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BackgroundThe addition of Dendritic cell vaccines (DCV) to neoadjuvant chemotherapy (NAC) could induce immune biomarker changes in those patients with residual disease (RD) by transforming tumor microenvironment.MethodsCore-diagnostic biopsies and surgical specimens from 80 patients (38 in the Vaccinated Group plus NAC (VG) and 42 in the Control Group (CG) treated only with NAC) were selected. We quantify TILs (CD8, CD4 and CD45RO) using Immunohistochemistry (IHC) and the Automated Cellular Imaging System (ACIS III) in the core-diagnostic biopsies and in the surgical specimen, to compare the amount of TILs in each group.ResultsA CD8 rise in TNBC samples was observed after NAC plus DCV, changing from 4.48% in the biopsy to 6.70% in the surgical specimen, not reaching statistically significant differences (p = 0.11). TNBC patients in the CG showed a TILs drop from 2.71% in the biopsy to 0.18% in the surgical specimen (p = 0.5). We also found that a 66.7% (4/6) of TNBC patients from VG registered an increase in TILs after treatment as compared with 20% (1/5) of TNBC patients in the CG (p=0.24). This phenomenon is not observed in the other biologic subtypes.An association between before NAC CD8 TILs (4% cut-off point ) and pathological complete response in VG was found in univariate and multivariate analysis (OR=1.41, IC95% 1.05-1.90; p=0.02, and OR=2.0, IC95% 1.05-3.9; p=0.03, respectively).ConclusionOur findings suggest that patients with TNBC especially benefit from the stimulation of the antitumor immune system by using DCV pulsed with tumor antigens.Trial registration: NCT01431196. Registred 19 May 2016. EudraCT 2009- 017402-36.

Background: Although surgical resection is the only potentially curative treatment for pancreatic cancer (PC), long-term outcomes of this treatment remain poor. The aim of this study is to describe the feasibility of a neoadjuvant treatment with induction polychemotherapy (IPCT) followed by chemoradiation (CRT) in resectable PC, and to develop a machine-learning algorithm to predict risk of relapse. Methods: Forty patients with resectable PC treated in our institution with IPCT (based on mFOLFOXIRI, GEMOX or GEMOXEL) followed by CRT (50 Gy and concurrent Capecitabine) were retrospectively analyzed. Additionally, clinical, pathological and analytical data were collected in order to perform a 2-year relapse-risk predictive population model using machine-learning techniques. Results: A R0 resection was achieved in 90% of the patients. After a median follow-up of 33.5 months, median progression-free survival (PFS) was 18 months and median overall survival (OS) was 39 months. The 3 and 5-year actuarial PFS were 43.8% and 32.3%, respectively. The 3 and 5-year actuarial OS were 51.5% and 34.8%, respectively. Forty-percent of grade 3-4 IPCT toxicity, and 29.7% of grade 3 CRT toxicity were reported. Considering the use of granulocyte colony-stimulating factors, the number of resected lymph nodes, the presence of perineural invasion and the surgical margin status, a logistic regression algorithm predicted the individual 2-year relapse-risk with an accuracy of 0.71 (95% confidence interval [CI] 0.56&ndash, 0.84, p = 0.005). The model-predicted outcome matched 64% of the observed outcomes in an external dataset. Conclusion: An intensified multimodal neoadjuvant approach (IPCT + CRT) in resectable PC is feasible, with an encouraging long-term outcome. Machine-learning algorithms might be a useful tool to predict individual risk of relapse. A small sample size and therapy heterogeneity remain as potential limitations.

Pancreatic ductal adenocarcinoma, which represents 80% of pancreatic cancers, is mainly diagnosed when treatment with curative intent is not possible. Consequently, the overall five-year survival rate is extremely dismal—around 5% to 7%. In addition, pancreatic cancer is expected to become the second leading cause of cancer-related death by 2030. Therefore, advances in screening, prevention and treatment are urgently needed. Fortunately, a wide range of approaches could help shed light in this area. Beyond the use of cytological or histological samples focusing in diagnosis, a plethora of new approaches are currently being used for a deeper characterization of pancreatic ductal adenocarcinoma, including genetic, epigenetic, and/or proteo-transcriptomic techniques. Accordingly, the development of new analytical technologies using body fluids (blood, bile, urine, etc.) to analyze tumor derived molecules has become a priority in pancreatic ductal adenocarcinoma due to the hard accessibility to tumor samples. These types of technologies will lead us to improve the outcome of pancreatic ductal adenocarcinoma patients. This work was funded by grants from Department of Health from Government of Navarra (Ref. 008-2018), REFBIO II Pyrenees Biomedical Network from Programa INTERREG V-A España-Francia-Andora (Ref. BMK_PANC) and Sociedad Española de Oncología Médica (SEOM) to A.V. I.G.-B. is supported by a predoctoral fellowship from Department of Economic Development Government of Navarre 'Ayudas para la contratación de doctorandos y doctorandas por empresas y organismos de investigación y difusión de conocimientos: doctorados industriales 2018–2020'.

