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The recent identification of rearrangements of neurotrophic tyrosine receptor kinase (NTRK) genes and the development of specific fusion protein inhibitors, such as larotrectinib and entrectinib, have revolutionized the diagnostic and clinical management of patients presenting with tumours with these alterations. Tumours that harbour NTRK fusions are found in both adults and children and are either rare tumours with common NTRK fusions that may be diagnostic, or more common tumours with rare NTRK fusions. To assess the currently available evidence, 3key Spanish medical societies (the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Pathology (SEAP) and the Spanish Society of Paediatric Haematology and Oncology (SEHOP) have brought together a group of experts to develop a consensus document that includes guidelines on the diagnostic, clinical and therapeutic aspects of NTRK-fusion tumours. It also discusses the challenges related to the routine detection of these genetic alterations in a mostly public health care system.

Purpose Osimertinib has proven efficacy in EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) patients; however, its benefits have not been evaluated in a real-world setting. Methods ASTRIS is a single-arm, open-label, multinational study to evaluate the efficacy and safety of osimertinib for the treatment of EGFR T790M mutation-positive NSCLC. We present the study design and preliminary cut-off analysis results (as of October 2017) describing the baseline characteristics and methodology for T790M mutation detection in the Spanish cohort. Results The Spanish cohort included 131 patients from a total 3014 patients. Forty patients (28.1%) were still undergoing therapy at the time of cut-off; 68.7% were women and 97.7% were Caucasian, with a mean age of 64.8 (SD 11.7) years. The most common type of sample for evaluating T790M mutations was tissue (55.0%), and samples were obtained from the primary tumor in 61.1% of cases. Mutation analysis was performed by the local laboratory in 60.3% of cases and using the Roche Cobas® EGFR assay in 43.5% of cases. Conclusions ASTRIS is expected to confirm the benefits of osimertinib in a real-world setting. Data on real-world practices for the detection of the EGFR T790M mutation may provide additional information for the designing of guidelines for best practices.

Objective: Long-term survivors (LS) of non-small cell lung cancer (NSCLC) without driver alterations, displaying an overall survival (OS) of more than 3 years, comprise around 10% of cases in several series treated with chemotherapy. There are classical prognosis factors for these cases [stage, Eastern Cooperative Oncology Group (ECOG), etc.], but more data are required in the literature. In this multi-center study, we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization. Methods: In the first step, we conducted a clinical-pathological characterization of the patients. Afterwards, we carried out a genetic analysis by comparing LS to a sample of short-term survivors (SS) (with an OS less than 9 months). We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS, and later confirmed these with reverse transcription-polymerase chain reaction (RT-PCR) for the rest of the samples. Results: A total of 94 patients were included, who were mainly men, former smokers, having adenocarcinoma (AC)-type NSCLC with an ECOG of 0–1. We obtained an initial differential transcriptome expression, displaying 5 over- and 33 under-expressed genes involved in different pathways: namely, the secretin receptor, surfactant protein, trefoil factor 1 (TFF1), serpin, Ca-channels, and Toll-like receptor (TLRs) families. Finally, RT-PCR analysis of 40 (20 LS/20 SS) samples confirmed that four genes (surfactant proteins and SFTP) were significantly down-regulated in SS compared to LS by using an analysis of covariance (ANCOVA) model: SFTPA1 (P = 0.023), SFTPA2 (P = 0.027), SFTPB (P = 0.02), and SFTPC (P = 0.047). Conclusions: We present a sequential genetic analysis of a sample of NSCLC LS with no driver alterations, obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

Background: Previous reports indicate that lung cancer patients are at an increased risk of severe COVID-19 disease and higher mortality rate compared to general population. However, prognostic factors are not yet clearly identified. The LunG canceR pAtients coVid19 Disease (GRAVID) study aimed to describe clinical characteristics, outcomes and predictors of poor prognosis in patients with lung cancer and COVID-19. Methods: In this large nationwide prospective study, medical records of lung cancer patients with COVID-19 diagnosis from 65 spanish hospitals were included. Clinical features, treatments and disease outcomes were collected. The primary endpoint was to determine any-cause mortality; secondary endpoints were hospitalization and admission at intensive care units (ICU). Risk factors of poor prognosis were identified by univariable and multivariable logistic regression models. Results: Overal, 447 patients were analysed. Mean age was 67.1 ± 9·8 years, and the majority were men (332, 74·3%) and current/former smokers (383 (85.7%). NSCLC was the most frequent cancer type (377, 84.5%), being adenocarcinoma (228, 51·0%) the predominant histology. 354 patients (79.2%) had unresectable stage III or metastatic disease, and 266 (59.5%) where receiving anticancer treatment, mostly first-line chemotherapy. 350 (78.3%) patients were hospitalized for a mean of 13·4 ± 11·4 days, 9 (2.0%) patients were admitted to ICU, and 146 (32.7%) patients died. Advanced disease and corticosteroid treatment at hospitalization were predictors of mortality. Non-terminal stage hospitalized patients with lymphocytopenia and high LDH showed an increased risk of death. Severity of COVID-19 correlated to mortality, admission at ICU and mechanical ventilation. Conclusion: With underlying comorbidities and immunocompromised status, patients with lung cancer and COVID-19 present high hospitalization and mortality rates. These outcomes, alongside the identification of prognostic factors, may inform physicians on risks and benefits for this population to provide individualized oncological care. Citation Format: Jose Maria Mazarico Gallego, Antonio Calles, Monica Antoñanzas, Cristina Pangua, Xabier Mielgo Rubio, Ernest Nadal, Rafael Lopez Castro, Ana Lopez-Martin, Edel del Barco, Manuel Domine, Virginia Calvo, Pilar Diz, Carmen Sandoval, Elia Sais Girona, Ivana Gabriela Sullivan, M. Angeles Sala, Gema Garcia Ledo, Jose Ramon Jarabo, Rosa Alvarez Alvarez, Javier Baena, Maria Gonzalez-Cao, Mariano Provencio. COVID-19 disease in patients with lung cancer in Spain: GRAVID Lung Cancer Patients Disease (GRAVID study) [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S12-04.

Despite decades of research, prognosis for SCLC patients remains poor, and treatment options limited. SCLC is an immunogenic tumor with high somatic mutation rates due to tobacco exposure resulting in potential neo-antigens, the presence of suppressed immune responses, and occurrence of paraneoplastic disorders. The use of T cell immune-checkpoint inhibitors (anti-PD1: nivolumab, pembrolizumab; anti-PD-L1: atezolizumab, durvalumab; anti-CTLA-4: ipilimumab, tremelimumab) have shown promising antitumor activity with the potential to prolong survival in SCLC patients. In fact, atezolizumab when combined with chemotherapy has achieved the milestone of being the first drug to improve survival in patients with newly diagnosed extensive-stage SCLC. Other immunotherapeutic approaches evaluated in clinical trials for SCLC include the use of cytokines, cancer vaccines, antiganglioside therapies, TLR9 inhibition, anti-Notch signaling, and anti-CD47. This review discusses the rationale and clinical evidence of immunotherapy in SCLC, the conflictive clinical results of novel immunotherapeutic agents and combinatorial therapies under evaluation in SCLC patients.

