bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of safety and efficacy of somatuline autogel in combination with molecular targeted therapies (MTT) in patients with neuroendocrine tumors (NETs): Data from one Spanish cohort.
Authors: Capdevila Jaume , Sevilla Isabel , Alonso Vicente , Aparicio Luis Anton , Jimenez Paula , Grande Enrique , Reina Juan J , Manzano Jose Luis , Alonso-Guadalajara Juan Domingo , Garcia Alfonso Pilar 
Published: March 2020

e14671 Background: Analysis of the mechanisms of action of somatostatin analogs (SSAs) and mTOR inhibitors or tyrosine kinase inhibitors suggest that they may provide synergistic effects when used in combination for the treatment of pts with NETs. Methods: This is a Spanish multicenter cohort of pts with NETs treated with the SSAs lanreotide (LAN) and MTTs at 35 Spanish referral centers. Data of 159 combined treatments (133 pts) was retrospectively collected in order to evaluate the efficacy and safety of such combinations. Results: 133 pts (52,6% M) with a median age of 59,9 years; ECOG 0/1/2/3: 34%/49%/16%/1%; Lung/Pancreas/Gastrointestinal//Unknown(UK) origin: 9%/48% /32%/11%; G1/G2/G3/UK: 41%/32%/1%/26%; Non Functioning/ Functioning (69%/31%) received treatment with MTT + LAN for synergistic antiproliferative purpose in 85% of the cases, hormonal control (13,5%) or both objectives (1,5%). 115 pts received one combination treatment and 18 pts received between 2 (12 pts) and 5 (1 pt). LAN was administrated in combination with sunitinib (61), everolimus (73), bevazucimab (9), sorafenib (8) and pazopanib (8). The reported toxicity was determined by the MTT profile with no significant additional severe adverse events related to the combination with LAN. The probability of progression-free survival (PFS) at 6, 12 and 18months was 89%, 73% and 67% respectively for those pts who received LAN and sunitinib (n=50) and 78%, 69% and 57%, respectively for those pts who received LAN and everolimus (n=56). Median PFS was not reached at the time of analysis. Conclusions: The combination of LAN and MTT, mainly everolimus and sunitinib, is widely used in clinical practice without unexpected toxicities. Median PFS will be higher than data observed in phase III studies with sunitinib and everolimus, raising the hypothesis of enhanced efficacy combining SSAs and MTT that should be confirmed in randomized prospective clinical trials. [Table: see text]
HER2 amplification, HER2 overexpression,and TOP2A abnormalities in gastroesophageal cancers: Do they predict responsiveness to epirubicin-based chemotherapy?
Authors: Personeni Nicola , Bozzarelli Silvia , Spaggiari Paola , Rubino Luca , Giordano Laura , Roncalli Massimo , Santoro Armando 
Published: March 2020

e14672 Background: Abnormalities of TOP2A, a major target of anthracyclines, have been reported as positive predictive markers of response to anthracycline-based therapy in breast cancer. We determined abnormalities of TOP2A and HER2, and HER2 protein expression, in a cohort of patients with gastric or gastro-oesophageal junction adenocarcinomas treated with epirubicin-based chemotherapy. Methods: We studied 50 patients that received either adjuvant (74%) or perioperative (26%) epirubicin, cisplatin and 5-fluorouracil. All patients were screened for TOP2A amplification/deletion by fluorescent in situ hybridization (FISH), and for HER2 protein expression by immunohistochemistry (IHC). For each patient at least two paired surgical samples were examined. Tumors exhibiting a HER2 score of 2+ were further screened for gene amplification by FISH. We studied the association of TOP2A abnormalities and HER2 amplification/expression with recurrence free survival (RFS) and overall survival (OS). Results: By IHC, HER2 overexpression (score 3+) was detected in 9 patients. Intra-tumor heterogeneity of HER2 staining, resulting in discrepant HER2 scores, was detected in 4 of 50 (8%) paired samples analyzed. HER2 amplification was detected in 1 of 8 tumors with a HER2 score 2+. TOP2A amplification was observed in 1 of 50 tumors; none exhibited TOP2A deletions. In patients whose tumors showed HER2 overexpression or gene amplification (HER2-positive) and in patients with HER2-negative tumors, median RFS was 11.0 and 13.9 months, respectively (p= 0.35); median OS was 28.8 and 29.9 months, respectively (p= 0.56). A pathological complete response was observed in 1 of 4 HER2-positive patients that underwent perioperative chemotherapy. Conclusions: In this cohort of patients with early-stage gastroesophageal cancers who were treated with epirubicin-based chemotherapy, neither HER2 amplification nor HER2 overexpression were associated with outcome. TOP2A abnormalities are rare and their putative role as a determinant of responsiveness to anthracycline-based chemotherapy in gastroesophageal cancers is not supported by our findings.
Beneficial trends of second-line chemotherapy in advanced pancreatic cancer.
Authors: Silva Milton Jose B. , Maia Joyce Maria L. , Ribeiro Adriana Regina G. , Chinen Ludmilla T. D. , Paiva Jr Tadeu Ferreira , Padua Fernando Vidigal , Pinto Flavio Augusto Ismael , Santos Elizabeth Santana , Mello Celso Lopes , Campanha Daniel , Pereira Augusto Akikubo Rodrigues , Fanelli Marcello Ferretti 
Published: March 2020

