI 5.88.8 months), respectively. No significant association with MGMT status was found in terms of OS or PFS. Six of 32 pts (19 %; 95 % CI 7.236.4) were long-term survivors, with a median PFS and OS (50 % events) of 9.5 months (95 % CI 7.923.6) and 15.4 (95 % CI 8.9NA), respectively: no differences in baseline characteristics were identified in comparison with total population. No unexpected toxicities or treatment-related deaths were observed. Conclusions. This regimen showed to be feasible and well tolerated in pts with recurrent GB pretreated with TMZ. Further investigation is warranted to identify subpopulations that are more likely to benefit from addition of BV to GB therapy (AU)
No disponible
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Femenino , Humanos , Masculino , Persona de Mediana Edad , Glioblastoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , ADN-Citosina Metilasas , Quimioradioterapia/instrumentación , Quimioradioterapia/métodos , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Metilación , Progresión de la EnfermedadRESUMEN
PURPOSE: The aim of this prospective and multicentric phase II study was to evaluate the efficacy and safety of temozolomide (TMZ) and bevacizumab (BV) in patients (pts) with recurrent glioblastoma (GB), previously treated with chemoradiotherapy and at least three cycles of adjuvant TMZ. PATIENTS AND METHODS: Patients with GB at first relapse received BV 10 mg/kg day every 2 weeks and TMZ 150 mg/m(2) days 1-7 and 15-21, every 28 days. Patients underwent brain magnetic resonance imaging every 8 weeks. RESULTS: Thirty-two evaluable pts were recruited in 8 sites. Fourteen pts (44%) had gross total resection. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 12 pts, unmethylated in 6 pts, and missing in 14 pts. The estimated 6-month progression free survival (PFS) rate was 21.9% (95% CI 9.3-40.0%). The median PFS and overall survival (OS) were 4.2 months (95% CI 3.6-5.4 months) and 7.3 months (95% CI 5.8-8.8 months), respectively. No significant association with MGMT status was found in terms of OS or PFS. Six of 32 pts (19%; 95% CI 7.2-36.4) were long-term survivors, with a median PFS and OS (50% events) of 9.5 months (95% CI 7.9-23.6) and 15.4 (95% CI 8.9-NA), respectively: no differences in baseline characteristics were identified in comparison with total population. No unexpected toxicities or treatment-related deaths were observed. CONCLUSIONS: This regimen showed to be feasible and well tolerated in pts with recurrent GB pretreated with TMZ. Further investigation is warranted to identify subpopulations that are more likely to benefit from addition of BV to GB therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Enfermedades Hematológicas , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Bevacizumab/administración & dosificación , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Glioblastoma/mortalidad , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , TemozolomidaRESUMEN
PURPOSE: The standard adjuvant treatment for glioblastoma is temozolomide concomitant with radiotherapy, followed by a further six cycles of temozolomide. However, due to the lack of empirical evidence and international consensus regarding the optimal duration of temozolomide treatment, it is often extended to 12 or more cycles, even in the absence of residual disease. No clinical trial has shown clear evidence of clinical benefit of this extended treatment. We have explored the economic impact of this practice in Spain. MATERIALS AND METHODS: Spanish neuro-oncologists completed a questionnaire on the clinical management of glioblastomas in their centers. Based on their responses and on available clinical and demographic data, we estimated the number of patients who receive more than six cycles of temozolomide and calculated the cost of this extended treatment. RESULTS: Temozolomide treatment is continued for more than six cycles by 80.5 % of neuro-oncologists: 44.4 % only if there is residual disease; 27.8 % for 12 cycles even in the absence of residual disease; and 8.3 % until progression. Thus, 292 patients annually will continue treatment beyond six cycles in spite of a lack of clear evidence of clinical benefit. Temozolomide is covered by the National Health Insurance System, and the additional economic burden to society of this extended treatment is nearly 1.5 million euros a year. CONCLUSIONS: The optimal duration of adjuvant temozolomide treatment merits investigation in a clinical trial due to the economic consequences of prolonged treatment without evidence of greater patient benefit (AU)
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Asunto(s)
Humanos , Antineoplásicos Alquilantes/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Dacarbazina/análogos & derivados , Glioblastoma/tratamiento farmacológico , Antineoplásicos Alquilantes/economía , Neoplasias Encefálicas/economía , Quimioterapia Adyuvante/economía , Quimioterapia Adyuvante/métodos , Dacarbazina/administración & dosificación , Dacarbazina/economía , Glioblastoma/economía , Pautas de la Práctica en Medicina , Encuestas y Cuestionarios , EspañaRESUMEN
PURPOSE: The standard adjuvant treatment for glioblastoma is temozolomide concomitant with radiotherapy, followed by a further six cycles of temozolomide. However, due to the lack of empirical evidence and international consensus regarding the optimal duration of temozolomide treatment, it is often extended to 12 or more cycles, even in the absence of residual disease. No clinical trial has shown clear evidence of clinical benefit of this extended treatment. We have explored the economic impact of this practice in Spain. MATERIALS AND METHODS: Spanish neuro-oncologists completed a questionnaire on the clinical management of glioblastomas in their centers. Based on their responses and on available clinical and demographic data, we estimated the number of patients who receive more than six cycles of temozolomide and calculated the cost of this extended treatment. RESULTS: Temozolomide treatment is continued for more than six cycles by 80.5 % of neuro-oncologists: 44.4 % only if there is residual disease; 27.8 % for 12 cycles even in the absence of residual disease; and 8.3 % until progression. Thus, 292 patients annually will continue treatment beyond six cycles in spite of a lack of clear evidence of clinical benefit. Temozolomide is covered by the National Health Insurance System, and the additional economic burden to society of this extended treatment is nearly 1.5 million euros a year. CONCLUSIONS: The optimal duration of adjuvant temozolomide treatment merits investigation in a clinical trial due to the economic consequences of prolonged treatment without evidence of greater patient benefit.