bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supplement use in patients with hepatocellular carcinoma.
Authors: Lee Valerie , Goyal Abhishek , Hsu Christine Cho-Shing , Rodriguez Rosa D. , Siegel Abby B. 
Published: March 2020

e15037 Background: Vitamin and herbal supplement use has been steadily rising in the United States. Few data are available evaluating this use in patients with hepatocellular carcinoma (HCC). We analyzed our prospective database of patients with HCC to determine predictors of supplement use and associations with survival. Methods: We prospectively enrolled 146 patients with newly-diagnosed HCC between 10/2008 and 11/2012. Upon enrollment, patients completed an epidemiologic questionnaire and provided detailed demographic and lifestyle data including diet, exercise, smoking and use of vitamins and herbal supplements. Clinical characteristics and overall survival were collected from medical records. We assessed if socioeconomic, lifestyle, or clinical characteristics predicted vitamin and herbal supplement use in HCC patients. We also evaluated if use was predictive of overall survival. Results: The median age was 62, and 79% were men. 60% had underlying HCV and 38% had HBV; 64% were Child-Pugh A and 19% were metastatic. 71% of our cohort used vitamins and 45% used herbal supplements. Most commonly used were antioxidants (including vitamins C, E, A and selenium) (51%), multivitamins (46%), vitamin D (25%), and milk thistle (23%). Vitamin D use was higher in women and those without HCV. Use of vitamin C was associated with being HBV positive (OR = 3.01, P = 0.01) while HCV patients were more likely to use milk thistle (OR = 2.80, P = 0.03). In a univariable model, use of milk thistle at baseline was associated with a trend toward worse overall survival (HR = 1.78, P = 0.09), despite not being associated with other poor prognostic signs like higher stage or AFP, or worse Child-Pugh score. Use of other vitamin or herbal supplements did not predict survival. Conclusions: The majority of patients with newly-diagnosed HCC have used some form of vitamin or herbal supplement, with almost a quarter having used milk thistle in their lifetime. In our analyses, use of milk thistle may be associated with worse survival. Though our cohort is small, this emphasizes the prevalence of supplement use in patients with HCC and the need to further evaluate the safety and efficacy of these alternative treatments in various patient populations.
A phase I study of temsirolimus as novel therapeutic drug for patients with unresectable hepatocellular carcinoma (HCC).
Authors: Chan Stephen Lam , Mo Frankie , Hui Edwin P. , Koh Jane , Chu CM , Hui Joyce , Li Leung , Loong Herbert H. , Ho Wing Ming , Ma Brigette , To Ka Fai , Yu Simon , Chan Anthony T. C. , Yeo Winnie 
Published: March 2020

e15048 Background: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in hepatocellular carcinoma (HCC). Preliminary studies on mTOR inhibitors such as temsirolimus show promising results but there is limited data on the dose limiting toxicities (DLTs) in chronic liver disease, a co-morbidities commonly occurring in HCC pts. This phase I study aims to determine DLTs and maximum tolerated dose (MTD) of temsirolimus in advanced HCC. Methods: Patient (Pt) eligibilitie criteria include unresectable disease, ECOG <= 2, adequate organ functions. Temsirolimus was given i.v. in 250ml NS over 30 min on day 1, 8, and 15 every 3 weeks; dose levels were: 20 (level I), 25 (level II) and 30 mg (level III). DLTs are defined as grade 4 hematological toxicity or grade 3/4 non-haematological toxicity during cycle 1 (according to NCI CTC v3), or treatment delay >2 weeks. The MTD is defined as the dose below which > 2 of 3 or > 2 of 6 patients experiencing DLT. After determination of the MTD, additional pts to make up to 10 patients were treated at this dose to further define toxicity. The study has been registered in ClinicalTrials.gov (NCT00321594). Results: 19 pts were entered; level I (n=3), level II (n=10), and level III (n=6). 2 of the 6 pts in level 3 developed DLT; 1 developed grade 3 syncope and 1 had treatment delay for >2 weeks due to prolonged neutropenia. In cycle 1, grade 3/4/5 toxicities included: raised ALP 2/0/0, oral mucositis 2/0/0, neutropenia 1/0/0, syncope 1/0/0, dehydration 1/0/0 and dysphagia 1/0/0. A total of 77 cycles were administered; overall grade 3/4/5 toxicities: raised ALT 2/0/0, raised ALP 2/0/0, raised bilirubin 2/0/0, cough 1/0/0, dehydration 1/0/0, dysphagia 1/0/0, dyspnea 1/0/0, abdominal distension 1/0/0, anemia 1/0/0, hemorrhoids 1/0/0, hyperglycemia 1/0/0, hypokalemia 2/0/0, hyponatremia 1/0/0, infection 5/0/0 (1 dental, 2 pulmonary, upper airway 2), oral mucositis 2/0/0, neutropenia 1/0/0, thrombocytopenia 2/0/0, pleural effusion 1/0/0, pneumonitis 1/0/0, syncope 1/0/0. Clinical benefit rate (PR, CR or SD ≥12 weeks) was 36.8% (7 of 19 pts had confirmed SD). Conclusions: At the MTD of 25 mg weekly every 3 weeks, temsirolimus is well tolerated with no DLTs. Clinical trial information: NCT00321594.