e14680 Background: Despite the lack of high-quality clinical trial data suggesting that second-line chemotherapy (SLC) may affect survival on metastatic pancreatic cancer (mPC), most of centers utilizes them after the failure of initial treatment in patients who maintain a good performance status. The aim of the present study was to review our institutional experience with SLC and estimate its role in overall survival (OS). Methods: We performed a retrospective matched case-control analysis based on search of medical records in 106 consecutive patients with mPC at our institution. Patients received first line chemotherapy (FLC) and SLC (n = 49) or FLC only (n =57) from September 2005 to December 2010. Case matching was performed with respect to age (< 60y versus ≥ 60y), topography (head of the pancreas versus body or tail), sites of metastasis. Overall survival was analyzed by Kaplan-Meier method. Results: Median age was 63 (32-86) and 60 (38-85) for SLC group and FLC group respectively. There was no significant difference between the two groups regarding topography, TNM stage at diagnosis, and sites of metastasis. The main site of metastasis was the liver (24,4%), followed by peritoneum (2,8%).Median follow-up of both groups was 8.4 months (0.23m-54.93m). First line treatment consisted of Gemcitabine (55.1% x 49.1%) and gemcitabine + cisplatin (18.4%x14%) in SLC and FLC group respectively. The most used second line treatment was Capecitabine (32.7%), followed by Folfox (16.3%), and Fluoracil (10.2%). The Kaplan-Meier estimate of the overall median survival, 1-year and 2-years survival rate was 15.72 months versus 7.2 months (p:0.021), and 60% vs. 32%, and 30% vs. 19% in SLC and FLC group, respectively. Conclusions: Our result suggests that second-line chemotherapy may be beneficial to improve overall survival in patients with advanced pancreatic cancer. It’s important that new and ongoing clinical trials clarify which is the best chemotherapy scheme in this setting.
Effects of metformin on pancreatic cancer survival among Medicare beneficiaries.
Authors: Witkowski Elan R. , Ragulin-Coyne Elizaveta , Chau Zeling , McDade Theodore P. , Ng Sing Chau , Tseng Jennifer F. 
Published: March 2020

e14691 Background: Evidence from preclinical models suggests that metformin may have antitumor activity against pancreatic adenocarcinoma. The effect in humans has not been well-described. A recent single-institution retrospective analysis suggested improved survival in diabetic patients who had been exposed to metformin. The current study was designed to determine whether metformin was independently associated with improved pancreatic cancer (PC) survival when compared to non-metformin controls using newly available national pharmacy data from Medicare Part D. Methods: Patients with diagnosed with AJCC Stage II-IV PC during 2007 were identified in the SEER-Medicare linked database. Part D events for oral diabetic medications were identified from the date of diagnosis until death or 12/31/2008, and divided into metformin-containing or non-metformin. Patients who did not receive an oral medication for diabetes, lacked continuous Part D prescription drug coverage, underwent surgical resection, or survived less than 30 days were excluded. Patient characteristics were compared by chi-square and Wilcoxon. Overall survival was compared by Kaplan-Meier log rank. Results: From an initial cohort of 899 patients, 100 met inclusion criteria and received oral diabetic medication. Of these, 31 received metformin and 69 non-metformin. Patient characteristics were similar among the groups, including median age (76.6 vs. 76.2, p=0.75), race distribution, Charlson comorbidity score and disease stage (p>0.05 for each). There was no statistically significant difference in median survival between the two groups: 5.6 months for metformin vs. 6.1 for non-metformin, p=0.93. Conclusions: This study using national Medicare Part D prescription drug claims revealed no detectable survival benefit for unresectable pancreatic cancer patients who received metformin when compared to non-metformin oral hypoglycemics. Sufficient power to detect modest benefits, however, will require additional subjects, which we anticipate in the near future. Additional studies are warranted and ongoing to determine the effect of metformin on pancreatic cancer survival.
Neuroendocrine tumors (NET) of the gastrointestinal tract: Experience at Winship Cancer Institute of Emory University.
Authors: Zafar Syed Farhan , Patil Dattatraya Hari , Kauh John S. , Adsay Volkan , Kooby David A. , Brutcher Edith , Maithel Shishir Kumar , El-Rayes Bassel F. 
Published: March 2020