The increased mortality reported among patient with rheumatoid arthritis (RA) has been attributed to cardiovascular disease. Metabolic syndrome (MS) is a cluster of major risk factors for cardiovascular disease such as dyslipidemia, obesity, hypertension, and diabetes. There is a lack of reporting on the prevalence of MS in RA patients in Argentina.The objectives of this study were to determine and compare the frequency of MS in patients with RA and a control group and to assess the factors associated with MS.This is a cross-sectional study involving 1033 (409 RA and 624 age- and sex-matched control subjects) patients, followed up at 9 different rheumatology units in Argentina. Metabolic syndrome was defined according to the Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF). The relationship between demographic variables, clinical data (disease duration, disease activity by Disease Activity Score of 28 joints, presence of rheumatoid factor [RF] and/or anti-cyclic citrullinated peptide antibody, presence of extra-articular manifestations), pharmacological treatment, and MS was examined by descriptive statistics. Variables with P ≤ 0.10 in these analyses were then examined by logistic regression.The frequency of MS in RA patients and the control group was 30% versus 39% (P = 0.002) when defined as per the ATP III and 35% versus 40% (P = 0.10) as per the IDF. Variables independently associated with MS in RA patients were age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06 [P = 0.01] for the ATP III and OR, 1.03; 95% CI, 1.01-1.05 [P0.001] for the IDF), the presence of RF and/or anti-cyclic citrullinated peptide antibody (OR, 2.91; 95% CI, 1.11-7.61 [P = 0.02] for the ATP III and OR, 2.37; 95% CI, 1.09-5.16 [P = 0.02] for the IDF), and the use of hydroxychloroquine (OR, 0.48; 95% CI, 0.23-0.97 [P = 0.04] only for the IDF).In this study, we were not able to demonstrate a higher frequency of MS in RA patients. However, older patients with positive RF or CCP have a higher risk of MS. A protective effect to develop MS was seen in the population treated with hydroxychloroquine.

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.

e20553 Background: NSCLC therapeutic paradigm has changed with immune checkpoint blockers. Biomarkers predicting clinical benefit are still lacking. As previously shown in melanoma, changes in absolute lymphocytes and neutrophils count (ALC and ANC) during IT (PD-1/PD-L1 inhibitors) may be related to response in NSCLC (Nakamuta et al, Oncotarget 2016). TTF1 expression has been associated with PD-L1 expression (Vieira et al, Lung Cancer 2016). We aimed to investigate TTF1 expression and changes in ALC and ANC after 2 cycles and their potential association with clinical outcomes to IT. Methods: We retrospectively analyzed 26 consecutive patients with stage IV NSCLC treated with IT at Clínica Universidad de Navarra (Spain) during 2016. Radiological response was evaluated according to RECIST v1.1. The potential correlation between ALC and ANC changes during the first two cycles and response to treatment [disease control rate (DCR) vs progression] was evaluated using Student’s T-test. Fisher’s exact test was used to study the association between changes in ALC ( < 1,000 vs > 1,000) and ANC ( < 4,000 vs > 4,000) after 2 cycles and response to IT. TTF-1 expression was correlated with treatment response. Overall survival (OS) was assessed with Kaplan-Meier analysis and Log-rank test according to ALC and ANC. Results: An ALC increase after 2 cycles was significantly associated with DCR compared to progression (192 vs -155; p = 0.043). ALC > 1,000 after 2 cycles was more frequent among patients experiencing DCR compared to progression (87% vs 50%; p = 0.07). ALC > 1,000 after 2 cycles was more frequently observed among patients with TTF1+ tumors (93% vs 55%; p = 0.03). Patients with ANC < 4,000 showed a longer median OS (NR vs 19.25 months; p = 0.03). TTF1 expression in adenocarcinoma (n = 18) was associated with response to IT (83% vs 16%, p = 0.01). Conclusions: Despite this retrospective small series’ limitations, our results show that ALC and ANC changes during IT and TTF1 expression may act as early predictors of clinical benefit in stage IV NSCLC patients treated with PD1/PD-L1 blockers. Our results warrant further investigation in larger prospective series.

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 ...

