bluuebunny/crossref_metadata_2025 huggingface dataset:
#malefitspo: Links between viewing fitspiration posts, muscular-ideal internalisation, appearance comparisons, body satisfaction, and exercise motivation in men
Authors: Fatt Scott J , Fardouly Jasmine , Rapee Ronald M
Published: January 2019

Exposure to fitspiration content via social media can influence women’s body satisfaction and exercise inspiration, but fitspiration exposure has not been investigated in men. This study examined links between the frequency of viewing fitspiration content on Instagram, and men’s body satisfaction, appearance-based exercise motivation and health-based exercise motivation, and whether those relationships were mediated by muscular-ideal internalisation and/or appearance comparison tendency. Participants were 17- to 27-year-old Australian men who used Instagram ( N = 118). Frequency of viewing fitspiration content was not directly associated with body satisfaction or reasons for exercise. However, significant indirect pathways were observed through greater muscular-ideal internalisation and appearance comparison tendency. Viewing more fitspiration content was associated with greater muscular-ideal internalisation and higher appearance comparison tendency, which in turn was associated with less body satisfaction, more appearance-based exercise motivation and less health-based exercise motivation. Fitspiration appears to be more closely related to appearance than health in men.
Glutathione peroxidase 4 functional variant rs713041 modulates the risk for cardiovascular autonomic neuropathy in individuals with type 1 diabetes
Authors: Admoni Sharon Nina , Santos-Bezerra Daniele Pereira , Perez Ricardo Vesoni , Patente Thiago Andrade , Monteiro Maria Beatriz , Cavaleiro Ana Mercedes , Parisi Maria Candida , Moura Neto Arnaldo , Pavin Elizabeth Joao , Queiroz Marcia Silva , Nery Marcia , Correa-Giannella Maria Lucia
Published: January 2019

Cardiac autonomic neuropathy is a neglected diabetic chronic complication for which genetic predictors are rarely reported. Oxidative stress is implicated in the pathogenesis of microvascular complications, and glutathione peroxidase 4 is involved in the detoxification of peroxides and of reactive oxygen species. Thus, the association of a functional variant in the gene encoding glutathione peroxidase 4 (rs713041) with this diabetic complication was investigated in 341 individuals with type 1 diabetes evaluated for cardiac autonomic neuropathy status (61.7% women, 34 [27–42] years old; diabetes duration: 21 [15–27] years; HbA1c: 8.3% [7.4–9.4]; as median [interquartile interval]). Cardiac autonomic neuropathy was present in 29% of the participants. There was an inverse association of the minor T allele of rs713041 with cardiac autonomic neuropathy (odds ratio = 0.39; 95% confidence interval = 0.17–0.90; p  = 0.0271) after adjustment for potential confounders. The functional glutathione peroxidase 4 variant rs713041 modulated the risk for cardiac autonomic neuropathy in the studied population with type 1 diabetes.
Microvascular complications among patients with diabetes: An emerging health problem in Saudi Arabia
Authors: Alwin Robert Asirvatham , Al Dawish Mohamed Abdulaziz
Published: January 2019

Diabetes mellitus, besides disrupting the carbohydrate metabolism process, also induces vascular disease and impacts nearly all the types and sizes of blood vessels. In fact, vascular complications cause majority of the morbidity, hospitalizations and mortality of patients with diabetes mellitus. Retinopathy, nephropathy and neuropathy (microvascular complications) impact hundreds of millions of diabetics and normally target those having long-term or uncontrolled forms of the disease; however, these disorders can also exist at the time of diagnosis or in those yet to be diagnosed. The Kingdom of Saudi Arabia is the biggest country in the Middle East that occupies around four-fifths of the Arabian Peninsula supporting a population of more than 33.3 million people. The prevalence of diabetes mellitus is increasing at an alarming rate in Saudi Arabia. Over 25% of the adult population is suffering and that figure is projected to more than double by 2030. In fact, diabetes mellitus has approximately registered a 10-fold upsurge in the past three decades in Saudi Arabia. However, the prevalence and risk factors of microvascular complications in diabetes mellitus patients have not yet been clearly documented in Saudi Arabia. Hence, in this review, we aim to provide an overview of the microvascular complications among patients with diabetes in Saudi Arabia, utilizing data from the currently available published literature. This is an attempt to facilitate the government and healthcare systems aware of the enormous worth of prevention, early detection and appropriate management of such microvascular complications.
Integrating Political Philosophy Into Health Policy Education
Authors: Martsolf Grant R. , Thomas Teresa H.
Published: January 2019

