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Introduction/Background* The study attempts to understand the impact of the different retrospective studies conducted by the SUCCOR group on the daily surgical practice among ESGO members. We intend to propose a new observational prospective European study, the SUCCOP study. We aim to know if the implementation of protective maneuvers in minimally invasive surgery (MIS) improves the outcome of patients with early cervical cancer (ECC). In this scenario, supported by the ESGO council, we have conducted a multinational survey to assess our ESGO members’ perspectives from the ethical and investigational viewpoints on this new observational prospective study. Methodology A 32-item questionnaire addressing multiple issues related to the SUCCOR study and surgical management of ECC was designed and sent from the ESGO account through a newsletter on February 23rd to all ESGO members from 54 countries of the ESGO directory. The survey was completely confidentially and could be completed in less than 5 minutes. Responses from 353 members were obtained. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher’s exact test, were used. Result(s)* 92.9% of responders were aware of the findings of the SUCCOR study. 73.4% expected the results obtained. 5 out of 10 of members confirmed that have changed their practice after the publication of the manuscript. Currently, 34.8% of responders admit that they usually perform MIS (laparoscopy/robotic) for cervical tumours smaller than 2 cm, while for tumours larger than 2 cm (FIGO IB2) 15.1% state that they continue to carry out MIS. Between 63 and 64.1% apply protective maneuvers during this procedure. In ECC who have undergone conization, 56.1% would performed MIS for tumours smaller than 2 cm while only 30% would offer it for tumours larger than 2 cm. Finally, 84.1% of ESGO members consider ethically acceptable the development of a new European prospective observational study (Image 1) to evaluate the surgical approach in ECC (IB1-IB2). Conclusion* According to the ESGO members’ perspectives regarding the approach to ECC, it seems that MIS still has an important role to play, which should be evaluated in a new prospective study that reflects the European reality (Image 2).

Introduction/Background* Ovarian cancer is the leading cause of death from gynecologic cancer in the developed countries. (1) Multimodality imaging approach with ultrasound, CT, MRI or PET/CT is often needed during the diagnosis and prior to the treatment. In AOC, a lot of studies have been done in order to demonstrate a better accuracy in staging advanced disease. Some studies showed PET/CT to be more accurate than traditional CT and MRI imaging, detecting LN metastases, extraabdominal disease and assessing equivocal findings in conventional imaging. (2–6) Besides, a greater number of distant metastases will be found when using PET/CT as preoperative staging tool and many patients will be upgraded. (7–9). The aim of this study was to compare the efficacy between preoperative PET/CT and ceCT findings according with the final pathology report in patients that underwent surgery for EOC treatment. Methodology The study is a retrospective unicentric national observational study reviewing data of patients diagnosed with epithelial ovarian cancer that were operated as part of the treatment between July 2018 and February 2021, both included. PET/CT with ceCT started to be used routinely at hour hospital in 2018 for EOC patients. At our institution, the PET/CT is independently evaluated by two imaging specialists: a nuclear medicine doctor (PET-CT) and an expert radiologist in gyn malignancies who evaluate only the CT images. Result(s)* 56 patients were included in the final analysis. Sensitivity and specificity for PET/CT and CT were: 85% and 94.3% vs 80% and 94.3% in the ovarie; 38.1% and 91.2% vs 23.8% and 97.1% in the rectum; 50% and 86.7% vs 30% and 95.6% in the pelvic nodes; 33.3% and 97.1% vs 33.3% and 97.1% in the diaphragm; and 25% and 97.7% vs 25% and 100% in the small bowel mesentery. When calculating PCI and comparing it to the surgery PCI, PET/CT showed a better intraclass correlation coefficient (0.856) than CeCT (0.751). Conclusion* Both techniques showed a poor sensitivity and a very good specificity when comparing findings to surgery in the different anatomical places. However, when stimating PCI before surgery, PET/CT showed a better correlation with surgery than CeCT.

Introduction/Background* Implementation of quality surgical care programs as a component of comprehensive multi-disciplinary management has been shown to improve outcomes in patients with colorectal cancer and other types of malignancies.1,2 In that scenario, the ESGO quality indicators for surgical treatment of cervical cancer were published. 3 The aim of this study was to validate quality indicators for surgical treatment of cervical cancer in a large European retrospective cohort and to analyze if its accomplishment may impact the disease-free survival (DFS) in patients with cervical cancer. Methodology The succor database was fulfilled in 2019 for the succor study 4, comprising a total of of 1272 patients who underwent radical hysterectomy for IB1 cervical cancer in Europe between 2013 and 2014. In March 2021 a survey was conducted among all the Succor participating centers. The questionnaire included questions regarding the accomplishment of the ESGO process and structural quality indicators, comprising a total of 9 items with a maximum punctuation of 10. Potential factors that may influence on the relapse risk in this cohort were previously analyzed. 5l A regression cox analysis including all these factors and quality indicators accomplishment was conducted. Good accomplishment of QI was defined as accomplishment of 8 or more of them. Result(s)* A total of 82 out of the 126 participating institutions answered the survey. The final cohort was composed of 877 patients. Percentages of accomplishment of quality indicators are showed in table 1. Two groups were defined according to the number of quality indicators accomplished (Group 1: 7 or less vs group 2: 8 or more). The rate of DFS at 4.5 year for patients who underwent surgery in centers that accomplished 7 or less quality indicators was 82.1% (78.8-85.6) and 89.9% (88.7-91.1%) in the other group. Low accomplishment of QI was associated with a lower rate of disease-free survival than High accomplishment of QI (HR, 1.61; 95% CI, 1.01 to 2.57; P=0.047). A difference that remained after adjustment for previous conization, tumour size >2cm, and minimally invasive approach. Conclusion* Good accomplishment of structural and process QI was associated with a better DFS in this European cohort.

