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Background Glioblastoma (GB) is the most common malignant CNS tumor. Incidence ingreases with age, peaking between 69 and 84 yers, and half of patients diagnosed have > 65 years. The question about how to treat these patients remains object of controversy. The purpose of this survey was to know the treatment recommendations for BG in academic Spanish hospitals. Methods In 2018, surveys were e-mailed to all members of GEINO (Spanish Group for Neurooncology Reseach). The survey contained specific questions on the routine clinical practice regarding treatment recommendations for elderly patients with GB and anaplastic astrocytoma in different clinical situations: depending on ECOG, morbility, MGMT promoter methylation, age intervals (between 65-70 y, 70-80 y, >80 y). Response options were: a) Stupp regimen, b) Perry regimen, c) Radiation or TMZ depending on MGMT status and d) supportive care. Participants were also asked if they used MGMT status to select patients for Stupp or Perry regimen. Results Twenty-six neuro-oncoligist from twenty-six hospitals completed the survey. Mean of hospital beds of the institutions were 833.19 (range 150-1500). Mean of hospital veds of the instituions were 833,19 (range 150-1500). Median number of new cases treated per year were 31 (range 8-80). In patients with ECOG 0-1 and between 65 and 70 years old, 80.8 % of participants would recommend treatment with Stupp regiment. For patients with ECOG 0-1 and between 70-80; 46.2 % recommenden Perry regimen in methylated (M) and unmethylated (UM) patients; 38.5 % recommended Stupp regimen in both. For with ECOG 0-1 and > 80 % yo, 46,2 % recommend Perry regimen in both M and UM; 3.8 % Stupp regimen; 15,4 % radiation or TMZ according to MGMT status. In patients with anaplastic astrocytoma aged 70-80 y, 46,2 % would recommend Perry regimen and 42,3 % Stupp regimen. Table: 411P . Most recommend treatment Percentage of responders Glioblastoma, age 70-80 (PS 0-1, minor comorbility) Perry Stupp 46.2 % 38.5 % Glioblastoma, age >80 (PS 0-1, mior comorbility Perry 46.2 % Glioblastoma, age 65-70 (PS 0-1, minor comorbility) Stupp 80.8 % Glioblastoma, no MGMT methylation 70-80 >80 65-70 Stupp Perry Stupp 50 % 34.6 % 68.5 % Glioblastoma >65, PS > 2 Stupp 36.8 % Anaplastic astrocytoma 70-80 yo Perry 30.8 % Anaplastic astrocytoma >80 Perry 34.6 % Anaplastic astrocytoma 65-70 Stupp 53.8 % Conclusions Our research demonstrates there is no uniform approach to the management of elderly patient with glioblastoma among academic neuro-oncologist. Legal entity responsible for the study GEINO (Grupo Espanol de Investigacion en Neurooncologia). Funding Has not received any funding. Disclosure M. Vaz Salgado: Advisory / Consultancy, Travel / Accommodation / Expenses: Pharmamar; Advisory / Consultancy: Lilly, Eisai y Celgene; Research grant / Funding (self): Pfizer. M. Vieito Villar: Travel / Accommodation / Expenses: Roche. R. Luque: Honoraria (self), Travel / Accommodation / Expenses: Janssen-Cilag; Honoraria (self), Travel / Accommodation / Expenses: Sanofi Aventis; Honoraria (self), Travel / Accommodation / Expenses: Astellas Medivation; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Travel / Accommodation / Expenses: Bristol Mayers Squibb; Honoraria (self), Travel / Accommodation / Expenses: EUSA Pharma. All other authors have declared no conflicts of interest.

