bluuebunny/crossref_metadata_2025_split huggingface dataset:
Occult tumor cells in peritoneal lavage in pancreatic carcinoma patients.
Authors: Srovnal Josef , Benedikova Andrea , Havlik Roman , Klos Dusan , Lovecek Martin , Cahova Dana , Melichar Bohuslav , Hajduch Marian 
Published: March 2020

e14556 Background: Pancreatic carcinoma is one of the most aggressive malignancies with a poor prognosis. Assessment of occult tumor cells could prevent aggressive surgery in patients with metastatic spread. The aim of this study was to investigate the prognostic significance of occult tumor cells in peritoneal lavage of patients with pancreatic carcinoma. Methods: This was a prospective study to assess the presence of occult tumor cells in peritoneal lavage of 96 pancreatic carcinoma patients at the time of surgery using real-time RT-PCR for carcinoembryonic antigen (CEA), epidermal growth factor receptor 1 (EGFR1) and human telomerase (hTERT). Gene expression of tested markers was correlated with clinical/pathological characteristics using Kruskal-Wallis Anova and Mann-Whitney tests. Kaplan-Meier methods and Gehan-Wilcoxon tests were used for overall survival analyses. Results: Overall, 65 of 96 (69.9%) pancreatic carcinoma patients died, the overall survival median was 10.3 months. A significant association between CEA expression in peritoneal lavage and the clinical stage was found (p<0.03). In addition, patients with high grade tumors had significantly higher expression of EGFR in peritoneal lavage compared to patients with low grade tumors (p<0.04). The patients with the presence of occult cancer cells detected in the peritoneal lavage using CEA and/or EGFR had significantly shorter overall survival (p<0.001; HR=2.14 [95% CI: 1.30-3.55]) with overall survival median 6.8 months. Conclusions: These data demonstrate that the presence of occult tumor cells in peritoneal lavage is a negative prognostic factor in pancreatic carcinoma patients. Occult tumor cells detection using PCR based methods can identify patients with advanced disease for whom radical surgery is of no benefit. Prospective studies should confirm usefulness of this method for the selection of patients for radical surgery. Acknowledgements: Supported by grants IGA MZ NS 9937‑4, MPOTIP FR-TI1/525, IGA UP LF_2011_018 and CZ.1.05/2.1.00/01.0030.
The prognostic impact of epidermal growth factor receptor (EGFR) in patients with metastatic gastric cancer.
Authors: Werner Dominique , Atmaca Akin , Pauligk Claudia , Steinmetz Kristina , Colak Havva , Altmannsberger Hans-Michael , Jäger Elke , Al-Batran Salah-Eddin 
Published: March 2020

e14557 Background: The prognostic role of the epidermal growth factor receptor (EGFR) in metastatic gastric cancer has not been established. Methods: EGFR was analyzed by immunohistochemistry (IHC) in a total of 357 patients (formalin-fixed, paraffin-embedded samples) and by real-time quantitative PCR (RTqPCR) in 130 patients with esophagogastric cancer. Staining intensity on IHC was scored in EGFR 0, 1+, 2+ and 3+. Staining intensity (alternatively intensity x % positive cells or the H-Score) and quantitative mRNA expression were correlated with progression-free (PFS) and overall survival (OS) and pathological and clinical characteristics. Results: On IHC, EGFR was negative, 1+, 2+, and 3+ in 205 (57%), 50 (14%), 62 (17%), and 40 (11%) patients, respectively. EGFR 3+ status correlated positively with intestinal type histology (p=.05) but no other correlations between baseline criteria such as age, sex, ECOG, tumor location, type of metastatic sites, and type of sampling and EGFR status were found. PFS and OS were similar in patients with EGFR-positive vs. those with EGFR negative gastric cancer, regardless whether positivity was defined as ≥1+ (PFS, 5.3 vs. 5.7 months, p=.185; OS, 10.6 vs. 10.9 months, p=.463) or as 3+ (PFS, 5.7 vs. 4.9 months, p=.159; OS, 8.6 vs. 10.8 months, p=.377) or when alternative scores were used such as the H-score. The multivariate overall survival analysis indicated that EGFR status is not an independent prognostic factor (hazard ratio 0.84, 0.56 to 1.12, p=.227). There were also no significant differences in progression-free or overall survival when patients were categorized according to median (PFS p=.173, OS p=.116) or quartile (PFS p=.634, OS p=.767) distribution of EGFR mRNA expression or when the cut-off with the highest predictive value was calculated (PFS p=.148, OS p=.189). Conclusions: EGFR status is not prognostic of patient’s outcome in metastatic gastric cancer.
