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1. Exploratory analysis of immunomodulatory factors identifies L1CAM as a prognostic marker in alveolar soft-part sarcoma

Author

José L. Mondaza-Hernandez, Nadia Hindi, Antonio Fernandez-Serra, Rafael Ramos, Ricardo Gonzalez-Cámpora, María Carmen Gómez-Mateo, Javier Martinez-Trufero, Javier Lavernia, Antonio Lopez-Pousa, Nuria Laínez, Jeronimo Martinez-Garcia, Claudia Valverde, María Ángeles Vaz-Salgado, Gabriel Garcia-Plaza, Isabel Marin-Borrero, Jaime Carrillo-Garcia, Marta Martin-Ruiz, Pablo Romero, Antonio Gutierrez, Jose A. López-Guerrero, David S. Moura, and Javier Martin-Broto

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Alveolar soft-part sarcoma (ASPS) is a rare tumor driven by the ASPSCR1-TFE3 fusion protein, with a propensity for metastasis. Prognostic factors remain poorly understood, and traditional chemotherapies are largely ineffective. Recent interest lies in immune checkpoint inhibitors (ICIs), yet predictive biomarkers for treatment response are lacking. Previous studies have shown promising results with ICIs in ASPS, indicating a need for further investigation into biomarkers associated with immune response. Objectives: To identify prognostic biomarkers in ASPS and to explore the role of immune-related markers, particularly L1CAM, in predicting patient outcomes. Design: A retrospective cohort study of 19 ASPS patients registered in the GEIS database. The study involved the collection of clinical and histopathological data, followed by an analysis of immune markers and gene expression profiles to identify potential prognostic indicators. Methods: Clinical and histopathological data were retrospectively collected from the GEIS-26 study cohort of 19 ASPS patients. Immunohistochemistry was performed to evaluate immune markers programmed death-1 ligand (PD-L1), programmed death-1, FAS, FASL, CD8, CD3, and CD4. An HTG ImmunOncology panel was conducted on formalin-fixed paraffin-embedded samples to explore gene expression. Effects of differentially expressed genes on survival were explored by Kaplan–Meier. Results: PD-L1 positivity was widely observed (63%) in tumors, and CD8+ lymphocytic infiltration was common. High CD8 density correlated with greater overall survival (OS) while not statistically significant. No associations were found for other immune markers. L1CAM was identified as differentially expressed in patients with low CD8 infiltration and correlated negatively with OS. Conclusion: High L1CAM expression correlated with poorer OS, highlighting its potential as a prognostic marker and therapeutic target in ASPS. Immunomodulatory interventions may hold promise, as evidenced by PD-L1 expression and CD8+ infiltration. Further research, including larger cohorts and international collaborations, is needed to validate these findings and explore therapeutic strategies targeting L1CAM in ASPS.

Published
2024
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2. A Growth Modulation Index-Based GEISTRA Score as a New Prognostic Tool for Trabectedin Efficacy in Patients with Advanced Soft Tissue Sarcomas: A Spanish Group for Sarcoma Research (GEIS) Retrospective Study

Author

Roberto Diaz-Beveridge, Luis Miguel De Sande-González, Antonio López Pousa, Jordi Rubió-Casadevall, Javier Martin-Broto, Pablo Luna, Juan Antonio Carrasco, Claudia M Valverde-Morales, Andres Poveda, Gloria Marquina, María Ángeles Vaz Salgado, Javier Martinez-Trufero, Antonio Gutierrez, Ana De Juan, Juana María Cano, Ibon Gurruchaga-Sotes, Isabel Sevilla, Josefina Cruz-Jurado, Jerónimo Martínez-García, Rosa Alvarez, David S. Moura, Institut Català de la Salut, [Martínez-Trufero J] Javier Martinez-Trufero, Medical Oncology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain. [De Sande-González LM] Medical Oncology Department, Complejo Asistencial Universitario de Leon, Leon, Spain. [Luna P] Medical Oncology Department, Hospital Universitario Son Espases, Palma de Mallorca, Spain. [Martin-Broto J] Medical Oncology Department, Hospital Universitario Virgen del Rocio, Instituto de Biomedicina de Sevilla (IBiS, CSIC, US, HUVR), Sevilla, Spain. [Álvarez R] Medical Oncology Department, Hospital Universitario Gregorio Marañon, Madrid, Spain. [Marquina G] Medical Oncology Department, Hospital Universitario Clinico San Carlos, Madrid, Spain. [Valverde-Morales CM] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, [Martínez-Trufero,J, Gurruchaga-Sotes,I] Javier Martinez-Trufero, Medical Oncology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain. [De Sande-González,LM] Medical Oncology Department, Complejo Asistencial Universitario de Leon, Leon, Spain. [Luna,P] Medical Oncology Department, Hospital Universitario Son Espases, Palma de Mallorca, Spain. [Martin-Broto,J] Medical Oncology Department, Hospital Universitario Virgen del Rocio, Instituto de Biomedicina de Sevilla (IBiS, CSIC, US, HUVR), Sevilla, Spain. [Álvarez,R] Medical Oncology Department, Hospital Universitario Gregorio Marañon, Madrid, Spain. [Marquina,G] Medical Oncology Department, Hospital Universitario Clinico San Carlos, Madrid, Spain. [Diaz-Beveridge,R] Medical Oncology Department, Hospital Politécnico La Fe, Valencia, Spain. [Poveda,A] Medical Oncology Department, Instituto Valenciano de Oncologia, Valencia, Spain. [Cano,JM] Medical Oncology Department, Hospital General de Ciudad Real, Ciudad Real, Spain. [Cruz-Jurado,J] Medical Oncology Department, Hospital Universitario Canarias, Santa Cruz de Tenerife, Spain. [López Pousa,A] Medical Oncology Department, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain. [Vaz Salgado,MA] Medical Oncology Department, Hospital Universitario Ramon y Cajal, RYCIS, CIBERONC, Madrid, Spain. [Valverde-Morales,C] Medical Oncology Department, Hospital Universitario Vall D’Hebron, Barcelona, Spain. [Sevilla,I] Investigación Clínica y Traslacional en Cáncer, Instituto de Investigaciones Biomédicas de Málaga (IBIMA), Medical Oncology Department, Hospitales Universitarios Regional y Virgen de la Victoria de Málaga, Malaga, Spain. [Martínez-García,J] Medical Oncology Department, Hospital Virgen de la Arrixaca, Murcia, Spain. [Rubio-Casadevall,J] Medical Oncology Department, Instituto Catalan Oncologia, Girona, Spain. [De Juan,A] Medical Oncology Department, Hospital Marqués de Valdecilla, Santander, Spain. [Carrasco,JA] Medical Oncology Department, Hospital Alvaro Cunqueiro, Vigo, Spain. [Moura,DS] Instituto de Biomedicina de Sevilla (IBiS, CSIC, US, HUVR), Sevilla, Spain. [Gutiérrez,A] Hematology Department, Hospital Universitario Son Espases, 07010 Palma de Mallorca, Spain., and This research was funded by the Spanish Group for Research on Sarcoma (grant number: NA) and partially by PharmaMar. PharmaMar S.A. did not have any role in study design, or in collection, analysis and interpretation of data.