AIMS: Immunotherapy is a rising alternative to traditional treatment in breast cancer (BC) patients in order to transform cold into hot immune enriched tumours and improve responses and outcome. A computational modelling approach was applied to quantify modulation effects of immunotherapy and chemotherapy response on tumour shrinkage and progression‐free survival (PFS) in naïve BC patients. METHODS: Eighty‐three Her2‐negative BC patients were recruited for neoadjuvant chemotherapy with or without immunotherapy based on dendritic cell vaccination. Sequential tumour size measurements were modelled using nonlinear mixed effects modelling and linked to PFS. Data from another set of patients (n = 111) were used to validate the model. RESULTS: Tumour size profiles over time were linked to biomarker dynamics and PFS. The immunotherapy effect was related to tumour shrinkage (P < .05), with the shrinkage 17% (95% confidence interval: 2–23%) being higher in vaccinated patients, confirmed by the finding that pathological complete response rates in the breast were higher in the vaccinated compared to the control group (25.6% vs 13.6%; P = .04). The whole tumour shrinkage time profile was the major prognostic factor associated to PFS (P < .05), and therefore, immunotherapy influences indirectly on PFS, showing a trend in decreasing the probability of progression with increased vaccine effects. Tumour subtype was also associated with PFS (P < .05), showing that luminal A BC patients have better prognosis. CONCLUSIONS: Dendritic cell‐based immunotherapy is effective in decreasing tumour size. The semi‐mechanistic validated model presented allows the quantification of the immunotherapy treatment effects on tumour shrinkage and establishes the relationship between the dynamics of tumour size and PFS.

The combination of Pegylated Liposomal Doxorubicin (PLD) plus Gemcitabine (GEM) has been previously investigated in the treatment of metastatic breast cancer (MBC). PLD is a doxorubicin formulation with prolonged circulation time and better tissue distribution. GEM is a nucleoside analog with nonoverlapping toxicity compared to PLD. The aim of our study was to assess efficacy, toxicity, and long-term outcome of this combination. Patients with heavily treated MBC were retrospectively analyzed. Chemotherapy consisted of PLD 25 mg/m2 and GEM 800 mg/m2 day 1, on a three-week schedule. Cardiac function was evaluated baseline and during treatment. Radiological response was graded according to RECIST criteria v1.1. Toxicity was scored according to CTCAE v4.0. Progression-free survival (PFS) and overall survival (OS) were evaluated. From 2001 to 2014, 122 pts were included. Median age was 55 (range: 28-84). Median previous treatment schedules in the metastatic scenario were 3 (range: 1-15). Most patients received prior anthracyclines (85%). Median number of metastatic sites was 2 (range: 1-7). Median number of cycles delivered was 5 (range: 1-36). Overall response rate was 31% (5% complete responses; 26% partial responses). Stable and progressive diseases were observed in 32% and 26% of patients. Grade ≥3 neutropenia was observed in 29 patients (24%). Grade ≥3 hand-foot syndrome was detected in 17 patients (14%), mostly since cycle 3 (88%). Median cumulative PLD dose was 125 mg/m2 . At a median follow-up of 101 months, median PFS and OS were 7 and 22 months, respectively. PLD-GEM combination achieves remarkable long-term outcomes with an acceptable toxicity profile in patients with MBC.

La hormonoterapia ha sido la primera terapia sistémica para el tratamiento del cáncer de mama. Hasta hace pocos años el Tamoxifeno y la ablación/supresión ovárica eran las mejores terapias hormonales de las que disponíamos tanto en enfermedad avanzada como en adyuvancia. Los inhibidores de la aromatasa así como los nuevos SERM y el nuevo antagonista de los receptores de estrógenos Fulvestrant han supuesto un importante avance en el tratamiento de esta enfermedad a la vez que han complicado la elección del tratamiento óptimo para cada paciente. En esta revisión pretendemos realizar un repaso a los tratamientos disponibles incidiendo especialmente en sus indicaciones.

Objective: We assessed trabectedin in patients with advanced uterine leiomyosarcoma (uLMS) in real-life clinical practice given according to the marketing authorization. Methods: Thirty-six women from 11 tertiary hospitals across Spain who received trabectedin after anthracycline-containing regimen/s were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Results: Median PFS and overall survival (OS) since starting trabectedin treatment were 5.4 (95%CI: 3.5-7.3) and 18.5 months (95%CI: 11.5-25.6), respectively. Median OS was significantly higher (P = 0.028) in patients receiving trabectedin in = 3rd (15.1 months) and with ECOG performance status = 2nd line/s (0.0% and 20.0%), whereas the DCR was similar across treatment lines. Reversible neutropenia was the most common grade 3/4 laboratory abnormality (19.4%). Conclusions: Trabectedin confers clinical benefit in patients with recurrent/metastatic uLMS, given after failure to an anthracycline-based regimen being comparable to those reported in clinical trials and with a manageable safety profile., This study was supported by funding from PharmaMar (Madrid, Spain).

Introduction/Background This study aims to understand what was the impact of the LACC trial (Laparoscopy in cervical cancer) among the members of ESGO. We have explored members’ understanding of the results and changes in the clinical practice. Methodology Methods A questionnaire addressing multiple issues related to the LACC trial and surgical management of early cervical cancer was designed and sent to ESGO members before and after the publication of the LACC trial in the NEJM. The survey was entirely confidentially and could be completed in a short period of time. Responses from 394 and 326 members from 33 European countries were obtained. The respondents were divided into two groups depending on whether or not they belong to European countries. Results Characteristics and perceptions of the responders are shown in tables 1 and 2. 97% of responders knew the results of the trial and 92% had read the manuscript. 83% did not expect the results. 56% of members confirmed that have changed their practice after the publication of the trial. Before the trial, only 29% operated cervical cancer by laparotomy and after the publication 63% does. figure 1 and 2. In cervical cancer patients who have undergone conization with clear margins 73% would offer MIS to the patient while only 49% would if the specimen margins was positive. Members consider that uterine manipulator an incorrect tumor handling occasioned the poorer result of MIS. 9 out 10 of members are willing to discuss the LACC trial with their patients and 80% consider unethical avoiding this discussion. 85% think that ESGO should promote a new randomized clinical trial and meanwhile 65% would be interested to participate in a observational study. Conclusion Among ESGO members, the publication of LACC trial has objectively modified the surgical approach in early cervical cancer. Disclosure Nothing to disclose.

