bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of brain metastases in HER2+ gastric or esogastric junction adenocarcinoma.
Authors: Blay Christophe , Chiforeanu Danchristian , Boucher Eveline , Cabillic Florian , Desgrippes Romain , Leconte Bérengère , Manfredi Sylvain , Meunier Bernard , Edeline Julien 
Published: February 2017

126 Background: HER2 overexpression is associated with a high risk for brain metastases in breast cancer. We aimed to study if the same correlation exists in gastric or oesogastric junction (OGJ) adenocarcinoma, where brain metastases are uncommon. Methods: We retrospectively reviewed data of patients treated at our institution for metastatic gastric or OGJ adenocarcinoma. We compared incidences with a Fisher’s exact test. Survival was analyzed by the Kaplan-Meier method. Results: Between 2007 and 2011, 74 patients were treated at our institution, 63 patients were analyzed for HER2 status. Median age was 62 (range: 22-81). There were 52 men (82.5%) and 11 women (17.5%). 36 patients (57.1%) had gastric cancer, 27 (42.9%) OGJ adenocarcinoma. After a median follow-up of 9.4 months, 52 patients progressed and 38 patients died. Median progression-free survival was 5.3 months and median overall survival was 15.9 months. 38 patients (60.3%) had hepatic metastases, 32 (50.8%) lymph node metastases, 20 (31.7%) peritoneal carcinomatosis, 12 (19.0%) lung metastases and 3 (4.8%) brain metastases. HER2 was overexpressed in 11 (17.5%) patients (confirmed by IHC in 58 patients, by FISH in 5 patients). Two HER2+ patients did not received trastuzumab. Three HER2+ patients (27.3%) had brain metastases, as compared with 0 (0%) HER2- patients (p=0.004). Control of brain metastases was obtained in all 3 patients with multimodal treatment (surgery for 1 patient, radiotherapy for 3 patients and trastuzumab-containing chemotherapy in 3 patients). Progression-Free Survival (PFS) was significantly higher in HER2+ patients treated with trastuzumab than in HER2- patients: median 9.4 months vs 5.0 months (p=0.049). There was no apparent difference in PFS or overall survival between patients with or without brain metastases, but the numbers are too small to conclude. Conclusions: In this retrospective single-center series, we showed an increased incidence of brain metastases in patients with HER2+ gastric or OGJ adenocarcinoma. Patients with brain metastases benefited from multimodal treatment. Prognosis of HER2+ patients treated with trastuzumab seems better than HER2- patients. These results need confirmation in a multicenter study.
Chemotherapy (CT) treatment patterns and neutropenia management in gastric cancer patients (pts) receiving myelosuppressive chemotherapy in Europe.
Authors: Kalinka-Warzocha Ewa , Gallego Plazas Javier , Mineur Laurent , Salek Tomas , Hendlisz Alain , Bendall Kate , Vogl Florian D. , Passalacqua Rodolfo 
Published: February 2017

128 Background: Granulocyte-colony stimulating factor (G-CSF) primary prophylaxis (PP) is recommended for pts undergoing CT who are at overall high risk for febrile neutropenia (FN). No single CT regimen is recognized as standard in gastric cancer and few regimens are represented in G-CSF guidelines. We therefore evaluated neutropenia management in pts receiving CT for gastric cancer. Methods: This was a multicentre prospective observational study that enrolled pts sequentially from 11/2009 to 06/2011. Adult gastric cancer pts (any stage) with ≥3 cycles of myelosuppressive CT scheduled and an investigator-assessed overall FN risk ≥20% were eligible. The primary outcome was the proportion of pts who received PP G-CSF (G-CSF in days 1-7 of cycle 1). Secondary outcomes included FN incidence, chemotherapy administration, and G-CSF use. Posthoc analyses investigated the subgroup who received DCF, including modifications from standard DCF (Van Cutsem. JCO. 2006), and the G-CSF support given up to the first FN (G-CSF prophylaxis given per label in each cycle up to that in which FN occurred). Results: Of 209 pts enrolled, 199 were eligible and their data analyzed. The mean (±SD) age was 62 (±12) years, 76% were male, 17% were ECOG 2 and none ECOG 3-4; 47% were treatment naïve. Planned CT was palliative in 74% of pts; overall, 27 different backbone regimens were planned (10 triplet, 12 doublet, 5 single drug regimens). The most common regimen used was DCF (54 pts, 27%), predominantly given as modified DCF (41 pts). Despite being assessed as high risk for FN, G-CSF PP was administered to only 35% of pts overall (n=70; 54 pegfilgrastim, 16 daily G-CSF) and to 69% of pts who received DCF. FN occurred in 14 pts (10%), 9 of whom received DCF. A large majority of FN pts (12/14, 86%) had not received prophylactic G-CSF per label up to the first FN occurrence; furthermore, 86% of FN pts did not receive G-CSF prophylaxis in the cycle following the FN event. Conclusions: The variety of CT used, frequent modifications to standard CT, and presence of pt risk factors makes FN risk estimation difficult in gastric cancer. Improved risk assessment and appropriate targeting of G-CSF PP to high risk pts is needed.
Combination therapy with radiation and weekly paclitaxel/carboplatin as definitive treatment for locally advanced esophageal cancer.
Authors: Doherty Mark , Cowzer Darren , Kelly Ciara Marie , Battley Jodie Emma , Leonard Gregory , Power Derek Gerard 
Published: February 2017