The role of tumor vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFR) polymorphisms in the prediction of clinical outcome for advanced hepatocellular carcinoma receiving sorafenib.
Authors: Faloppi Luca , Scartozzi Mario , De Minicis Samulele , Svegliati Baroni Gianluca , Bianconi Maristella , Giampieri Riccardo , Maccaroni Elena , Bittoni Alessandro , Del Prete Michela , Mandolesi Alessandra , Loretelli Cristian , Belvederesi Laura , Biagetti Simona , Bearzi Italo , Benedetti Antonio , Cascinu Stefano 
Published: March 2020

e14561 Background: Hepatocellular carcinoma (HCC) still represents a medical challenge in cancer therapy. In recent years the introduction of new targeted therapies has radically changed the approach to the disease and patients outcome. Currently the therapeutic stronghold is a TKIs directed against the VEGF family (sorafenib). Polymorphisms of VEGF and its receptor genes are involved in regulating angiogenesis and lymphangiogenesis and thus in growth tumor control. The aim of our study is to evaluate the potential predictive and prognostic role of VEGF and VEGFR polymorphisms in determining the clinical outcome of HCC patients receiving sorafenib. Methods: 38 histologic samples (biopsies and surgical specimens) of HCC patients receiving sorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients time to progression (TTP) and overall survival (OS) were analysed. Results: VEGF-AI rs25648 C>T polymorphism was statistically significant in OS (15.0 months for C vs 9.4 months for T; p=0.025). VEGF-AII rs10434 G>A was statistically significant for TTP (4.1 months for G vs 1.2 months for A; p=0.0076) and OS (14.2 months for G vs 1.7 for A; p<0.0001). VEGF-CII rs7664413 C>T was significant in TTP (13.4 months for C vs 2.0 for T; p=0.0125) and OS (14.7 months for C vs 5.6 for T; p=0.0007). VEGR2-I rs1870377 A>T was significant in TTP (19.9 months for A vs 3.0 for T; p=0.0271) and OS (29.6 months for A vs 11.9 for T; p=0.0096). Conclusions: In our analysis patients with G polymorphism at rs10434, C polymorphism at rs7664413 and A polymorphism at rs1870377 seem to have a better response (PFS and OS) during treatment with sorafenib. Patients with C polymorphism of rs25648 seem to have an advantage only for OS. These polymorphisms of the VEGF-A gene are probably connected with a better control of the neoangiogenesis process during TKIs therapy, maybe leading to vasculature normalization. VEGF-C is a ligand of VEGR2 and seems to have a closely relationship with lymphangiogenesis.
Factors predicting outcome of G1/2 GEP NET after PRRT with Lu177-octreotate.