Introduction/Background To develop an ultrasound-based score for predicting debulking surgery outcome in advanced stage ovarian cancer. Methodology Retrospective analysis of data from a prospective cohort study comprising 65 women (mean age: 59 y.o.) with surgically confirmed stage IIB–IV epithelial ovarian cancer and ECOG status performance 0–2. All women had undergone transabdominal and transvaginal ultrasound evaluation for assessing disease spread prior to surgery. 12 anatomical areas were evaluated for the presence/absence of disease (recto-sigma involvement, carcinomatosis of pelvic peritoneum, major omentum, carcinomatosis of upper abdomen peritoneum, root of mesentery, pelvic lymph nodes, aorto-cava lymph nodes, lesser omentum, liver, spleen, hepatic hilum and ascites). All women included underwent surgery at our institution (diagnostic laparoscopy followed by upfront surgery if patient deemed adequate for optimal (R Parameter Score CA-125 >500 1. Bowel 1. Mesogastrium 1. Major omentum 1. Pelvic lymph nodes 1. Root mesentery 2. Liver parenchyma 2. Spleen parenchyma 2. Para-aortic lymph nodes 2. Hepatic hilium 2. Results Cytoreduction was complete or optimal in 51 patients (78.5%), suboptimal in 3 (4.6%) and upfront surgery was discarded in 11 women (16.9%). A score >3 predicted correctly 44 out 51 patients (86%) with complete/optimal cytoreduction in and 8 out of 14 (57%) of those with suboptimal or non-cytoreduction surgery. AUC was 0.76, with correct prediction in 80% of all cases. Conclusion Albeit the series is small, the developed ultrasound-based score has a good performance for predicting surgical results in IIB–IV stage epithelial ovarian cancer. Disclosure Nothing to disclose.

Introduction/Background Next Generation Sequencing (NGS) technology enables for the simultaneous study of multiple gene alterations in the patient‘s tumor with potential implications for genetic risk assessment, prognosis, and therapy. Methodology CUN opened a new hospital in Madrid in January 2018. During the first year, new patients (pts) with EOC at both CUN were offered to perform a NGS-based tumor testing. Local test consisted in Oncomine Comprehensive Assay (161 gene panel, ThermoFisher Scientific) and external test in Foundation Medicine (Foundation Medicine, Cambridge, MA). This is a descriptive analysis of the rate of implementation, the molecular alterations found, and the therapeutic implications derived. Results 104 new pts were evaluated from January 1st until December 31st. 5 (4.80%) LOGSOC, 81 (77.89%) HGSOC, 11 (10.58%) CCC, 6 (5.77%) Endometrioid, 1 (0.96%) Mucinous. 44 pts with primary disease and 60 pts with recurrent disease. All but two patients were tested with Oncomine with a median turn-around time of 14 days. Table shows the rate of patients tested according to histology and context of disease. Subtype N Tested in First Line Tested in recurrence. LGSOC 5 2/2 (100%) 1/3 (33.33%). HGSOC 81 17/34 (50%) 14/47 (29,78%). Endometrioid 6 1/2 (50%) 0/4 (0%). CCC 11 3/6 (50%) 1/5 (20%). Mucinous 1 0/0 0/1 (0%). TOTAL 104 23/44 (52.57%) 16/60 (26.67%). sBRCA mutation was detected in 6/23 primary diagnosis (26.1%) and 2 pts (both gBRCAwt) received olaparib maintenance after SOLO-1 publication. In the recurrent setting, 5/16 pts (31.25%) had at least one actionable mutation with available matched therapy and 3 pts received matched therapy (18.76%). Non-BRCA genes associated to hereditary EOC were detected in 4 pts. Conclusion Integration of a precision medicine program with NGS tumor testing was feasible in routine practice in a private university hospital. This is an ongoing program and the rate of tumor testing should improve in subsequent years. Disclosure Advisory for Roche and Tesaro.

ObjectivesThe aim of this study was to determine the long-term results of a 7-week schedule of external beam radiation therapy, high dose rate brachytherapy, and weekly cisplatin and paclitaxel in patients with locally advanced carcinoma of the cervix.MethodsThirty-seven patients with International Federation of Gynecology and Obstetrics stages IB2 to IVa cervical cancer were treated with 40 mg/m2 per week of intravenous cisplatin and 50 mg/m2 per week of intravenous paclitaxel combined with 45 Gy of pelvic external beam radiation therapy and 28 to 30 Gy of high dose rate brachytherapy.ResultsSixteen patients (43.2%) were able to complete the 6 scheduled cycles of chemotherapy. The median number of weekly chemotherapy cycles administered was 5. Thirty-six (16.2%) of 222 cycles of chemotherapy were not given because of toxicity. The mean dose intensity of cisplatin was 29.6 mg/m2 per week (95% confidence interval, 27.0–32.1); that of paclitaxel was 40.0 mg/m2 per week (95% confidence interval, 36.9–43.1). Thirty-four patients (91.8%) completed the planned radiation course in less than 7 weeks. Median radiation treatment length was 43 days. After a median follow-up of 6 years, 7 patients (18.9%) experienced severe (RTOG grade 3 or higher) late toxicity. No fatal events were observed. Ten patients have failed, 1 locally and 9 at distant sites. The 14-year locoregional control rate was 96.7%, and the 14-year freedom from systemic failure rate was 64.6%. Fourteen-year actuarial disease-free survival and overall survival rates were 44.8% and 50%, respectively.ConclusionsThis study demonstrates excellent very long-term results and tolerable toxicity although the target weekly dosage of cisplatin and paclitaxel needs to be adjusted in the majority of the patients.

Resumen En diciembre de 2014 hemos tenido la oportunidad de ampliar nuestro conocimiento en el Simposio Internacional de Cancer de Mama, celebrado en San Antonio, resaltando: 1) en el escenario basico, la adquisicion de mutaciones durante el proceso de carcinogenesis y metastasis, aumentando la clonalidad y heterogeneidad tumoral, el papel pronostico de los neoantigenos y los linfocitos infiltrantes en el residuo tumoral tras la neoadyuvancia, asi como el mayor conocimiento de alteraciones en el receptor de estrogeno asociadas a hormonorresistencia; 2) en el translacional, el empleo de xenoinjertos derivados de tumores de pacientes en modelos murinos para evitar las resistencias terapeuticas, y los biomarcadores liquidos para descartar enfermedad minima residual en cancer de mama precoz; y 3) en clinica los resultados tanto en prevencion como en adyuvancia con hormonoterapia, la quimioterapia en triples negativos y las novedades en inmunoterapia.