133 Background: Definitive chemoradiotherapy (CRT) is an established treatment option in localised esophageal cancer. While most patients are treated with cisplatin and fluorouracil, alternative chemotherapy regimens have been used. The combination of carboplatin and paclitaxel (CP) has been validated in a neoadjuvant CRT trial by the CROSS study. There has also been a phase II study (v. Meerten, ASCO 2010, e14508) showing efficacy and tolerability of this regimen in the definitive setting with radiation doses of 50.4Gy/28#. We report our experience using this strategy in two Irish centres. Methods: Patients treated with weekly CP and definitive radiation between Jan 2010 and Aug 2012 were identified from our pharmacy database. Clinicopathologic details were obtained from electronic medical records. The group contains patients with locally advanced unresectable disease, or those medically unfit for esophagectomy. Results: Between Jan 2010 and Aug 2012, we identified 22 patients. Thirteen patients had squamous histology, while 9 had adenocarcinoma. Staging was performed with CT, EUS, and PET/CT – 1 patient had T2 disease, while the remainder had T3/T4, and 10 patients had positive nodes. Reasons for not pursuing surgical resection were extent of disease and poor performance score. In total, 86% of patients received full dose treatment, with reasons for dose delay/reduction being grade 3 sepsis, grade 3 gastrointestinal toxicity, and decline in performance status. Overall 5 (23%) patients needed hospital admission during treatment. At a median follow up of 14 months (range 9-23 months), 19 patients are alive with no evidence of disease, 2 patients have died of disease, and 1 patient is alive with relapsed disease. Our 1-year recurrence free survival rate is 86%. Conclusions: Definitive CRT with CP is a tolerable regimen that can be administered on an outpatient basis, and provides a treatment option in those who are unsuitable for surgical resection or Herskovic type CRT. Our results compare favorably with previous studies in this population. Further investigation is warranted in a prospective study to validate the efficacy of this approach.
Brain metastasis from esophageal cancer: Changing pattern of failure?
Authors: Ashman Jonathan Ben , Jaroszewski Dawn E. , Patel Naresh P. , Fleischer David , Rule William G. , Pannala Rahul , Ramirez Francisco , Lanza Louis , Paripati Harshita , Harold Kristi L. , Faigel Douglas , Ross Helen J. 
Published: February 2017

134 Background: Brain metastasis (BM) is an uncommon site of failure in patients (pts) with esophageal cancer (EC) with reported rates between 1-6%. EC pts are living longer with the wider adoption of trimodality therapy and, as with other malignancies, this may change the patterns of failure. We evaluated the incidence and outcomes of BM in EC at Mayo Clinic in Arizona. Methods: A retrospective review identified pts who developed BM from cancer of the esophagus or gastroesophageal junction. A total of 321 patients treated for stage I-IV EC (adenocarcinoma, n = 273; squamous, n = 46; small cell, n = 2) were identified between 1997 and 2012. Fisher’s exact test was used for comparisons. Actuarial survival was calculated using Kaplan-Meier analysis. Results: BM developed in 13 pts (4%), all of whom had adenocarcinoma. Nine pts initially presented with T3 and/or node-positive disease. Four pts presented with metastatic disease to other sites, but only 1 of this group was diagnosed with BM at initial presentation. The median time from initial diagnosis to BM detection was 12 months (range 0-40). All pts were symptomatic at diagnosis. BM was solitary in 6 pts, multiple in 6 pts, and unknown in 1 pt. The posterior fossa was involved in 9 pts. The brain represented the first site of failure in 9 pts. Treatment included surgical resection (n = 5), stereotactic radiosurgery (n = 4), and whole brain radiotherapy (n = 9). Median overall survival was 24 months from initial diagnosis and 5 months from BM detection. Among pts with adenocarcinoma, 3/119 (2.5%) were diagnosed between 1997-2006 compared to 10/154 (6.5%) between 2007-2012 (P = 0.1). Conclusions: The brain remains an uncommon site of failure among pts with EC. A recent series reported an incidence of BM in 13% of pts, raising the possibility of a changing failure pattern. In our series, BM was detected in only 4% of pts. Our study is suggestive of a trend towards increased incidence of BM in more recent years, although it did not reach statistical significance and could be a consequence of the retrospective nature of the study. Both series found BM limited only to pts with adenocarcinoma, and a possible association has been reported between HER-2 overexpression and BM in EC. Therefore, BM in EC may be an interesting area for future study.
Is neoadjuvant therapy beneficial in clinically staged T2N0 esophageal cancer?
Authors: Kaur Taranjeet , Dolan James P. , Diggs Brian S. , Luna Renato , Sheppard Brett C. , Schipper Paul , Tieu Brandon , Holland John M. , Thomas Charles R. , Gatter Ken , Vaccaro Gina M. , Hunter John G. 
Published: February 2017