KRAS, BRAF, PIK3CA, and human papilloma virus (HPV) status in squamous cell anal carcinoma (SCAC).
Authors: Casadei Gardini Andrea , Capelli Laura , Ulivi Paola , Giannini Massimo , Freier Eva , Tamberi Stefano , Passardi Alessandro , Rosetti Paola , Calistri Daniele , Saragoni Luca , Puccetti Maurizio , Valgiusti Martina , Amadori Dino , Frassineti Giovanni Luca 
Published: March 2020

e15055 Background: In literature three studies have described KRAS status in SCAC: they analyzed 139 patients, only 1, 4% were mutated. In this study we analyzed BRAF and PIK3CA status. The evaluation of these two genes is important for predicting the response to anti-EGFR drugs. There is one study that values the positivity of HPV in SCAC. This study with few patients shows that the positivity of HPV16 is predictive for improvement of progression free survival (PFS). Methods: 79 patients were treated for anal cancer at the Oncology center of Forlì, Ravenna and Faenza in the last ten years. Up to now we analyzed 29 patients (9 with relapse of disease). DNA was extracted from paraffin-embedded sections and KRAS, BRAF and PIK3CA gene status were assessed by Pyrosequencing methodology, using 3 different kits: anti-EGFR MoAb response (KRAS status), anti-EGFR MoAb response (BRAF status), and anti- EGFR MoAb response (PIK3CA status) (Diatech, Jesi, Ancona, Italy). Reactions were run on a PyroMark Q96 ID (Qiagen). The presence and genotyping of Human Papilloma Virus (HPV) were assessed using the AMPLIQUALITY HPV-HS Bio and AMPLIQUALITY HPV-Type (AB ANALITICA, Padova, Italy) kit. Results: KRAS and BRAF genes were wild-type in all cases. Conversely, PIK3CA gene resulted mutated in 9 of 31 cases (28.1%). In particular, 7 mutations occurred in exon 9 (4 E454K and 3 E542K) and 2 in exon 20 (H1047R and H1047L) of the PIK3CA gene. Patients without relapse of disease were positive in 94% of cases for HPV16 and in 40% for mutation of PIK3CA. Patients with relapse of disease were positive in 70% of cases for HPV16 and 37,5% for mutation of PIK3CA. Conclusions: KRAS and BRAF genes were wild type in 100% of cases. This study demonstrates that the SCAC could potentially respond to an anti-EGFR drug.The mutation of PIK3CA does not seem to be predictive for response to treatment. Positivity for HPV16 seems predictive for PFS and overall survival. Furthermore, the study shows that PIK3CA mutation may contribute to carcinogenesis in some cases of this tumor. In addition, patients with a mutation of PI3K could have benefit from specific drugs that inhibit this kinase.
Weekly nab-paclitaxel in combination with cisplatin as neoadjuvant chemotherapy in patients (pts) with locally advanced esophageal squamous cell carcinoma (SCC): Preliminary results of a phase study.