e14692 Background: NET are relatively uncommon malignancies with variable natural history and often indolent clinical behavior. Pancreatic neuroendocrine tumors (PNET) have been reported to have worse outcomes as compared to neuroendocrine tumors of the gastrointestinal tract other than pancreatic (GNET). The objective of our study was to compare the clinicopathologic characteristics, presentation, treatment and survival outcomes in PNET and GNET. Methods: After IRB approval, we identified 125 patients (pts) with NET of the gastrointestinal tract from 2006-2011 in the Winship Institute cancer registry. A retrospective chart review was performed. Patients were categorized in mutually exclusive groups of PNET and GNET. Results: Demographic information and comparison of basic characteristics are listed in the table. Treatment modalities employed for PNET included surgery (72%), chemotherapy (30%), biological therapy (13%) and somatostatin analogues (11%). Liver-directed therapies were employed for hepatic metastases in 9 pts with PNET. Most common modality was radiofrequency ablation (4 pts) followed by Yttrium-90 embolization (3 pts), chemoembolization (1 pt) and bland embolization (1 pt). Majority of GNET were of midgut origin (47%) followed by foregut (35%) and hidgut (13%). Treatment for GNET included surgery (64%), chemotherapy (11%) and somatostatin analogues (17%). 90% of pts in PNET and 89% in GNET were alive at median follow up of 82 months. Conclusions: Overall, pts with NET have good prognosis. In our series, patients with PNET and GNET, had comparable survival outcomes even in advanced stage. These patients should be evaluated by a multidisciplinary team as new therapies become available. [Table: see text]
Role of chemoradiotherapy in advanced biliary cancers.
Authors: Nayak Asha , Arora Sameer , Kruse Edward J. 
Published: March 2020

e14694 Background: Patients with metastatic biliary tract cancers have a poor outcome and radiotherapy is administered largely to patients with an intent of palliation. We analyzed our institutional biliary tract cancer database to compare the outcome between chemotherapy alone vs. chemoradiotherapy. Methods: From January 2005 to December 2010, 126 metastatic and inoperable biliary cancer patients were retrospectively analyzed. 59(46.8%) patients received chemoradiotherapy(CRT) and 67(53.1%) patients received chemotherapy alone. Chemotherapy regimens consisted of 5-fluorouracil, gemcitabine, or cisplatin. CRT patients received 3D-CRT with a median dose of 30 Gy (range, 25-35Gy ) at 1.8-2 Gy per fraction per day.Patients were categorized into Gall bladder, extrahepatic or intrahepatic bileduct cancers .The follow-up time was calculated from the time of diagnosis to the date of death or the last contact. Kaplan-Meier analysis was used to calculate the overall survival (OS). Results: Median OS was 6.6 months for all patients. Median OS was 6.9 months (0.8-26.0) for patients treated with chemotherapy alone and 10.2 months (0.8-46.9) for those treated with chemoradiotherapy (p = 0.002). Univariate survival analysis of categorical variables for patients treated with chemoradiotherapy revealed that age, race, gender, location of metastatic site, site of primary tumor ,T stage (T3 v. T4) or nodal stage were not significant. However, ECOG performance status (1 v. 2/3) and the dose of radiation (<30 v. >30 Gy) received were associated with improved survival (p = 0.002, p=0.032). Median OS was 13.2 months for ECOG 1 vs. 4.3 months for ECOG 2/3. Median OS was 12.3 months for patients treated with radiotherapy dose more than 30 Gy vs. 6.4 months for those who received less than 30 Gy. 12/59(20.3%) patients who received chemoradiotherapy lived approximately 2 years longer. Conclusions: Metastatic biliary tract cancer patients with good performance score may benefit from chemoradiotherapy, and this modality did not increase the mortality. Long-term survival was observed in this selected group.
Impacts of epidermal growth factor receptor, HER2, and mTOR status on outcomes of patients with gastric cancer.
Authors: Aydin Kubra , Okutur Kerem , Bozkurt Mustafa , Namal Esat , Ozturk Akin , Planci Kezban Nur , Akcali Zafer , Tecimer Coskun , Demir Gokhan 
Published: March 2020