Among all Soft Tissue sarcomas there are some subtypes with low incidence and/or peculiar clinical behaviour, that need to be consider separately. Most of them are orphan diseases, whose biological characteristics imply a clearly different diagnostic and therapeutic approach from other more common sarcoma tumors. We present a brief and updated multidiciplinary review, focused on practical issues, aimed at helping clinicians in decision making. In this second part we review these subtypes: Alveolar Soft Part Sarcoma, Epithelioid Sarcoma, Clear Cell Sarcoma, Desmoplastic Small Round Cell Tumor, Rhabdoid Tumor, Phyllodes Tumor, Tenosynovial Giant Cell Tumors, Myoepithelial Tumor, Perivascular Epithelioid Cell Neoplasms (PEComas), Extraskeletal Myxoid Chondrosarcoma, NTRK-fusions Sarcomas. Most of them present their own radiological and histopathological feautures, that are essential to know in order to achieve early diagnosis. In some of them, molecular diagnosis is mandatory, not only in the diagnosis, but also to plan the treatment. On the other hand, and despite the low incidence, a great scientific research effort has been made to achieve new treatment opportunities for these patients even with approved indications. These include new treatments with targeted therapies and immunotherapy, which today represent possible therapeutic options. It is especially important to be attentive to new and potential avenues of research, and to promote the conduct of specific clinical trials for rare sarcomas.

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.

Introduction Patients with cancer may be at increased risk of more severe COVID-19 disease; however, prognostic factors are not yet clearly identified. The GRAVID study aimed to describe clinical characteristics, outcomes, and predictors of poor outcome in patients with lung cancer and COVID-19. Methods Prospective observational study that included medical records of patients with lung cancer and PCR-confirmed COVID-19 diagnosis across 65 Spanish hospitals. The primary endpoint was all-cause mortality; secondary endpoints were hospitalization and admission to intensive care units (ICU). Results A total of 447 patients with a mean age of 67.1 ± 9.8 years were analysed. The majority were men (74.3 %) and current/former smokers (85.7 %). NSCLC was the most frequent type of cancer (84.5 %), mainly as adenocarcinoma (51.0 %), and stage III metastatic or unresectable disease (79.2 %). Nearly 60 % of patients were receiving anticancer treatment, mostly first-line chemotherapy. Overall, 350 (78.3 %) patients were hospitalized for a mean of 13.4 ± 11.4 days, 9 (2.0 %) were admitted to ICU and 146 (32.7 %) died. Advanced disease and the use of corticosteroids to treat COVID-19 during hospitalization were predictors of mortality. Hospitalized, non-end-of-life stage patients with lymphocytopenia and high LDH had an increased risk of death. Severity of COVID-19 correlated to higher mortality, ICU admission, and mechanical ventilation rates. Conclusions Mortality rate was higher among patients treated with corticosteroids during hospitalization, while anticancer therapy was not associated with an increased risk of hospitalization or death. Tailored approaches are warranted to ensure effective cancer management while minimizing the risk of exposure to SARS-CoV-2.

Background: Immune checkpoint inhibitors are a new standard of care for patients with advanced non-small-cell lung cancer (NSCLC) without EGFR tyrosine kinase or anaplastic lymphoma kinase (ALK) genetic aberrations (EGFR−/ALK−), but clinical benefit in patients with EGFR mutations or ALK rearrangements (EGFR+/ALK+) has not been shown. We assessed the effect of durvalumab (anti-PD-L1) treatment in three cohorts of patients with NSCLC defined by EGFR/ALK status and tumour expression of PD-L1. Methods: ATLANTIC is a phase 2, open-label, single-arm trial at 139 study centres in Asia, Europe, and North America. Eligible patients had advanced NSCLC with disease progression following at least two previous systemic regimens, including platinum-based chemotherapy (and tyrosine kinase inhibitor therapy if indicated); were aged 18 years or older; had a WHO performance status score of 0 or 1; and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Key exclusion criteria included mixed small-cell lung cancer and NSCLC histology; previous exposure to any anti-PD-1 or anti-PD-L1 antibody; and any previous grade 3 or worse immune-related adverse event while receiving any immunotherapy agent. Patients in cohort 1 had EGFR+/ALK+ NSCLC with at least 25%, or less than 25%, of tumour cells with PD-L1 expression. Patients in cohorts 2 and 3 had EGFR−/ALK− NSCLC; cohort 2 included patients with at least 25%, or less than 25%, of tumour cells with PD-L1 expression, and cohort 3 included patients with at least 90% of tumour cells with PD-L1 expression. Patients received durvalumab (10 mg/kg) every 2 weeks, via intravenous infusion, for up to 12 months. Retreatment was allowed for patients who benefited but then progressed after completing 12 months. The primary endpoint was the proportion of patients with increased tumour expression of PD-L1 (defined as ≥25% of tumour cells in cohorts 1 and 2, and ≥90% of tumour cells in cohort 3) who achieved an objective response, assessed in patients who were evaluable for response per independent central review according to RECIST version 1.1. Safety was assessed in all patients who received at least one dose of durvalumab and for whom any post-dose data were available. The trial is ongoing, but is no longer open to accrual, and is registered with ClinicalTrials.gov, number NCT02087423. Findings: Between Feb 25, 2014, and Dec 28, 2015, 444 patients were enrolled and received durvalumab: 111 in cohort 1, 265 in cohort 2, and 68 in cohort 3. Among patients with at least 25% of tumour cells expressing PD-L1 who were evaluable for objective response per independent central review, an objective response was achieved in 9 (12·2%, 95% CI 5·7–21·8) of 74 patients in cohort 1 and 24 (16·4%, 10·8–23·5) of 146 patients in cohort 2. In cohort 3, 21 (30·9%, 20·2–43·3) of 68 patients achieved an objective response. Grade 3 or 4 treatment-related adverse events occurred in 40 (9%) of 444 patients overall: six (5%) of 111 patients in cohort 1, 22 (8%) of 265 in cohort 2, and 12 (18%) of 68 in cohort 3. The most common treatment-related grade 3 or 4 adverse events were pneumonitis (four patients [1%]), elevated gamma-glutamyltransferase (four [1%]), diarrhoea (three [1%]), infusion-related reaction (three [1%]), elevated aspartate aminotransferase (two [

BackgroundLi–Fraumeni syndrome (LFS) is an autosomal dominant hereditary disease. It is associated with the loss of function of the p53 protein and an increased risk of malignant tumor development at early age. The most frequently detected tumors include breast cancer, sarcomas, leukemia, brain tumors, and adrenocortical carcinomas. While sarcomas account for only 1% of solid tumors, they are more frequently detected in these families.Case presentationWe report a simultaneous diagnosis of hepatic perivascular epithelioid cell tumor (PEComa), a very rare subtype of sarcoma, in two siblings with a LFS.ConclusionsThe simultaneous diagnosis of PEComa in two siblings presented in this case allowed us to review the frequency of PEComa in this genetic syndrome previously reported, which was very little. Despite its rarity, PEComa must be considered in the differential diagnosis of new-onset liver lesions in patients who were previously diagnosed with LFS.