Authors: Jiang Youhua , Yun Fan , Chen Qixun , Zhou Xinming , Huang Zhiyu , Gong Lei , Yang Haiyan , Yu Haifeng , Liu Jinshi , Chen Pengcheng , Zhao Qiang , Mao Weimin 
Published: March 2020

e15062 Background: This phase II study was aimed to define the pathological response rate and safety of combining weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy in pts with locally advanced esophageal SCC. Methods: Pts with resectable locally advanced thoracic esophageal SCC staged by EUS, CT and/or PET-CTscan. All pts received nab-paclitaxel (100 mg/m2, d1, d8, d22 and d29) and cisplatin (75 mg/m2, d1 and d22) as neoadjuvant chemotherapy, followed by esophagectomy.Postoperation: 2 cycles of adjuvant chemotherapy with same regimen was given in 4-6 weeks after the resection.The primary endpoint was pathological response rate. The second endpoints included R0 resection rate,down-staging rate, 3 years overall survival (OS) and progression-free survival (PFS). Results: From 01/2011 to 10/2012, 31 pts were enrolled . 28 male:3 females; II A/II B/III A/III B/III C in 2 (6.5%), 4 (12.9%), 9 ,(29.0%), 8 (25.8), and 8 (25.8%) pts. 26/31 pts went to surgery (83.9%). 26 had R0 resection (100%).Pathological complete response (pCR) was achieved in 3 pts (11.5%). Near pCR (microfoci of tumor cells on the primary tumor without lymph nodal metastases) in 1 pt (3.8 %). Down-staging was observed in 15 of 26 patiens (57.7%). 5 pts did not going to surgery: 2 for progressive disease (6.5%), 3 for refused. 20/26 pts (76.9%) received adjuvant chemotherapy,3 pts (11.5%) received adjuvant chemoradiotherapy. Grade 3/4 toxicities in 31 evaluable pts during chemotherapy were as follow: neutropenia (12.9%), anemia (6.5%), thrombocytopenia (3.2%), nausea/vomiting (12.9%), neutropenia fever (6.5%), asthenia (12.9%). Surgical complications: 1anastomotic leaks (3.8%). No treatment-related death. At a median follow up of 9 months, 26 pts were all disease-free survival. Conclusions: In pts with locally advanced esophageal SCC, weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy achieved a high pathological response rate and R0 resection rate .The toxicity was well tolerated. Evaluation of nab-paclitaxel and cisplatin in randomized trials was warranted. Clinical trial information: NCT01258192.
Uptake and patterns of use of gemcitabine for stage IV pancreatic cancer.
Authors: Oberstein Paul Eliezer , Hershman Dawn L. , Chabot John A. , Khanna Lauren , Insel Beverly J. , Neugut Alfred I. 
Published: March 2020

e15074 Background: Gemcitabine was approved by the FDA in 1996 and subsequently became the standard of care for patients with advanced pancreatic cancer. We investigated the frequency and predictors of gemcitabine use among the elderly with stage IV pancreatic cancer. Methods: We used the SEER-Medicare database to identify subjects >65 years who were diagnosed with stage IV pancreatic cancer between 1/1/98-12/31/05, and survived for >30 days following diagnosis. After excluding patients who received non-gemcitabine chemotherapy, we used multivariate logistic regression models to analyze the association between patient and tumor characteristics and receipt of gemcitabine compared to no chemotherapy. Results: Among 3,208 patients analyzed, 1,614 (50.3%) received gemcitabine chemotherapy, 1,480 (46.1%) received no chemotherapy; 114 (3.5%) received non-gemcitabine therapy and were excluded from multivariate analysis. Among patients diagnosed early in the study period (1998-2000) the rate of gemcitabine use was 44.9%. In multivariate analysis, gemcitabine use was not associated with gender, race, tumor histology, or increasing comorbidities. Unmarried patients were less likely to receive gemcitabine (OR=0.65, 95% CI 0.55-0.76), and use decreased with increasing age (for those 75-79, OR=0.72. 95% CI 0.58-0.90, for those 80-84, OR=0.38, 95% CI 0.30-0.49, for those >84, OR=0.21 95%CI 0.15-0.30) compared to those 65-69. Patients diagnosed in 2004-2005 (OR= 1.51, 95% CI 1.23-1.84) were more likely to receive gemcitabine compared to those diagnosed in 1998-2000. Higher socioeconomic status were associated with increased utilization of gemcitabine (highest quintile OR=2.14, 95% CI 1.60-2.85, second and third quintile OR=1.45, 95%CI 1.10-1.93, compared to lowest quintile.) Conclusions: Although chemotherapy for stage IV pancreatic cancer confers a small survival benefit, uptake of gemcitabine was rapid with 55% of elderly patients receiving this therapy by 2004-2005. Future studies should explore the reasons behind the increased use in patients with higher socioeconomic status.