Authors: Ezziddin Samer , Attassi Mared , Yong-Hing Charlotte Jane , Sabet Amir , Ahmadzadehfar Hojjat , Willinek Winfried , Gruenwald Frank , Guhlke Stefan , Biersack Hans-Juergen 
Published: March 2020

e14565 Background: Outcome analyses of G1/2 NEN stage IV after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. This study aims to establish predictors of survival. Methods: Retrospective analysis of 74 consecutive GEP NET patients undergoing PRRT with 177Lu-octreotate. Patients had unresectable metastatic disease and a G1/2 grading (33 pancreatic, 41 non-pancreatic GEP- NET), documented morphologic or clinical progression within < 12 months and/or uncontrolled disease. Response (modified SWOG criteria) was correlated with potential impact factors: origin, function, burden, and uptake of tumor, age, Ki-67-index, Karnofsky score, baseline tumor marker levels. Predictors for survival were analyzed with Kaplan-Meier curves (log-rank test) and multivariate analysis (p<0.05). Results: The response rates were 36.5% PR, 17.6% MR, 35.1% SD, and 10.8% PD for the entire cohort, 54.5% PR, 18.2% MR, 18.2% SD, and 9.1% PD for pancreatic NET, and 22.0% PR, 17.1% MR, 48.8% SD, and 12.2% PD for non-pancreatic GEP-NET. The median progression-free (PFS) and overall (OS) survival was 26 months (95% CI, 18.3 - 33.7) and 55 months (95% CI, 48.8–61.2), respectively. The only factor associated with decreased PFS was a Ki-67 index >10% (p=0.002). For OS, besides the Ki-67 index, a Karnofsky score ≤70% and a baseline NSE of >15 ng/ml independently predicted shorter survival (each p<0.005, HR 3.0 - 3.4). Patients with a Ki-67 index >10% still had a median PFS and OS of 19 and 34 months, respectively. Conclusions: This study confirms the favorable outcome of G1/2 NET after PRRT. Independent predictors of survival are the Ki-67 index, the patient‘s performance status and the baseline NSE level. Nevertheless, patients with a Ki-67 >10% may still benefit from PRRT as demonstrated by the long-term outcome.
Metronomic therapy with 5-FU, weekly nab-paclitaxel, leucovorin, and oxaliplatin, plus bevacizumab for advanced pancreatic cancer: A phase II study.
Authors: Isacoff William H. , Reber Howard A. , Hines Oscar J , Donahue Timothy R. , Purcell Fay M. , Clerkin Barbara M. , Clerkin Kara M. 
Published: March 2020

e14582 Background: The objective of this open label phase 2 study was to evaluate low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy for patients with advanced pancreatic cancer. Continuous infusion of 5FU, calcium leucovorin plus paclitaxel and oxaliplatin has been shown to be active in patients with pancreatic cancer. As a protracted low dose infusion, 5FU is anti-angiogenic and has been demonstrated to be synergistic with bevacizumab. Bevacizumab and nab-paclitaxel are synergistic as seen in the treatment of breast cancer. Methods: Since July 2008, we treated 40 patients with 5FU (180mg/m2/day x 14 days) via an ambulatory pump. Calcium leucovorin (20mg/m2) IVP, nab-paclitaxel (100mg/m2) IV as a 30 minute infusion and oxaliplatin (75mg/m2) IV as a 60 minute infusion were given on days 1, 8, and 15. Bevacizumab (5mg/kg) IV over 30 minutes was given on days 1 and 15. Cycles were repeated every 35 days. There were 24 females and 16 males. The median age was 58. 34 patients had stage IV disease. Results: The median overall survival is greater than 17 months. A partial response was observed in 50% of the patients. There were 22 patients with prior treatment, 11 of whom responded to the protocol. 34 patients began treatment with an elevation of their CA19-9 greater than 40. Of these, 26 patients were subsequently noted to have greater than 50% reduction in their CA 19-9; 17 of whom had an objective CT scan response to therapy. Toxicity (grade 3 and 4) included stomatitis, diarrhea, fatigue, nausea, neuropathy, hypertension and renal failure. Hematologic toxicity included anemia, neutropenia and thrombocytopenia. 19 patients stopped treatment due to disease progression, 18 patients stopped due totoxicity. There were no chemotherapy related deaths. Conclusions: This non-gemcitabine based regimen resulted in response rates and survival benefits greater than that which is ususally observed with gemcitabine based therapy. Low dose continuous (metronomic therapy) cytotoxic chemotherapy when combined with anti-angiogenic therapy is safe and effective for patients with advanced pancreatic cancer.