Subjects
0301 basic medicine, Oncology, Advanced soft tissue sarcomas, Cancer Research, Multivariate analysis, sarcoma, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Trabectedina, España, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Sarcoma [Medical Subject Headings], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Metastasis, Prognostic score, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Trabectedin, Tumors de parts toves, Soft tissue sarcoma, Pronóstico, Soft tissue, Liposarcoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, prognostic score, GEISTRA, L-sarcoma, growth modulation index, prognostic score, sarcoma, trabectedin, 030220 oncology & carcinogenesis, trabectedin, Sarcoma, L-sarcoma, medicine.drug, medicine.medical_specialty, Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Thiazoles::Thiamine::Thiamine Triphosphate [Medical Subject Headings], GEISTRA, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Analysis of Variance::Multivariate Analysis [Medical Subject Headings], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Neoplasms::Neoplasms by Site::Soft Tissue Neoplasms [DISEASES], epidemiología y bioestadística::epidemiología::usos de la epidemiología::efectividad [SALUD PÚBLICA], lcsh:RC254-282, Article, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Sarcoma::Leiomyosarcoma [Medical Subject Headings], 03 medical and health sciences, Internal medicine, medicine, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Sarcoma::Liposarcoma [Medical Subject Headings], neoplasias::neoplasias por localización::neoplasias de los tejidos blandos [ENFERMEDADES], Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, Retrospective cohort study, medicine.disease, 030104 developmental biology, Spain, Medicaments - Eficàcia, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Epidemiology and Biostatistics::Epidemiology::Uses of Epidemiology::Effectiveness [PUBLIC HEALTH], Leiomiosarcoma, business, growth modulation index
Abstract

The aim of this study was to identify an easily reliable prognostic score that selects the subset of advanced soft tissue sarcoma (ASTS) patients with a higher benefit with trabectedin in terms of time to progression and overall survival. A retrospective series of 357 patients with ASTS treated with trabectedin as second- or further-line in 19 centers across Spain was analyzed. First, it was confirmed that patients with high growth modulation index (GMI &gt, 1.33) were associated with the better clinical outcome. Univariate and multivariate analyses were performed to identify factors associated with a GMI &gt, 1.33. Thus, GEISTRA score was based on metastasis free-interval (MFI ≤ 9.7 months), Karnofsky &lt, 80%, Non L-sarcomas and better response in the previous systemic line. The median GMI was 0.82 (0–69), with 198 patients (55%) with a GMI &lt, 1, 41 (11.5%) with a GMI 1–1.33 and 118 (33.1%) with a GMI &gt, 1.33. The lowest GEISTRA score showed a median of time-to-progression (TTP) and overall survival (OS) of 5.7 and 19.5 months, respectively, whereas it was 1.8 and 3.1 months for TTP and OS, respectively, for the GEISTRA 4 score. This prognostic tool can contribute to better selecting candidates for trabectedin treatment in ASTS.

Published
2021

3. Phase II Trial of Palbociclib in Recurrent Retinoblastoma-Positive Anaplastic Oligodendroglioma: A Study from the Spanish Group for Research in Neuro-Oncology (GEINO)

Author

A. Sánchez, Elena Vicente, Vanessa Pachón, Juan M. Sepúlveda-Sánchez, Laura Oleaga, José Muñoz-Langa, Miguel Navarro Martín, Amaya Hilario, María Cruz Martín-Soberón, Miriam Alonso-García, Carlos Mesia Barroso, Gema Durán, Guillermo Velasco, Miguel Gil-Gil, Yolanda Ruano, Diana Cantero Montenegro, Robert Morales-Llombart, Aurelio Hernández-Laín, Estela Pineda, Manuel Benavides, María Ángeles Vaz Salgado, Ramon De Las Penas, Pilar Sánchez-Gómez, and Pfizer

Subjects
0301 basic medicine, Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Pyridines, medicine.medical_treatment, Population, Oligodendroglioma, Neutropenia, Palbociclib, Piperazines, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, Clinical endpoint, Medicine, Humans, Pharmacology (medical), education, Adverse effect, Protein Kinase Inhibitors, Aged, education.field_of_study, Chemotherapy, business.industry, Retinoblastoma, Middle Aged, medicine.disease, 030104 developmental biology, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business
Abstract