Delphi consensus; Sarcoma treatment; Panel of experts Consenso Delphi; Tratamiento del sarcoma; Panel de expertos Consens Delphi; Tractament del sarcoma; Panell d'experts Soft tissue sarcomas (STS) constitute a heterogeneous group of rare solid tumors associated with significant morbidity and mortality. The evaluation and treatment of STS require a multidisciplinary team with extensive experience in the management of these types of tumors. National and international clinical practice guidelines for STS do not always provide answers to a great many situations that specialists have to contend with in their everyday practice. This consensus provides a series of specific recommendations based on available scientific evidence and the experience of a group of experts to assist in decision-making by all the specialists involved in the management of STS.

A man in his 60s presented with increased oedema in the lower limbs and dyspnoea. Chest X-ray showed right pleural effusion and a body CT scan revealed a severe right pleural effusion as well as presence of solid nodules and pleural plaques. It was decided then to obtain a CT-guided pleural biopsy. Pathology of this biopsy showed an epithelioid mesothelioma. Blood test showed hypoproteinaemia (4.2 g/dL) with hypoalbuminaemia (2.2 g/dL), proteinuria of 1.4 g /24 hours and non-oliguric acute renal failure with serum creatinine of 3.28 mg/dL. A renal biopsy was performed (online supplementary appendix 1). ### Supplementary data [jclinpath-2019-206298supp001.pdf] Review the high quality, interactive digital Aperio slides at http://virtualacp.com/JCPCases/jclinpath-2019-206298/001/, http://virtualacp.com/JCPCases/jclinpath-2019-206298/002/, and http://virtualacp.com/JCPCases/jclinpath-2019-206298/003/, and consider your diagnosis. 1. A (secondary) amyloidosis 2. Collapsing variant of focal segmental glomerulosclerosis 3. Diabetic nephropathy 4. Membranous nephropathy 5. Minimal change disease. The correct answer is after the Discussion. A clinical suspicion of secondary membranous nephropathy (MN) was made due to the increase …

To improve the curative resection rates and prognoses, a variety of neoadjuvant (NA) strategies have been explored in PDAC. In our institution, non-metastatic PDACs have been treated with a NA intent with induction multiagent chemotherapy and SBRT. The primary endpoint was to increase R0 resection rate. The secondary endpoints were the analysis of the clinical tolerance, the pathological response, the local control (LC) and the OS. All consecutive patients with non-metastatic PDAC underwent SBRT as part of the NA strategy were included. A total dose of 40–62 Gy were delivered in 5–10 fractions. Surgery was performed after SBRT and restaging. Since February 2014 to December 2018, 45 patients were enrolled. Thirty-two patients underwent surgery (71.1%), 10 out of 15 were initially unresectable disease patients (66.75%). R0 resection rate was 93% (30 patients) and pN0 status was achieved in 20 patients (60.6%). Tumour regression grade (TRG): 12 patients with complete response or marked response (TRG 0–1: 37.5%), 16 patients with moderate response (TRG 2: 50%) and four patients with poor response (TRG 3: 12.5%). The median follow-up was 16.2 m (range 6.6–59.6 m) since diagnosis. The LC rate achieved was very high (95.5%). Actuarial 12 and 24 m OS was 67.4% and 35.9% respectively. No grade 3 or higher toxicity related to SBRT was observed. The results are encouraging, suggesting that SBRT has a significant role in the management of these patients and further studies will be necessary to prove these findings.

Background Myxoid liposarcoma (ML) exhibits a special sensitivity to trabectedin (T) and radiation therapy (RT). Preclinical data suggest a synergistic effect. We aimed to study safety, feasibility and activity of the administration of pre-operative concurrent T and RT in patients affected by localized resectable ML. Methods Patients received 3 cycles (C) of T in combination with RT (45 Gy) in 25 fractions (1.8 Gy/fraction). Dose Levels for T were: − 1 (1.1 mg/m2), 0 (1.3 mg/m2) and 1 (1.5 mg/m2). Primary endpoint was safety; antitumor activity was assessed by RECIST and Choi criteria. This study is registered at ClinicalTrials.gov , number NCT02275286 . The phase 1 part of the study is complete and phase 2 is ongoing. Findings From February 2015 to May 2016, 14 patients (M/F 7/7), median age 36 years (range 24–70) and median tumor size 12.5 cm (range 7–17 cm), were enrolled. One dose limiting toxicity (G3 transaminitis) occurred at Level 0 and one (sepsis due to catheter infection) at Level 1. All patients completed RT. Five patients achieved PR (36%), 8 SD (57%), 1 distant PD (7%) by RECIST, while 12 achieved PR (86%), 1 SD (7%) and 1 distant PD (7%) by Choi criteria. Twelve patients underwent surgery. Median viable residual tumor was 5% (0–60). Interpretation T in combination with RT showed a favorable safety profile and antitumor activity in localized ML. T dose of 1.5 mg/m2 is the recommended dose for the phase 2 study, which is ongoing. Funding This study was partially supported by Pharmamar.

Objectives: Concomitant chemo-radiation is the standard treatment for unresectable stage III non-small cell lung cancer (LA-NSCLC), The aim of this study was to assess the safety and efficacy of oral vinorelbine and cisplatin (OVP) compared with etoposide and cisplatin (EP), both in combination with radiotherapy, in this setting. Material and methods: An open-label, randomized phase II trial was undertaken including 23 hospitals in Spain. Adults with untreated unresectable stage III NSCLC were randomizedl:1 to receive: oral vinorelbine (days 1 and 8 with cisplatin on day 1 in 3-week cycles; 2 cycles of induction, 2 cycles in concomitance) or etoposide (days 1-5 and 29-32 with cisplatin on days 1 and 8 in 4-week cycles; 2 cycles in concomitance). Both groups received concomitant radiotherapy 2 Gy/day (66 Gy). The primary endpoint was progression free survival (PFS). Results: One hundred and forty patients were enrolled. Sixty-nine patients received OVP and 71 received EP. Globally adverse events grade 3/4 per cycle were fewer in the vinorelbine arm (19.4%) than in the etoposide arm (62.6%) (p < 0.001). One patient (1.5%) in the OVP arm and 12 pts (17.6%) in the EP arm presented esophagitis grade 3/4 (p = 0.002). Median PFS was similar in both groups (10.8 [95% CI 7.7-13.8] and 9.6 months [95% CI 4.4-14.8]; p = 0.457, respectively). Preliminary median overall survival was 30 months in the OVP arm and 31.9 months in the EP arm (p = 0.688). Conclusions: Our findings show that OVP could be considered a standard combination with similar efficacy and better safety profile for the treatment of LA-NSCLC patients.