Twenty-first century America is marked by deep and seemingly incommensurable divisions in terms of public policy solutions to our most intractable issues. Health policy challenges are not immune to these deep divisions, as the debate during and since the passage of the Affordable Care Act illustrates. Positions on key public policy issues are driven by largely implicit and unarticulated philosophical presuppositions that guide individuals’ notions of the nature of government, individuals’ moral obligations to each other, how society assesses quality of life, and what it means to be a community. If faculty in schools of nursing are to prepare graduate nurses to enter into these heated public policy debates, we must help students understand, identify, and articulate the philosophical presuppositions that undergird reasoning related to health policy issues. In this article, we present a working taxonomy that can help faculty members provide students with a basic understanding of core philosophical principles. We attempt to categorize all of western political philosophy into four distinct traditions or “impulses,” describing each of these four traditions in detail. We illustrate each tradition’s approach to political reasoning using a specific health policy case study. We conclude with some guidance about how to implement this content within a doctoral-level public policy curriculum.
Better off without You? How the British Media Portrayed EU Citizens in Brexit News
Authors: Walter Stefanie
Published: January 2019

The United Kingdom is the first country to withdraw its membership from the European Union (EU). Immigration featured high on the Brexit news agenda and EU citizens’ rights to work and live in the United Kingdom are likely to be affected by the country’s exit from the EU. This study analyzes how salient EU citizens were in Brexit news, and investigates whether there was a relationship between the negative portrayal of EU citizens and the type of news outlet. The analysis is based on 19,367 news stories published between June 1, 2015, and June 23, 2016. Automated content analysis was used to determine whether EU citizens were mentioned. The results do not reveal a divide between tabloids and broadsheets, but between national and regional papers. It is only in regional papers from England and Wales that EU citizens were more likely to be mentioned if the tone of a news story was more negative. The findings also suggest that the news media presented the Brexit referendum as a vote about migration in general rather than about intra-EU migration.
Validation of the Individuation Test for Emerging Adults–Short (ITEA-S) in Austrian and German Emerging Adults
Authors: Komidar Luka , Zupančič Maja , Sirsch Ulrike
Published: January 2019

Individuation Test for Emerging Adults–Short (ITEA-S) is a self-report instrument for measuring five aspects of individuation in emerging adulthood. The test consists of two equivalent forms for assessing individuation in relation to mother and father separately. In this study, we adapted the ITEA-S for use in Austrian and German emerging adult populations. In both samples, the two ITEA-S forms demonstrated satisfactory factorial validity and internal consistency. The scores on the five scales were meaningfully related to the Emotional, Functional, and Conflictual Dependence Scales of the Psychological Separation Inventory and also to life satisfaction as measured by the Satisfaction With Life Scale. The results of the multiple-group factor analyses supported the hypotheses of full metric and scalar invariance for both ITEA-S forms across the Austrian and German samples of emerging adults.
President's Page
Authors: Tubman Ken
Published: January 2019

So, let's talk a bit about inclusion. That's a term that gets thrown around a lot these days. I'm pretty sure it means something different to different people. To some, diversity and inclusion mean more of the same — just another corporate initiative, or here we go again.
Introduction to this special section: Case studies: Conventionals
Authors: Oppert Shauna , Casey Matthew , Spikes Kyle T.
Published: January 2019