[Background]: The cell cycle checkpoint G1/S, dependent on cyclin-dependent kinase (CDK) 4 amplification/overexpression and retinoblastoma phosphorylation, is altered in most anaplastic oligodendrogliomas (AOs). [Objective]: We aimed to evaluate the efficacy of palbociclib, an oral inhibitor of CDK4/6 with proven efficacy in breast cancer, in patients with AO. The primary endpoint was progression-free survival at 6 months. [Patients and Methods]: We conducted a multicenter, open-label, phase II trial evaluating the efficacy and safety of palbociclib in patients with AO who progressed on radiotherapy and chemotherapy with histologically and molecularly confirmed grade 3 oligodendroglioma and conserved retinoblastoma protein (pRb) expression by immunohistochemistry. Patients were treated with palbociclib (125 mg/day) for 3/1 weeks on/off. [Results]: Overall, 34 patients were enrolled across 10 hospitals in the Spanish Group of Neuro-Oncology (GEINO) study. The study was stopped early owing to the lack of efficacy, with 74% of evaluable patients progressing within 6 months, which was insufficient to consider palbociclib as an active drug in this population. Within the median follow-up of 12 months, the median progression-free survival was 2.8 months [95% confidence interval (CI) 2.6–3.1] and the median overall survival was 32.1 months (95% CI 5.1–59.2). There were no partial or complete responses; only 13 patients (38%) achieved stable disease as the best response. Palbociclib was well tolerated, with neutropenia (grade 3 or higher: 58.8%) and thrombocytopenia (grade 3 or higher: 14.7%) as the most common adverse events (AEs). Both AEs had no significant impact. [Conclusion]: Despite the good tolerance, palbociclib monotherapy did not show favorable efficacy against recurrent AO., Palbociclib was provided by Pfizer under a cooperative research agreement with the Spanish Group for Research in NeuroOncology (GEINO). Funding research was supported by Pfzer under the Investigator-Initiated Research Award, number WI174842.

Published
2020

4. Pazopanib for treatment of advanced extraskeletal myxoid chondrosarcoma: a multicentre, single-arm, phase 2 trial

Author

A. Lecesne, Dominga Racanelli, Jean-Yves Blay, Anna Maria Frezza, Marie Karanian, Silvia Brich, Daniel Bernabeu, Antonio Lopez-Pousa, María Ángeles Vaz Salgado, Paolo G. Casali, Sarah Dumont, Silvia Stacchiotti, Carlo Morosi, Chiara Castelli, Josefina Cruz, Monica Brenca, Antonio Gutierrez, Giovanni Grignani, Roberta Maestro, Nicolas Penel, Stefano Ferrari, Nadia Hindi, Andrés Redondo, Gianpaolo Dagrada, Javier Martin-Broto, Emanuela Palmerini, Paola Collini, Enrique de Álava, Antoine Italiano, Viviana Vallacchi, Grupo Español de Investigación en Sarcomas, Italian Sarcoma Group, French Sarcoma Group, GlaxoSmithKline, Novartis, Stacchiotti S., Ferrari S., Redondo A., Hindi-Muniz N., Palmerini E., Vaz Salgado M.A., Frezza A.M., Casali P.G., Gutierrez A., Lopez-Pousa A., Grignani G., Italiano A., LeCesne A., Dumont S., Blay J.Y., Penel N., Bernabeu D., de Alava E., Karanian M., Morosi C., Brich S., Dagrada G.P., Vallacchi V., Castelli C., Brenca M., Racanelli D., Maestro R., Collini P., Cruz J., and Martin-Broto J.

Subjects
0301 basic medicine, Oncology, Male, musculoskeletal diseases, medicine.medical_specialty, Indazoles, animal structures, Population, Chondrosarcoma, Soft Tissue Neoplasms, Disease-Free Survival, Pazopanib, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, education, Aged, Neoplasm Staging, Retrospective Studies, education.field_of_study, Sulfonamides, business.industry, Retrospective cohort study, Extraskeletal Myxoid Chondrosarcoma, Middle Aged, medicine.disease, musculoskeletal system, extraskeletal myxoid chondrosarcoma, pazopanib, target therapy, angiogenesis, 030104 developmental biology, Pyrimidines, Treatment Outcome, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Cohort, embryonic structures, Female, Sarcoma, business, Neoplasms, Connective and Soft Tissue, medicine.drug
Abstract

[Background] Extraskeletal myxoid chondrosarcoma is a rare sarcoma with low sensitivity to cytotoxic chemotherapy. Retrospective evidence suggests that antiangiogenic drugs could be a treatment option. We aimed to investigate the activity of pazopanib, an antiangiogenic drug, in patients with advanced extraskeletal myxoid chondrosarcoma., [Methods] In this single-arm, open-label phase 2 trial, three parallel independent cohorts of different histotypes of advanced sarcomas were recruited (extraskeletal myxoid chondrosarcoma, typical solitary fibrous tumour, and malignant-dedifferentiated solitary fibrous tumour). In each cohort, patients received pazopanib. In this Article, we report the results of the cohort of patients with advanced extraskeletal myxoid chondrosarcoma. Separate reporting of the three cohorts was prespecified in the study protocol. In this cohort, adult patients (aged ≥18 years) with a diagnosis of NR4A3-translocated, metastatic, or unresectable extraskeletal myxoid chondrosarcoma, who had Response Evaluation Criteria in Solid Tumors (RECIST) progression in the previous 6 months, and had an Eastern Cooperative Oncology Group performance status of 0–2, were enrolled at 11 study sites of the Spanish, Italian, and French sarcoma groups. Patients received oral pazopanib (800 mg/day) continuously, until disease progression, unacceptable toxicity, death, non-compliance, patient refusal, or investigator's decision. The primary endpoint was the proportion of patients achieving an objective response according to RECIST 1·1 in the modified intention-to-treat population (patients who provided consent and had a central molecularly confirmed diagnosis of extraskeletal myxoid chondrosarcoma). The safety analysis included all patients who received at least one dose of pazopanib. This study is registered with ClinicalTrials.gov, number NCT02066285., [Findings] Between June 24, 2014, and Jan 17, 2017, 26 patients entered the study and started pazopanib. Of these, 23 met the eligibility criteria for the modified intention-to-treat analysis. Median follow-up was 27 months (IQR 18–30). 22 patients (one patient died before the primary analysis) were evaluable for the primary endpoint: four (18% [95% CI 1–36]) had a RECIST objective response. No deaths or grade 4 adverse events occurred. The most frequent grade 3 adverse events were hypertension (nine [35%] of 26 patients), increased concentration of alanine aminotransferase (six [23%]), and increased aspartate aminotransferase (five [19%])., [Interpretation] Pazopanib had clinically meaningful antitumour activity in patients with progressive and advanced extraskeletal myxoid chondrosarcoma, and could be considered a suitable option after failure to respond to first-line anthracycline-based chemotherapy in these patients., Funding: Spanish Group for Research on Sarcomas, Italian Sarcoma Group, French Sarcoma Group, GlaxoSmithKline, and Novartis.

