bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between plasma BRCA1 mRNA expression and sensitivity to docetaxel and cisplatin in gastric cancer.
Authors: Shen Jie , Wei Jia , Guan Wen xian , Wang Hao , Ding Yi tao , Qian Xiaoping , Yu Lixia , Zou Zhengyun , Xie Li , Taron Miquel , Rosell Rafael , Liu Baorui 
Published: March 2020

e14509 Background: Tumor-derived RNA species successfully detected in plasma may have potential for use in disease and treatment assessment. Although BRCA1 mRNA expression levels in tumor are associated with cisplatin sensitivity but docetaxel resistance, the role of plasma BRCA1 mRNA as a predictive biomarker remains to be known. The aim of this study was to investigate the association between plasma BRCA1 mRNA expression and in vitro chemosensitivity to docetaxel and cisplatin in gastric cancer. Methods: 150 freshly-removed gastric tumor specimens and corresponding blood samples before surgery were collected. Docetaxel and cisplatin sensitivity was determined by histoculture drug response assay (HDRA) procedures. Plasma and tumor BRCA1 mRNA expression levels were determined by quantitative RT-PCR. Results: A significant correlation was observed between plasma and tumor BRCA1 mRNA expression levels (rho=0.558, P<0.001). Plasma BRCA1 mRNA expression level was positively correlated with in vitro sensitivity to docetaxel (docetaxel-sensitive sub-group: 1.25, 95% CI: 1.04-1.47; docetaxel-resistant sub-group: 0.50, 95% CI: 0.23-0.78; p<0.001) but negatively correlated with sensitivity to cisplatin in gastric cancer (cisplatin-sensitive sub-group: 0.84, 95% CI: 0.61-1.08; cisplatin-resistant sub-group:1.20, 95% CI: 0.84-1.56; p=0.083). There was no significant association between clinical characteristics and plasma BRCA1 mRNA levels or in vitro chemosensitivity. Conclusions: It was demonstrated for the first time that plasma BRCA1 mRNA expression was associated with in vitro chemosensitivity to docetaxel and cisplatin, which provided preliminary evidence for using plasma mRNA expression as an approach to predict response to docetaxel or cisplatin based chemotherapy in the clinic.
Multi-institutional experience using 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in patients with pancreatic cancer (PCA).
Authors: Goncalves Priscila Hermont , Ruch Joshua Michael , Byer Jennifer , Shields Anthony Frank , Choi Minsig , Kim Richard D. , Zalupski Mark M. , Philip Philip Agop 
Published: March 2020

e14519 Background: FOLFIRINOX resulted in significant improvement in survival in a recent phase III trial. However, the toxicity associated with its use may be significant. Theobjectives of this study were to determine the tolerability and outcome in patients with advanced PCA treated with FOLFIRINOX in 3 cancer centers in the USA. Methods: This was a retrospective analysis in pts with PCA treated with FOLFIRINOX at Karmanos Cancer Center (Detroit, MI), University of Michigan (Ann Arbor, MI) and Moffitt Cancer Center (Tampa, FL) from 2010 to 2012. Results: 54 patients with advanced PCA (61%males, median age 57.5 years [range 34-73], 72 % Caucasians) were evaluable. 67% of the primary tumors were in the head of the pancreas and 48% of patients had biliary stents prior to treatment. ECOG performance status (PS) was 0-1 in 91%. 91% of the patients had stage IV disease mostly with liver metastases. The median number of cycles received per patient was 5 (1-24). At the outset of treatment, bolus 5FU was omitted in 15% of pts and granulocyte growth factor was given in 89% of the cases. 80% of patients experienced at least one grade 1 or 2 toxicity (fatigue in 44%). Grade 3 toxicities occurred in 26 (48%) pts (fatigue [9]; neutropenia [7]; vomiting [7]; diarrhea [5]; neuropathy [4]; anemia [4]; thrombocytopenia [2] and infection [2]). 13% of patients (7) experienced grade 4 toxicities (vomiting [3]; febrile neutropenia [2] and neutropenia [2]). There was no grade 5 toxicity. Dose reduction was necessary in 87% of pts. 17% of pts required hospitalization during treatment. Partial responses were documented in 39% and stable disease in 29%. Side effects were the reason for treatment discontinuation in 35% of this population. Median PFS and OS were 3.8 (0.9 – 13.6) and 7.2 (0.5 – 17.8) months, respectively. Conclusions: In this multi-institutional experience in pts with PCA, significant grade 3 and 4 toxicities were associated with the FOLFIRINOX regimen leading to treatment discontinuation in a third of the population. PFS and OS represented a modest improvement over what would be expected from using single agent gemcitabine despite the relatively high objective response rate.
A multicenter analysis of prognostic factors in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib.
Authors: Smith Alan D. , Chan Kelvin K. , Lim Howard John , Cheung Winson Y. 
Published: March 2020