Case studies, with a focus on conventional systems, provide insight of seismic and well data sets in terms of characterizing reservoirs with innovative techniques and approaches. This special section contains three such papers from three different regions: offshore Brazil, the North Sea, and the Middle East. Each contribution presents a different geologic problem ranging from siliciclastics to volcanics to carbonates. The challenges faced in each paper were tackled using innovative approaches to reservoir characterization in complex geologic regions.
Revitalizing seismic data with new imaging solutions to positively impact field development
Authors: Venfield Gareth , Townsend Michael , Cattermole Paul , Martin Tony , Fairhead Stuart
Published: January 2019

Evaluating, planning, and forecasting are integral parts of asset development and continue throughout the life cycle of a producing field. The right decisions are required to lower risk and maximize economic recovery in challenging environments. The Claymore Complex is located in the North Sea and was discovered in 1977. A number of geologic challenges affect the imaging and hence field development including a system of shallow interweaving Quaternary channels, numerous high-contrast layers of varying composition, overburden structural complexity, and a sequence of tilted fault blocks containing the main reservoir systems. Historically, seismic processing over the area has not fully solved these challenges, resulting in significant imaging uncertainty. The Claymore Complex has an abundance of data including a large population of well information and interpretation. As part of a data revitalization process, geostatistical integration of these auxiliary data into a velocity model building sequence using full-waveform inversion and wavelet shift tomography enabled the generation of an accurate high-resolution velocity model. Access to a recent 3D survey acquired obliquely to existing data improved subsurface illumination for both the model building and imaging phases. Near-surface imaging effects and their impact on reservoir positioning and clarity were improved using the upgraded velocity model and dual-azimuth data. Shallow imaging challenges were mitigated by utilizing the additional illumination and angular diversity contained within the multiple reverberations. The revitalization of the Claymore area seismic data has challenged the current understanding of the geologic framework. Confidence has been improved by solving depth conversion problems and increasing the understanding of fault positioning and reservoir connectivity, which are invaluable for future field development.
A high-density, high-resolution joint 3D VSP–3D surface seismic case study in the Canadian oil sands
Authors: Charles Sylvestre , Lin Jiwu , Kuzmiski Rick , Leung Philip , Mouaki Ahmed , Looi Shiang Yong , Liu Qinglin
Published: January 2019

This Canadian oil sands case history illustrates how a high-density, high-resolution joint 3D vertical seismic profile (VSP)–3D surface seismic survey was designed, acquired, and processed to successfully meet the objective of obtaining a detailed image of the subsurface, including the cap rock, the internal architecture of the oil sands reservoir, the underlying carbonates, and the fault and fracture network that runs from surface to basement. The VSP-driven processing was essential in determining the effects of attenuation, multiples, and converted waves, and in quantifying the anisotropy for imaging and time-to-depth conversion. The joint 3D tomography inversion of the VSP and surface seismic data provided an accurate velocity model to migrate the 3D surface seismic data and the 3D VSP data in depth. Each of the 28 wells located within the survey area tied in to the final seismic volume very well. Depth imaging resolved the shallow velocity variations that the initial time processing could not. The apparent (but erroneous) azimuthal velocity effects in the time processing were minimized in the depth processing, resulting in an anisotropy velocity model that was in accordance with the 3D VSP data. A 3D full-waveform inversion test complemented this case history.
Near-Surface Geophysics Technical Section holds first-ever panel discussions at 2018 Annual Meeting
Authors: Morton-Rupert Sarah , Malecek Steven , Legg Mark
Published: January 2019

The 2018 Annual Meeting marked the largest near-surface geophysics technical program in the history of the Society of Exploration Geophysicists. In Anaheim, attendees could participate in nine near-surface oral presentations, six poster sessions, one preconference short course, two postconference workshops, and for the first time, three panel discussions. These panels add a new platform to the Annual Meeting to help diversify the technical program and facilitate discussions on geophysical hot topics among professionals from varying but complementary fields.
M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-β, in Asian patients with pretreated recurrent or refractory gastric cancer: Preliminary results from a phase I trial.
Authors: Kang Yoon-Koo , Doi Toshihiko , Kondo Shunsuke , Chung Hyun-Choel , Muro Kei , Helwig Christoph , Watanabe Morihiro , Bang Yung-Jue
Published: January 2019