Background Prognosis of patients with glioblastoma multiforme (GBM) remains dismal, with median overall survival (OS) of about 15 months. It is therefore crucial to search alternative strategies that improve these results obtained with conventional treatments. In this context, immunotherapy seems to be a promising therapeutic option. We hypothesized that the addition of tumor lysate-pulsed autologous dendritic cells (DCs) vaccination to maximal safe resection followed by radiotherapy and concomitant and adjuvant temozolomide could improve patients’ survival. Methods We conducted a phase-II clinical trial of autologous DCs vaccination in patients with newly diagnosed patients GBM who were candidates to complete or near complete resection. Candidates were finally included if residual tumor volume was lower than 1 cc on postoperative radiological examination. Autologous DCs were generated from peripheral blood monocytes and pulsed with autologous whole tumor lysate. The vaccination calendar started before radiotherapy and was continued during adjuvant chemotherapy. Progression free survival (PFS) and OS were analyzed with the Kaplan–Meier method. Immune response were assessed in blood samples obtained before each vaccines. Results Thirty-two consecutive patients were screened, one of which was a screening failure due to insufficient resection. Median age was 61 years (range 42–70). Karnofsky performance score (KPS) was 90–100 in 29%, 80 in 35.5% and 60–70 in 35.5% of cases. MGMT (O6-methylguanine-DNA-methyltransferase) promoter was methylated in 45.2% of patients. No severe adverse effects related to immunotherapy were registered. Median PFS was 12.7 months (CI 95% 7–16) and median OS was 23.4 months (95% CI 16–33.1). Increase in post-vaccination tumor specific immune response after vaccines (proliferation or cytokine production) was detected in 11/27 evaluated patients. No correlation between immune response and survival was found. Conclusions Our results suggest that the addition of tumor lysate-pulsed autologous DCs vaccination to tumor resection and combined radio-chemotherapy is feasible and safe. A multicenter randomized clinical trial is warranted to evaluate the potential survival benefit of this therapeutic approach. Trial registration This phase-II trial was registered as EudraCT: 2009-009879-35 and ClinicalTrials.gov Identifier: NCT01006044 retrospectively registered

Background Based on the synergistic effect between immuno- and chemotherapy (CT), we have elaborated an autologous vaccine with dendritic cells loaded with patients´ own tumor antigens (lysate), and we have already demonstrated that the addition of the vaccines to a standard neoadjuvant CT schedule has increased total pCR (breast+ axilla) in stages II-III non-overexpressing HER2 breast cancer patients (Santisteban M, SABCS 2012). Both cohorts, the control (C) and the vaccinated (V) were well balanced related to demographic characteristics. Toxicity has been similar in both the C and the V cohorts. Moreover, we have analyzed the phenotypic changes in peripheral blood induced by the vaccine and its correlation with pathologic responses. Indeed, we have studied if the amount of lysate used to load the dendritic cells or the total dendritic cell numbers received by the patients in the first five doses (before surgery) is correlated with pCR Methods Twenty-eight patients with stage II-III HER2 negative breast cancer have started on sequential neoadjuvant CT based on dose dense antracyclines (E 100mg/m2 and C 600 mgr/m2) x4 cycles plus GM-CSF followed by taxanes (DOC 75-100 mgr/m2) x4 cycles plus vaccination. The C historic cohort was composed of thirty patients who received the same treatment except for the absence of the vaccines. Vaccine calendar was started after the 4th EC and alternated with DOC and as maintenance up to a maximum of a 2 year-period. The first 5 vaccines were administered before breast surgery. Changes in different lymphocytes populations were measured in peripheral blood of patients at different points by flow cytometry (absolute cell counts). To date, twenty-one patients have both determinations of lymphocyte subpopulations before the 1st and the 6th vaccine. Paired samples t-tests and Fisher exact were used Results pCR was superior in the V cohort (24% versus 3.3%, p = 0.04). Lymphocyte subpopulations were measured in peripheral blood (cells/uL) and a stimulation of the immune system was found after the 5 vaccines schedule at the time of surgery as follows: NK (p Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-13-04.

Interesting neurological and cytological response rates after intrathecal (i.t) liposomal cytarabine have been observed in patients with leptomeningeal carcinomatosis (LMC) from solid tumors. However, the potential use of those responses as early predictors of time-to-progression (TTP) and overall survival (OS) is unexplored. 27 consecutive patients with LMC treated with 50 mg i.t liposomal cytarabine under compassionate drug use were retrospectively studied. All patients received i.t treatment every 2 weeks during induction and every 4 weeks during maintenance periods. Neurological and cytological responses were assessed before every liposomal cytarabine cycle. Most of the patients were female (17/27) diagnosed with breast cancer (15/27). A complete neurological response was seen among 11 % of the patients; partial response in 22 % of the patients; stable disease in 30 % of the patients and progressive disease in 37 % of them. Cytological assessment was available in 11/27 patients showing a 26 % complete response rate. The median time to neurological and cytological response was 15 days and 14 days, respectively. Patients showing a combined neurological and cytological response showed a significantly longer median TTP (122 vs. 3 days; p = 0.001) and OS (141 vs. 3 days; p = 0.002) compared to those showing both neurological and cytological progression. No grade 4 toxicities were recorded. According to these preliminary results, early neurological and cytological responses may be further studied as early predictors of TTP and OS in patients receiving i.t liposomal cytarabine for LMC.

