SEOM clinical guidelines for diagnosis and treatment of glioblastoma (2017)

Glioblastoma (GB) is the most common brain malignancy and accounts for over 50% of all high-grade gliomas. Radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ) chemotherapy is the current standard of care for patients with newly diagnosed GB up to age 70. Recently, a new standard of care has been adopted for elderly patients (≥ 65 years) based on short course of RT and TMZ. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent GB is not well defined, and decision-making is usually based on prior strategies as well as several clinical and radiological factors. The presence of neurologic deficits and seizures can significantly impact quality of life (AU9

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SEOM clinical guidelines for diagnosis and treatment of glioblastoma (2017).

Glioblastoma (GB) is the most common brain malignancy and accounts for over 50% of all high-grade gliomas. Radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ) chemotherapy is the current standard of care for patients with newly diagnosed GB up to age 70. Recently, a new standard of care has been adopted for elderly patients (≥ 65 years) based on short course of RT and TMZ. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent GB is not well defined, and decision-making is usually based on prior strategies as well as several clinical and radiological factors. The presence of neurologic deficits and seizures can significantly impact quality of life.

[Highly aggresive pulmonary epithelioid hemangioendothelioma: a case report]. / Hemangioendotelioma epitelioide de alta agresividad: Caso clínico.

Pulmonary epithelioid hemangioendothelioma is an uncommon neoplastic disease of endothelial origin, with an incidence inferior to one in a million. It usually behaves as a low-grade malignancy; nevertheless, a few cases have been described in which this tumour manifests a highly aggressive behavior, spreading throughout the organism. We report the case of a 77-year-old woman who was diagnosed with metastatic pulmonary epithelioid hemangioendothelioma with severe symptoms, requiring urgent treatment to palliate them. Key words. Epithelioid hemangioendothelioma. Lung.

Prevalence of EGFR mutations in newly diagnosed locally advanced or metastatic non-small cell lung cancer Spanish patients and its association with histological subtypes and clinical features: The Spanish REASON study.

BACKGROUND AND OBJECTIVES: The aim of the REASON study is to determine the frequency of EGFR mutation in advanced non-small cell lung cancer (aNSCLC) patients in Spain (all histologies), and to better understand the clinical factors (gender, smoking habits and histological subtypes) that may be associated with EGFR mutations, in an unselected sample of aNSCLC patients. METHODS: All newly diagnosed aNSCLC patients from 40 selected centers in Spain were prospectively included for a 6-month period. Patient characteristics were obtained from clinical records. Mutation testing was performed on available tumor samples. Exploratory analyses were performed to characterize the clinico-pathological factors associated with presence of EGFR mutations. RESULTS: From March 2010 to March 2011, 1113 patients were included in the study, of which 1009 patients provided sample for EGFR mutation analysis (90.7%). Mutation analysis was not feasible in 146/1113 patients (13.1%) due to either sample unavailability (79/1113; 7.1%) or sample inadequacy (67/1113; 6.0%). Twenty-five out of 1113 patients (2.3%) were excluded due to unavailable information. Most patients (99.5%) were Caucasian, 74.5% were male, and predominantly were current (38.1%) or former smokers (44.0%). Median age was 66 years (range 25-90) and 70.7% of patients had non-squamous histology (57.8% adenocarcinoma, 1.8% bronchoalveolar, 11.1% large-cell carcinoma). Exon 19 deletions and the exon 21 L858R point mutation were analyzed in 942/1009 (93.4%) samples. Mutation rate was 11.6% (82.6% exon 19 dels and 17.4% L858R). To be never smoker (38.1%), female (25.4%), with bronchioloalveolar carcinoma (22.2%) or adenocarcinoma (15.4%) histology was associated with a higher prevalence of EGFR mutations. Exons 18, 20 and 21 (excluding L858R) were analyzed in 505/942 samples, and EGFR mutations were found in 22/505 samples (4.4%). CONCLUSION: The estimated prevalence of sensitizing EGFR mutations (exon 19 del, exon 21 L858R) in an unselected samples of newly diagnosed aNSCLC patients in Spain (all histologies) is consistent with previous published data in Caucasian patients. When a sample is available, EGFR mutation testing is feasible in over 90% of cases, and may therefore be suitable for routine clinical practice. CLINICALTRIALS. GOV IDENTIFIER: NCT01081496.