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Background: Inhibiting the transforming growth factor β (TGF-β) pathway, which plays a key role in tumor immunosuppression, may enhance the response to programmed death 1/programmed death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs). M7824 (MSB0011359C) is an innovative first-in-class bifunctional fusion protein composed of a mAb against PD-L1 fused with the extracellular domain of TGF-β receptor II, which serves as a TGF-β “trap.” We report preliminary results in Asian patients with heavily pretreated gastric cancer. Methods: In this expansion cohort of the ongoing, phase 1, open-label trial NCT02699515, patients with recurrent or refractory unresectable stage IV gastric or gastroesophageal junction adenocarcinoma for which no standard therapy exists or standard therapy has failed receive M7824 1200 mg q2w until confirmed progressive disease, unacceptable toxicity or trial withdrawal. The primary objective is safety; secondary objectives include best overall response (BOR) per RECIST v1.1. Results: As of 6 September 2017, 31 heavily pretreated patients with advanced gastric cancer (67.7% received ≥3 prior anticancer therapies) received M7824 for a median duration of 6.1 (range: 2-30) weeks (median number of M7824 infusions: 3 [range: 1-13]); 8 patients remained on treatment. Four patients (12.9%) experienced grade 3 treatment-related adverse events (anemia and diarrhea 1 each and 2 rash). No treatment-related grade 4 AEs occurred. One grade 5 event (total 5 doses received) was considered possibly treatment related, but suspected rupture of preexisting thoracic aortic aneurysm was cited as other probable cause by the investigator. There were 5 confirmed partial responses (4 ongoing after 4-6 months of follow-up) based on investigator assessment of BOR (overall response rate: 16.1%). This is an ongoing study; updated data will be presented. Conclusions: These preliminary data show that M7824 resulted in a manageable safety profile in heavily pretreated Asian patients with gastric cancer. Early signs of clinical efficacy are encouraging. Clinical trial information: NCT02699515.
Safety and antitumor activity of ramucirumab plus pembrolizumab in treatment naïve advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: Preliminary results from a multi-disease phase I study (JVDF).
Authors: Chau Ian , Penel Nicolas , Arkenau Hendrik-Tobias , Santana-Davila Rafael , Calvo Emiliano , Soriano Andres O. , Mi Gu , Jin Jin , Ferry David , Herbst Roy S. , Fuchs Charles S.
Published: January 2019

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Background: Preclinical evidence suggests simultaneous blockade of vascular endothelial growth factor receptor 2 (VEGFR-2) and programed cell death 1 protein (PD-1) induces synergistic antitumor effects. We assessed safety and preliminary efficacy of ramucirumab (anti-VEGFR-2) plus pembrolizumab (anti-PD-1) in patients (pts) with treatment naïve advanced G/GEJ adenocarcinoma. Methods: This ongoing, multi-cohort, phase 1a/b trial enrolled ECOG PS 0-1 pts with treatment naïve advanced G/GEJ adenocarcinoma with measurable disease and baseline tumor tissue. PD-L1 status was assessed by DAKO PD-L1 22C3 IHC pharmDx assay using the combined positive score with ≥1% being positive. Ramucirumab was administered at 8 mg/kg on Days 1 & 8 with pembrolizumab 200 mg on Day 1 q3W. Primary objective was safety and tolerability of study treatment; preliminary efficacy was examined. Results: As of 31-July-2017, 28 treatment naïve G/GEJ adenocarcinoma pts were treated. Median age was 63 y, 75% male, 57% had ECOG PS of 0, and 68% were PD-L1 positive. At data cutoff, 8 (28%) pts continued to receive study treatment. Median duration of follow-up was 8.1 mo (IQR 6-10). Median treatment duration was 4.3 mo (IQR 2-7). All grades treatment-related adverse events (TRAEs) occurred in 27 (96%) of patients; TRAEs in ≥15% of pts were fatigue (36%), hypertension (25%) and headache (18%). Seventeen (61%) pts experience grade 3 TRAEs, most commonly hypertension (14%), diarrhea (11%), and elevated alanine (7%) or aspartate (7%) aminotransferase. No grade 4-5 TRAEs occurred. An objective response was achieved by 7 (25%) pts, 6 positive and 1 negative for PD-L1. Disease control rate was 68%. Median time to response was 2.7 mo (95% CI 1.3-2.8) and median duration of response was 10 mo (95% CI 9.7-10.3). Median progression-free survival was 5.3 mo (95% CI 3.2-11). Median overall survival has not been reached. Conclusions: Ramucirumab plus pembrolizumab demonstrated encouraging antitumor activity in treatment naïve advanced G/GEJ adenocarcinoma with no grade 4 TRAE observed. Clinical trial information: NCT02443324.
Preoperative therapy for gastric adenocarcinoma in relation to oncologic outcomes in patients with complications after gastrectomy.
Authors: Vicente Diego , Ikoma Naruhiko , Chiang Y. Sabrina , Fournier Keith , Mansfield Paul F. , Ajani Jaffer A. , Badgwell Brian D.
Published: January 2019