Background: Cancer patients represent a vulnerable population for COVID-19 illness. We aimed to analyze outcomes of lung cancer patients affected by COVID-19 in a tertiary hospital of a high-incidence region during the pandemic. Methods: We retrospectively collected all lung cancer patients diagnosed with COVID-19 at our institution (HGUGM; Madrid, Spain) between February 24th, 2020 to May 12th, 2020. Patients must have a confirmatory SARS-CoV-2 RT-PCR to be included in the study. Clinically suspected cases and cases with close contact to COVID-19 confirmed cases were not included if either not tested or tested negative by RT-PCR. Results: On March 4th, 2020, we confirmed our first lung cancer patient with COVID-19 in our institution. Since then, 23 lung cancer pts developed COVID-19 confirmed by SARS-CoV-2 PCR. Median age was 69 years-old (range 49-86), predominantly male (78%), with smoking history (former, 52%; current, 35%), and 87% presented comorbidities. Histology was 61% adenocarcinoma, 26% squamous cell carcinoma (SqCC), and 9% small-cell lung cancer (SCLC). Stage IV was the most commonly found (IVa 22%, IVb 39%), followed by stage III (35%) and stage I-II (4%). 70% of pts were receiving active treatment at the time of COVID-19 diagnosis (30-day window for systemic treatment, 15 days for radiation therapy): chemotherapy (n=4), immune checkpoint inhibitors (n=5), targeted therapy (n=1), thoracic chemo-radiation (n=1), and nonradical nonthoracic radiation therapy (n=6). All lung cancer patients had at least 1 COVID-19 related symptom; cough (48%), shortness of breath (48%), fever (39%), and low-grade fever (30%) were the most common COVID-19 symptoms. Time from symptoms onset to first positive SARS-CoV-2 PCR was 5.5 days (range 1-17), with 13% of cases needing a 2nd PCR to confirm diagnosis. High variability on thoracic imaging findings were found (no pneumonia, n=4; unilobar, n=1; multilobar, n=17). 87% of pts received treatment for COVID-19: hydroxychloroquine (n=20), lopinavir/ritonavir (n=17), azithromycin (n=3), interferon (n=3), and tocilizumab (n=1). In our series, hospitalization rate was 74%, and 39% of pts developed ARDS within 6 days after symptoms initiation (range 2-22 days). Only 1 patient was admitted in the ICU for VM and received tocilizumab and was discharged 42 days after admission. Case fatality rate was 35% (8/23), with 3 pts still on 30-day follow-up period. Considering only those patients with lung cancer who were actively receiving systemic therapy during the pandemic in our institution, we estimated a 4.5% incidence and a 2.1% mortality from COVID-19. Analysis of prognostic factors of mortality is under way. Conclusions: Lung cancer patients represent a vulnerable population for COVID-19, according to the high rate of hospitalization, onset of ARDS, and high mortality rate. Although larger series are needed, no differences in mortality were found by type of cancer treatment. Measures to minimize the risk of SARS-CoV-2 infection remain key to protect lung cancer patients. Citation Format: Antonio Calles, Inmaculada Aparicio, Manuel Alva, Marianela Bringas, Natalia Gutierrez, Javier Soto, Mar Galera, Rosa Alvarez. Outcomes of COVID-19 in patients with lung cancer treated in a tertiary hospital in Madrid [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-031.

Background: We aimed to describe how patients with lung cancer affected by COVID-19 recovered and were subsequently treated. Methods: From March 4th to May 12th, 2020, we have previously identified 23 COVID-19 lung cancer patients confirmed by SARS-CoV-2 RT-PCR in our institution (HGUGM; Madrid, Spain). After symptom recovery patients were tested weekly with nasopharyngeal swabs for SARS-CoV2. We did not start any anticancer treatment until at least 1 PCR confirmed a negative SARS-CoV-2 result. We reviewed treatment records, hospitalization, and outcomes of patients who recovered from COVID-19. Results: With a median follow-up of 9.7 weeks after COVID-19 diagnosis (range 3.7-13 weeks), 15 patients are clinically recovered (65%) and 8 patients died (35%) from COVID-19. In COVID-19 survivors, time to SARS-CoV-2 PCR negativization from symptoms onset was 31 days (range 13-54 days). Three patients remain SARS-CoV-2 RT-PCR positive to date. Of the 12 patients who negativized for SARS-CoV-2, 8 pts have started systemic anticancer treatment as follows: immune checkpoint inhibitors (n=3), chemotherapy (n=3), and initiation of definitive thoracic chemoradiation (n=2). All 3 pts on immunotherapy resumed the same treatment that they were receiving before COVID-19 (pembrolizumab, atezolizumab), as 2 out of 3 pts did with chemotherapy (pemetrexed; carboplatin + paclitaxel). With a median time on treatment of 40 days (range 22-48 days), only 1 patient has developed treatment-related adverse events so far (grade 1 thrombocytopenia after cycle 1, and grade 2 neutropenia after cycle 2 of carboplatin plus etoposide in a patient with relapsed SCLC previously treated with chemoradiation). The 4 patients with negative SARS-CoV-2 PCR who did not start any further treatment had either already completed planned treatment just before COVID-19 or were under surveillance without evidence of disease. Readmission was required in 4/15 patients: 1 pt due to tumor progression and pulmonary embolism, 1 pt due to brain edema from known brain metastasis, 1 pt due to Salmonella gastroenteritis, and 1 pt with hematuria due to prostate cancer. Of note, 1 patient who previously tested negative for SARS-CoV-2 -and who already resumed chemotherapy tested positive again upon admission without COVID-19-related symptoms. Conclusions: Lung cancer patients who survived COVID-19 can be considered for cancer treatment without preliminary early safety concerns. Long-term efficacy and safety evaluation by treatment modality is needed. Citation Format: Antonio Calles, Mar Galera, Inmaculada Aparicio, Manuel Alva, Marianela Bringas, Natalia Gutierrez, Javier Soto, Victoria Tirado, Rosa Alvarez. Safety outcomes of resuming anticancer treatment in patients with lung cancer affected by COVID-19 illness [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-036.