Published
2019

5. Dacomitinib: an investigational drug for the treatment of glioblastoma

Author

Ricardo Gargini, Juan Manuel Sepúlveda, María Ángeles Vaz Salgado, Carmen Balana, and Pilar Sánchez-Gómez

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Investigational drug, medicine.medical_treatment, EGFR, Newly diagnosed, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, tyrosine kinase inhibitors, medicine, Overall survival, Animals, Humans, Pharmacology (medical), Protein Kinase Inhibitors, Quinazolinones, Pharmacology, Temozolomide, business.industry, Standard treatment, Gene Amplification, glioblastoma, General Medicine, Drugs, Investigational, medicine.disease, Dacomitinib, Radiation therapy, ErbB Receptors, Survival Rate, EGFR tyrosine kinase inhibitor, high grade glioma, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Mutation, Neoplasm Recurrence, Local, business, Glioblastoma, medicine.drug
Abstract

Introduction: Standard treatment of newly diagnosed glioblastoma (GB) is surgery with radiotherapy and temozolomide, but tumors will recur with a median overall survival of only 15months. It seems imperative to explore new possibilities of treatment based on targetable alterations known to be present in GB. Among others, Epidermal Growth Factor Receptor or EGFR (HER1) mutations or amplifications are the most prevalent alterations in GB. In fact, around 40% of GB cases show amplification of EGFR gene, and half of these patients carry the EGFRvIII mutation, a deletion that generates a continuous activation of the tyrosine kinase domain of the receptor.Areas covered: We review the current knowledge about Dacomitinib, an oral, irreversible, second-generation, pan-HER tyrosine kinase inhibitor, in the treatment of glioblastoma. Dacomitinib has noteworthy antiglioma activity in preclinical models and has been tested in one phase II trial in patients with recurrent GB with EGFR amplification.Expert opinion: Despite the poor global results of Dacomitinib in recurrent GB shown in a phase II trial, some patients had a significant benefit. Therefore, it is necessary to improve the knowledge about the mechanisms of failure or resistance to EGFR inhibitors in GB.

Published
2018

6. Updated analysis of the national registry of nervous system tumours in Spain (RETSINE). RETSINE: National registry of nervous system tumours of the Spanish research group in neuro-oncology (GEINO) and Spanish infrequent and orphan tumours group (GETHI)

Author

Oscar Gallego, R. de las Penas Bataller, I. Ceballos Lenza, T. Quintanar, F. García-Piñon, P. Perez Segura, M.A. Ivars, I. Fernández Pérez, María Ángeles Vaz Salgado, and S. Del Barco

Subjects
medicine.medical_specialty, Neurologic Oncology, medicine.diagnostic_test, business.industry, Neuro oncology, Incidence (epidemiology), Hematology, medicine.disease, Oncology, Internal medicine, Glioma, Biopsy, Medicine, Low-Grade Glioma, National registry, business, Cognitive impairment
Abstract

Background The Spanish Research Group in Neuro-oncology (GEINO) and Spanish Infrequent and Orphan Tumors Group (GETHI) initiated a Nervous System Tumors Registry (RETSINE) in September 2017 with the aim of evaluating accurate, basic data concerning this oncological pathology in Spain. (Spanish Agency of Medicines and Medical Devices code: GG-TIN-2017-01). Methods The RETSINE database collects demographic, diagnostic and treatment data from all the hospitals participating in the project. Secondarily, each researcher indicates if there is a tumor sample available for future studies that arise from the registry. Results From September 2017 to April 2019, the registry has included 1021 patients (p) from 26 different hospitals. P have been included at a rate of 60 per month. With a median age of 60 y (range: 16-89), there is a discrete predominance in males (56.1%). The main symptoms at presentation are seizures, cognitive impairment and ataxia (26.1%, 16.8% and 6.6% of p). Histology provided in 841 p = 764/841 glioma (90,8%) [High Grade Glioma 618/764 (80.9%), Low Grade Glioma 146/764 (19.1%)], 77/308 no glioma (9,2%). Primary surgical treatment= 42.4% total tumor removal; 38.9% subtotal tumor removal and 7.7% biopsy. The median overall survival is 18.1 m (95% CI 15.5-20.6): 115.6 m (95% CI 38.8-192.4) in Low Grade and 17.5 m (95% CI 15.4-19.5) in High Grade Glioma. Conclusions RETSINE is a valuable tool for analyzing the current situation of Nervous System Tumors in Spain. The possibility of carrying out clinical studies in tumors of low incidence will be increased and improved with records of cases with associated biological sample. The database provides medical information that can also assist the orientation of healthcare policies. Legal entity responsible for the study Spanish Research Group in Neuro-oncology (GEINO) and Spanish Infrequent and Orphan Tumors Group (GETHI). Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Published
2019
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7. ED-33ELDERLY PATIENTS WITH GLIOBLASTOMA: SHOULD BE TREATED IN A DIFFERENT WAY?