Background The limited efficacy of neoadjuvant schedules to obtain pCR in breast cancer together with a prompt relapse of triple negative breast cancers has opened up the development of new strategies involving the immune system, which is essential in cancer control. We have elaborated an autologous vaccine with dendritic cells loaded with patients' own tumor antigens. Based on the synergistic effect between immunotherapy and chemotherapy our hypothesis is that the combination of both strategies could improve pCR with an excellent tolerance and could increase DFS and OS. Methods Two centers are enrolling patients from February 2011. Twenty-one patients with stage II-III HER2 negative breast cancer have started on sequential neoadjuvant chemotherapy based on dose dense antracyclines (E 100mg/m2 and C 600 mgr/m2) × 4 cycles plus GM-CSF followed by taxanes (DOC 75–100 mgr/m2) × 4 cycles plus vaccination. Vaccine calendar was started after the 4th EC and alternated with taxane schedule and after chemotherapy up to a maximum of a 2 year-period. SNB biopsy was performed before neoadjuvant chemotherapy. pCR in the breast and the axilla is the main endpoint, measured by Miller&Paine classification. Data were analyzed using SPSS and alpha was set at 0.05 (two-tailed). We have compared these results in the vaccinated cohort (V) with our historic cohort (C) of 19 patients treated in the same way but without the vaccine. Results Both cohorts (V and C) were well balanced for age, histologyc type, differentiation grade, Ki67>15%, tumor size ≤ 5 cm, stage and expression of hormone receptors. All patients except one in the vaccine cohort achieved 8 cycles of chemotherapy. According to grade ¾ toxicities we did not find significant differences except for hand-foot syndrome in the V cohort (19% vs 0%; p = 0.04) and vomiting in the C cohort (0% vs 21%; p = 0.02). Lymphopenia was the most common adverse event (81% in V vs 89.5% in C; p = 0.45). Other toxicities were anemia (0% vs 5.3%; p = 0.28), thrombopenia (0% vs 10% p = 0.12), leukopenia (9.5% vs 15.8% p = 0.55) and neutropenia (14% vs 21%, p = 0.57). Gastrointestinal toxicity was similar in both groups: mucositis (0% vs 5.3%, p = 0.28); gastritis (5% in both cohorts), nausea (19% vs 16%, p = 0.78), diarrhea (5% in both cohorts), constipation (0% vs 15% in C, p = 0.06). Myalgias were seen in 19% in V vs 11% in C (p = 0.45). We did not see any local grade ¾ toxicity related to the intradermal vaccines. Regarding efficacy data, clinical complete response by MRI was shown in 38% in the V as compared to 16% in the C (p = 0.06). Breast-conserving surgery was more common in the V cohort (62% vs 53%, p = 0.55). Total pCR (T plus N) was superior with the addition of the vaccine (24% vs 5% p = 0.014). Moreover in three more patients in the V group we find isolated tumor cells in the breast (Titc). Conclusions The addition of autologous dendritic cell vaccines to neoadjuvant chemotherapy significantly increased the rate of pathological complete responses among patients with HER2-negative breast cancer. Vaccination does not seem to add any toxicity to the schedule. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-16-03.

Background: Vitamin D (VD) is known to play a proapoptotic and antiproliferative role in cancer cells. Recent studies have shown that low serum VD may be associated with worse prognosis in cancer patients (pts). However, levels of VD are not routinely measured in daily clinical practice. Methods: We retrospectively evaluated pts diagnosed with non-metastatic breast cancer between January 2010 and November 2015. Serum 25(OH)-VD and bone density were measured any time after surgery, during either adjuvant treatment or the follow-up. VD insufficiency (VDi) and deficiency (VDd) were defined as serum VD levels of 20-30 ng/ml and Results: 98 pts that met the above described criteria were included in the analysis. Median (M) VD was 20.68 (range, 3 – 65.60). 72.4 % of pts had VD under 30 ng/ml (23.4% had VD insufficiency and 49% had deficiency). AJCC stages II-III were more frequent in patients with low VD levels (Normal: 48%; VDi: 52%; VDd: 65%). VD levels were similar across IHC subtypes (Normal VD levels: Luminal A: 51%; Luminal B: 30%; Triple Negative: 14%; VDi: LA: 52%; LB: 35%; TN: 13%; VDd: LA: 39%; LB: 48%; TN: 13%). Undifferentiated tumors were more frequent among pts with VD levels Conclusions: Lower levels of 25(OH)-Vitamin D may be associated with more advanced and aggressive non-metastatic breast cancer. 25(OH)-VD should be evaluated at diagnosis. Although it may be a promising biomarker, further research in this field is required.Background: Vitamin D (VD) is known to play a proapoptotic and antiproliferative role in cancer cells. Recent studies have shown that low serum VD may be associated with worse prognosis in cancer patients (pts). However, levels of VD are not routinely measured in daily clinical practice. Methods: We retrospectively evaluated pts diagnosed with non-metastatic breast cancer between January 2010 and November 2015. Serum 25(OH)-VD and bone density were measured any time after surgery, during either adjuvant treatment or the follow-up. VD insufficiency (VDi) and deficiency (VDd) were defined as serum VD levels of 20-30 ng/ml and Results: 98 pts that met the above described criteria were included in the analysis. Median (M) VD was 20.68 (range, 3 – 65.60). 72.4 % of pts had VD under 30 ng/ml (23.4% had VD insufficiency and 49% had deficiency). AJCC stages II-III were more frequent in patients with low VD levels (Normal: 48%; VDi: 52%; VDd: 65%). VD levels were similar across IHC subtypes (Normal VD levels: Luminal A: 51%; Luminal B: 30%; Triple Negative: 14%; VDi: LA: 52%; LB: 35%; TN: 13%; VDd: LA: 39%; LB: 48%; TN: 13%). Undifferentiated tumors were more frequent among pts with VD levels Conclusions: Lower levels of 25(OH)-Vitamin D may be associated with more advanced and aggressive non-metastatic breast cancer. 25(OH)-VD should be evaluated at diagnosis. Although it may be a promising biomarker, further research in this field is required. Citation Format: Baraibar I, Martín P, Sala P, Gardeazabal I, Salas D, Zubiri L, Santisteban M, Espinós J, Aramendía JM. Vitamin D as a potential biomarker of aggressiveness in non-metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-32.