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...

e13057 Background: Recurrent high grade malignant gliomas (MGs) have a short survival. Initial standard therapy is based on surgery followed by concurrent radiotherapy with Temozolomide (TMZ) and s...

122 Background: In recent years many drug combinations have demonstrated clinical activity in heavily pretreated patients (pts) with metastatic breast cancer (MBC). Eribulin (E) in monotherapy has shown a beneficial effect in overall survival (OS) with slight rate of objective responses (OR) and poor effect in progression free survival (PFS). The Eribulin – Carboplatin (Cb) combination has been studied in other types of tumors in a phase Ib with promising results. We initiated an exploratory program with an off-label combination of E – Cb in pts with visceral disease and ECOG < 2. Methods: We retrospectively analyzed pts with MBC previously treated with anthracyclines, taxanes, and Capecitabine. Chemotherapy regimen consisted of E 1.1mg/m2 on days 1 and 8 and Cb AUC: 5 on day 1 every 21 days. Toxicity was assessed according to CTC criteria v 4.0. OR, PFS and OS rates were also evaluated. RECIST criteria were used to appraise radiological response. Results: Treatment was delivered in 10 pts. Median (M) age was 56 (range, 39-65). Pts characteristics were defined as follows: ECOG 0 (1 pt), 1 (6 pts) and 2 (3 pts); histological subtypes: luminal 9 pts and Her-2, 1 pt. M of previous lines was 7 (3-11). M of metastatic localizations were 3 (1-4). M of administered cycles was 6’5 (1-10). Grade 2 toxicity was asthenia 40%, peripheral neuropathy 10% and nausea - vomiting 10%. G 3 anemia and thrombopenia were noted in 20%. G 3-4 neutropenia was observed in 5 pts. Two pts required hospital admission due to febrile neutropenia. OR rate: complete response 10%, partial response 50% and stable disease 40%. Biochemical response rate was 80%. M of follow-up was 11 months, with M PFS and OS of 8 (4-11) and 18 months (4-18) respectively. Conclusions: Eribulin and Carboplatin is feasible, achieving remarkable response and survival rates with an acceptable toxicity profile in heavily pretreated patients with metastatic breast cancer. Preliminary results are promising and encourage us to continue recruiting patients.

4636 Background: Neoadjuvant therapy is an increasingly used approach in patients with resectable pancreatic cancer (PC). A positive link between chemotherapy dose intensity and patients’ outcome has been suggested in PC. The aim of this study was to rule out whether 5-FU pharmacokinetic (PK) parameters correlate with outcome in resectable PC patients treated with preoperative FOLFOXIRI. Methods: Patients with resectable and borderline resectable PC treated with Oxaliplatin (85mg/m2), Leucovorin (400mg/m2), Irinotecan (150 mg/m2) and 5-FU (initial dose of 3200 mg/m2 in 46h infusion and subsequent doses based on PK-guided dose adjustements targeting an AUC of 25-30 mcg*h/ml) were included. 5-FU PK analysis was performed taking two plasma samples during 5-FU infusion in at least two cycles. Drug concentrations were analysed by High-Perfomanced Liquid Chromatography. After induction polychemotherapy (IPCT), patients with no progressive disease received chemoradiation (CRT) (50.4 Gy with concurrent Capecitabine and Oxaliplatin) followed by surgical resection 4 to 6 weeks after the completion of CRT. Subsequent follow-up until disease progression was remained. An exploratory analysis with Log-Rank test was performed to assess progression free survival (PFS) based on 5-FU AUC values. Results: From November 2012 to October 2018, 29 patients were retrospectively assessed: median age 63 (46-75); M/F rate 20/9; R0 resection rate of 90% in the intention-to-treat analysis. The pathological response according to CAP classification was 0, 1, 2 and 3 in 14, 58, 19.5 and 8.5%, respectively; and median number of resected lymph nodes was 11 (2-22), with lymph node infiltration (ypN1) in 14% of patients. Grade 3-4 IPCT related toxicities and grade 3 CRT related toxicities were reported in 40 and 30% of patients, respectively. Median PFS was 723 days (24 months) and median 5-FU AUC 28.5 mcg*h/ml (23-53). Median PFS for patients with 5-FU AUC ≥27 mcg*h/ml was 29 months versus 15 months in patients with 5-FU AUC < 27 mcg*h/ml (adjusted hazard ratio for disease progression 0.223; 95% CI = 0.059-0.848; p = 0.028; in a model controlled by age, sex and irinotecan dose intensity). Conclusions: 5-FU pharmacokinetic parameters achieving a target of AUC ≥ 27 mcg*h/ml seem to correlate with longer PFS in this subset of patients.