e14532 Background: Established clinical prognostic systems for advanced HCC were previously developed in the era of conventional chemotherapy. In 2008, the molecularly targeted agent sorafenib became the new standard of care. It is unclear if these existing models provide useful prognostic information for patients receiving sorafenib. Our aims were to: 1) evaluate the current utility of 4 known prognostic systems, including the Okuda, CLIP, BCLC, and French classification systems; and 2) identify new prognostic factors for patients treated with sorafenib. Methods: All patients diagnosed with advanced HCC from 2008 to 2010 and treated with sorafenib at any 1 of 6 regional cancer cancers in either British Columbia or Ontario, Canada were reviewed. Patients were risk-stratified using each of the 4 established prognostic systems to determine if these correlated with overall survival (OS). Cox proportional hazards models were also constructed to examine for associations between other clinical factors and OS. Results: Of 205 patients identified, 193 were evaluable: median age was 66 years, 79% were men, and 49% / 19 % / 16% had hepatitis B, C, and alcohol-related liver disease, respectively. The mean number of sorafenib cycles was 5.5 and median OS was 7.1 months. Of the 4 known prognostics models, only the French system proved useful where the high, intermediate, and low risk groups demonstrated a median OS of 2.4, 7.0, and 16.8 months, respectively (p<0.0001). Among other clinical factors, univariate analyses showed that poor performance status, presence of ascites, and large tumor size >5cm were associated with worse OS as were an elevated serum AFP, AST, GGT, or ALP level and a low albumin or hemoglobin level (all p<0.05). In multivariate analyses, none of these clinical factors continued to be independently predictive of outcome (all p>0.05). Conclusions: Except for the French classification system, clinical prognostic factors that were identified in the era of conventional chemotherapy were not useful in this Western cohort of advanced HCC patients treated with sorafenib. There is a need for molecular biomarkers that may provide better prognostic information.
Survival trends of patients with metastatic pancreatic cancer: A Surveillance Epidemiology and End Results registry trend analysis from 1988 to 2008.
Authors: Worni Mathias , Guller Ulrich , White Rebekah Ruth , Pietrobon Ricardo , Cerny Thomas , Gloor Beat , Koeberle Dieter 
Published: March 2020