Background: We aimed to analyze the impact on treatment delivery in patients with lung cancer during the COVID-19 pandemic and to describe the patterns of treatment change. Methods: We accessed treatment records of all lung cancer patients treated from 02/20 to 06/20 at the oncology day hospital in our institution (HGUGM; Madrid, Spain). We have prospectively identified all COVID-19 lung cancer patients confirmed by SARS-CoV-2 RT-PCR and included all those on active treatment ( Results: A total of 242 patients with lung cancer were receiving active treatment as follows: chemotherapy (117 pts, 48%), immunotherapy (56 pts, 23%), targeted therapy (52 pts, 21%), chemo-immunotherapy (13 pts, 5%), radio-immuno-chemotherapy (4 pts, 2%). Intention of treatment was palliative in 84% vs. curative in 16% (28 pts on chemoradiation; 11 pts on adjuvant/neoadjuvant therapy). Median number of treatment lines was 1 (range 1-6). 11 patients had confirmed COVID-19 illness during active cancer treatment, and 5 patients died due to COVID-19. On average, 61 patients with lung cancer were treated per week before the pandemic. After an initial peak during the first week of pandemic, treatment delivery dropped by -62.2% four weeks after the first case confirmed in our institution (chemotherapy, -58.2%; immunotherapy, -72.6%; chemo-immunotherapy, -100.0%; targeted therapy, -59.0%) and came back to normal at week +7. Treatment interruption or dose delay was observed in 125 pts (28% temporal, 24% definitive). Overall, 23 patients refused to continue treatment due to fear or mobility restrictions due to the pandemic. Additionally, we identified doses skipped in 51 pts (21%), increase on dose intervals in 42 pts (17%), and dose reductions in 16 pts (7%). Route of administration remained the same for all pts but 1 (i.v. to oral). Although absolute use of G-CSF fell by -57.9% during the pandemic, tied to less administration of chemotherapy, the relative use of G-CSF increased in patients receiving chemotherapy-based treatments: G-CSF was initiated in 31 pts who were not previously receiving G-CSF, and expanded in days of use in 7 pts already on treatment. Telemedicine was used in 106/242 patients (44%) to minimize physical presence in the hospital. Drug home delivery system was initiated in 22 patients (9% of total), all of them on targeted therapy (representing 42% of all active patients on targeted therapy). Of the 32 patients who were receiving treatment in clinical trials (10 pts immunotherapy; 8 pts targeted therapy; 8 pts chemo-immunotherapy; 2 chemotherapy, 4 radio-chemo-immunotherapy), neither treatment delays nor COVID-19 illness was documented in any patient. Conclusions: COVID-19 pandemic significantly modified treatment patterns in patients with lung cancer who were receiving active treatment. Measures were taken to reduce the number of visits to outpatient facilities, and treatment home delivery was facilitated when feasible. Citation Format: Antonio Calles, Manuel Alva, Inmaculada Aparicio, Javier Soto, Natalia Gutierrez, Marianela Bringas, Vicente Escudero, Roberto Collado, Mar Galera, Rosa Alvarez. Impact of COVID-19 in continuity of cancer treatment for lung cancer patients [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-021.

This study aims to determine the incidence of nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC), under medical practice conditions and the accuracy with which physicians perceive CINV. Chemotherapy-naive patients receiving MEC between April 2012 and May 2013 were included. Patients completed a diary of the intensity of nausea and number of vomiting episodes. Complete response and complete protection were assessed as secondary endpoints. Of 261 patients included, 240 were evaluated. Median age was 64 years, 44.2 % were female and 11.2 % were aged less than 50 years; 95.3 % of patients received a combination of 5-hydroxytryptamine 3 (5-HT3) antagonist + corticosteroid as antiemetic treatment. Vomiting within 5 days of chemotherapy administration occurred in 20.8 %, nausea in 42 % and significant nausea in 23.8 % of patients. An increase in the percentage of patients with significant nausea (from 9.4 to 21.7 %) and vomiting (from 9.2 to 16.5 %) was observed from the acute to the delayed phase. Complete response was 84.2 % in the acute phase, 77 % in the late phase and 68.9 % in overall period. Complete protection was 79.5 % in the acute phase, 68.8 % in the late phase and 62.4 % throughout the study period. Physicians estimated prophylaxis would be effective for 75 % of patients receiving MEC, compared with 54.1 % obtained from patients' diary. Despite receiving prophylactic treatment, 31 % of patients did not achieve a complete response and 38 % complete protection. In general, nausea was worse controlled than vomiting. The results also showed the late phase was worse controlled than the acute phase in all variables. Healthcare providers overestimated the effectiveness of antiemetic prophylaxis., All authors have declared no conflicts of interest. The research has been funded by Merck Sharp & Dohme (MSD). Merck Sharp & Dohme Spain-a subsidiary of Merck & Co. Inc., Whitehouse Station, New Jersey, USA-provided Financial Support for the conduct of the study.

Development of hyperbilirubinaemia is common in patients with advanced pancreatic adenocarcinoma, both at diagnosis as well throughout disease evolution. For this reason, hyperbilirubinaemia determines chemotherapy treatment selection, and therefore it should be considered one of the most relevant conditions. There is very little evidence for the use of chemotherapy in this setting. This article summarises the main causes of hyperbilirubinaemia, how to treat them as well as their differential diagnosis. The current clinical evidence of the available drugs as well as the recommendations of use different combinations in the context of hyperbilirubinaemia are also reviewed.

Primary malignant bone tumors are uncommon and heterogeneous malignancies. This document is a guideline developed by the Spanish Group for Research on Sarcoma with the participation of different specialists involved in the diagnosis and treatment of bone sarcomas. The aim is to provide practical recommendations with the intention of helping in the clinical decision-making process. The diagnosis and treatment of bone tumors requires a multidisciplinary approach, involving as a minimum pathologists, radiologists, surgeons, and radiation and medical oncologists. Early referral to a specialist center could improve patients' survival. The multidisciplinary management of osteosarcoma, chondrosarcoma, chordoma, giant cell tumor of bone and other rare bone tumors is reviewed in this guideline. Ewing's sarcoma will be the focus of a separate guideline because of its specific biological, clinical and therapeutic features. Each statement has been accompanied by the level of evidence and grade of recommendation on the basis of the available data. Surgical excision is the mainstay of treatment of a localized bone tumor, with various techniques available depending on the histologic type, grade and location of the tumor. Chemotherapy plays an important role in some chemosensitive subtypes (such as high-grade osteosarcoma). In other subtypes, historically considered chemoresistant (such as chordoma or giant cell tumor of bone), new targeted therapies have emerged recently, with a very significant efficacy in the case of denosumab. Radiation therapy is usually necessary in the treatment of chordoma and sometimes of other bone tumors.

