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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.

[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.

e14047 Background: Glioblastoma (GBM) is the most common brain primary tumor. Almost all patients have recurrent disease after initial treatment with surgery, radiotherapy and chemotherapy. After disease recurrence, there is no standardized treatment and reoperation is common but there is no proven benefit in randomized trials. Here we retrospectively review the Spanish national database to identify the frequency of reoperations in recurrent GBM and to analyze the impact of surgery on survival in this setting. Methods: We retrospectively reviewed relapsed GBM patients from the Spanish national database RETSINE (Registro Nacional Español de Tumores del Sistema Nervioso Central) supported by the GEINO group. Kaplan-Meier curves and log rank test were used to compare survival. Results: The number of patients with recurrent GBM analyzed was 538, 40% were women and 60% were men. The MGMT status was: methylated 30.9%, unmethylated 33.8%, unknown 35.3%. A total of 89.9% of the patients received radiotherapy and 88.7% received chemotherapy after initial surgery. The median progression-free survival until first recurrence was 7.63 months (IC95% 6.97-8.29). Median overall survival (OS) from GBM diagnosis was 11.96 months (IC95% 10.69- 23.23). At the time of the first progression, surgery was performed in 75 patients, (13.9%), 18 cases were treated with a second radiotherapy (3.3%), second line CT was administered in 268 patients (49.6%), 221 cases received only chemotherapy (40.9%), 47 cases were treated with both surgery and chemotherapy (8.7%); 28 were treated with surgery without chemotherapy (5.2%), 19 cases had a surgery procedure but we have no data about CT, 223 cases did nor receive CT nor surgery (41%). Median overall survival after relapse was 4.06 months (IC95% 3.25-4.87). For those patients without surgery, median OS after relapse was 3.1 m (IC95% 2.84-3.71) and for patients reoperated, median OS was 12.2 m (IC95% 10.8-13.52) p=0.00 Median overall survival after relapse was 1.7 months (IC95% (IC 1.31-2.08) for patients that did not had CT and 7.03 for those with CT(IC95%5.9-8.16) p=0.00 We also compared the results from different treatment options: median OS was 1.6 m (IC95% 1.11-2.08), for patients without treatment; 6.33 m (IC95% 5.34-7.32) for patients treated with chemotherapy; 12.2 m (IC95%11.05-13.34) for patients treated with surgery and CT;12.1 m(IC95% 4.64-19.55) for patients with surgery. Conclusions: Recurrent glioblastoma is a very aggressive disease. In this retrospective study, patients treated with surgery and surgery and CT could have a clinical benefit in terms of survivalin comparison with those not treated with reoperation. Randomized prospective trials are needed to clarify the role of surgery in recurrent GBM.

[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.

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.

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.

2038 Background: The pRB-dependent cell cycle checkpoint is altered in the vast majority of anaplastic oligodendrogliomas (AO), either by homozygous deletion or by hypermethylation of CDKN2A and/or CDKN2B, or by amplification and/or overexpression of CDK4. Palbociclib is an oral inhibitor of CDK4 and 6 that has already been shown to be highly active in breast cancer. Methods: We conducted a multicenter, open-label, phase II trial evaluating efficacy and safety of Palbociclib in patients with AO that progressed to radiotherapy and more than one chemotherapy regimen containing Temozolomide and/or Lomustine. Inclusion criteria included: histologically and molecularly confirmed grade III oligodendroglioma (WHO 2016 classification, IDH1/2 mutation and 1p/19 codeletion were mandatory), recurrence after radiotherapy and 1 or 2 chemotherapy regimens and conserved RB protein expression by immunohistochemistry (IHC). Patients were treated with Palbociclib 125 mg/daily 3 weeks on/1off. The primary objective of the study was progression-free survival at 6 months (6M-PFS). Results: Between October 2015 and September 2018, 34 patients were enrolled across ten hospitals. The study was stopped early secondary to lack of efficacy, with 74% of evaluable patients progressing within 6 months. Number of patients alive and free from progression at 6 months after the enrollment was 9 (26%) out of the first 34 patients, below the minimum number required (18 out of 40) to consider Palbociclib as an active drug in this population. With a median follow-up of 11.2 months, the median PFS was 3 months (95% CI: 2.5-3.5 months). Median overall survival (OS) was 23.1 months (95% CI: 17.2-25 months). There were no partial or complete responses and only 11 patients (32%) achieved stable disease as best response. Palbociclib was well tolerated with neutropenia (Grade 3 or 4: 40%) and thrombocytopenia (Grade 3 or 4: 15%) as the most common adverse effects (AEs). Both AEs had no significant impact since there were no episodes of febrile neutropenia or bleeding. Conclusions: Despite the good tolerance and drug exposure, Palbociclib monotherapy did not show favorable activity in recurrent AO. Clinical trial information: NCT02530320.