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Background: Postoperative complications (POC) are associated with poor oncologic outcomes in gastric cancer, however, it is unknown if preoperative therapy has any impact on this association. We sought to evaluate the impact of POC on survival in patients with gastric cancer treated with upfront surgery versus those treated with preoperative therapy. Methods: We analyzed data from a prospectively maintained database of patients who had undergone resection of their gastric cancer at our institution between 1995 and 2015. Patients with T1N0 or M1 lesions, recurrent disease, mortality within 90 days, and GEJ tumors were excluded. Cox regression analyses were used to examine factors associated with overall survival (OS) and disease free survival (DFS). Interaction terms between complications and preoperative therapy were used in the multivariate model to determine their impact on OS and DFS. Results: 421 patients underwent resection of gastric cancer: 30% underwent upfront surgery, and 51% had a POC. Variables associated with POCs included total gastrectomy (p = 0.02) and additional organ resection (p = 0.05). Among patients who had POCs, 71% were infectious, 41% experienced multiple complications, and 55% were classified as Clavien-Dindo grade III or IV. On multivariable analysis, the presence of a POC had the strongest association with diminished OS (HR 3.5, 95% CI 1.9-6.5). Among patients who underwent upfront surgery, patients with a POC had shorter OS (5-year, 85% vs. 47%; p < 0.001) and DFS (5-year, 76% vs. 46%; p < 0.001) than those without a POC. In contrast, there was no difference in OS (5-year, 63% vs. 57%; p = 0.77) and DFS (5-year, 52% vs. 52%; p = 0.52) between patients with and without POC who received preoperative therapy. Interaction terms between preoperative therapy and complication in the multivariable Cox regression model were significant on OS (3.53 [95%CI: 1.92-6.52]) and DFS (2.84 [95%CI: 1.59-5.08]), which indicated that the negative impact of complications were reduced if patients received preoperative therapy. Conclusions: The use of preoperative therapy negated the impact of POCs on OS and DFS in patients undergoing resection for gastric cancer.
A survival analysis of a prospective multicenter observational study of surgical palliation in patients treated for malignant gastric outlet obstruction caused by incurable advanced gastric cancer.
Authors: Terashima Masanori , Fujitani Kazumasa , Ando Masahiko , Sakamaki Kentaro , Kawabata Ryohei , Ito Yuichi , Yoshikawa Takaki , Kondo Masato , Kodera Yasuhiro , Kaji Masahide , Oka Yoshio , Imamura Hiroshi , Kawada Junji , Takagane Akinori , Shimada Hideaki , Tanizawa Yutaka , Yamanaka Takeharu , Morita Satoshi , Ninomiya Motoki , Yoshida Kazuhiro
Published: January 2019