Altres ajuts: This work was supported by Primary Healthcare University Research Institute IDIAP Jordi Gol, Barcelona, Spain. Background: Heart failure (HF) diagnosis as reported in primary care medical records is not always properly confirmed and could result in over-registration. Objectives: To determine the proportion of registered HF that can be confirmed with information from primary care medical records and to analyse related factors. Methods: A cross-sectional study. The medical records of 595 HF patients attended in two primary healthcare centres in Barcelona (Spain) were revised and validated by a team of experts who classified diagnosis into confirmed, unconfirmed, and misdiagnosis. Variables potentially related to the confirmation of the diagnosis were analysed. The revision of medical records and data collection took place from 15 January to 31 March 2014. Results: Mean (standard deviation) age was 78 (10) years and 58% were women. The diagnosis could be confirmed in 53.6% of patients. Factors associated with a greater probability of having a confirmed diagnosis were age (yearly OR: 0.97, 95%CI: 0.95-0.99), cardiologist follow-up (OR: 3.66, 95%CI: 2.46-5.48), history of ischaemic heart disease (OR: 2.18, 95%CI: 1.36-2.48), atrial fibrillation (OR: 2.01, 95%CI: 1.34-3.03), and prescription of loop diuretics (OR: 3.24, 95%CI: 2.14-4.89). Conclusion: Only in half of the patients labelled as HF in primary care medical records could this diagnosis be further confirmed. Variables regularly registered in clinical practice could help general practitioners identify those patients requiring a revision of their HF diagnosis.

The management of patients with pancreatic cancer has advanced over the last few years. We convey a multidisciplinary group of experts in an attempt to stablish practical guidelines for the diagnoses, staging and management of these patients. This paper summarizes the main conclusions of the working group. Patients with suspected pancreatic ductal adenocarcinoma should be rapidly evaluated and referred to high-volume centers. Multidisciplinary supervision is critical for proper diagnoses, staging and to frame a treatment plan. Surgical resection together with chemotherapy offers the highest chance for cure in early stage disease. Patients with advanced disease should be classified in treatment groups to guide systemic treatment. New chemotherapeutic regimens have resulted in improved survival. Symptomatic management is critical in this disease. Enrollment in a clinical trial is, in general, recommended., The support for medical writing was supported by Fundacion ECO.

e20621 Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors include stage, weight loss and ECOG, but more information is missing in the literature. Recently, EGFR, ALK and ROS 1 population (less than 20%) reach OS longer than 2 years. Immunotherapy has demonstrated very promising results with more LS compared to chemotherapy in first and second line setting. In this study, we focused in the analysis of LS patients with advanced NSCLC EGFR wt (wild type) and ALK nt (non-translocated), defined as those with OS greater than 36 months, in 7 hospitals in Madrid. Methods: In this serie, first of all, we will try to make a clinical, histopathological characterization collecting data from clinical reports according to a previously defined information. In a second step, we will carry out a genetic analysis of these patient samples comparing to an opposite extreme short survivors (SS) samples (OS less than 9 months). Initially, we used a NGS method of RNA-seq technology to identify differentiating profiles of gene expression between the two opposite populations. And finally, we confirmed this preliminary profile by RT-PCR in the rest of samples. Results: Ninety-six patients were initially included. The majority were men, smokers or former with adenocarcinoma and ECOG 0- 1. We have obtained a differential transcriptome expression between samples from 6 LS and 6 SS, resulting 13 over-expressed and 42 down-expressed genes in LS comparing to SS transcriptome expression. Some of the genes involved in this initial profile belong to different cellular pathways: Secretin Receptor, Surfactant Protein, Trefoil Factor 1, Serpin Family, Ca-bindings Protein channel and Toll like Receptor family. Finally, we carried on by RT-PCR in 40 samples of SS and LS survivors and only four genes were significantly down-regulated in SS compared to LS in the multivariate analysis. These 4 genes were related to Surfactant Proteins: SFTPA1 (p = 0.023), SFTPA2 (p = 0.027), SFTPB (p = 0.02) and SFTPC (p = 0.047). Conclusions: We present a sequential genetic analysis of a LS population with NSCLC EGFR wt (wild type) and ALK nt (non-translocated), obtaining a differential RNA seq- and RT-PCR gene profile based on different surfactant proteins expression. A further confirmation in a larger sample is ongoing.

Soft-tissue sarcomas are uncommon and heterogeneous tumors of mesenchymal origin. A soft-tissue mass that is increasing in size, greater than 5 cm, or located under deep fascia are criteria for suspicion of sarcoma. Diagnosis, treatment, and management should preferably be performed by a multidisciplinary team in reference centers. MRI and lung CT scan are mandatory for local and distant assessment. A biopsy indicating histological type and grade is needed previous to the treatment. Wide surgical resection with tumor-free tissue margin is the primary treatment for localized disease. Radiotherapy is indicated in large, deep, high-grade tumors, or after marginal resection not likely of being improved with reexcision. Neoadjuvant and adjuvant chemotherapy improve survival in selected cases, usually in high-grade sarcomas of the extremities. In the case of metastatic disease, patients with exclusive lung metastasis could be considered for surgery. First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice. New drugs have shown activity in second-line therapy and in specific histological subtypes.

Purpose Doxorubicin and trabectedin are considered active drugs in soft tissue sarcoma (STS). The combination of both drugs was hypothesized to be advantageous and safe on the basis of preclinical evidence and a previous phase I trial, respectively. The aim of this study was to compare the clinical outcome of trabectedin plus doxorubicin with doxorubicin as first-line treatment of advanced STS patients. Patients and Methods In this open-label randomized phase II trial, the main end point was progression-free survival (PFS). Trabectedin 1.1 mg/m2 in a 3-hour infusion plus doxorubicin 60 mg/m2 as the experimental arm and doxorubicin 75 mg/m2 as the control arm were administered for up to six cycles. Translational research was planned to correlate the expression of apoptotic and DNA repair genes with clinical outcome. Results In 115 randomly assigned patients, the median PFS was 5.5 months in the control arm and 5.7 months in the experimental arm (hazard ratio, 1.16; 95% CI, 0.79 to 1.71; P = .45) in the intent-to-treat analysis. The trial was stopped for futility after the interim analysis, because the results in the experimental arm showed the risk reduction for the main end point to be < 9.64%. The proportion of patients with grade 3 or 4 thrombocytopenia, asthenia, and liver toxicity was significantly higher in the experimental arm. FAS and p53 were shown to be prognostic factors for PFS (7.0 months if FAS+ and p53−; 3.4 months if FAS+/p53+ or FAS−/p53−; and 0.7 months if FAS− and p53+; P < .001) and for overall survival. Conclusion Trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS. The prognostic role of apoptotic key genes, FAS and p53, was shown to be robust enough to continue this research line.

11544Background: Patients (pts) with advanced STS who require tumor shrinkage beyond first line, have very limited options since the approved drugs exhibit less than 10% of RECIST response. Trabect...

e21128Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors ...

Subjective and objective measures of quality of life (QoL) were obtained for adults with autism spectrum disorders (ASDs) living in Andalusia (Spain). Seventy-four families responded to question- naires about objective QoL indicators such as employment, health, adaptive behaviour and social network, and were asked to act as proxies for subjective QoL measures. Outcome on objective QoL was extremely poor. Social networks were most frequently composed of family members. Community-oriented resources were absent in most cases. For two-thirds of the families, the ability to act as proxies for subjective QoL was seriously limited by the participants’ poor social and communicative abilities. The results are indicative of the need for additional support to families of adults with ASD and increased community-based resources. Further conceptualization of indicators and measurement of subjective QoL in individuals with severe disabilities and ASD is also needed in order to include their own perspective in the evaluation of service provision.