2001 Background: The GEINO-14-01 trial (NCT02209948) investigated the role of extending temozolomide (TMZ) for 6 cycles after the standard 6 cycles to improve 6m-PFS, SLP and OS in newly diagnosed glioblastoma (GBM) patients (p). Methods: Between 08/2014 and 11/2018, 166 p were screened and 159 randomized to extend (80p) or not (79p) TMZ treatment for 6 cycles after proving stable disease in the MRI performed before inclusion. Centralized review of histology and determination of MGMT status, if not previously available, were performed before randomizing patients. Two criteria of stratification were used: MGMT status and presence/absence of residual disease on the basal MRI (defined as a residual enhancement larger than 1cm in one). The primary endpoint was differences in 6mPFS, secondary endpoints were differences in PFS, OS, toxicity, between arms and per stratification factors. Results: Median age was 60.3 (range 29-83), 97p (61%) were methylated, basal MRI showed residual disease in 57p (35.8%). After a median follow up of 14.0 months, with 121 p(76.1%) already progressed and 81p (50.9%) already dead, median PFS is presented. Median (m) PFS is 8.0 months (95%CI: 5.7-10.2). There is no difference in mPFS between arms (adjusted HR = 0.98, 95% CI: 0.82-1.18, P = 0.907). Methylated tumors had longer mPFS (HR=0.57, 95% CI: 0.39-0.83, P=0.004) irrespectively to the study treatment. Conclusions: There is not apparent benefit of continuing TMZ treatment for more than 6 cycles. Data will be actualized for the congress.Supported by a Grant of the ISCIII: PI13/01751. Clinical trial information: NCT02209948.

e13517 Background: Glioblastoma (GB) is an aggressive tumor. Circulating Endothelial Cells (CECs) can be detected in peripheral blood and have been related to angiogenesis. CECs have an unclear prognostic value in patients with glioblastoma. The objective of this study was to quantify the presence and number of CECs in GB patients and determine its potential prognostic role. Methods: In this prospective, single center study, peripheral blood samples were obtained at the time of GB diagnosis. For the detection of CECs, 4 ml of blood was analyzed using the CellSearch system (Veridex). CEC blood samples were classified as CD146+, CD105+, CD45− and DAPI+. CEC detection was performed prior to surgery in a total of 26 patients and 22 patients with glioblastoma were included in the final analysis. We mesured progression free survival (PFS) and overall survival (OS). Results: Between 2014 and 2016, twenty two patients with histologically confirmed glioblastoma were studied. There were 14 males and 8 females with an average age of 63 years (range 42-81). A complete resection was achieved in 50% of cases, partial or subtotal resection in 31.8% and biopsy in 18%. The mean number of CECs was 59.3 cells/mL (range 0-954). Patients were classified into two groups depending on the number of CECs: group 1 had a CEC count below the mean and group 2 had a CEC count above the mean. A total of 17 patients (77.2%) were in group 1 and 5 patients (22.7%) were in group 2.The median OS was 14.4 months (range -0.36-33.36) for the entire study population. The median OS was 17.4 months (IC95% 11.47-23.37) for patients in group 1 and 8.12 months for patients in group 2 (IC 95% 4.38-11.85) p = 0.002. The median PFS was 8.94 m (IC95% 5.1-12.69) for group 1 and 3.95 for group 2 (IC 95% 2.91-4.98) p = 0.097. Conclusions: CECs can be detected in recently diagnosed GB patients. The present study demonstrates a possible prognostic value for CEC determination in GB cases at the time of diagnosis.

TPS3123Background: Solid pediatric tumors that appear in adulthood are a heterogeneous group that share some characteristics such as low incidence, lack of standard therapeutic options and reduced ...

Las metastasis en la region selar e hipotalamica son raras y la principal manifestacion clinica es la diabetes insipida. Un hipopituitarismo concomitante se produce en muy pocas ocasiones. Presentamos el caso de un varon de 54 anos con carcinoma microcitico de pulmon e hipopituitarismo. Una resonancia magnetica cerebral revelo una lesion en la cara anterior del tercer ventriculo sin etiologia clara. El paciente inicio tratamiento con quimioterapia y la lesion desaparecio. Por lo tanto, el paciente fue diagnosticado de hipopitituarismo secundario a metastasis hipotalamica de carcinoma microcitico de pulmon.