Metformin in diabetic pancreatic cancer patients: Benefit or not—Multicenter experience.
Authors: Esbah Onur , Oksuzoglu Berna , Eren Tulay , Helvaci Kaan , Guler Tunc , Duran Ayse Ocak , Bal Oznur , Ozdemir Nurıye Yıldırım , Aksoy Sercan ,   on behalf of the Anatolian Society of Medical Oncology
Published: March 2020

e15110 Background: Risk factors for the pancreatic cancer are cigarette smoking, obesity, family history, chronic pancreatitis and type 2 diabetes mellitus. Diabetes mellitus is associated with 2-3 fold increase in the risk of pancreas cancer development. Down-regulation of mTOR pathway which begins with the insulin signaling is the possible protective effect of metformin in the oncogenesis of pancreatic cancer. In this study, we aimed to evaluate whether the use of metformin in diabetic pancreas cancer patients has an advantage or not. Methods: The data of 467 patients with the diagnosis of pancreas cancer in from 2003 to 2012 were analyzed, retrospectively. Results: Four hundred and sixty seven patients with the median age of 62 (20-85) were reviewed Median tumour size was 42 mm (14-145 mm). According to 2010 TNM staging, 23 patients had stage 1 (4.9%), 97 patients stage 2 (20.8%), 70 patients stage 3 (15%) and 277 patients had stage 4 disease (59.3%). Diabetes mellitus was detected in 173 (37%) patients. In this group 23 patients had stage 1 (4.9%), 97 patients stage 2 (20.8%), 70 patients stage 3 (15%) and 98 patients had stage 4 disease (56.6%). Thirty seven percent (64 patients) of the patients with diabetes were using metformin. Median time for metformin usage was 14±2,3 months. Median follow-up time was 7 months (1-88 months). Median overall survival (OS) of all pancreas cancer patients was 8 months. Surprisingly, median OS of diabetic pancreas cancer patients and non-diabetics was 9 and 8 months, respectively (statistically not significant). Median OS of diabetic patient subgroup who use metformin or not was 7 versus 10 months, respectively (statistically not significant). In the subgroup of stage 3 pancreatic cancer patients with diabetes mellitus, the median OS were 16 months and 10 months according to metformin usage or not, respectively (p=02). Conclusions: In this study, the median OS of diabetic pancreas cancer patients was superior from the non-diabetics. Multi-center prospective trials including large number of patients are needed to understand well enough the benefit of metformin in diabetic pancreas carcinoma patients.
A phase II clinical and translational study of MK-2206 in patients with metastatic neuroendocrine tumors (NETs).