135 Background: The optimal treatment strategy for clinical stage T2N0 (cT2N0) esophageal cancer is poorly defined. The specific aims of this analysis were to determine the impact of neoadjuvant therapy (NAT) in cT2N0 esophageal cancer patients on overall survival, nodal metastasis, staging, and pathological complete responders (pCR) NAT. Methods: We reviewed a retrospective cohort of 27 patients with cT2N0 esophageal cancer at Oregon Health & Science University, an NCI-Designated Cancer Center from 1999 to 2011. All patients were staged pre-operatively using Endoscopic Ultrasound (EUS), CT +/- FDG-PET. Patients were identified into two cohorts: NAT followed by surgery and surgery alone. We compared overall survival between the cohorts using Kaplan-Meier analysis. Results: Eleven patients (41%) received NAT followed by surgery and sixteen patients (59%) underwent surgery alone. Minimal invasive esophagectomy and decreased length of stay (p < 0.05) were associated with the presence of neoadjuvant therapy. The difference in overall survival rate was not statistically significant between NAT and surgery alone groups (p = 0.96). Three of 11 patients (27%) had a pCR and 8 (73%) were partial or non responders after NAT. In the surgery only group, nine of 16 patients (56%) were understaged, 6 (38%) were overstaged and 1 (6%) was correctly staged. Despite being clinically node negative, 14/27 (52%) had node positive disease in both groups with 5/11 (45%) in NAT group and 9/16 (56%) in surgery group. Conclusions: The benefit of NAT in cT2N0 esophageal cancer patients remains unclear. However, our finding of significant clinical understaging and frequent positive nodes in clinically node negative patients suggests a clinical benefit to NAT for some cT2N0 patients before surgery. These observations support design of a prospective clinical trial to define the role of NAT in patients with cT2N0 esophageal cancer.
Induction of MT1-MMP expression and enhancement of gastric cancer cells invasion by DARPP-32-CXCR4 interaction.
Authors: Zhu Shoumin , Belkhiri Abbes , El-Rifai Wael 
Published: February 2017