BACKGROUND: Immunotherapy is being increasingly investigated as a treatment for glioblastoma (GBM). Recent non-randomized clinical trials and monocentric series describe the feasibility and safety of dendritic cells vaccinations, and suggest efficacy of this therapeutic approach. We describe a retrospective single-center series of newly diagnosed GBM patients who were treated with complete or near complete resection followed by standard radiotherapy plus concomitant and adjuvant temozolomide, and who additionally received vaccination with autologous dendritic cells pulsed with tumor lysate as compassionate use. MATERIAL AND METHODS: Between January 2011 and May 2017, twenty four patients with newly diagnosed GBM were treated with autologous dendritic cells vaccination as compassionate use in addition to standard radio-chemotherapy. An attempt at maximum resection was made in every case using fluorescence-guided surgery with 5-aminolevulinic acid. Less than 1 cc of residual tumour and histological confirmation of GBM was required for definite inclusion in the vaccination treatment programme. Vaccines were prepared with autologous dendritic cells pulsed with tumour lysate and matured ex vivo. Vaccination calendar started 3 weeks after surgery and 1 week before initiation of radiotherapy. Patients also received standard radiotherapy with concomitant and adjuvant temozolomide. Safety and outcome data are analyzed. RESULTS: The median age of the 24 patients was 61 years (range: 43 to 78). Median Karnofsky Performance Score was 80% (range: 40% to 100%). Complete resection was achieved in 20 (83%) patients. O6-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 13 (54%) patients. Enough tumor lysate and dendritic cells were available in every case to produce at least 6 vaccination doses. The median number of administrated vaccines was 7 (range: 2 to 16). Median Progression-Free Survival was 9.2 months and median Overall Survival was 21.1 months (95% CI: 15.4–26.7 months). No adverse events attributable to immunotherapy were identified. These results are similar to those obtained in a previous non-randomized trial conducted at our institution. CONCLUSION: These results confirm that autologous dendritic cells vaccination is feasible and safe in the clinical practice setting. Wether the addition of this immunotherapeutic modality to tumor resection and standard radio-chemotherapy increases survival of patients with newly diagnosed GBM still needs to be clarified in a randomized trial. Centers investigating this approach should associate to develop such a study.

Background: Pretreated advanced melanoma is a poor prognosis scenario with few, if any, active therapeutic options. The antibody against vascular endothelial growth factor, bevacizumab, has demonstrated increased activity in combination with chemotherapy in many tumors. We intended to evaluate the activity of the combination of weekly paclitaxel and bevacizumab in previously treated metastatic melanoma. Patients and Methods: Patients with previously treated metastatic melanoma received paclitaxel 70 mg/m2 weekly and bevacizumab 10 mg/kg biweekly for 5 consecutive weeks every 6 weeks. Results: Twelve patients were treated. Two patients (16.6%) achieved a partial response and 7 patients (58.3%) stable disease. Responses were seen in soft tissue, lung and brain metastases. Median disease-free and overall survival times were 3.7 and 7.8 months, respectively. Treatment was well tolerated. Main toxicities were grade 3 asymptomatic lymphopenia in 6 patients, grade 3 leucopenia in 2 patients, and grade 3 thrombocytopenia in 1 patient. Conclusions: Our preliminary results suggest that the combination of bevacizumab and weekly paclitaxel is active and safe in patients with metastatic melanoma, warranting further investigation.

BACKGROUND: Immunotherapy is emerging as a promising therapeutic modality for the treatment of glioblastoma (GBM). Recent clinical trials have supported the use of different therapeutic vaccines for high-grade gliomas, demonstrating promising feasibility and safety data. However, the wide variety of approaches and the limitations characterizing most studies preclude firm conclusions regarding efficacy. A phase II trial evaluating the efficacy and safety of autologous dendritic cells vaccination in addition to fluorescence-guided surgery and standard radio-chemotherapy with temozolomide in patients with newly diagnosed GBM was undertaken. PATIENTS AND METHODS: All consecutive patients aged 18 to 70 years who were candidates for resection of a suspected GBM were screened. An attempt at maximum resection was made in every case using fluorescence-guided surgery with 5-aminolevulinic acid. Less than 1 cc of residual tumour and histological confirmation of GBM were required for definite inclusion in the trial. Vaccines were prepared with autologous dendritic cells pulsed with tumour lysate and matured ex vivo. Vaccination calendar started before radiotherapy. Patients also received standard treatment consistent on radiotherapy with concomitant and up to 12 cycles of adjuvant temozolomide. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), safety, quality of life, and immune response. RESULTS: Thirty-two patients were screened between February 2009 and December 2011. One patient was excluded because of insufficient tumour resection (>1 cc of residual tumour). The mean age of the 31 included patients was 59 years. Median Karnofsky Performance Score (KPS) was 80% (range 60-100%). According to recursive partitioning analysis (RPA), 10% of the patients were RPA class III, 42% were class IV and 48% were class V. O6-methylguanine-DNA methyltransferase (MGMT) promoter was found to be unmethylated in 53% of the patients. Enough tumor lysate and dendritic cells were available in all cases to produce at least 6 vaccine doses. The median number of available vaccine doses was 11,2 (range, 6 to 17). Median PFS was 8.0 months and median OS was 27.4 months (95% CI: 20.9-33.0 months). No severe adverse events attributable to immunotherapy were identified. CONCLUSION: These results suggest that autologous dendritic cells vaccination is feasible and safe, and that the addition of this immunotherapy modality to gross total resection and standard radio-chemotherapy appears to increase survival in patients with newly diagnosed GBM.

1081Background: Levels of tumor infiltrating lymphocytes (TILs) at diagnosis have shown to improve survival in TNBC and HER2 overexpressing breast cancer (BC) patients. Indeed, high levels of TILs ...

Objectives: This study was undertaken to determine the tolerability of a 7-week schedule of external beam radiation therapy, high-dose-rate brachytherapy, and weekly cisplatin and paclitaxel in patients with locally advanced carcinoma of the cervix. Methods: Twenty-nine patients with International Federation of Gynecology and Obstetrics stages IB2 to IVa cervical cancer were treated with 40 mg/m2 per week of intravenous (i.v.) cisplatin and 50 mg/m2 per week of i.v. paclitaxel combined with 45 Gy of pelvic external beam radiation therapy and 30 Gy of high-dose-rate brachytherapy. Results: Eleven patients (37.9%) were able to complete the 6 scheduled cycles of chemotherapy. The median number of weekly chemotherapy cycles administered was 5 (range, 2-7). Thirty-five (20.1%) of 174 cycles of chemotherapy were not given because of toxicity. The median dose intensity of cisplatin was 31 mg/m2 per week (95% confidence interval [CI], 25.2-36.8); that of paclitaxel was 44 mg/m2 per week (95% CI, 39.9-48.3). Twenty-two patients (78.6%) were able to complete the planned radiation course in less than 7 weeks. Median radiation treatment length was 45 days (95% CI, 43.4-46.6). After a median follow-up of 48 months, 7 patients (24.1%) experienced severe (Radiation Therapy Oncology Group grade 3 or higher) late toxicity. No fatal events were observed. Seven patients have failed, 1 locally and 6 at distant sites. The 8-year local/pelvic control rate was 95.7%, and the 8-year freedom from systemic failure rate was 76.1%. Eight-year actuarial disease-free survival and overall survival were 63.1% and 75.9%, respectively. Conclusions: This study demonstrated unacceptable toxicity of combining the stated doses of concurrent cisplatin and paclitaxel chemotherapy with definitive radiotherapy for patients with advanced cervical cancer. Additional phase I/II trials are recommended to clearly establish the recommended phase II dose for these drugs.