In high risk gastric and gastroesophageal adenocarcinoma, adjuvant radiochemotherapy with 5-fluorouracil bolus became a standard adjuvant treatment, showing significant improvement in overall survival after surgery, although with substantial toxicity. We explored the efficacy and toxicity of a modified 5-fluorouracil continuous infusion scheme.We conducted an observational retrospective study in our centre. Gastric/gastroesophageal junction adenocarcinoma patients were treated with a schedule consisting in four infusions of bolus 5-fluorouracil 400 mg/m(2) iv with leucovorin 200 mg/m(2) iv and 1200 mg/m(2) in 46-hour infusion of 5-fluorouracil (D'Gramont scheme), followed by concomitant radiochemotherapy (45 Gy in 25 fractions of 1.8 Gy) with 5-fluorouracil continuously infusion 225 mg/m(2)/day and four additional infusions of chemotherapy one month after complete radiochemotherapy.Between January 2007 and December 2013, 55 patients received a mean of 3.16 bi-weekly adjuvant infusions followed by 4.6 weeks of continuous treatment concurrent with radiotherapy and 3.72 bi-weekly infusions after radiotherapy treatment. During adjuvant treatment, grade III toxicity was mostly haematologic, while gastrointestinal and cutaneous toxicity was predominant during concurrent treatment. There were no grade IV- or treatment-related deaths during this study. Disease-free survival (DFS) was 79.2 months (56.3-102.1 months), and the 3-year survival rates were 52.7 %.This 5-fluorouracil infusional scheme has an excellent tolerability profile and favourable efficacy results.

Background The role of cfDNA-based analyses in the management of patients (pts) receiving ICIs is still poorly understood. We have implemented a translational program to systematically obtain blood samples of pts receiving ICIs in phase I clinical trials for cfDNA monitoring. Methods Since August 2018, 92 pts were prospectively included and baseline blood samples and prior to every cycle were collected. Plasma cfDNA was isolated using QIAamp Circulating Nucleic Acid Kit and measured using Qubit fluorometer. DNA fragments length and profile were assessed using Agilent 2100 Bioanalyzer. Pts with baseline and prior to cycle 2(preC2) blood samples and at least 1 tumor assessment have been included in the analysis. We established 2 groups based on variations of cfDNA levels on preC2 related to baseline: 1) cfDNA progression group as increase (>0% cfDNA change) 2) cfDNA response group as decrease ( Results 92 pts with different advanced tumor types were included. Median number of previous lines was 2.38. Median time from baseline cfDNA to preC2 was 22.82 days and from preC2 to first tumor assessment was 32.18 days. PFS in the cfDNA response group (38 pts) was higher compared with cfDNA progression group (54 pts); median 4.87 m (3.11 – 6.62) and 3.0 m (2.24-3.76), respectively (HR = 0.49 [0.28-0.86] p Conclusion The monitoring of early changes of cfDNA levels is a fast approach to predict response to ICI therapy in our cohort. Further validation of these results and correlation with circulating tumor DNA is ongoing. Legal entity responsible for the study The authors. Funding This research has been partially funded by the Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI), supported by the Banco Bilbao Vizcaya Argentaria Foundation (BBVA Foundation) - Grant 9/2017. Disclosure C. Hierro Carbo: Research grant / Funding (self): Bayer; Honoraria (self): Ignyta; Honoraria (self), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Travel / Accommodation / Expenses: Roche. J. Martin-Liberal: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Bristol-Myers Squibb; Travel / Accommodation / Expenses: Astellas. I. Brana: Speaker Bureau / Expert testimony, Research grant / Funding (self): Bristol-Myers Squibb; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): Regeneron; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Incyte; Speaker Bureau / Expert testimony, Research grant / Funding (self): Orion Pharma; Research grant / Funding (institution): Merck Serono; Research grant / Funding (self): Celgene; Research grant / Funding (self): Janssen; Research grant / Funding (self): Kura; Research grant / Funding (institution): Pfizer. M. Vieito Villar: Travel / Accommodation / Expenses: Roche. E. Elez: Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Speaker Bureau / Expert testimony, Research grant / Funding (self): Merck Serono; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Speaker Bureau / Expert testimony: Servier. E. Felip: Speaker Bureau / Expert testimony: ABBVIE; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Blueprint; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Advisory / Consultancy: Guardant; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy: Janssen. R. Dienstmann: Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Research grant / Funding (self): Merck Serono; Advisory / Consultancy: Symphogen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: IPSEN; Advisory / Consultancy: Astellas. A. Gros: Research grant / Funding (institution): Novartis. J. Tabernero: Advisory / Consultancy: Array; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Beigene; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Chugai; Advisory / Consultancy: Genetech; Advisory / Consultancy: Genmab; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Roche; Advisory / Consultancy: Inflection Bioscience; Advisory / Consultancy: IPSEN; Advisory / Consultancy: Kura; Advisory / Consultancy: Lilly; Advisory / Consultancy: Menarini; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck; Advisory / Consultancy: Merrimarck; Advisory / Consultancy: Merus; Advisory / Consultancy: Molecular Partners. E. Garralda: Advisory / Consultancy: ROCHE; Advisory / Consultancy: Ellipses; Advisory / Consultancy: Neomed; Advisory / Consultancy: Janssen; Advisory / Consultancy: Boehringer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): MSD; Advisory / Consultancy: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