e14544 Background: Pancreatic adenocarcinoma (PAC) is a disease with dismal prognosis. Only a minority of patients with PAC presents with a resectable tumor and can potentially be cured. Therapeutic options for non-resectable, metastatic tumors are limited and chemotherapy with or without radiation is purely palliative. The aim of the present study was twofold: first, to evaluate predictors of overall survival (OS), and second, to assess trends in OS and in the use of palliative radiotherapy among patients with metastatic PAC. Methods: Patients with metastatic PAC were extracted from the SEER cancer registry from 1988 to 2008. While SEER does contain information regarding radiotherapy and surgery, data on chemotherapy cannot be ascertained. Predictors and trends of OS were assessed using univariate and multivariable Cox proportional hazard models. The trend in use of radiotherapy was analyzed using univariate and multivariable logistic regression models. Results: Overall, 23,387 patients were included (mean age: 68.0±11.8 years); 47.0% of patients were female, tumor location was in the pancreatic head in 57.7% of all patients. Median OS was 3 months. In risk-adjusted analyses, tumor location in the pancreatic body/tail was associated with worse overall survival compared to tumors of the pancreatic head (HR: 1.10, CI: 1.07-1.13, p<0.001). Increasing age, African-American ethnicity, male gender, and non-married civil status were associated with significantly worse OS. From 1988 to 2008, OS increased from a median survival of 2 (95% CI: 2-2) to 3 months (CI: 3-4) months (HR per year: 0.978, CI: 0.976-0.981, p<0.001). From 1988 to 2008, radiotherapy use decreased from 13.2% to 5.8% (adj. OR per year: 0.95, CI: 0.93-0.96, p<0.001). Conclusions: Metastatic PAC remains a disease with poor prognosis with only minimal improvement in OS over a 20-year time-period. The use of palliative radiotherapy has decreased. Tumor location in the body/tail of the pancreas, increasing age, African-American ethnicity, male gender, and non-married civil status were associated with worse OS. Future research is needed to improve OS of metastatic PAC on a population-based level.
A nomogram associated with high probability of malignant nodes in the surgical specimen after trimodality therapy of patients with esophageal cancer (EC).
Authors: Blum Mariela A. , Hayashi Yuki , Xiao Lianchun , Suzuki Akihiro , Sabloff Bradley , Maru Dipen M , Taketa Takashi , Welsh James , Lin Steven H , Lee Jeffrey H , Bhutani Manoop S. , Weston Brian , Hofstetter Wayne Lewis , Swisher Stephen , Ajani Jaffer A. 
Published: March 2020

e14547 Background: The presence of malignant lymph nodes (+ypNodes) in the surgical specimen after preoperative chemoradiation (trimodality therapy) in patients with EC portends a poor prognosis for overall survival (OS) and disease-free survival (DFS). Currently, none of the clinical variables highly correlates with +ypNodes. We hypothesized that a combination of clinical variables could generate a model that associates with high likelihood of +ypNodes after trimodality therapy in EC patients. Methods: We report on 293 consecutive EC patients who received trimodality therapy. A multivariate logistic regression analysis that included pretreatment and post-chemoradiation variables identified independent variables that were used to construct a nomogram for +ypNodes after trimodality in EC patients. Results: Of 293 patients, 91 (31.1%) had +ypNodes. OS (p=0.0002) and DFS (p<0.0001) were shorter in patients with +ypNodes compared to those with –ypNodes. In multivariable analysis, the significant variables for +ypNodes were: baseline T-stage (odds ratio [OR], 7.145; 95% confidence interval [CI], 1.381-36.969; p=0.019), baseline N-stage (OR, 2.246; 95% CI, 1.024-4.926; p=0.044), tumor length (OR, 1.178; 95% CI, 1.024-1.357; p=0.022), induction chemotherapy (OR, 0.471; 95% CI, 0.242-0.915; p=0.026), nodal uptake on post-chemoradiation positron emission tomography (OR, 2.923; 95% CI, 1.007-8.485; p=0.049), and enlarged node(s) on post-chemoradiation computerized tomography (OR, 3.465; 95% CI, 1.549-7.753; p=0.002). The normogram after internal validation using the bootstrap method (200 runs) yielded a high concordance index of 0.756. Conclusions: Our nomogram highly correlates with the presence of +ypNodes after chemoradiation and upon validation; it could prove useful in individualizing therapy for EC patients. Supported by UTMDACC and generous donors.
Inverse-probability weighted and propensity score-based analysis of long-term clinical outcomes comparing 3D conformal radiotherapy (3DCRT) with intensity-modulated radiation therapy (IMRT) in the treatment of esophageal cancer.
Authors: Lin Steven H. , Wang Lu , Myles Bevan H , Thall Peter F. , Hofstetter Wayne Lewis , Swisher Stephen , Lee Jeffrey Edwin , Bhutani Manoop S. , Maru Dipen M , Ajani Jaffer A. , Ho Linus , Cox James D. , Komaki Ritsuko , Liao Zhongxing X. 
Published: March 2020