PURPOSE: Capecitabine is eVective against metastatic breast cancer (MBC). We hypothesized that sequential treatment with dose-dense epirubicin/cyclophosphamide (EC) and docetaxel/capecitabine would be active and tolerable in the adjuvant/neoadjuvant setting. METHODS: In this prospective phase II clinical trial patients with HER2-negative and node-positive or locally advanced tumors were eligible to receive four cycles of EC (100/600 mg/m(2)) every 2 weeks with G-CSF on days 3–10, followed by four cycles of docetaxel/capecitabine (75/1,000 mg/m(2) b.i.d., days 1–14) every 3 weeks. RESULTS: Fifty-five patients were enrolled with median age of 49, and 80% had hormone receptor-positive disease. The median tumor size was 2.5 cm, with a median of two axillary nodes involved. Seventy-five percent of the first 20 patients had grade 2/3 hand-foot syndrome (HFS). Dose reduction of capecitabine to 800 mg/m(2) reduced the grade 2/3 HFS incidence to 31% in the remaining patients. No grade 4/5 toxicities were observed. All 20 patients treated preoperatively responded, with 5 (25%) pathologic complete responses and 3 additional pT(0)N(1) tumors. At a median follow-up of 48 (range 28–60) months, the event-free and overall survival rates are 91 and 98%, respectively. CONCLUSIONS: Sequential treatment with dose-dense EC followed by docetaxel/capecitabine, using a lower capecitabine dose than that approved for MBC, has an acceptable toxicity profile and encouraging activity when used as neoadjuvant or adjuvant treatment of breast cancer.

e11617 Background: Amplification of the HER-2 gene occurs in 20% of breast cancer (BC) patients (pts). Trastuzumab administered concurrently with chemotherapy (CT) is the standard of care in the neoadjuvant setting. Moreover, the use of a combination of antiHER2 therapies with CT are related to an increased pCR, which could be a surrogate marker for survival. Methods: We retrospectively analyzed three historic cohorts with overexpressing HER2 BC. They received neoadjuvant CT based on dose dense anthracyclines followed by three schedules of antiHER2 therapy: 1) docetaxel plus trastuzumab (DT; n = 33 pts); 2) DT plus CBDCA (DTP; n = 17 pts); and 3) DT plus double blockade with triweekly pertuzumab or daily L (750mg/day; n = 12) (DTD; n = 14) before surgery. Study endpoints were safety, pCR (breast + axilla) based on Miller&Payne criteria and DFS. Results: Sixty-four pts with HER2 overexpressing BC were studied since 2005. Baseline characteristics were well balanced. The median age was 48 (range 23-80). Coex...

2055 Background: Previous studies showed that FT may be useful as treatment in recurrent high-grade glioma (HGG). The present study evaluate the activity and toxicity of FT in recurrent malignant g...

Ixabepilone is a novel microtubule-stabilising agent used as monotherapy or in combination with capecitabine to treat taxane- and anthracycline-refractory breast cancer. We report the case of a patient who experienced an unusual motor neuropathy after the first cycle. This is a very uncommon secondary effect, but it must be taken into account as a possible complication of treatment with ixabepilone.

PURPOSE: Hedgehog (HH) pathway has been implicated in maintenace and survival of breast cancer and cancer stem cells, EMT regulation, breast carcinogenesis and resistance to chemoradiation in solid tumors. Dysregulation of this pathway occurs in more than 50% of breast cancers. We have already demonstrated that immune-induced epithelial to mesenchymal transition (EMT) leads to the generation of breast cancer stem cells (BCSCs) from a parental epithelial breast cancer cell line in an in vivo murine model (Cancer Research 2009). The aim of our study is to demonstrate that resistance in the BCSCs is linked to HH hyperactivation and that the selective blockade of this pathway could eradicate this subpopulation of BCSCs in preclinical models. METHODS: One parental epithelial (E) and three mesenchymal BCSCs cell lines (M1, M2 and M3) were used for all the in vitro experiments. qRT-PCR was used to quantify the expression of the gene components of the pathway and gene targets. Measurement of Gli1, caspase 3 and Cyclin D1 protein expression was determined by Western blot. Cell viability assays were performed with Paclitaxel and the HH inhibitor GDC-0449. Apoptosis assays were performed when cell lines were treated with paclitaxel (10nM), GDC-0449 (25uM) or the combination of them. For the in vivo xenografted mouse model, 106 cells (E and M2) were inoculated sc respectively into the flank of 6–8 week-old syngeneic female FVB/N-TgN (MMTVneu) 202Mul/J mice. Treatment was started on daily GDC-0449 (ip), paclitaxel (ip on days 1, 4 and 8) or both drugs when tumors reached 0.5 cm2. Statistical analysis was performed using one-way ANOVA with the Bonferroni multiple comparison test. RESULTS: Activity of the HH measured by the expression of Gli1 was increased in BCSC cell lines as compared to E cell line (p < 0.001). This was antagonized as expected by treatment with GDC-0449. Reporter and expression assay showed that GDC-0449 decreases Gli1 transcriptional activity and levels of a HH downstream target gene, cyclin D1. In all BCSC lines (but not in the E cell line), a synergistic effect was showed with the combination treatment as compared to control (p ≤ 0.01) and to paclitaxel or GDC-0449 alone (p ≤ 0.05 respectively) as well as a highly increased apoptotic activity (p ≤ 0.001 with control and p ≤ 0.05 with monotherapy). Tumors derived from M2 injection regressed when the combination schedule was administered (p ≤ 0.05) at 2 weeks after the start of the treatment. CONCLUSION: The inhibition of the HH pathway with GDC-0449 plus paclitaxel demonstrates a synergistic therapeutic effect in comparison to monotherapy, as shown by increased apoptotic activity, cell cycle arrest and significant reduction of tumor size in vivo. Together these results provide the rationale for future clinical trials including the blockade HH and standard chemotherapy in order to eradicate the whole population of tumor cells (also BCSCs) within the tumors and avoid disease relapse and metastasis in breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-03-07.