Background Life expectancy longer than 12 weeks(w) is a common inclusion criteria for most Ph1. Despite the presence of several prognostic indeces in drug development, their value for patient selection in clinical trials is not well established. VIO is a immune-oncology score validated in patients treated in Ph1 with immunotherapy (Hierro C. ESMO 2018), which includes 5 variables: albumin upper limit normal, dNLR (derived neutrophil/(leukocytes minus neutrophils) ratio) >3, >2 sites of metastases, and presence of liver metastases. Methods VIO variables were retrospectively collected from 384 patients with advanced disease treated in Ph1 with immune checkpoint inhibitors (ICIs) or targeted agents (TAs) since 2011 to 2017 at Vall d´Hebron Hospital. The following VIO clusters were defined based on Kaplan Meier OS estimates: good prognosis (0‐1), intermediate (2‐3) and poor prognosis (4‐5). We aimed to improve patient selection for Ph1 (independent of treatment type) by developing a composite VIO score that is associated with overall survival (OS), progression free survival (PFS) and objectively estimated life expectancy at 12 w. Results From the 384 patients treated with ICIs (53.6%) or TAs (45.4%) in Ph1, 206 (53.6%) were female, 210 were treated with monotherapy (54.7%). Most frequent tumor types were: colorectal (17.4%), breast (14.1%) and lung (9.4%). The median follow-up was of 8.4 months (m) [IC95% 7.3-9.5]. Estimated median OS in good prognosis (33.3% of all pts), intermediate (54.2%) and poor prognosis (12.5%) was 16.2 m (13.3‐19.1), 7.8 m (6.9‐8.6) and 2.9 m (2.1-3.8), respectively (log rank test, p Conclusions VIO score is a strong prognostic index independent of the treatment type and it could be useful as a tool to estimate objectively life expectancy Legal entity responsible for the study The authors. Funding This research has been funded by the Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI) supported by the Banco Bilbao Vizcaya Argentaria Foundation (FBBVA) (grant 89/2017). Disclosure J. Martin-Liberal: Advisory / Consultancy: Bristol-Myers Squibb, Novartis, Pierre Fabre, Roche; Speaker Bureau / Expert testimony: Astellas, Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre, Pfizer, Roche; Honoraria (self): Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Ipsen. A. Azaro: Honoraria (self), Advisory / Consultancy: Novartis, Roche, Orion. I. Brana: Advisory / Consultancy: Orion pharma; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Merck Serono; Research grant / Funding (self): AstraZeneca, BMS, Celgene, Gliknik, GSK, Janssen, KURA, MSD, Novartis, Northern Biologics, Orion Pharma, Pfizer, Roche.. M. Vieito Villar: Honoraria (self), Travel grant: Roche. E. Munoz-Couselo: Advisory / Consultancy: Amgen, Bristol-Myers Squibb, Merck, Sharp & Dohme, Novartis, Pierre Fabre, and Roche; Honoraria (self): Amgen, Bristol-Myers Squibb, Merck, Sharp & Dohme, Novartis, Pierre Fabre, Sanofi and Roche. E. Elez Fernandez: Honoraria (institution): Array, MSD, Abbvie, Amgen, GSK, AstraZeneca,Bristol-Myers Squibb, Novartis, Boehringer Ingelheim, Hoffman La-Roche; Advisory / Consultancy: Hoffman La-Roche, Bristol-Myers Squibb, Servier, Amgen, Merck Serono, Array, Sanofi. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie, AstraZeneca, Blueprint medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant Health, Janssen, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Touchtime; Research grant / Funding (self): Fundacion Merck Salud, Grant for Oncology Innovation EMD Serono.. J. Carles: Research grant / Funding (self): AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, INC, Astellas Pharma., AstraZeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim Espana, S.A., Bristol-Myers Squibb Inter; Advisory / Consultancy: Bayer / Johnson & Johnson / Bristol-Myers Squibb / Astellas Pharma / Pfizer / Sanofi / MSD Oncology / Roche/ AstraZeneca; Speaker Bureau / Expert testimony: Bayer / Johnson & Johnson / Asofarma / Astellas Pharma. J. Tabernero: Advisory / Consultancy: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Part. R. Dienstmann: Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Roche, Symphogen, Ipsen, Amgen, Sanofi, MSD, Servier; Research grant / Funding (self): Merck. E. Garralda: Advisory / Consultancy: F.Hoffmann-La Roche,Ellipses Pharma ,Neomed Therapeutics1 Inc,Boehringer Ingelheim ,Janssen Global Services; Speaker Bureau / Expert testimony: Bristol-Mayers Squibb; Honoraria (self): Menarini, Glycotope, Menirarini. All other authors have declared no conflicts of interest.