Immunodiagnosis in sheep presents problems of sensitivity and specificity, limiting its applicability in surveillance systems. The objective of this study was to develop a sensitive, specific and accessible technique for diagnosing cystic echinococcosis in naturally infected sheep and to evaluate the validity of necropsy as a reference test. A total of 247 sheep were studied at slaughterhouses, confirming the parasitological diagnosis with histology. Serum was processed with enzyme immunoassay (EIA) using three antigen preparations: total hydatid liquid (LHT), purified fraction of LHT (S2B) and purified lipoprotein (B). Western Blot (WB) was used as a control. EIA proved effective for differentiating Echinococcus granulosus from larval stage of Taenia hydatigena and intestinal cestodes in all three antigen preparations. Serums from macroscopically negative sheep were reactive to EIA and positive with WB. In the whole flock, sensitivity was 89.2% for LHT, 80.0% for S2B and 86.4% for B. Sensitivity in lambs was 78.6% for LHT, 75.0% for S2B and 64.3% for B. Macroscopic diagnosis at the time of slaughter was found to have limitations as a reference test for immunodiagnosis of cystic equinococcosis in sheep, so it was necessary to include histology and WB as reference tests. LHT was the antigen preparation of greatest value and EIA proved to be a sensitive and specific technique, adequate for surveillance systems and for evaluating control programmes.

11061 Background: Myxoid liposarcoma/round cell liposarcoma (ML) exhibits especial sensitivity to trabectedin (T). In prospective series, long-lasting T treatment showed responses in 44% of patients (pts) with ML. ML is also sensitive to radiation therapy (RT) and preclinical data suggested radiosensitizing properties of T. Preoperative short-course of T with concurrent low-dose RT was conducted in a multicenter, European, phase I/II trial. We present here data from the phase I part in pts with centralized diagnosis of locally advanced, resectable ML. Methods: Pts received 3 cycles (C) of T in combination with RT (45 Gy) in 25 fractions (1.8Gy/fraction). The phase I had the classic 3+3 design. Dose Levels for T were: -1 (1.1 mg/m2), 1 (1.3 mg/m2) and 2 (1.5 mg/m2). Dose-limiting toxicity (DLT) were defined as grade ≥3 events excluding G3/4 neutropenia lasting < 5 days and G3-4 nausea/vomiting due to inadequate prophylaxis. RECIST responses were evaluated preoperatively at week 10. Surgical specimens were processed for histologic changes and residual tumor. Results: From February 2015 to May 2016,14 pts (M/F 7/7) with median age 36y (24-71) and median tumor size 12.5 cm were enrolled. 7 pts received T at dose Level 1 and 7 pts at Level 2. One DLT (G3 transaminitis) occurred at Level 1 and another (sepsis due to catheter infection) at Level 2. Overall, grade G 3/4 AEs were: ALT elevation (n = 6, 43%), and GGT elevation, neutropenia, anemia, epithelitis and sepsis (n = 1, 7% each). There were no deaths. One pt developed metastasis after C3 and did not undergo surgery; another one had a sepsis after C1 and received definitive RT. All pts completed RT. 13 pts were evaluable for response: 5 achieved PR (38%), 7 SD (53%), 1 distant PD (8%). 12 pts underwent surgery (7 R0/5 R1). Median viable residual tumor was 5% (0-60) with 9/12 pts (75%) with ≤ 10% viable remaining tumor, 3/12 (25%) complete responses. Conclusions: T in combination with RT was feasible and well tolerated in the preoperative setting. T dose of 1.5 mg/m2 is the recommended phase II dose. A high proportion of patients achieved a good pathological response, with 3/12 (25%) complete responses. Clinical trial information: 2014-001549-26.

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

11071 Background: There are currently several second-line options for the treatment of ASTS as gemcitabine combinations, trabectedin, pazopanib, eribulin or olaratumab plus doxorubicin in cases where anthracyclins are still possible. There is an unmet need for predictive biomarkers which hinders the rational selection of the best sequence in second line. We already published the prognostic value of FAS in first line of ASTS while this study analyzes its predictive role in different second line schemes. Methods: Most relevant selection criteria for this study were having received trabectedin in 2nd line or beyond for ASTS, progressive disease after at least one previous line for ASTS and signed CI. A TMA was set up for FAS staining (Cell Signaling) with blocks from diagnostic time. Two expert blinded pathologists reviewed and classified the cases as negative, weak or strong. Kaplan–Meier estimations were used for time-to-event variables and the log-rank test was used to compare groups. Results: A series of 198 patients accomplished selection criteria. Metastases at diagnosis occurred in 46 (24%) and median time to metastases was 18.8 months (CI 16,3; 21.3). Previous line to trabectedin consisted of gemcitabine combination 83 (42%), Doxorubicin-based 65 (33%) and others 50 (25%). Median PFS for previous and trabectedin lines were 3.5 (2.8-4.2) and 3.4 (2.8-4) months respectively. FAS positive entailed significantly better PFS for the previous trabectedin line: 4.1 (1.5-6.7) vs 3.0 (2.5-3.5) months, p = 0.01 whereas FAS positive was related with worse PFS for the trabectedin line 2.5 (2.2-2.8) vs 3.7 (2.7-4.8) months, p = 0.028. These results were more notorious for L-sarcoma cases: 7.0 (3.6-10.5) vs 4.3 (1.9-6.6) months, p = 0.017 in previous line and 2.4 (2.2-2.6) vs 6.5 (3.8-9.3) months, p < 0.001 in trabectedin. From trabectedin administration, FAS+ had significantly worse OS especially in L-sarcomas: 11.9 (5.2-18.7) vs 21.7 (12.7-30.8) months, p = 0.002. Conclusions: FAS showed predictive value in PFS and OS for trabectedin administration in ASTS. The different prognostic role of FAS across distinct lines and its relevance in L-sarcomas deserve further attention.