14 Background: Dopamine and cAMP-regulated phosphoprotein, Mr 32000 (DARPP-32) is amplified and overexpressed in approximately 70% of gastric cancers. The prognosis for gastric cancer patients remains poor, especially in more advanced stages. Recently, it was suggested that CXCL-12 and its receptor, CXCR4, are involved in gastric cancer metastasis. However, the detailed mechanism of gastric cancer metastasis is still not completely understood. Methods: Cells invasive activity was determined by invasion assay and HUVEC invasion assay. The association between DARPP-32 and CXCR4 was evaluated by immunofluorescence and co-immunoprecipitation assays. CXCR4 degradation was analyzed by Ubiquitination Assay. Results: Overexpression of DARPP-32 in AGS cells increased cell invasion with about as three-fold invasive cells as the vector control (p<0.01). As measured by HUVEC invasion assay, overexpression of DARPP-32 in AGS cells also had a significant increase in the invasive activity (p<0.001). We found that DARPP-32 led to increased CXCR4 and MT1-MMP protein levels in DARPP-32 expressing AGS cells. The co-immunoprecipitation and immunofluorescence experiments demonstrated the existence of DARPP-32 and CXCR4 in the same protein complex. AGS cells expressing DARPP-32 displayed stable protein levels of CXCR4. IP-Western blot showed reduced ubiquitination of CXCR4 protein following the overexpression of DARPP-32 and treatment with CXCL-12, as compared to controls. Using AMD3100 (0.2 ng/ml) overnight blocked DARPP-32-induced cell invasion. The knockdown of endogenous DARPP-32 by lentiviral DARPP-32 shRNA in MKN-45 cell line reversed these signaling effects and decreased cell invasive activity, as measured by invasion and HUVEC invasion Assay (p<0.01, p<0.05). Conclusions: The in vitro studies indicate that DARPP-32 plays a role in invasion and metastasis; DARPP-32 promotes invasion and metastasis of gastric cancer cells by interacted with CXCR4, delaying CXCL-12-induced CXCR4 Ubiquitination and blocking CXCR4 degradation, activating MMP2 by increasing MT1-MMP expression. The in vivo experiments are ongoing to determine the efficacy of DARPP-32 in mediating CXCR4 overexpression and metastasis.
Use of pharmacogenomic modeling in pancreatic cancer for prediction of chemotherapy response and resistance.
Authors: Sangar Vineet , Ricigliano Mark , O'Reilly Eileen Mary , Abou-Alfa Ghassan K. , Lowery Maeve Aine , Saltz Leonard , Crotty Joseph F , Gary Kristen , Choi Eun Yong , Yin Jing , Hidalgo Manuel , Yu Kenneth H. 
Published: February 2017

142 Background: Pancreatic adenocarcinoma (PDAC) is uniformly lethal; despite this, modern cytotoxics (C) can induce tumor responses and extend life. Xenograft models have shown that pharmacogenomic (PGx) modeling of C can predict efficacy. Chemo-sensitivity and gene expression profiling of tumor progenitor (TP) cells isolated from peripheral blood may predict tumor response, progression and resistance. Methods: A prospective MSKCC study is ongoing with 46 of 60 planned patients accrued. 10 mL of peripheral blood is collected from patients with unresectable PDAC prior to C and at disease progression. Clinical data is prospectively collected. Circulating TP cells are isolated (Vita-Cap, Vitatex Inc.), total RNA is extracted and gene-expression analysis is performed. PGx models for twelve chemotherapy drug combinations used in PDAC were created from the GI50 data obtained from the NCI-60 cell lines (CellPath Therapeutics, Inc., Baltimore, MD). Expression data were normalized through GCRMA then probed to identify expression differences between the 35 patients with continued disease response and the 11 patients with disease progression. Analysis was performed at the pathway and individual gene level. Results: TP cells were isolated and gene expression and chemo-sensitivity patterns were obtained in all 46 evaluable patients prior to initiating C and in all 11 patients at 1st line disease progression. Preliminary analysis demonstrates clinical benefit for patients treated with C predicted to be effective versus C predicted to be ineffective (TTP 4.4 mo versus 2.7 mo, p=0.016). Changes in chemo-sensitivity patterns were evident at disease progression, reflecting treatment resistance. Hedgehog pathway over-expression was associated with resistance to gemcitabine but clinical response to 5-FU based treatment. Pathway analysis revealed that ErbB3, ARE/Nrf2 and Insulin pathways distinguished patients with disease progression. Conclusions: Isolation and gene expression profiling of TP cells can be performed reliably in unresectable PDAC. Preliminary analysis suggests that C profiling can predict response. Repeat PGx profiling identifies key pathways associated with treatment resistance. Clinical trial information: NCT01474564.
Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer (JASPAC-01 study).
Authors: Uesaka Katsuhiko , Fukutomi Akira , Boku Narikazu , Kanemoto Hideyuki , Konishi Masaru , Matsumoto Ippei , Kaneoka Yuji , Shimizu Yasuhiro , Nakamori Shoji , Sakamoto Hirohiko , Morinaga Soichiro , Kainuma Osamu , Imai Koji , Sata Naohiro , Hishinuma Shoichi , Nakamura Takayuki , Kanai Michio , Hirano Satoshi , Yoshikawa Yukinobu , Ohashi Yasuo 
Published: February 2017