Introduction Although there has not been a direct comparison between neoadjuvant chemotherapy followed by chemor-radiation with the standard treatment of concurrent chemor-radiation, neoadjuvant chemotherapy is active in squamous cervical cancer. Material and methods In this open label 1 arm phase two trial we accrued 19 patients from 2007 to 2011 diagnosed with squamous cervical cancer deemed to be unresectable and poor candidates to concurrent chemor-radiation. Patients had to be over 18 years of age, give informed consent, have a PS0-1 and adequate organ function. They received neoadjuvant chemotherapy with paclitaxel 80mg/m2 and cisplatin33mg/m2 days 1,7,15/28 for two cycles and then external radiation in 1.8 Gy/ fraction with concurrent cisplatin 40mg/m2/weekly followed by brachytherapy in 5-6 applications. After completion of neoadjuvant treatment and after concurrent chemor-radiation patients were evaluated by RECIST 1,1 criteria for tumor response with a CT scan and pelvic MNR and data of dose intensity and toxicity was accrued. Results Median age at diagnosis was 51 years (27 to 72 years); all the patients had PS1 due to local pain, asthenia or genital discharge. Neoadjuvant treatment was feasible in all patients with manageable toxicities; the dose intensity delivered was 97% of the preplanned dose. Only 2 episodes of grade III anemia were observed. In the first radiologic evaluation 4 patients had a complete response, 12 had partial response and 3 disease stabilization. Patients received external radiotherapy in fractions of 1.8 Gy achieving a dose of 66 GY in patients that could not receive brachytherapy. Mean EQD2C for those who did (68%) was 72 GY. Only 68% of the patients received the full preplanned concomitant dose due to toxicity, mainly grade III anemia and diarrhea. In the second radiological evaluation 9 patients had a complete response, 9 partial and only 1 stable disease. At a mean of 24 months of follow up only 5 patients (26%) thus far have developed recurrent disease, all of the recurrences were simultaneously local as well as systemic. Conclusion Our weekly cisplatin-paclitaxel regimen has been demonstrated to be feasible and effective in terms of dose delivery, tolerance and radiological responses without compromising definitive treatment with chemor-radiation. Disclosure All authors have declared no conflicts of interest.