e14548 Background: IMRT has clear dosimetric advantages in the sparing of normal tissues when compared to the more conventional 3DCRT technique for the treatment of esophageal cancer, but there is currently no clinical outcomes evidence to support the use of IMRT. We hypothesized that the theoretical advantages of IMRT should translate to clinical outcomes benefits compared to 3DCRT. Methods: We analyzed a cohort of 676 patients (3DCRT=413, IMRT=263) treated with chemoradiation with or without surgery between 1998-2008. To correct for potential bias inherent in observational studies, we employed inverse probability of treatment weighted (IPW) methods based on propensity scores. Treatment probabilities (propensity scores) were estimated using logistic regression. Results: IMRT patients were less likely to receive induction chemotherapy and had poorer performance status. A fitted multivariate IPW-adjusted Cox model showed that overall survival was significantly associated with age, KPS, having surgery, tumor location, stage, having PET for staging, and radiation modality. Compared to IMRT, 3DCRT patients had a significantly greater risk of dying (72.6% vs 52.9%, IPW log rank test: p<0.0001) and for local-regional recurrence (LRR) (p=0.0038). The improvement in LRR was only apparent in the non-surgically treated patients due to better tumor control in the primary site, but not in the recurrence in regional nodal sites. There was no difference in cancer-specific mortality, distant metastasis, or postoperative deaths between the two groups. An increased cumulative incidence of cardiac deaths was seen in the 3DCRT group (p=0.049), but the cause of most deaths were unknown (5 year estimate: 11.7% in 3DCRT vs 5.4% in IMRT, Gray’s test, p=0.0029). Analyses using propensity score as a covariate gave very similar results. Conclusions: Our results indicate IMRT improves treatment outcomes in the management of esophageal cancer when compared to 3DCRT. These results, while retrospective, support the use of IMRT for the treatment of esophageal cancer.
Baseline demographics of neuroendocrine tumor patients presenting to seven National Comprehensive Cancer Network (NCCN) institutions: Development of a multi-institutional outcomes database.
Authors: Zornosa Carrie C. , Choti Michael A. , Bobiak Sarah , Kulke Matthew , Yao James C. , Bergsland Emily K. , Nakakura Eric K. , Bloomston Mark , Benson Al B. , Shah Manisha H. , Strosberg Jonathan R. 
Published: March 2020

e14551 Background: Diagnostic strategies, management paradigms, and clinical outcomes of patients with neuroendocrine tumors (NETs) are diverse and poorly characterized. The National Comprehensive Cancer Network (NCCN) created a comprehensive database to characterize patients treated for NETs at seven participating institutions. Preliminary results from the database are reported. Methods: Member IRB approval was obtained to identify patients at least 18 years of age presenting to each of seven NCCN institutions between 2004 and 2007 with pathologically confirmed newly or previously diagnosed NETs via hospital medical records. Eligible patients included those with carcinoid (any site); goblet cell or adenocarcinoid; composite carcinoid; poorly differentiated gastrointestinal small cell tumor; pancreatic NET; NET of unknown primary site; pheochromocytoma; and paraganglioma. Baseline demographic characteristics were summarized for this analysis. Results: Among the 2,798 patients identified with a NET diagnosis, patients most frequently presented with carcinoid tumor (53%), pancreatic NET (26%) and NET of unknown primary site (8%). Median age at diagnosis was 56 (SD=14). Fifty-three percent of patients were female. Most (86%) were Caucasian and 8% were African American. Thirty percent of patients were diagnosed with NET before presenting to the NCCN. Among these, the median time between initial NET diagnosis and presentation to the NCCN was 2 years (SD=6). Significant differences in provider specialty referral patterns were observed between institutions. The institutional point of entry for the majority of patients was medical oncology (institutional range: 17-93%) or surgery (institutional range: 3-62%). Conclusions: The baseline demographic characteristics of NET patients in this new database are consistent with those previously reported in population-based registries. The database will provide a valuable resource for further exploration of patterns of diagnosis, treatment, and consistency with established guidelines, as well as clinical outcomes in patients with this condition.
A phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in low-grade neuroendocrine tumors.
Authors: Rajguru Saurabh , Lubner Sam Joseph , Mulkerin Daniel , Schelman William R. , Winterle Natalie , Holen Kyle D. , Leverson Glen , Chen Herbert , LoConte Noelle K. 
Published: March 2020