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Background: We previously reported that surgical palliation maintained patients’ quality of life (QOL) while improving the solid food intake with an acceptable surgical safety in patients with malignant gastric outlet obstruction (GOO) caused by advanced gastric cancer. To elucidate the impact of the improvement in the QOL on the survival, we performed a survival analysis according to the changes in the QOL. Methods: Eligibility criteria included (1) no or liquids-only oral intake, (2) aged ≥20 , (3) surgically fit, (4) ECOG PS of 0-2, and (5) written informed consent. Patients underwent either palliative gastrectomy or gastrojejunostomy. Validated QOL instruments (EORTC QLQ-STO22 and EuroQol-5D) assessed the QOL at baseline, 2 weeks, 1 month, and 3 months following surgical palliation, and postoperative improvement in the oral intake was also evaluated. Univariate and multivariate survival analyses were performed according to baseline characteristics and changes in QOL 2 weeks, 1 month, and 3 months after the operation. Results: The median survival time in the 104 patients was 11.30 months. In the univariate analysis, the survival was significantly better in the patients who received gastrectomy, received adjuvant chemotherapy, had a better PS, and had a worse baseline EQ5D score. Changes in the QOL scores had no marked impact on the survival at 2 weeks and 1 month after operation. However, in patients with an improved or stable EQ5D score at 3 months post-surgery, the survival was significantly better (p = 0.0043). An improved oral intake on the GOO score system (GOOSS) had a positive impact on the survival. A multivariate analysis in the patients survived more than 3 months after the operation revealed that adjuvant chemotherapy, a better baseline PS, a worse baseline EQ5D, an improved or stable EQ5D score, and an improved oral intake on the GOOSS at 3 months after surgical palliation were independent prognostic factors. Conclusions: In patients who received surgical palliation for malignant GOO caused by advanced gastric cancer, an improved oral intake and QOL score at 3 months after operation predicted a good survival. Clinical trial information: 000023494.
Histopathological tumor regression or ypN: Which better predicts survival of patients who received neoadjuvant chemotherapy and surgery for non-type 4 locally advanced gastric cancer?
Authors: Fujitani Kazumasa , Nakamura Kenichi , Mizusawa Junki , Kuwata Takeshi , Shimoda Tadakazu , Katayama Hiroshi , Kushima Ryoji , Taniguchi Hirokazu , Yoshikawa Takaki , Boku Narikazu , Terashima Masanori , Fukuda Haruhiko
Published: January 2019

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Background: Histopathological tumor regression with < 10% residual tumor is a globally accepted prognostic factor in gastric cancer patients who received neoadjuvant chemotherapy (NAC) and curative surgery, however, impact of ypN remains unclear. Methods: Previously, Japan Clinical Oncology Group (JCOG) had conducted 3 phase II trials to evaluate NAC with irinotecan/CDDP (JCOG0001) and S-1/CDDP (JCOG0405) for extensive nodal disease, and with S-1/CDDP (JCOG0210) for large type 3 and type 4 (linitis plastica) disease. Prognostic factors, including ypN and histopathological tumor regression with < 10% residual tumor, were analyzed in patients with curative resection excluding type 4 advanced gastric cancer in these trials by univariable and multivariable analyses using the Cox proportional hazards model. Results: Among 85 patients, 5-year OS was 46.0% (95% CI, 35.0-56.4). Median OS was not reached in patients with < 10% residual tumor (n = 26), whereas that was 2.7 years (95% CI, 1.4-4.5) in patients with > 10% residual tumor (n = 59) (p = 0.008). Median OS was not reached in patients with ypN0-1 (n = 25), whereas that was 2.6 years (95% CI, 1.5-4.0) in patients with ypN2-3 (n = 60) (p = 0.003). On multivariable analysis, only ypN2-3 was an independent predictor of OS (hazard ratio, 3.67; 95% CI, 1.55 to 8.69), whereas < 10% residual tumor was not (hazard ratio, 2.24; 95% CI, 0.98 to 5.10). Conclusions: It is suggested that ypN may have greater impact on the survival than histopathological tumor regression in patients who received NAC and surgery for AGC.
Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for local advanced gastric or Siewert II/III GEJ cancer: A retrospective analysis.
Authors: Li Guichao , Wo Jennifer Y , Blaszkowsky Lawrence Scott , Zheng Hui , Clark Jeffrey W. , Mullen John , Rattner David W , Berger David L. , Eyler Christine , Keane Florence K. , Zhu Andrew X. , Murphy Janet E. , Goyal Lipika , Parikh Aparna Raj , Allen Jill N. , Ryan David P. , Zhang Zhen , Hong Theodore S.
Published: January 2019