AIM: To assess whether the addition of a customized, active immunotherapy to standard of care including fluorescence-guided surgery, may provide hints of an improved survival for patients with poor-prognosis, incurable glioblastoma multiform. METHODS: Preliminary to our ongoing, phase-II clinical trial, we conducted a small pilot study enrolling five consecutive patients with resectable glioblastoma. In terms of Recursive Partitioning Analysis, four patients were class V and one was class IV. In all five cases, fluorescence-guided surgery was employed, followed by rapid steroid discontinuation. Patients were then treated with a combination of standard radio-chemotherapy with temozolomide and tumor lysate-pulsed, mature dendritic cell-based vaccinations. RESULTS: Though all five patients ultimately progressed, with any further treatment left to the sole decision of the treating oncologist, active immunotherapy was very well tolerated and induced specific immune responses in all three patients for whom enough material was available for such an assessment. Median progression-free survival was 16.1 mo. Even more important, median and mean overall survival were 27 mo and 26 mo, respectively. Three patients have died with an overall survival of 9 mo, 27 mo and 27.4 mo, while the other two are still alive at 32 mo and 36 mo, the former receiving treatment with bevacizumab, while the latter has now been off therapy for 12 mo. Four of five patients were alive at two years. CONCLUSION: Active immunotherapy with tumor lysate-pulsed, autologous dendritic cells is feasible, safe, well tolerated and biologically efficacious. A phase-II study is ongoing to possibly improve further on our very encouraging clinical results.

e11510 Background: We retrospectively analyzed the efficacy and safety of the combination of PLD and gemcitabine in patients (pt) with metastatic breast cancer (MBC) treated in our institution. Met...

635 Background: Recent improvements in adjuvant chemotherapy for HER2- BC include: 1) dose density and 2) concurrent or sequential anthracycline/taxane regimens. Further, the addition of capecitabi...

12001 Background: The level of angiogenic activity in breast cancer has been shown to be a determinant of disease progression. Adding an antiangiogenic agent to chemotherapy has demonstrated to imp...

8534 Background: Angiogenesis has an important role in melanoma progression. A prognostic value has been suggested for serum VEGF in melanoma. The novel agent bevacizumab (Bev) has demonstrated in combination with chemotherapy high activity in other tumors. We studied the combination of weekly paclitaxel (TXL) and bevacizumab (Bev) in previously treated metastatic melanoma patients (pts) and analyzed serum VEGF levels before and during treatment. Methods: TXL 70 mg/m2 weekly and Bev 10 mg/kg biweekly during 5 consecutive weeks every six weeks. VEGF levels pre-treatment and at response evaluation were analyzed with enzyme-linked immunoassays. Results: 13 pts have been treated: male/female: 4/9, median age: 45 (29–71), median PS ECOG: 2 (0–3), stage distribution M1b/ M1c: 2/11, high LDH levels: 8 pts. Median number of previous lines: 3 (1–6). Hematological toxicity: G III lymphopenia in 6 pts, G III leucopenia in 2 pts, G III thrombocytopenia in 1 pt and G I anemia in 3 pts. Non-hematological toxicities: alopecia in 7 pts, diarrhea G I in 4 pts, epistaxis G I in 8 pts. Response (and time to progression, months [m]): 2/12 PR (6 m and 4 m), 1/12 MR (6 m), 7/12 SD (7+ m, 7 m, 4 m, 4+ m, 3 m, 3 m, 3+ m), 2/12 PD. Responses were seen in soft tissue, lung and brain metastases. Overall survival at 12 months was 43.3%. Pre-treatment serum levels were high in five patients and they became negative at response evaluation (1 pt achieved MR, 3 pts SD and 1 pt PD). Unexpectedly patients with high pre-treatment VEGF levels had long survival: 4/5 patients remain alive and 2 pts have survived over one year: 12+ m, 12+ m, 5 m, 3+ m, 3.5+ m.VEGF was undetectable pre-treatment and at response evaluation in 7 pts, only 2/7 pts remained alive: 15+ m, 8 m, 7.5 m, 7 m, 6.8+ m, 3 m, 2.6 m. Conclusions: The combination of Bev and weekly TXL is active in melanoma and it has a good tolerance profile. Serum VEGF could be a good marker in this setting. Further research is needed to confirm these results. No significant financial relationships to disclose.

3758 Background: Preclinical data have shown a synergistic effect when MMC and CPT-11 are combined. In addition, this combination proved to be effective and well-tolerated in patients with fluoropyrimidine-resistant metastasic colorectal cancer Methods: To evaluate the safety and efficacy of MMC 5 mg/m2 day 1 plus CPT-11 200 mg/m2 on day 1, every three weeks, in a retrospective series of heavily pretreated metastasic CCR patients with good performance status (ECOG 1–2). Results: From September 2002 to October 2003, 20 pts (M/F: 13/7; ECOG 2: 50%; Median age: 55) were included. Sites of metastasic disease included peritoneal carcinomatosis (65%), lung (35%), liver (65%) and bone (15%). 12 pts (60 %) had received at least 3 lines of therapy. Prior chemotherapy included 5-fluorouracil (90%), oxaliplatin (100%) irinotecan (65%), capecitabine (85%) and raltitrexed (60%). Previous FOLFOX, FOLFIRI, FOLFOXIRI or XELOX had been administered in 50%, 15%, 25% and 35% of the patients, respectively. 4 pts (20%) achiev...

4252 Background: To determine the activity and tolerance of gemcitabine, 5-fluorouracil, leucovorin and cisplatin in patients with metastatic pancreatic cancer. Methods: Thirty-two patients with co...