The outcome of peptide receptor radionuclide therapy (PRRT) in North American patients with advanced well-differentiated neuroendocrine tumors (WD-NETs).
Authors: Naraev Boris , Sharma Nancy , Engelman Eric Steven , Bushnell David L , O'Dorisio Thomas M. , Halfdanarson Thorvardur Ragnar 
Published: March 2020

e14600 Background: PRRT is frequently used in Europe for patients with advanced WD-NETs, but it is not yet readily available in the USA. We analyzed data on 135 North American patients seen at our institution who underwent PRRT. Methods: Cases were identified by searching the University of Iowa Neuroendocrine Tumors Database. Groups were compared using a Wilcoxon rank-sum test, and survival was calculated with the Kaplan-Meier method. Results: Men were 64%, women 36%; median age at diagnosis was 51 years (18 – 78). The primary tumor originated in the small bowel (SBNET) in 37.8%, pancreas (PNET) 26.0%, lung 13.3%, unknown primary 9.6%, other sites 13.3%. PRRT was performed at the University of Basel, Switzerland in 68.8%, University of Iowa in 25.2%, and elsewhere in 6%. 90Y was used in 83.2% and 177Lu in 15.3% for the first PRRT. Median dose of radiation was 180 mCi (range 7.6 – 360). 116 patients received two treatments with median time between the treatments 2.1 months (range 0.4 – 110). Survival is shown in the table. Radiographic responses (any) at 1-6 months after PRRT were observed in 65.8%, 11.1% had a mixed response, and 15.4% progressed. A biochemical response (>50% reduction in chromogranin A and pancreastatin levels) was seen in 18% and 17.3% respectively but data was frequently missing. Conclusions: North American patients with WD-NETs have a relatively long survival. The OS from 1st PRRT was much less than OS after diagnosis, suggesting that PRRT is used late in the disease course. PRRT appears to be a valuable treatment option for WD-NETs, especially SBNETS, and its role earlier in the disease course warrants investigation. [Table: see text]
Neoadjuvant chemoradiotherapy for potentially resectable esophageal squamous cell carcinoma and the significance of Rad51 expression as a factor predictive of the treatment response.
Authors: Saeki Hiroshi , Nakanoko Tomonori , Ohtsu Hajime , Kawano Hiroyuki , Ando Koji , Oki Eiji , Ohga Takefumi , Morita Masaru , Kakeji Yoshihiro , Toh Yasushi , Maehara Yoshihiko 
Published: March 2020

e14601 Background: The clinical significance of neoadjuvant chemoradiotherapy (NACRT) for potentially resectable esophageal squamous cell carcinoma (ESCC) and its effect on the development of postoperative complications are unclear. On the other hand, the Rad51 expression is related to the sensitivity to chemotherapy or radiotherapy; however, the significance of the Rad51 expression in ESCC has not yet been clarified. Methods: 1) One hundred sixty-eight patients with clinical Stage II-III (cStageII-III) ESCC were classified into two groups consisting of 76 who received NACRT followed by esophagectomy and 92 patients who received surgery alone. The prognosis and incidence of postoperative complications were retrospectively compared between the two groups. The pathological response to NACRT as well as the patient prognosis were also analyzed for the NACRT group patients. 2) The expression of Rad51 was investigated in pretreatment biopsy specimens in 41 ESCC cases who underwent surgery after NACRT, and the findings were compared with the pathological response to NACRT. Results: 1) The 5-year survival rate was 47.7% in the surgery alone group and 56.5% in the NACRT group, and the difference was not a statistically significant (p=0.4831). However, the 5-year survival rates of patients in whom NACRT was Grade 3 (markedly effective), was obviously better than that of the other patients (Grade0/1 – ineffective/slightly effective: 36.9%, Grade 2 - moderately effective: 53.8%, Grade 3 - markedly effective: 100%). The incidence of postoperative complications was 31.5% in the surgery alone group and 40.8% in the NACRT group, and the difference was not a statistically significant (p=0.2121). 2) Grade 3 was more frequently observed in Rad51-negative cases (n=13) than Rad51-positive cases (n=28; 71.4% vs. 28.6%, p=0.0239). Conclusions: The pathological complete response of NACRT is critical for improving the survival of patients with cStageII-III ESCC. The Rad51 expression in pretreatment biopsy specimens was therefore suggested to be a useful predictive factor for the response to NACRT.