Author

José Antonio Gutierrez Cerco, Vanessa Pachón Olmos, Luis Ley Urzaiz, Héctor Pian, Ana Gómez Rueda, Marta Del Álamo de Pedro, Alfredo Carrato Mena, Jacobo Muñoz del Toro, and María Ángeles Vaz Salgado

Subjects
Cancer Research, medicine.medical_specialty, Temozolomide, business.industry, Nausea, Neutropenia, medicine.disease, Surgery, law.invention, Regimen, Abstracts, Oncology, Randomized controlled trial, law, Concomitant, Cohort, medicine, Neurology (clinical), Progression-free survival, medicine.symptom, business, medicine.drug
Abstract

BACKGROUND: The management of glioblastoma (GB) in elderly patients is not well established, since until recently they have been excluded from randomized trials and there are concerns about the toxicity. METHODS: The authors retrospectively reviewed 53 patients at a single institution from 2005 to 2013. Patients were 70 years of age and older with histologically confirmed GB. RESULTS: Median age was 75 years (70-88y). Fifty-six percent men, 43% women. Majority had some kind of minor morbidity (89%), mainly arterial hypertension (55%). Complete resection was performed in 52%. Biopsy in 8%. 90% had presurgical KPS >70. Seven (14%) had worse KPS after surgery. 71% received radiotherapy, in 45% 60 Gy and in 26% 30 Gy. Nearly 40% were treated with concomitant and adjuvant temozolomide. The median number of cycles was 4,43 (1-14). 6% had grade 3 or 4 neutropenia or trombocitopenia. 24% had grade 1 asthenia or nausea and vomits. Median overall survival (OS) for the whole cohort was 7,36 m (95% CI 4,8-9,8). Median progression free survival was 5.9 m (3-8.7m). Treatment with temozolomide concomitant and adjuvant (Stupp regimen) was associated with longer OS (11,16 vs 4,1m p = 0.008 ). The median OS was 8,3 m. for those who received radiotherapy and 1,5m for those who did not (p = 0,046). No statistical differences were found between those treated with 60 or 30 Gy (p = 0.143). Nearly 10% was older than 80. Median OS in these patients was 4,2m even though 71% had a complete resection. CONCLUSION: In our experience, in selected patients with newly diagnosed glioblastoma over the age of 70, more intensive treatment was associated with prolonged OS, and results are close to those obtained in younger patients. Nevertheless these are retrospective data, selection bias should be considerer. Further randomized trial should be conducted to investigate this topic.