11070 Background: The GMI is a marker of drug activity and represents an intra-patient comparison of successive time to progression (TTP), defined as the TTP ratio between the second (or later) line (TTPn) of therapy divided by the prior line (TTPn−1). Defining a clinical profile of pts with GMI >1.33 could help to identify pts who can gain greater benefit from T. Methods: We retrospectively evaluated the concordance between the GMI and the efficacy outcomes and clinical profiles of 198 pts with ASTS treated with trabectedin 1.5 mg/m² (24-h infusion q3w) as a 2nd or further-line treatment from Jan 2007 to Jun 2016. Results: After a median follow-up of 58 months (m; range: 18-172) median overall survival from ASTS diagnosis (MOS) and from T (MT-OS) were 27.5 m (23-32.1) and 10.8 m (8.9-12.7), respectively, while median TTP from T (MT-TTP) and T-1 were 3.4 m (2.8-4) and 3.5 m (2.8-4.2). Overall, 106 pts (53%) had a GMI 1.33. A high GMI (1.33) correlated with favorable efficacy outcomes: MT-OS: 23 vs 36 m (p 8.1 m (2.24, 95%CI 1.19-4.18) and Karnofsky >80 (2.3, 95%CI 1.00-5.28) as factors independently associated to GMI> 1.33. Based on these 3 variables we defined a new GEISTRA score assigning 1 point for each adversely affected variable: non L-Sarcoma, MFI

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.

790 Background: The role of adjuvant chemotherapy (AC) after chemoradiotherapy and surgery in stage II and III of rectal cancer is not well defined. Neither the regimen nor the duration is clear. Besides, guidelines from different expert groups are conflicting. Methods: 224 patients diagnosed from January 2003 to December 2013 with rectal adenocarcinoma T3/T4 and/or positive node staged by ultrasound or magnetic resonance imaging was collected retrospectively from the Pathology Department data base. Results: Of the 224 patients 61.6% were male, median of age at diagnosis 68.6 years (range 31.3-85.4). All of them received 50.4 Gy with different concomitant regimens (capecitabine, continuous infusion of fluoracil or bolus of fluoracil-leucovorin). 13.4% of patients achieved a pathological complete response. 76.8% of the cohort received adjuvant chemotherapy. The main reasons for not receiving chemotherapy were ECOG ≥ 2, surgery complications and a decision of the patient. 51.2% of patients received an oxaliplatin based regimen and the median time of chemotherapy duration was 4 months (range 1-6 months). Local relapse was diagnosed in 6.3% of patients while a systemic relapse was found in 22.3%. Patients without AC had a mean overall survival (OS) of 85.5 months (CI 95% 70.7-100.4) versus 119.8 monts (CI 95% 110.8-128.8) in the AC cohort (p 0.002) without reaching the median after 58 months (range 8-153.9) median follow-up. Disease free survival (DFS) was also better in the AC cohort with a mean DFS of 104 months (CI 95% 94.3-113.6) versus 71.4 months (CI 95% 55.4-87.4), p = 0.01. Conclusions: AC after chemoradiotherapy and surgery in stage II and III rectal cancer as a standard does not exist. In our cohort, AC showed a significant improve in OS and DFS, but the limitations of a retrospective study should be considered, as well as the impact of surgery on metastasis and salvage chemotherapies. Randomized studies are clearly needed.

e15145Background: Data of outcomes of elderly patients ( ≥ 70) with stage II and III rectal cancer treated with multimodal treatment (neoadjuvant chemoradiotherapy, surgery and adjuvant chemotherap...

737 Background: There is some evidence relating delay of surgery (DS) by more than 8 weeks after the end of chemoradiotherapy and achievement of complete pathological response (ypCR). However, the relationship with overall survival (OS) seems to be negative. Methods: Records of 171 patients diagnosed from January 2003 to December 2011 with rectal adenocarcinoma T3/T4 and/or positive node staged by ultrasound or MRI were collected retrospectively from the Pathology Department database. Results: Of the 171 patients, 62% were male, median age at diagnosis 69.3 years (31.3 years -85.3 years). All of them received 50.4 Gy with different concomitant regimens (capecitabine, continuous infusion of fluoracil or bolus of fluoracil-leucovorin). 72.5% of the cohort received adjuvant chemotherapy. 13% of patients achieved ypCR, independently of DS (13.7% in DS vs 11.8%, p 0.722). OS was significantly worse among DS patients (67.9 months vs 54.8 months, p 0.016). In addition, more sphincter preservations (SP) were not achieved (60.8% in DS vs 57.1%, p 0.881). Conclusions: In contrast with published literature, in our cohort DS failed to show higher rates of ypCR. Neither an improvement in OS or SP was observed with DS. It is recommended that clinical trials be designed in order to establish ideal surgical timing.

e21520 Background: Kaposi Sarcoma (KS) is a lymphoangioproliferative disease, related to immunodeficiency and may be associated with human herpes virus 8 (HHV-8). KS is classified into four types: ...

e14539 Background: The role of adjuvant chemotherapy (AC) after chemo-Rt and surgery in stage II and III of rectal cancer is not well defined. Neither the regimen nor the duration is clear. Besides...

10530 Background: There are few reports focusing on systemic treatment in osteosarcoma (OS) patients progressing after most active drugs. Preclinical data showed activity of rapamycin in xenograft ...