Background CChRT is recommended as the evidence-based approach for the management of patients (p) with locally advanced stage III NSCLC and a good performance status, although a clearly superior regimen has not been identified. The aim of our study was to evaluate the effectiveness and toxicities of CChRT with bi-weekly Docetaxel (D) and Cisplatin (C) and thoracic radiotherapy. Methods Between May 2009 and March 2012, 43 chemo-naive p with histologically confirmed inoperable locally advanced NSCLC, stage IIIAN2/IIIB (no pleural T4) and adequate lung function (FEV1 > 1, V20 Results The p characteristics were: mean age 60 years (34-75); male/female 39/4; ECOG PS 0/1 in 11/32 p; squamous/adeno/large cell carcinoma: 62.8%/27.9%/9.3%; stage IIIAN2 11 p (25.6%) and stage IIIB 32 p (74.4%). 39 p were evaluable for response (in treatment 4 p) and 43 p for toxicity. 39 p completed CChRT and were evaluable with 4 CR, 25 PR (RR 74,4%; 95% CI:60-88), 4 SD (10.2%) and 6 PD (15.4%). The median PFS was 15 months (95% CI: 13-17) and median OS was 19 months (95% CI:13-25). The PFS and OS at 1/2 years were 59%/38% and 85%/46% respectively. A total of 43 cycles of D-C induction chemotherapy were given; main toxicities (NCI-CTC 3.0) per p Grade (g) 1-2/3-4 (%) were as follows: neutropenia 2.3/13.9; anemia 13.9/0; nausea/vomiting 23.2/2.3; diarrhea 25.5/2.3; febrile neutropenia, 2 p. Main toxicities per p in CChRT (D-C doses: 147, 3.4 per p; mean doses RT: 63,4 Gys) were g1-2/3 (%): neutropenia 25.5/6.9; anemia 43.9/0; nausea/vomiting 18.6/0; fatigue 37.2/4.6; esophagitis 46.5/2.3 and pneumonitis 39.5/0; there were three episodes of hospitalization: febrile neutropenia, 2 p and g3 esophagitis, 1 p. Conclusions CChRT with bi-weekly Docetaxel and Cisplatin and thoracic radiotherapy is a feasible treatment option for inoperable locally advanced stage III NSCLC, showing good clinical efficacy and tolerability with promising survival. Disclosure All authors have declared no conflicts of interest.

Background Chromosomal rearrangements in the receptor tyrosine kinase (RTK) ROS1 define a new molecular subset of NSCLC. ALK inhibitors can inhibit ROS1 kinase activity in cell lines. We examined the efficacy and safety of crizotinib, a small molecule inhibitor of two other RTKs, MET and ALK, in patients with advanced, ROS1-rearranged NSCLC. Methods Patients with advanced NSCLC harboring ROS1 rearrangement, as determined using a break-apart FISH assay, were recruited into an expansion cohort of the original phase 1 study of crizotinib. Patients were treated with crizotinib at the standard oral dose of 250 mg BID. The objective response rate (ORR) was determined based on RECIST v1.0. The disease control rate (DCR; stable disease [SD] + partial response [PR] + complete response [CR]) was evaluated at weeks 8 and 16. Results At the time of data cut-off on April 19, 2012, 15 patients with ROS1 NSCLC had received crizotinib and 14 were evaluable for response. The median age was 54 years (range 31–72). Fourteen patients were never-smokers and all had adenocarcinoma histology. All patients were confirmed negative for ALK rearrangement. The median number of prior treatments was 1 (range 0–6). The first ROS1 patient received crizotinib on October 19, 2010. To date, the ORR is 57% (8/14; 95% CI 28.9–82.3), with 7 PR and 1 CR. There were 4 SD, one of which was unconfirmed as PR at the time of data cut-off. The DCR at 8 weeks was 79% (11/14). Median duration of treatment was 25.7 weeks (range 0.1 + to 65.3 + ), and 12 patients continue on study. The pharmacokinetics, antitumor activity and safety profile of crizotinib in this group of patients were similar to those observed in patients with ALK-positive NSCLC. Conclusions Crizotinib is associated with clinically significant antitumor activity in patients with ROS1 NSCLC. Similar to ALK, ROS1 rearrangement defines another unique molecular subset of NSCLC patients for whom crizotinib therapy may be highly effective. Importantly, this study represents the first clinical investigation of ROS1 as a driver mutation and therapeutic target in cancer. Disclosure S.I. Ou: Advisory role: Pfizer, Genentech. Compensated Honoraria: Pfizer, Genentech, Lilly. Myself Research funding: Pfizer. Myself (institution). D.R. Camidge: Advisory role: Pfizer. Myself. Honoraria: Pfizer. Myself. L. Tye: Employment: Pfizer. Clinician. Myself. Stock Ownership; Pfizer. Myself. K. Wilner: Emplyement: Pfizer. Senior Director. Myself. Compensated. Stock ownership: Pfizer. Myself. M. Varella-Garcia: Honoraria: Abbott Molecular. Myself. funding for the trial provided by NIH - yes. A.T. Shaw: Advisory role: Pfizer, Ariad, Chugai, Novartis, Daiichi-sankyo. Myself. Compensated Research funding: Astra Zeneca, Novartis. Myself. All other authors have declared no conflicts of interest.

e12553 Background: The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 12 to 24 weeks. The combination of irinotecan and bevacizumab was showed as a...