Published
2014

8. NEURO/MEDICAL ONCOLOGY

Author

Irene Helenowski, Naoya Hashimoto, Jan J. Heimans, Toshiki Yoshimine, Johan A F Koekkoek, Evelyne Emery, José L. Asencio, Andrea Chamczuck, Carly Bridge, Gilbert Faure, Barbara-Ann Millar, Arthur Rosiello, Michela Casanova, John Freymann, Giulio Bertani, Jun-ich Adachi, Christian LaFougere, Julianne Bloom, Paul Vincent Opinaldo, Tobey J. McDonald, Alexander Khandji, Maciej M. Mrugala, Agnieszka Kowalska, Clifford G. Robinson, Josef Pichler, Jayesh Mehta, Lisa M. DeAngelis, Katie Slusarz, Rachel Grossman, Juan Armando Mejía, Sadhana Kannan, In Ah Kim, Pierre Soubeyran, Nabil Ahmed, Matthew J. Matasar, David A. Reardon, Marie-Laure Tanguy, Andrea Pace, Vani Santosh, Tackeun Kim, Adrienne C. Lahti, John E. Donahue, Pavlina Poloskova, Marc H. A. Jansen, Nilanjana Banerji, Margaret Schwartz, Matthias Kirsch, Robert Jeraj, Guus A.M.S. van Dongen, Samuel Singer, Tom J. Snijders, Santosh Kesari, Riccardo Soffetti, Takashi Sasayama, Diana Ly, Kaoru Kurisu, Carsten Friedrich, Shinji Kawabata, Cedric Revil, Michael A. Jacobs, Ryuichi Hirayama, Wan-Soo Yoon, Kathleen Lupica, Christopher Reilly, Takuichiro Hideo, Miguel Gil, Josep Garcia, Ming Zheng, Edward K. Avila, Mairéad G McNamara, Hartmut Uschmann, Jeffrey S. Weinberg, Craig H. Moskowitz, Jörg Hense, Manmeet Ahluwalia, Georg Bjarnason, David Corwin, Shakti Ramkissoon, Jad Alshami, Eric C. Leuthardt, Paul Dilfer, Margaret Patton, Lindsey Heathcock, Cees van Montfort, Rakesh Kumar Gupta, Akihiko Yoshida, Carmine Maria Carapella, Guy K. Mckhann, Marian Hajduch, Meinhard Nevinny-Stickel, Patricia Bruns, Ashish Suri, Hernán Carranza, David A. Gutman, Carlos Yepes, Patrick Y. Wen, T. Cloughesy, Anna Kaltenboeck, Carlos Bartels, Paul D. Brown, Lisa Fichtel, Lorenzo Giammattei, Steven Hamilton, Nobuyuki Takayama, Nan Lin, Jan Drappatz, Roland Eils, Akihiro Tsuboi, Patrick Urban, Minesh P. Mehta, Remy Gressin, Zarnie Lwin, Clarence Eng, Ian F. Dunn, Sin-Soo Jeun, Alva B. Weir, Elisa Trevisan, silviya Meletath, Fumiyuki Yamasaki, Scott N. Hwang, Navya Nambudiri, Timothy F. Cloughesy, Paolo Rampini, Kathryn J. Ruddy, Justin Kirby, Marc C. Huisman, Normand Laperriere, Abajo Guijarro, Alberto González-Aguilar, David M. Peereboom, Antoine F. Carpentier, Steven M. Greenberg, Chikashi Ishioka, Sarah C. Gaffey, Sneha Arya, Guy M. McKhann, Richard Curry, Takashi Watanabe, Keishi Makino, Radek Trojanec, Hideo Takeshima, Joseph F. Megyesi, Jasmina I. Ivanova, Victor Rodriguez Berrocal, Marcel Kool, Eric Burton, Sandra K. Johnston, Hideyuki Arita, Konstantina Karabatsou, Robert C. Rostomily, Sean Grimm, Ralph G. Dacey, Karl Olson, Sonia Gómez, Harry C. Schouten, Christof M. Kramm, Fred H. Hochberg, Darren Hargrave, Kazuhiko Sugiyama, Wilhelm Boogerd, Stefano Tiziani, Christine McCluskey, Albert H. Kim, Tejpal Gupta, Ida Martinelli, Friedrich-Wilhelm Kreth, Lennea Coombs, Keith L. Ligon, J. Manuel Sarmiento, David R. Macdonald, Holly Dickinson, Cristian Massacesi, Basile Wittwer, Jung-Il Lee, Volker Hovestadt, Mark Smolkin, Sampath Somanna, Ingo K. Mellinghoff, Nancy Ann Oberheim Bush, Sanjeev Francis, Roland Goldbrunner, Jai Ho Choi, John Sampson, Roy Allan Dominique Torcuator, Kathleen R. Lamborn, Simon V. Liubinas, Daniel J. Sargent, Christina K. Cramer, Francine Armentano, Heather Leeper, Stefan Rutkowski, Prakash Shetty, Arivazhagan Arimappamagan, Alicia Ortega, Enrique Jiménez, Kazuhiro Tanaka, Kolette D. Fly, Seunggu Han, Nicolas U. Gerber, David Schiff, Antonella Castellano, Isabel Arrillaga-Romany, Robert J. Wechsler-Reya, Sophie Taillibert, Macarena de la Fuente, Wolfgang Wick, Monica Bennett, Francesco Cognetti, John de Groot, Michael Gonzales, Leon D. Ortiz, Yoshiaki Shiokawa, George Sachs, Ivo Tremont, Charles A. Conrad, Michael D. Taylor, Igor J. Barani, Shannon Langmead, Lisa Sturla, Doosik Kong, Rebecca D. Folkerth, Garrett Riggs, Yoon-La Choi, Carole Soussain, Calvin Soh, Peter Canoll, Mariza Daras, Melissa Hoag, James Rigas, Dana Cernea, Liu Diane, Kenji Wakiya, Sandra Silberman, Ivan A. Reveles, Jeffrey S. Wefel, Wenting Wu, Marie Blonski, MA Majaid, Vanessa A. Nestor, Maurits W.C.B. Sanders, Cynthia Harrison, Ruxandra Costa, Andrea Hawkins-Daarud, Mark R. Gilbert, Ruth Katz, Masayuki Kanamori, Tomek Janicki, Aaron C. Spalding, Dong-Sup Chung, Lauren Foresman, Fateme Salehi, Allan H. Friedman, Eric P. Winer, Robert Kwiecien, Joachim Kuehl, Motoo Nagane, Stanislaw Burzynski, Tomokazu Aoki, Gregory N. Fuller, Nina Paleologos, Darell D. Bigner, Max Wintermark, Adam E. Flanders, Eiichi Ishikawa, Subramanian Hariharan, Doreen Pachow, Glen Stevens, Ulrich Schüller, Jennifer Lycette, Jennifer Garst, Jeffery T. Williams, Gordana Vlahovic, Tjeerd J. Postma, Tribhwan Vats, Isabel Arrilaga, Krista Follmer, Henry S. Friedman, Kenneth Schwartz, James Perry, Jonas M. Sheehan, Christian Grommes, Annette M. Molinaro, Seung-Ho Yang, Peter Lichter, Naoki Kagawa, Trish Whitcomb, Monica Loghin, Amanda L. Bergner, Miroslav