Authors: Reidy Diane Lauren , Pietanza Maria Catherine , Segal Michal , Capanu Marinela , Saltz Leonard 
Published: March 2020

e15133 Background: Up-regulation of the phosphoinositide-3 phosphate kinase (PI3K) pathway is associated with poor prognosis in NET cell lines. In patients treated with mTOR inhibitors, up-regulation of AKT may be a key driver in development of resistance. We hypothesized that blockade of AKT in patients with refractory NETs would result in eliminating one of the key drivers of tumor growth and prolong PFS. We evaluated the safety and efficacy of MK-2206, an orally active, allosteric Akt inhibitor of human Akt1, Akt2, and Akt3 as monotherapy in metastatic well differentiated progressive neuroendocrine patients. Methods: A phase II study was performed in which patients received MK-2206 at a dose of 200 mg PO once weekly. Archived pretreatment tumor tissue was obtained for putative biomarkers. Results: The study terminated early on the basis of a business decision by the sponsor. Eight patients were treated (6 carcinoid, 2 pNET); female, 25%; median age, 58.5 years, range 66-25). There were no complete or partial responses. 1 patient (atypical thymic carcinoid with brain metastases refractory to all standard therapies including mTOR and VEGF inhibitors) experienced a 17% decrease in tumor size (SD) for over 10 months and an additional 3 patients had SD for 12 weeks or longer by RECIST 1.0 (4/8, 50%; range 4.2-10.2 months). The most common grade 3 adverse events potentially related to MK-2206 were hyperglycemia (3 pts, 37.5%), elevated liver function tests (3 pts, 37.5%), and rash (3 pts, 37.5%). There were no serious adverse events (SAEs) related to MK-2206. Tumor from the patient with greatest radiographic response was evaluated by next generation sequencing, which failed to identify mutations in the AKT pathway (i.e., PTEN, AKT, and PI3KCA). Conclusions: MK-2206 alone was well tolerated, except for hyperglycemia, transaminitis, and rash, all of which were manageable. Although the study was incomplete, evidence of antitumor response in a refractory carcinoid tumor is of interest. Further evaluation of agents targeting AKT and/or PI3K are warranted in NETS. Preclinical studies are ongoing to better define a potential targeted population. Clinical trial information: NCT01169649.
Perioperative epirubicin, oxaliplatin, and capectabine (EOX) in locally advanced resectable gastroesophageal junction and gastric adenocarcinoma.
Authors: Kalachand Roshni Deepa , Mongan Anne-Marie , Doherty Mark , King Sinead , O'Farrell Niamh , Reynolds John Vincent , O'Byrne Kenneth John 
Published: March 2020

e15142 Background: Perioperative chemotherapy with epirubicin, cisplatin and fluorouracil (ECF) confers a 13% absolute 5-year survival benefit over surgery alone in resectable gastroesophageal cancer. In the metastatic setting, the EOX regimen is at least as effective as ECF, with a favourable toxicity profile. This retrospective analysis presents the experience of a high-volume tertiary referral center with perioperative EOX in patients with resectable GEJ and gastric adenocarcinoma. Methods: Patients with cTxN+/cT3N0 gastroesophageal adenocarcinoma treated between 2006-2012 with perioperative EOX (epirubicin 50mg/m2 d1 q22d, oxaliplatin 130mg/m2 d1 q22d and capecitabine 625 mg/m2 bd d1-21 q22d), given as three neoadjuvant and three adjuvant cycles, were retrospectively identified from a prospectively recorded upper gastrointestinal cancer database. Efficacy and toxicity data were assessed. Results: 52 patients, including 41 (82%) males, with a median age of 62 (range 35-79) received perioperative EOX with curative intent. GEJ tumours represented 39 (75%) of cases, and the others were gastric cancers. 47 patients (90%) completed 3 cycles of neoadjuvant EOX. One patient died of non-neutropenic sepsis after cycle 2. 44 (85%) of patients progressed to surgery, 5 of whom were deemed unresectable. 28 (71%) surgeries were D2 resections, and the R0 resection rate was 67%. There was one postoperative death, due to pancreatitis. 28 (54%) of patients commenced adjuvant EOX, and 25 (48%) completed the planned treatment. Grade 3-4 toxicities were observed in 17% of patients, with the commonest being fatigue (8%) and nausea (4%). Pathological response rate, as defined by Mandard Tumour Regression Grade 1-3, was seen in 26%, with 3 (6%) pathological complete response. The median progression-free survival was 7 months, with a median overall survival of 22 months, and a 2-year survival rate of 45%. Conclusions: In our institution, perioperative EOX in gastroesophageal cancer is associated with a reasonable safety profile, and efficacy consistent with that reported in the MAGIC trial.
HER2 expression and response to neoadjuvant chemoradiotherapy in esophagogastric adenocarcinoma.