e14698 Background: Expression of EGFR, Her-2 and mTOR have been linked to clinical outcomes in several solid tumors. However clinical significance of these biomarkers in gastric cancer remain unclear. This study was designed to detect the clinical implications of these three biomarkers in Turkish population. Methods: Paraffin-embedded tissue microarray blocks containing gastric cancer tissue obtained from 30 patients were constructed. Expression of mTOR, EGFR were detected by immunohistochemistry. Her-2 gene ampflication was detected by FISH. The correlation of these biomarkers to clinicopathologic features and survival of patients with gastric cancer was studied. Results: The overall rates of positive mTOR, EGFR and Her-2 status were 36.7%, 63.3% and 23.3% respectively. The EGFR expression(any grade) was significantly correlated with better OS(Overall Survival)(p=0.01). Median survival time is 34.7 months in EGFR +patients and 10.6 months in EGFR - patients. There was no significant correlation with Her-2 status and survival. But 5 of these 7 Her-2 positive patients have already took trastuzumab treatment. Also we find that her-2 pozitive tumors significantly metastasized much more frequently to liver than her-2 negative tumors.(p= 0.043) In Contrast, her-2 positive tumors significantly metastasized less commonly to periton, over, omentum as seeding than her-2 negative tumors.(p=0.009). There was no association was noted between the expression of mTOR and survival time. Conclusions: EGFR is good prognostic marker in gastric cancer patients.
What is the clinical impact of PET/CT in evaluating patients for recurrent pancreatic cancer, and is it a useful tool in suspicious pancreatic lesions?
Authors: Alkaied Homam , Asaad Razan , Popalzai Muhammad Jawad , Brenner Arnold 
Published: March 2020

e14704 Background: Recurrence of pancreatic cancer after surgery is difficult to detect with conventional computed scan (CT) which has limited ability to distinguish local recurrence from postoperative changes. FDG – (18-fluorine deoxyglucose) positron emission tomography/computed tomography (PET/CT) evaluates biologic tumor activity related to glucose metabolism. Hence, it may improve the diagnostic accuracy postoperatively for pancreatic carcinoma. PET/CT can also evaluate suspicious pancreatic lesions to predict their malignant potential. Methods: 31 PET/CT scans were reviewed retrospectively for 18 patients with pancreatic lesions found on abdominal CT. Results: 14 of 18 patients had documented pancreatic cancer. 9 patients underwent resection; 7 had Whipple procedure; 2 had distal pancreatectomy with splenectomy. All 9 patients who underwent resection had recurrent disease; 4 (44%) of them had recurrence detected by PET/CT that was not detected on CT performed within 4 weeks of the PET/CT, potentially altering their management and prognosis. 1 patient had a recurrent lesion resected and 3 patients were started on chemotherapy or chemo-radiation therapy. In 2 cases with recurrence, PET/CT was able to distinguish pancreatic bed recurrence from postsurgical changes in comparison with CT. 4 of 18 patients had suspicious pancreatic findings on CT. PET/CT in these patients showed no FDG avid pancreatic lesion. Among these 4 patients, 1 had no pancreatic biopsy performed due to comorbidity and is still alive 3.5 years later. 1 had benign finding on pancreatic biopsy. 2 had a non diagnostic pancreatic biopsy. 1 expired 2 years later due to sepsis, and the other patient was 86 years old and expired a year later of unknown cause. Conclusions: FDG PET/CT is valuable in evaluating patients with suspected recurrent pancreatic carcinoma. PET/CT is helpful in managing patients with a suspicious CT pancreatic lesion who lack histologic confirmation. If the lesion is not metabolically active, this may allow follow up with observation and reduction in unnecessary intervention in selected patients.
Identification of two HCC phenotypes based on thrombocytopenia.
Authors: Carr Brian I. 
Published: March 2020

e14720 Background: Clinical phenotypes of small and larger HCCs are not well characterized. Aims. To characterize small HCC phenotypes. Methods: A cohort of 430 small HCCs that were diagnosed through screening, were dichotomized by size of < 3cm or > 3cm maximum tumor diameter and compared for radiologic and blood test parameters and analyzed by Chi-square test for categorical variables and Mann-Whitney test for continuous variables. Results: Significant differences between the tumor size groups included AFP values and platelet counts, with thrombocytopenia and elevated bilirubin levels being associated with smaller tumors. In comparing PVT+ and PVT- patients, AFP levels and platelet counts were also significantly different between the 2 groups. Conclusions: Larger tumors were associated with normal platelets and bilirubin levels, compared to smaller tumors that were more typically found in the presence of thrombocytopenia, suggesting that smaller and larger HCCs might have different developmental pathways.
Neoadjuvant chemoradiation for potentially resectable gastric cancer.
Authors: Barfield Michael E. , Untch Brian R. , Arcury Justin T. , Czito Brian G. , Willett Christopher , Pappas Theodore N. , White Rebekah Ruth , Tyler Douglas S. , Blazer Dan G. 
Published: March 2020