Vaverka, Jayashree Kalpathy-Cramer, Chitra Sarkar, Thomas Davidson, Nithya Ramnath, Leland Rogers, Roberta Rudà, Steven A. Toms, Martin Gore, Khê Hoang-Xuan, Emmanuel Gyan, Hani Malone, Jun-ichi Adachi, Jennifer Rifenburg, Stefan M. Pfister, Luis Carlos Mayor, Vanja Vaccaro, Hannah E. Goldstein, Karen Fink, Eva Dombi, Timothy Cloughsey, Sabina Eigenbrod, Jiri Ehrmann, Li Li, Pamela R. Jackson, Makoto Ohno, Craig Nolan, Gerald P. Linette, Tatjana Seute, Eric Bouffet, Patricia M. M. B. Soetekouw, David J. Pisapia, Marc Remke, Susan Snodgras, David Tran, Keiichi Kobayashi, Warren P. Mason, Setsu Sakamoto, Chiara Bosa, Gabriele Schackert, Alfred Yung, David Cachia, Toshihiko Kuroiwa, María Ángeles Vaz Salgado, F. Lonnqvist, Francesca Piludu, Alvina Acquaye, Keisuke Ueki, Jung Ho Han, Kathy Newell, Mythili Shastry, Yoon Jae Cho, Marco Riva, Laura M. Fayad, Kristin Diefes, André O. von Bueren, Ina Ly, Beatrix Lutiger, Hiroyoshi Suzuki, Jeanette K. Doorduijn, Eiji Kohmura, Olivier Chinot, Ichiyo Shibahara, Nathalie Jansen, Marta Del Álamo de Pedro, Scott L. Pomeroy, Andreas Zwergal, Terri S. Armstrong, Elmar Kirches, Daniel P. Cahill, Howard A. Fine, Cezary Szczylik, Stéphane Oudard, Gregg C. Shepard, Mark G. Kris, Andrea Milbourne, Dominique Jennings, Marco Locatelli, Dereck Amakye, Takumi Kudo, Simon Bailey, Alessandra Fabi, Taketoshi Maehara, Soumen Khatua, Caroline Houllier, Klaus J. Müller, Jaishri O. Blakeley, Karen Kelly, Jonathon Yun, Thomas Gergel, Diane Liu, Eric T. Wong, Alin Borha, Brian J. Williams, Rakesh Jalali, Birgit Geoerger, Naosuke Nonoguchi, Julie Walker, Jasmin Jo, Manmohan Singh, Mary Noel, Denise Lally-Goss, Tracy T. Batchelor, Andrea Falini, Maximilian Niyazi, Jeffrey Raizer, Martin J. van den Bent, Aleksandra Gruslova, Phioanh L. Nghiemphu, Kristin R. Swanson, Maaike J. Vos, Jethro Hu, Rebeca Alcalce Pampliega, Craig S. Sauter, Leena Ketonen, Michael A. Vogelbaum, Donald Picker, Robert Hawkins, Chris Halpin, Otto S. Hoekstra, Elizabeth Vera-Bolanos, Ahmad Awada, Sawan Kumar, Alexandra Benouaich-Amiel, Joseph Pernicone, Noriyuki Kawabata, Andrew H. Kaye, David Brachman, Kurt A. Jaeckle, Cameron J. Nowell, Maria Carlo, Tom Mikkelsen, Jorg Dietrich, Tomonari Suzuki, Kohei Fukuoka, Philippe Aftimos, Christine Schmid-Tannwald, Vera Wenter, Valeria Conte, Scott Turner, Brian J A Gill, John D. Cullen, Jiayi Huang, Saurabh Dahiya, Vincent Delwail, Lien Bekaert, Priya Kumthekar, Roberta Seidman, Scott R. Plotkin, Priya Deshpande, Christopher Zalewski, Vaibhav Patel, Peter Kurniali, Martha Nowosielski, Zvi Ram, Susan M. Chang, Dannis G. van Vuurden, Stuart A. Grossman, Vaishali Suri, Rajan Jain, Christine Carico, Ying Yuan, Yoji Yamashita, Bojana Milojkovic-Kerklaan, Yannick Kerloeguen, Michael B. Sisti, Rameen Beroukhim, Andrea Artoni, Frances McSherry, John J. Evans, Mark E. Shaffrey, Lauren E. Abrey, Akshal S. Patel, Laura Bernal-Vaca, Rolf-Dieter Kortmann, Robert Grubb, Mimi Lee, Jörg-Christian Tonn, Shinobu Yamada, Andrés Quintero, Kazuhiko Mishima, Ania Marszalek, Stephen Gancher, Amal Melhem-Bertrandt, Takamitsu Fujimaki, Monika Warmuth-Metz, George Avgeropoulos, Rifaquat Rahman, Franck Bourdeaut, Frank Feleppa, Jennifer Clarke, Meredith A. Reid, Maria Werner-Wasik, Andrew D. Norden, Kenneth D. Swanson, Jeffrey N. Bruce, Chae-Yong Kim, Steven S. Rosenfeld, Haiyan Jiang, Oliver Schnell, Toshihiro Kumabe, Michael J. Sullivan, W. Gladdines, Glenn J. Lesser, Chang-Ho Yun, Epari Sridhar, Sophie Lebouvier-Sadot, Andrea Baldwin, Chirag G. Patil, Thomas Smith, Shin-Ichi Miyatake, Renato LaRocca, Kent C. Shih, Russell C. Rockne, Katsu Mizukawa, Antonio Omuro, Ryuta Saito, Mohamed H. Hamza, Eunju Hurh, Silke Soucek, Michel Lacroix, Brian J. Scott, Thomas Kaley, Tetsuya Yamamoto, Gregory J. Zipfel, Andrew Lin, Elena Pentsova, Carlos Emilio Restrepo, Utkarsh Bhagat, Masao Matsutani, Andrew B. Lassman, Stephanie L. Pugh, Yasuji Miyakita, Manabu Kinoshita, Christian Hagel, D. Brandsma, Jorge M. Otero, Marco Timmer, Ke Zhang, S. Altintas, Thierry Lamy, Hirofumi Hirano, Mehar Chand Sharma, Wafik S. El-Deiry, Peter A. Sims, Evanthia Galanis, Yong-Kil Hong, Terence J. O'Brien, Haruo Sugiyama, Dieta Brandsma, Loretta Barron, Joshua J. Jacobs, Roger Henriksson, Albert Lai, David White, Xiao-Tang Kong, John D. Hainsworth, Petronella J Lugtenburg, Paul A. Northcott, Maryline Barrie, Kenneth J. Cohen, Tanuj Saaraswat, Xiaobu Ye, Sandra Ruland, Diana M. Haninger, Surasak Phuphanich, Marc C. Chamberlain, Kenneth Aldape, Ewa Matczak, Phyo Kim, Peter Bartenstein, Lumir Hrabalek, Howard Y. Chang, Donatella Tampieri, Fumi Higuchi, Katherine S. Panageas, Allicia C. Girvan, Majid Khan, Stevie Threatt, Tareq Juratli, Mitchel S. Berger, Linda Dirven, Michele Nikolai, Emmanuelle DiTomaso, Sarah Leary, Jan H.M. Schellens, Chuanlu Jiang, Michael Glantz, Harald Sontheimer, Michael D. Prados, Mauricio Lema, Marie-Christine Guiot, Shesh N. Rai, Minhee Won, Carlos Vargas, Eva Galanis, Kazunori Arita, David