Phase II study of nimotuzumab combination with paclitaxel and cisplatin as the first-line treatment in patients with local advanced or metastatic esophageal squamous cell cancer (ESCC): An interim analysis.
Authors: Zhang Xiaodong , Lu Ming , Gong Jifang , Gao Jing , Wang Xicheng , Zhang Xiaotian , Li Jie , Li Yan , Li Jian , Zhou Jun , Lu Zhihao , Shen Lin 
Published: March 2020

e14604 Background: Nimotuzumab is a genetically engineered humanized antibody (mAb) that recognizes an epitope located in the extracellular domain of human EGFR. Evidences have shown that nimotuzumab is effective and safe in SCCHN. The combination of paclitaxel/cisplatin (TP) is a standard regimen for advanced or metastatic ESCC. This open uncontrolled phase II study was designed to determine the efficacy and safety of nimotuzumab in combination with TP as the first-line treatment in advanced ESCC. Methods: All patients have histology/cytology confirmed advanced or metastatic ESCC with ECOG PS 0-2. The treatment plan is as the following: paclitaxel administered intravenously (IV) 175 mg/m2 on d1 and cisplatin IV 30-35mg/ m2/d on d1-2, every 21 days for 6 cycles, and nimotuzumab IV 200mg weekly. For patients with stable disease (SD) and better, nimotuzumab will be given continuously after 6 cycles of TP. The primary endpoint is objective response rate (RR) with 56 patients enrollment (target RR >60%); secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety/ tolerability. The coordinations between EGFR and ERCC1 with response of treatment will be analyzed. Results: Up to date, 25 patients (male/female, 20/5; median age 58) have been enrolled. All patients were evaluated for toxicity and 22 are evaluable for response. 14 (63.6%) had a confirmed partial response (PR) and 7 (31.8%) had SD as their best responses with disease control rate of 95.4%. Only one patient had progressive disease (PD). Grade 3 or 4 neutropenia, neutropenic fever and anemia occurred in 52.2%, 4% and 13% respectively. Nonhematological toxicities were generally mild with grade 1 or 2 alopecie, hypodynamia, anorexia, nausea, arthralgia, and itch of skin occurring in 80%, 60.9%, 43.5%, 34.8%, 30.4%, and 21.7%. One patient had a grade 3 haematuria. Conclusions: The interim analysis showed that the combination of nimotuzumab with TP is tolerated reasonably well in patients with advanced or metastatic ESCC and encouraging efficacy. The study is ongoing with coordination of biomarkers and response as well.
5-FU/leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) induction followed by chemoXRT in borderline resectable pancreatic cancer.