EPB41L3, TSP-1 and RASSF2 as new clinically relevant prognostic biomarkers in diffuse gliomas.

Hypermethylation of tumor suppressor genes is one of the hallmarks in the progression of brain tumors. Our objectives were to analyze the presence of the hypermethylation of EPB41L3, RASSF2 and TSP-1 genes in 132 diffuse gliomas (astrocytic and oligodendroglial tumors) and in 10 cases of normal brain, and to establish their association with the patients' clinicopathological characteristics. Gene hypermethylation was analyzed by methylation-specific-PCR and confirmed by pyrosequencing (for EPB41L3 and TSP-1) and bisulfite-sequencing (for RASSF2). EPB41L3, RASSF2 and TSP-1 genes were hypermethylated only in tumors (29%, 10.6%, and 50%, respectively), confirming their cancer-specific role. Treatment of cells with the DNA-demethylating-agent 5-aza-2'-deoxycytidine restores their transcription, as confirmed by quantitative-reverse-transcription-PCR and immunofluorescence. Immunohistochemistry for EPB41L3, RASSF2 and TSP-1 was performed to analyze protein expression; p53, ki-67, and CD31 expression and 1p/19q co-deletion were considered to better characterize the tumors. EPB41L3 and TSP-1 hypermethylation was associated with worse (p = 0.047) and better (p = 0.037) prognosis, respectively. This observation was confirmed after adjusting the results for age and tumor grade, the role of TSP-1 being most pronounced in oligodendrogliomas (p = 0.001). We conclude that EPB41L3, RASSF2 and TSP-1 genes are involved in the pathogenesis of diffuse gliomas, and that EPB41L3 and TSP-1 hypermethylation are of prognostic significance.

Oftalmoplejía producida por fenitoína / Ophthalmoplegia produced by phenytoin

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Quality of Life assessment through the EORTC questionnaires of colorectal cancer patients in advanced disease stages

PURPOSE: The purpose of the present work is to evaluate Quality of Life in a group of colorectal cancer patients in advanced stages of their disease, along a standard chemotherapy treatment protocol, through the EORTC core questionnaire QLQ-C30 and the colorectal cancer module QLQ-CR38. These two questionnaires had previously been validated in our country. The present study has the novelty of its use during the chemotherapy treatment. MATERIALS AND METHODS: A consecutive sample of 44 colon o rectal cancer patients in stage IV, from an initial group of 46 patients who were addressed, have filled in the questionnaires, in three moments during their treatment process. Clinical and demographic data have also been recorded. Quality of Life scores and changes in them among the three assessments have been calculated. RESULTS: The quality of life scores of patients who have followed the treatment have been >70 points (100) in most dimensions, and has shown similar to the clinical data. Changes of >20 points in the quality of life scores during the treatment process appear in areas related to toxicity, fatigue and insomnia. Quality of life has been stable or has had small changes (between 10 and 20 points) in most dimensions. CONCLUSIONS:Quality of Life in the present sample has been good in general. The treatment has been administered to patients who could tolerate it adequately (AU)

Quality of life assessment in Spanish lung cancer patients by the EORTC questionnaires