I. Sandberg, Gianluca Ardolino, Sylvain Choquet, Ondrej Kalita, Michael Rytting, Lorenzo Bello, Luis Ley Urzaiz, Martin J.B. Taphoorn, Kourosh Jafari-Khouzani, Alfred Rademaker, Juan Martinez San Millan, Isabelle Aerts, Sergio Bracarda, John Norton, Mark D. Anderson, Barbara Zarino, Jun Ichi Kuratsu, Nicholas Butowski, Derek R. Johnson, James E. Herndon, Diana Giannarelli, Debra LaFrankie, Filippo Cogiamanian, Yasuyoshi Chiba, Hideo Nakamura, Agnes Jager, Caroline Chung, Paula Warren, Frans S. S. Leijten, Peter Hau, Yusuke Oji, Yuichi Hirose, Kathryn Gilliland, Sadao Kaneko, W. K. Alfred Yung, Roger Stupp, Amy Chung, Yutaka Hata, Mary Frances McAleer, Hee-Won Jung, Miloslava Zlevorová, Brendan Killory, Raymond Sawaya, Anita Chawla, John Trusheim, H. Ian Robins, Judy Lima, Prakash Ambady, Barbara O'Brien, Sonia Bermúdez, Howard Colman, Matthias Gromeier, Jean-Sébastien Guillamo, Maria C. Pietanza, Antonello Vidiri, Laura Guyman, Kristin Swanson, Paul Rosenblatt, Joshua L. Dowling, Lakshmi Nayak, Ashlee Drawz, Yu Jung Kim, Mikael L. Rinne, Shlomit Yust-Katz, Jessi Stevens, Katharine J. Drummond, Patricia Wing, Sarah Taylor, Joshua E. Allen, Ron Schaafsma, John DeGroot, Shigetoshi Yano, Paula Rauschkolb, Anupam Kumar, Soichiro Shibui, M. E. van Linde, Shirish M. Gadgeel, Yoshitaka Narita, Nicholas G. Avgeropoulos, Luca Bertero, Hongjun Wang, Jason K. Rockhill, Suriya Jeyapalan, Yukihiko Sonoda, Hikaru Sasaki, Shirley L. Markant, Masamitsu Nishihara, Daniel J. Brat, Alexandra Flowers, Monica Sierra del Rio, Morgan Prust, Adam M. Sonabend, Pierre A. Robe, James J. Dignam, Julia C. Chisholm, Gregory J. Riely, Mary Gerard, Sajeel Chowdhary, Natalie Jäger, Giovanna M. D'Abaco, James J. Culhane, Tatsunori Okamura, Erik P. Sulman, L. Adriana Esparza, Ivo W. Tremont-Lukats, Emily Porensky, Yoshihiro Oka, Marcelo De Carvalho, Brigitte C. Widemann, Stacey Kalambakas, Rolf D. Kortmann, Stewart Goldman, Jaap C. Reijneveld, Andrew Brenner, Jacob Mandel, Riccardo Draghi, Yunus Arik, Shinji Yamashita, Torsten Pietsch, Tanweer Zaidi, Dawid Schellingerhout, Marta Penas-Prado, Veronica Villani, Adriana Olar, Vanessa L. Merker, Matthias Holdhoff, Joke W. Baars, Katrina H. Smith, Arnab Chakravarti, Giorgio Carrabba, Gertjan J.L. Kaspers, Susan Boulton, Peter A. Forsyth, David T.W. Jones, Anne Baldock, Meier Hsu, Soham Dasgupta, Jeremy Rudnick, Arun Rai, Jessica Sun, Naoki Shinojima, Christian Mawrin, Eita Uchida, Jaswinder Jutla, Koichi Ichimura, Alona Muzikansky, Jean Philippe Maire, Louis B. Nabors, Yuko Matsushita, Emilie Le Rhun, Annick Desjardins, Magali Lecavalier-Barsoum, Laurie Rice, Bradford A. Moffat, Kelly Hempfling, Andrew A. Kanner, Mark W. Kieran, Stephanie M. Robert, Hervé Ghesquières, Alba A. Brandes, E. Sander Connolly, Jingxia Liu, David T. Dicker, Katherine B. Peters, Gregory S. Burzynski, Charles Sweeley, Deborah T. Blumenthal, Nicolás Useche, Tulika Ranjan, Thierry Muanza, Mercedes Garcia Villanueva, Fernando Hakim, Yana Krutoshinskaya, Shintaro Fukushima, Ryo Nishikawa, Damien C. Weber, Michael R. Chicoine, Motomasa Furuse, André Busson, Joseph R. Simpson, Gabriele Röhn, Susanne Koeppen, Arjun Sahgal, Fabio M. Iwamoto, Leland Graves, Sarah Iglseder, Taro Yanagawa, Michael Lahn, Ramaswamy Govindan, Eduardo Roberts Cervantes, Eric S. Wong, Nadine Kliese, Feng Tai, Katja von Hoff, Vincenzo Anelli, Trevor J. Pugh, Andrés F. Cardona, Gebra Cuyun Carter, Yuko Watanabe, Bogdana Suchorska, Manuela Caroli, José Luis Asencio, Eudocia Q. Lee, John Floyd, Lucas Moreno, Samantha J Mills, Jun-ichiro Kuroda, Susan Chi, David N. Louis, Aanchal Kakkar, Elizabeth R. Gerstner, Annika Schlamann, Robert Cavaliere, John L. Villano, Asha Das, Petr Kavan, Takaaki Yanagisawa, Luc Taillandier, Jonathan Fratkin, Günther Stockhammer, Tomasz Janicki, Sherese Fralin, Wafik Zaky, Lisa Scarpace, Kazunari Yoshida, Magalie Hilton, Andrey Korshunov, Aliasgar Moiyadi, Alexandra Gorelick, Alfredo Carrato Mena, Yuya Nishiyama, Riccardo Soffietti, Marina Donativi, Andrew S. Chi, Lauren Schaff, Andrew P. Morokoff, Sophie E. M. Veldhuijzen van Zanten, Hans-Joachim Reimers, John G. Stewart, Clare Ferrigno, Jackson Hamilton, Do-Hyun Nam, Samantha Hammond, Regina Krel, Mika Watanabe, Anna K. Nowak, Elina Tsyvkin, Michael W. McDermott, Jacoline E C Bromberg, Teiji Tominaga, Laila M. Poisson, Lisa Doherty, Alessia Lodi, Vino Apok, Magdalena Kneblova, Michelle Bell, Carl Jaffe, Sunita Dahr, Maria Koh, Pedro Garciarena, J. Gregory Cairncross, Ana Gómez Rueda, Augustus Perez, Ho Jun Seol, Frank Saran, Camillo Porta, Grace Elzinga, Michael Cloney, and Charles P. Hart

Subjects
Cancer Research, medicine.medical_specialty, business.industry, 010403 inorganic & nuclear chemistry, 01 natural sciences, 0104 chemical sciences, 03 medical and health sciences, Abstracts, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, medicine, Medical physics, Neurology (clinical), business
Published
2013

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