e14724 Background: Outcomes are poor in patients with gastric cancer, and recurrence is common. Perioperative chemotherapy and adjuvant chemoradiation therapy (CRT) improve survival in patients with resectable disease. Experience with neoadjuvant CRT for potentially resectable disease is limited, and its role remains undefined. We report our experience using neoadjuvant CRT for potentially resectable gastric cancer. Methods: An IRB-approved, retrospective review from 1994 to 2007 identified 23 patients with biopsy-proven, potentially resectable gastric cancer. Patients had T2/T3 and/or N1 disease and no evidence of metastatic disease by endoscopic ultrasound and cross-sectional imaging. All underwent neoadjuvant external beam radiation with concurrent 5-FU or platinum-based chemotherapy followed by restaging and surgery if appropriate. Results: Of the 23 patients, 20 completed neoadjuvant CRT and surgical exploration. Two patients (n=2) had radiographic disease progression during neoadjuvant CRT and did not undergo resection. One patient (n=1) developed a perforated gastric ulcer during CRT and underwent emergent resection. The median time from diagnosis to surgery and completion of neoadjuvant CRT to surgery was 104 days and 37.5 days, respectively. Gastrectomy was performed in 17 (85%) patients who completed neoadjuvant CRT. Metastatic disease was identified in the remaining 3 (15%) patients. Following gastrectomy, a complete pathologic response was observed in 4 (23.5%) patients, a partial response in 11 (64.7%) patients, and no response was identified in 2 (11.8%) patients. One (6%) patient had microscopic positive margins, and 9 (53%) had positive lymph nodes. There was no perioperative mortality. Two (11.8%) patients had anastomotic leaks, which were managed non-operatively. The median length of stay was 10 days. The median disease-free survival was 10.5 months, and median overall survival was 19.6 months. Conclusions: Gastric cancer carries a poor prognosis. Surgical resection after neoadjuvant CRT has low treatment-associated morbidity and mortality. Survival and complete response rates are comparable to published series. Further evaluation of this treatment strategy is warranted to assess its efficacy.
CF102 for the treatment of hepatocellular carcinoma: A phase I/II, open-label, dose-escalation study.
Authors: Stemmer Salomon M. , Benjaminov Ofer , Medalia Gal , Ciuraru Noa , Silverman Michael H. , Bar Yehuda Sara , Fishman Sari , Harpaz Zivit , Farbstein Motti , Cohen Shira , Petoka Renana , Singer Barak , Kerns William D , Fishman Pnina 
Published: March 2020

e14731 Background: The A3 adenosine receptor (A3AR) is over-expressed in hepatocellular carcinoma (HCC) cells as well as in the peripheral blood mononuclear cells (PBMCs) of patients with HCC. The orally active drug candidate CF102, an A3AR agonist, induces in vivo apoptosis of HCC cells via de-regulation of the Wnt signaling pathway. In this open label phase I/II trial, the safety and clinical effects of CF102 were assessed in patients with advanced unresectable HCC. Methods: The primary objectives of this trial were to examine the safety and pharmacokinetic (PK) behavior of CF102 given orally twice daily in continuous cycles of 28 days each. Evaluation of anti-tumor effects and the utilization of A3AR as a biological predictive marker of response to CF102 were the secondary objectives. Results: 18 patients received CF102, six at each dose level (1 mg, 5 mg and 25 mg BID). No serious drug-related adverse events or dose-limiting toxicity were observed. Most adverse events were of grade 1-2 severity. CF102 demonstrated good oral bioavailability and linear PK behavior. Median overall survival in the study population, 67% of whom were sorafenib failures, was 7.8 months (range, 3·5-27·3 months) and for Child-Pugh B patients (28%) was 8.1 months. Stable disease (SD) by RECIST was observed in four patients for at least 4 months. CF102 had no adverse effect on routine measures of liver function over a 6 months period in 12 patients. A direct correlation between A3AR expression levels at baseline and patients’ response to CF102 was found. Conclusions: CF102 is safe and well-tolerated and shows favorable PK characteristics and hepatoprotective effects in patients with HCC. CF102 has shown preliminary evidence of clinical activity in Child-Pugh A and B HCC patients, justifying further clinical development.