Authors: Duckworth Lizette Vila , Chan Ellie , Alkhasawneh Ahmad , Zuluaga-Toro Tania , Lu Xiaomin , Hughes Steven J. , George Thomas J. 
Published: March 2020

e15145 Background: Targeting HER2 overexpression with trastuzumab in metastatic esophagogastric adenocarcinoma (EGA) improves survival with clinical trials currently examining the impact of HER2 inhibition in early stage disease. This study analyzed the pattern of HER2 overexpression in matched-pair tumor samples of patients (pts) undergoing neoadjuvant chemoradiotherapy (chemoRT). Methods: This analysis included pts with EGA who underwent neoadjuvant chemoRT followed by esophagectomy at the University of Florida from 2001 to 2011 who did not receive anti-HER2 therapy. Demographics, risk factors, tumor features, and outcome data were analyzed. Central blinded IHC was performed on paraffin embedded tumor specimens with HER2 expression scored as negative (-) (0, 1+), indeterminate (2+) or positive (+) (3+). Descriptive statistics, Chi-square exact test, uni and multivariate analyses were used for statistical analyses. Results: 49 pts (41M/8F) were analyzed with median age 65 years (39-87). Most tumors were stage II (55%) or III (43%). 9/49 pts (18%) had pathologic complete response (pCR), another 10/49 had near pCR or not enough tumor (NET) to examine. HER2 expression was more common in lower stages (stage I, II vs III). Baseline HER2 expression did not correlate with treatment response. Univariate analysis did not show significant correlation of age, stage, smoking, pre or post treatment HER2 expression with survival. For matched-pair samples failing to achieve pCR or NET (n=30), pre and post treatment HER2 expression profiles are presented in the Table. HER2 expression appears UP regulated in response to neoadjuvant chemoRT. Conclusions: Our study demonstrated the degree of pre-treatment HER2 expression in EGA does not predict the response to chemoRT. However, HER2 overexpression is more frequent in post treatment samples without pCR. This suggests that HER2 may be upregulated by chemoRT with unreliable concordance between pre and post treatment samples. This has implications for both early and advanced stage therapeutic interventions with targeted therapies. [Table: see text]
Optimal cycles of fluoropyrimidine-based adjuvant chemotherapy for patients with resectable gastric cancer.
Authors: Liu Yunpeng , Qu Xiujuan , Qu Jinglei , Zhang Jingdong , Liu Jing 
Published: March 2020

e15160 Background: Although several clinical trials have suggested that postoperative adjuvant chemotherapy could improve survival, there has no study on the optimal cycles of treatment. This retrospective analysis was carried out to evaluate the outcomes of gastric cancer patients treated with 5-6 cycles of FU-based treatment as compared to a cohort treated with 3-4 cycles or 7-8 cycles. Methods: We retrospective identified 254 patients with stage IB-IIIC gastric cancer who received 3-8 cycles of adjuvant chemotherapy after gastrectomy with D1 or D2 lymphadenectomy. The endpoint was overall survival. Factors associated with prognosis were also analyzed. Results: Of the 254 patients, 74 patients treated with 3-4 cycles, 112 patients treated with 5-6 cycles and 68 patients treated with 7-8 cycles. The 3-year OS rates for 3-4 cycles, 5-6 cycles and 7-8 cycles cohort was 56.6%, 73.9% and 67.7%, respectively. Patients who received 5-6 cycles were more likely to have better OS than those received 3-4 cycles (p=0.003), two further cycles of treatment did not improved OS (p=0.885). In the multivariate analysis, cycles of chemotherapy were associated with OS independent of clinical covariates (p=0.008). Subgroup analysis was suggested that for patients with older adult (age ≥60), FU-platinum combined chemotherapy, stage III, poorly differentiation, and gastrectomy with D2 lymph node dissection, 5-6 cycles of adjuvant chemotherapy was associated with a statistically significant benefit of OS (P<0.05). Conclusions: Our result indicated that 5-6 cycles of adjuvant chemotherapy may lead to a favorable outcome for gastric cancer patients following primary surgical treatment. In view of the limited resources of medication, reduced incidences of toxicity and better quality-of-life with shorter duration of treatment, optimal cycles of adjuvant treatment should be explored further.