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Background: Radiation therapy has improved survival in gastric cancer in some randomized trials. However, post-operative fields have been difficult tolerate, and completion rates have been low. Preoperative therapy may afford the opportunity to radical therapy, and potentially improve the resectability in advanced patients. Methods: Patients with Siewert II/III GE junction or gastric cancer treated at Massachusetts General Hospital were evaluated with Institutional Review Board approval. Clinical parameters and prognostic factors including gender, age, clinical stage, pathological stage, radiation parameters, concurrent chemotherapy, non-radiation chemotherapy, toxicity and survival were included in the analysis. Results: From Jul 2005 to Jan 2017, we enrolled 88 patients had chemoradiotherapy (CRT) and surgery, 48 preoperative and 40 postoperative CRT patients. In the preoperative group, 16.7% (8/48) had nodes outside a standard D2 dissection range, and the pathologic complete regression (pCR) rate was 18.8% (9/48). Median preoperative and postoperative radiation dose was 50.4 Gy and 45 Gy. Two-drug regimen was the most commonly used preoperative concurrent chemotherapy: 60.5% and single drug was the most commonly used postoperative concurrent chemotherapy: 97.5%. Except concurrent chemotherapy, 25 preoperative CRT patients received induction FOLFOX (median 8 cycles); 9 postoperative CRT patients also received 5-FU and 23 received FOLFOX (or EOX) chemotherapy. The estimated 3-year relapse-free survival (RFS) and overall survival (OS) in the preoperative and postoperative group was 51% vs. 34.3% (p = 0.286), and 71.2% vs. 45.9% (p = 0.179), respectively. In preoperative CRT group, there was more hematological toxicity but less gastrointestinal toxicity than postoperative CRT group, more distant metastasis but less peritoneal recurrence rate. Conclusions: Compared to postoperative chemoradiotherapy, preoperative chemoradiotherapy option has the trend of better tolerance, higher RFS and OS in patients with local advanced gastric cancer. Different chemoradiotherapy strategy may lead to different recurrence patterns.
Recombinant humanized anti-PD-1 monoclonal antibody (JS001) as salvage treatment for advanced esophageal squamous cell carcinoma: Preliminary results of an open-label, multi-cohort, phase Ib/II clinical study.
Authors: Xu Rui-hua , Wang Fenghua , Shi Jianhua , Feng Ji Feng , Shen Lin , Yang Shujun , Hu Xi-Chun , Dai Guanghai , Xu Nong , Jiang Yi , Yongqian Shu , Zhang Qingyuan , Chen Ye , Yuan Xianglin , Lin Xiaoyan , Ba Yi , Li Qi , Li Wei , Huang Haixin , Yao Sheng
Published: January 2019