In order to evaluate clinical presentation and to determinate classification criteria of type I diabetes (I-DM) in the elderly, we carried out a study in 258 patients more than 60 years old of which 40% used insulin by failure to oral hipoglycemic agents (OHA). The prevalence of ischemic cardiovascular disease was 36%, peripheralvascular disease 34% and stroke 30%; non-proliferative retinopathy 47%, peripheral neurophaty 37% and nephropathy 16%. Obesity (36%), hypertension (33%) and hypercholesterolemia (12%) were evaluated. The average duration of diabetes was 20 years. Postglucagon C-Peptide, HLA-DR antigens and islet cell antibodies (ICA), were measured in 75 older diabetic patients on treatment of which 24 used insulin, 40 OHA and 11 diet. Older patients on insulin had longer duration of disease, less obesity, low basal level of C-Peptide and a low response post glucagon; C-Peptide (0.94+0.5 pmol/ml) compared with patients on diet (1.8+0.9 pmol/ml) and OHA (1.8+0.8 pmol/ml). Older diabetics on insulin therapy had a greater frequency of HLA-DR3 (42%) and HLA-DR4 (21%). The ICA wasnegative in most patients. This study shows the high prevalence of macrovascular and microvascular disease in elderly patients with diabetes mellitus and that the most reliable parameter in classifying I-DM is the measurement of basal and postglucagonC-Peptide. HLA-DR specific markers can be used with this parameter because their expression is partly shared. This approach appears useful in the older diabetic patients to help classify diabetes and its management.

Hemimegalencephaly (HME) is a developmental abnormality of the central nervous system (CNS) which may present as either a syndromic or isolated case. Here, we present two cases of early prenatal diagnosis of HME. Prenatal CNS ultrasound and MRI in the first case revealed ventricular asymmetry, midline shift with displacement of the occipital lobe across the midline, large dilatation mainly at the posterior horn of the left lateral ventricle, and a head circumference in the 90th percentile without involvement of the brain stem and cerebellum, as well as abdominal lymphangioma. Right hemispherectomy was performed at 3 months of age due to intractable seizures. The pathological specimen showed findings characteristic of HME, including a disorganized cytoarchitecture with lack of neuronal lamination, focal areas of polymicrogyria, and neuronal heterotopias with dysplastic cells. In the second case, 2D and 3D neurosonography demonstrated similar findings (asymmetry of cerebral hemispheres, midline shift, and dilation of the posterior horn of the left lateral cerebral ventricle). Posterior fossa structures were unremarkable. HME was diagnosed and the pregnancy was terminated. Autopsy findings confirmed the diagnosis of HME.

A case of prenatally diagnosed aortopulmonary window is reported. The mother was referred for fetal echocardiography at 26 weeks' gestation because of suspected congenital heart disease. Prenatal echocardiography showed an aortopulmonary septum defect close to the pulmonary artery bifurcation and a left-to-right shunt flow in systole and early diastole detected by color flow Doppler. Postnatal echocardiography confirmed prenatal diagnosis, the aortopulmonary window was a 9-mm type III aortopulmonary window. An atrial septal defect with shunt flow left to right was also found. Surgical repair was performed 4 weeks after birth, the postsurgical period was uneventful and the newborn was discharged without complications 7 days after surgery.

Aim: There is a need to develop biomarkers to predict the outcome of patients with metastatic colorectal cancer (CRC) treated with chemotherapy (Ch) plus Bevacizumab (B). It has been reported that during exposure to B there is a switch in the plasma levels of angiogenesis growth factors and related cytokines called angiogenic switch (AS). It is not known if changes in these circulating factors affect the response of patients with CRC to Ch + B. The aim of this study is to determine the influence of AS in the PFS in pts with metastatic CRC treated with Ch + B. Methods: Treatment naive, ECOG 0-1, metastatic CRC pts were eligible. Patients received induction treatment with XELOX-B or XELIRI-B at standard doses x 6 cycles followed by maintenance treatment with B plus Capecitabine until progression. Angiogenic related cytokines (HGF, PIGF, MCP-3, MM-9, Eotaxin, bFGF and IL-18) were prospectively analyzed at baseline and at the time of each CT evaluation (every eight weeks). AS + was defined by A) doubling of PIGF compared to baseline or B) PIGF elevation with a simultaneous elevation of any two of bFGF, HGF, MCP-3, IL-18 or MMP-9 compared to baseline. Results: Of 62 patients enrolled, 24 (36.7%) have progressed. Median PFS is 15.6 (95% CI: 8.3 to 16.4) months for the entire population. Twenty-five pts (40.3%) were AS + , out of which 23 were detected at first on-study evaluation (week 8). 18 were classified as AS+ based on both criteria, 4 based on criteria A) and 3 based on criteria B). One year (95% CI) PFS for AS+ pts was 82.6% (53.0% to 94.4%) versus 32.9% (13.9% to 53.5%) for AS- pts (p Conclusions: There is a statistically significant improved PFS amongst metastatic CRC AS+ pts treated with first line Ch + B combination compared with AS–pts. Disclosure: All authors have declared no conflicts of interest.

Background.Experimental undernutrition in animals, during the critical brain development period, produces retardation of brain growth as well as a number of different morphologic and functional abnormalities in neurons, mainly in the dendritic synaptic apparatus. These alterations are the cause of the poor neurointegrative development that occurs in experimental malnutrition. Severe malnutrition during early postnatal life in humans is known to produce similar neurointegrative disorders as well as mental retardation, but there are very few studies describing the morphology of the dendritic apparatus in infants suffering from this condition.Objective.To study the dendritic spine density and morphology in dendrites from cortical neurons in infants dying from severe malnutrition.Methodology.Brain sections from the somestesic, motor, and occipital cortical areas of 13 infants who died of severe malnutrition and 7 eutrophic infants who died of other causes were studied by means of the rapid Golgi method. Apical dendritic spines from neurons of the fifth cortical layer were studied and counted in all sections.Results.Apical dendrites were significantly shorter in malnourished infants than in the control group (581.54 ± 54.32 μm in severe malnutrition vs 846.3 μm in normal infants). The number of dendritic spines per dendrite was also significantly diminished (185.3 ± 36.1 in malnourished vs 374.3 ± 41.6 in eutrophic infants). There were marked morphologic abnormalities in the dendritic spines of infants dying of severe malnutrition that were classified as dysplastic.Conclusions.Short apical dendrites, fewer spines, and dendritic spine abnormalities occur in severe infant malnutrition. These anatomic anomalies might be related to the neuropsychological deficits that occur in these children.

Electron microscopy together with glial fibrillary acidic protein (GFAP) and vimentin immunocytochemistry reveals the presence of a specialized glial region in the octavolateral area of the medulla oblongata of adult and juvenile grey mullets, Chelon labrosus. Glial cells, which can he characterized as ependymal and subependymal cells, originate in the walls of the lateral recess of the fourth ventricle. They contain numerous gliofilaments and are connected through frequent gap junctions. Electron microscopy also reveals the lack of nerve cell parikarya and processes in this region. Immunocytochemistry reveals that the glial cells are strongly GFAP-positive in both adults and juveniles, whereas vimentin is only detected in this region in juveniles. The meninges associated with this glial region contains connective fibres, formed of very thick collagen fibres, that arc metachromatic and PAS-positive under light microscopy. These findings strongly support a structural role for this medullary specialization. Differences between adults and juveniles in the distribution of GFAP- and vimentin-immunoreactive structures in other regions of the medulla oblongata are also reported.