145 Background: Gemcitabine (GEM) has been a standard treatment of adjuvant chemotherapy for resected pancreatic cancer (PC). S-1 is an oral fluoropyrimidine, and shown to be non-inferior to GEM on overall survival (OS) for unresectable PC. The aim of this study is to determine non-inferiority of S-1 to GEM on OS as an adjuvant chemotherapy for resected PC. Methods: Patients (pts), who met the following criteria; histologically confirmed ductal adenocarcinoma of the pancreas, R0 or R1 resection, pathological stage I, II, or III with resection of the celiac axis, age >20, no prior chemotherapy or radiotherapy within 3 years, and adequate organ functions, were randomly assigned to GEM (1000 mg/m2, div on days 1, 8 and 15, repeated every 4 weeks, for 6 courses) or S-1 (40-60 mg according to the body surface, twice a day, for 4 weeks, repeated every 6 weeks, for 4 courses). Primary endpoint was OS. With 180 pts in each, the study had 80% power to prove non-inferiority with a non-inferiority margin of hazard ratio (HR) 1.25 on the basis of expected HR 0.87, at 0.05 two-sided alpha. An interim analysis was planned after 180 deaths. Results: From 4/2007 to 6/2010, 385 pts were enrolled (GEM: 193, S-1: 192) from 33 hospitals in Japan. In 378 pts (GEM: 191, S-1:187) of the full analysis set, background factors were well balanced between groups. Based on the interim analysis on survival data obtained by 7/2012, the independent data monitoring committee recommended to publish the results soon. The HR for S-1 to GEM was 0.56 (95% CI, 0.42-0.74, p<0.0001 for non-inferiority, p<0.0001 for superiority). The 2-year survival rates were 53% (95% CI, 46-60) for GEM and 70% (63-76) for S-1. The reasons for treatment discontinuation (recurrence/toxicity/patient’s refusal/others) were 27/48/5/2 in GEM and 9/40/3/0 in S-1. Incidences (%) of grade 3/4 toxicities in GEM/S-1 were fatigue (4.7/5.4), anorexia (5.8/8.0), leukopenia (38.7/8.6), thrombocytopenia (9.4/4.3), anemia (17.3/13.4), and elevated AST (5.2/1.1). Conclusions: S-1 adjuvant chemotherapy is shown non-inferior, and furthermore, even superior to GEM. S-1 may be considered as the new standard treatment for resected PC pts. Clinical trial information: UMIN000000655.
Venous thromboembolism in patients with pancreatic cancer: Incidence and effect on survival in east Asian ethnic groups.
Authors: Lee Jong-Chan , Cho Junhyeon , Park Yohan , Ro Young Sun , Choi Hyejin 
Published: February 2017

151 Background: Pancreatic cancer is known to be most frequently associated with venous thromboembolism (VTE), with the incidence of 10~20% in Western countries. As for the East Asian ethnic groups, just one small retrospective study showed lower incidence (5.3%) than other ethnic groups. However, there have been no large retrospective cohort studies of VTE in pancreatic cancer of East Asian ethnic group. Methods: We retrospectively reviewed the medical records of patients diagnosed with pancreatic adenocarcinoma in 2005~2010 at Severance Hospital, Seoul, Korea. Principal outcomes were incident VTE events and mortality. Cox proportional hazards models were used to analyze associations between specific risk factors and principal outcomes. Results: We investigated 1334 patients with pancreatic adenocarcinoma and 218 (16.3%) patients were excluded due to incomplete medical records and loss to follow-up. Among 1116 eligible patients, the overall and 1-year cumulative VTE incidence were 13.9% and 11.2% respectively. The incidence rate during the half year, 1-year and 2-years were 23.4, 17.7, 15.6 events per 100 person-years, respectively. Among total of 155 VTE patients, abdominal VTE was 52.9%, deep vein thrombosis was 21.3%, pulmonary thromboembolism was 19.4%, and head and neck VTE was 18.7%. In multivariable analyses, significant predictors of developing VTE included advanced metastatic stage (HR=2.08, 95% CI 1.37 to 3.17) and treatment of chemotherapy or radiotherapy, including CCRT (HR=1.52, 95% CI 16 to 1.99). VTE was a significant risk factor of 1-year and overall mortality (HR=1.44, 95% CI 1.15 to 1.79 and HR=1.45, 95% CI 1.21 to 1.73). Among 155 VTE patients, head and neck (H&N) VTE revealed highest risk of overall mortality (HR=2.05, 95% CI 1.27 to 3.33, versus non-H&N VTE). Conclusions: Approximately 13.9% of pancreatic adenocarcinoma patients developed VTE in East Asian ethnic group and this incidence was not significantly different from other ethnic groups. Advanced metastatic stage was the strongest predictor of VTE which would be a significant risk factor of 1-year mortality. Among VTE patients, head and neck VTE was 18.7% and showed the highest risk of overall death.