e14554 Background: Neuroendocrine tumors (NETs) are a diverse and rare group of neoplasms arising from the neuroendocrine system. The most common subtypes are pancreatic islet cell tumors and carcinoid tumors. Although they represent only 2% of all gastrointestinal malignancies, given their overall favorable prognosis, the prevalence is much higher. Histone deacetylase (HDAC) inhibitors have already been shown to suppress tumor growth and induce apoptosis in a variety of solid tumors in preclinical data. We have previously shown that in NET cells, HDAC inhibitors have resulted in increased Notch1 expression and subsequent inhibition of growth. Methods: A single arm phase II study was performed. Adult patients with histologically confirmed, metastatic, low-grade NETs and an ECOG performance status of ≤ 2 were treated with the oral HDAC inhibitor panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. Results: 15 patients were accrued and 13 were evaluable for response (66.7% male, age range 40-80 years old (mean 59.4 years old), 66.7% carcinoid, 33.3% pancreatic NET). The median number of prior therapies was 1 (range 0-2) and no patient had previously received everolimus. The response rate was 0%. The stable disease rate was 92.3% as defined by stability seen on the first CT scan. Median progression-free survival was 11.8 months. The 1 year PFS was 42%. Thrombocytopenia and fatigue were the most common treatment-related grade 3 toxicities. There was one grade 4 toxicity of thrombocytopenia. The study was stopped early at the planned interim analysis based on lack of meaningful clinical efficacy outlined in the Simon two-stage design. Conclusions: The HDAC inhibitor panobinostat had infrequent grade 3 and 4 events in this patient population and resulted in a large percentage of subjects with disease control. The disease control rate, however, needs to be considered in the context of the typical slow growth rate of NETs. These data alone do not support continued evaluation of HDAC inhibitors in low-grade NETs. This study was supported by Novartis.
Complete clinical (CC) responders to definite chemoradiation or radiation therapy (CRT/RT) for esophageal cancer (EC): A survival analysis.
Authors: Mirabel Xavier , Tresch Emmanuelle , Romano Olivier , Dewas Sylvain , Amela Eric , Fournier Charles , Clisant Stephanie , Mariette Christophe , Adenis Antoine 
Published: March 2020

e14560 Background: For pts with EC being treated with definite CRT/RT, predictors of outcome are baseline nutritional status and CC response to CRT. As data concerning predictors of outcome for CC responders are lacking, we tried to identify them. Methods: Among 402 consecutive pts with EC who underwent definite CRT/RT in our institution from 1/1998 to 12/2003, 110 were found CC responders, and were retrospectively reviewed. Baseline staging included endoscopy with biopsies, and CT-scan and/or EUS. CC responders were defined as pts without evidence of tumor on morphological examination with biopsies, 4 to 6 weeks after treatment. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. Results: Pts were staged according to EUS-AJCC staging (stage I-II=39, stage III-IVa=37, ukn=34) and/or CT staging (stage I-II=54, stage III-IVa=32, ukn=24). Baseline pt and tumor characteristics were as follows: M/F = 98/12, median age = 60, ADK/SCC = 7/103, tumor site (upper/middle/lower third) = 41/50/19, weight loss none/<10%/≥10% = 36/45/29, dysphagia gr.0/1/≥2 = 30/14/65. Pts received a median dose of RT of 50.4Gy (30-65), and concomitant chemotherapy in 95/110 cases. Post treatment nutritional characteristics were : weight loss during treatment none/<10%≥10% = 35/38/37, remaining dysphagia gr.0/1/≥2 = 54/24/32. During follow up (median: 6 [0.4-9.8] years), 16 pts got esophagectomy (recurrence: 3, some reasons: 13). Median survival was 2.5 years, and 3- and 5-year survival rates were 46.9%, and 33.5%, respectively. Neither TNM classification nor stage grouping, histological type, gender, or treatment types were found to have any influence on outcome. Predictors of improved OS were: absence of weight loss during treatment, and absence of dysphagia with normal oral intakes after treatment. Conclusions: One EC pt out of 3 with CC response after definite CRT/RT is still alive at 5 years. The absence of weight loss during treatment, and of remaining dysphagia after treatment are significant predictors of better survival in pts found CC responders to definite CRT/RT for EC.