Authors: Kharofa Jordan , Kelly Tracy R. , Ritch Paul S. , George Ben , Wiebe Lauren Allison , Thomas James P. , Christians Kathleen K. , Evans Douglas B. , Erickson Beth 
Published: March 2020

e14613 Background: FOLFIRINOX improves overall survival compared to gemcitabine in patients with metastatic PCa. We retrospectively evaluated the feasibility of using induction FOLFIRINOX followed by chemoXRT to improve resectability in borderline resectable PCa. Methods: All patients with borderline resectable, biopsy-proven PCa treated with the FOLFIRINOX between 1/2009 -11/2011 were reviewed. Borderline resectable PCa was defined by computerized tomography (CT) imaging as tumor-induced SMA abutment of <180 degrees, SMV occlusion, or findings suspicious but not diagnostic for metastatic disease. CT imaging was obtained following induction chemotherapy and after chemoXRT prior to surgery. Results: Twelve patients with borderline resectable disease were treated with FOLFIRINOX induction (median of 4 cycles [range 3-8]). Chemotherapy details are listed in table 1. Tumors in 9 patients had SMA abutment or SMV occlusion and the median pre-treatment CA 19-9 was 297 U/ml (1-3432 U/ml ). Following induction chemotherapy, all patients proceeded to chemoXRT (50.4 Gy [1.8 Gy/fx] with concurrent gemcitabine [n=8] or capecitabine [n=4]). The median CA 19-9 reduction following systemic therapy alone was 58%. One patient did not complete chemoXRT due to infectious and hematologic toxicities. Following all neoadjuvant treatment, 7 (58%) of the 12 patients underwent successful PD. All 7 patients who underwent PD had an RO resection and only one patient had lymph node metastases. The median survival has not been met with median follow up of 13 months. Conclusions: In medically fit patients with borderline resectable PCa, induction FOLFIRINOX followed by chemoXRT is feasible and may facilitate a margin negative resection and histologic response in regional lymph nodes. [Table: see text]
Efficacy of tumor treatment field (TTF) therapy alone and in combination with chemotherapyin pancreatic cancer preclinical models.
Authors: Giladi Moshe , Schneiderman Rosa S. , Porat Yaara , Itzhaki Aviran , Mordechovich Daniel , Weinberg Uri , Palti Yoram 
Published: March 2020

e14616 Background: TTF therapy is a novel, non-invasive treatment modality for solid tumors and was recently approved by the FDA for recurrent glioblastoma. It utilizes alternating electric fields to inhibit tumor growth, by mitotic spindle disruption and destruction of plasma membrane integrity during cytokinesis. TTF inhibits the growth of many solid tumor cell lines in vitro and in vivo. The optimal treatment for pancreas cancer remains elusive, thus we sought to evaluate the efficacy of TTF in pre-clinical pancreatic cancer models. Methods: Cultures of hamster and human pancreatic adenocarcinoma cell lines (PC1-0 and AsPC-1, respectively) were treated with TTF (frequencies ranging from 75 to 300 kHz), using two pairs of perpendicularly oriented insulated transducer arrays. Once determining optimal frequency, TTF was combined with chemotherapy (gemcitabine or 5-Fluorouracil, 5-FU). Hamsters bearing syngeneic, orthotopic pancreatic tumors were treated with either TTF alone or in combination with gemcitabine or 5-FU. Results: TTF treatment had significant inhibitory effect on proliferation of pancreatic cancer cultures. The maximal inhibitory effect for PC1-0 and ASPC-1 was observed when TTF frequencies of 100 and 150 kHz were applied (respectively). The application of TTF to cultures treated with either gemcitabine or 5-FU resulted in an additive inhibitory effect. In-vivo, TTF therapy, either alone or in combination with chemotherapy, resulted in a significant decrease in tumor weight and volume. Compared to chemotherapy alone, TTF increased tumor response to both gemcitabine and 5-FU. Histological analysis demonstrated higher mitotic index in TTF-treated tumors, consistent with the mitotic arrest previously shown in TTF treated cultures. Conclusions: TTF therapy demonstrated efficacy in pancreatic adenocarcinoma in both in vitro and in vivo models. These results support the evaluation of this novel treatment modality in combination with standard chemotherapy in pancreatic cancer patients. A pilot study is in development to test the clinical benefit of combined TTF and gemcitabine in patients with advanced pancreatic adenocarcinoma.