• Propósito: el objetivo de este trabajo es evaluar la calidad de vida de una muestra de pacientes con cáncerde pulmón durante el tratamiento.• Metodos: 170 pacientes con cáncer de pulmón, microcítico con enfermedad limitada y avanzada, y nomicrocítico estadíos III y IV. Los pacientes han contestado el cuestionario EORTC QLQ-C30 y el módulo depulmón EORTC-LC13 en tres momentos a lo largo del tratamiento y seguimiento. Se han recogido datos demográficosy clínicos. Se han comparado grupos formados en función del estadio y tratamiento, y se han estudiadolos cambios en la calidad de vida a lo largo del tiempo.• Resultados: las puntuaciones de calidad de vida de los pacientes que han recibido los protocolos propuestosson aceptables en las tres mediciones al igual que las puntuaciones de toxicidad. En la medición de líneabase hay limitaciones en las áreas de síntomas de la enfermedad y la calidad de vida global. Hay pocas diferenciasentre grupos organizados según tipos de tratamiento y estadio de la enfermedad. Las puntuaciones decalidad de vida son muy similares en las tres mediciones. Los tratamientos tienen un efecto específico en la segundamedición, que mejora en la tercera en algunas áreas de toxicidad, y en otras persiste.• Conclusiones: la calidad de vida de los pacientes que han recibido los protocolos completos es adecuada.Los pacientes que reciben los tratamientos pueden tolerarlos adecuadamente

• Purpose: To assess the quality of life of a sample of lung cancer patients during their treatment.• Material and methods: 170 patients with limited and advanced small-cell lung cancer (SCLC), andwith stages III and IV non-small cell lung cancer (NSCLC) were considered. Patients filled the EORTC QLQC30questionnaire, and the EORTC-LC13 lung module at three different times during the treatment andfollow-up. Demographic and clinical data were also recorded. We compared the groups according to the stageand treatment modality, and studied the changes of the quality of life throughout time.• Results: The quality of life scores of the patients under the given protocols: were acceptable in the threeconsidered measurements, as were also the toxicity scores. At the base line there are limitations in the areas ofsymptoms of disease and quality of life. Few differences were observed between the groups at different stagesand under the different treatment modalities. The quality of life scores were similar according to the threemeasurements. Treatment modality showed a specific effect in the second measurement, while in the third oneit improved in some toxicity areas and persisted in others.• Conclusions: The quality of life of the patients receiving the complete protocols was acceptable. Thepatients under treatment stood it adequately

Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study.

The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. Anthracycline-naive patients (n = 21) received cyclophosphamide 2.5 g/m(2) plus doxorubicin 80 mg/m(2) alternating every 14 days with paclitaxel 200-350 mg/m(2) plus cisplatin 120 mg/m(2). Patients who had previously received anthracyclines (n = 22) received cisplatin 120 mg/m(2) plus etoposide 600 mg/m(2) alternating with paclitaxel 200-350 mg/m(2) plus ifosfamide 8 g/m(2). Peripheral blood stem cells were infused after every course except the first, with a median CD34(+) dose of 2.1 x 10(6)/kg per cycle. Positive selection of CD34(+) cells was performed in good mobilizers. The median number of cycles administered was six (4-8), and the time interval between them was 17 days. Median summation dose intensities (SDI) actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69, respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection or neutropenic fever occurred in 50% of the cycles. There was one treatment-related death. After a median follow-up of 26 months, the median event-free-survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These high dose-intensity induction treatments seem to be feasible with sequential stem cell support.

Factors determining the actual received dose intensity in a program of multicyclic dose-intensive alternating chemotherapy with sequential stem cell support.

Dose intensity has been related to clinical outcome in several solid tumors. We studied the influence of clinical and cellular parameters on dose intensity received in a series of 53 patients with metastatic breast cancer or advanced ovarian cancer. They received courses of cisplatin 120 mg/m(2) plus etoposide 600 mg/m(2) alternating every 14 days with ifosfamide 8 g/m(2) plus paclitaxel 200--350 mg/m(2). Blood stem cell support was administered after every course except for the first one. Patients with excellent mobilization underwent immunomagnetic selection of CD34+ cells. We found a significant inverse correlation between the CD34+ cell dose infused and the delay for the administration of the next cycle. A CD34+ cell dose between 1.5 and 5 x 10(6)/kg per cycle was found to be feasible and was followed by a median delay of 1 day (not different from doses above 5 x 10(6)/kg). Three factors independently predicted the actually received dose intensity in a multiple regression model (R(2) = 0.4): previous autologous transplantation, eligibility for immunomagnetic selection (excellent response to mobilization) and median CD34+ cell dose received along the treatment.

Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma.

BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.