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Background: Patients with Esophageal squamous cell carcinoma (EC) often present with advanced and metastatic stage disease, which has poor prognosis and limited treatment options, and represent an important unmet medical need especially in China/Asia. JS001, a humanized recombinant IgG4 antibody against PD-1, selectively blocks the interactions of PD-1 with its ligands PD-L1 and PD-L2, and promotes antigen specific T-cell activation. A phase I study of JS001 in Chinese patients with heavily pretreated solid tumors has demonstrated an acceptable safety profile in doses up to 10 mg/kg Q2W. Here we report the safety and efficacy of JS001 in a phase Ib/II clinical study in Chinese patients with refractory/metastatic EC. (Clinical trial ID: NCT02915432) Methods: Refractory/metastatic EC Patients receive JS001 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease will be assessed for clinical response every 8 weeks according to the RECIST 1.1 criteria. Tumor PD-L1 expression as well as additional potential predictive biomarkers are monitored for correlation with clinical response. Results: Between Apr 19 2017 and Sep 11 2017, 56 EC pts (84.9% received at least 2 Lines of treatment) were enrolled into the study. Treatment related adverse events occurred were mostly grade 1 or 2. As of Sep 11 2017, 34 EC pts have been evaluated for clinical efficacy. Among these pts, 8 PR (partial response) and 14 SD (stable disease) were observed (ORR 23.5% and DCR 64.7%). The PD-L1 expression positivity (defined as positive staining ³1% on Tumor Cell [TC] or on Immune Cell [IC] by SP142) in EC tumor tissue was 21.4% (12/56). 2/10 (20%) PD-L1+ patients and 6/24 (25%) PD-L1 negative patients achieved partial responses. Conclusions: JS001 showed a promising preliminary clinical activity in heavily pre-treated metastatic EC pts with a manageable safety profile. Clinical response was not correlated with PD-L1 expression. Pts will be continuously monitored for safety and efficacy upon JS001 treatment. Clinical trial information: NCT02915432.
Updated results of phase 1 study of DS-8201a in subjects with HER2-expressing gastric cancer.
Authors: Iwasa Satoru , Shitara Kohei , Takahashi Shunji , Park Haeseong , Kadowaki Shigenori , Modi Shanu , Nonagase Yoshikane , Tamura Kenji , Yamaguchi Kensei , Muro Kei , Tsurutani Junji , Shahidi Javad , Lee Caleb C. , Sugihara Masahiro , Kawaguchi Yoshinori , Doi Toshihiko
Published: January 2019

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Background: DS-8201a is a HER2 targeting antibody-drug conjugate of high drug to antibody ratio (7 to 8) with a novel linker and topoisomerase I inhibitor. In preclinical studies, DS-8201a demonstrated a broad antitumor spectrum including efficacy against low HER2 expressing cancers. Interim results of the first-in-human phase 1 trial reported an overall confirmed response rate of 40.2% across several tumor types including breast and gastric (data cutoff of May 11, 2017). Here, we present updated results focusing on HER2 expressing gastric cancer (GC) subjects as of August 1, 2017. Methods: The trial consists of part 1, dose-escalation, and part 2, dose expansion cohorts. Part 2 included the cohort for subjects with HER2 expressing GC previously treated with trastuzumab. HER2 status was determined by IHC, and/or FISH according to ASCO CAP guidelines. Results: Seven GC subjects were enrolled in Part 1and 41 subjects were enrolled in Part 2. The median number of prior anticancer treatment was 3. In Part 1, confirmed ORR across doses was 43% (3/7). One out of two subjects with HER2 low (IHC2+/ISH-) showed PR. In Part 2, confirmed ORR and DCR were 44% (16/36) and 78% (28/36), respectively with 83% of subjects experiencing tumor shrinkage. Currently, the median DoR and PFS are ≥31 weeks and 25 weeks, respectively. For subjects enrolled in part2b, the most common AEs of any grades were nausea (All 71%; ≥Gr3 2%), decreased appetite (All 61%; ≥Gr3 10%), vomiting (All 22%; ≥Gr3 0%) and platelet count decreased (All 32%; ≥Gr3 17%). Five subjects (10%) discontinued drug treatment due to AE. Conclusions: DS-8201a demonstrated promising antitumor activity in heavily pretreated subjects with HER2 expressing GC. Clinical trial information: NCT02564900.
Clinical significance of lymphatic flows around pylorus identified by sentinel node mapping in patients with gastric cancer.
Authors: Aoyama Junya , Kawakubo Hirofumi , Mayanagi Shuhei , Fukuda Kazumasa , Suda Koichi , Nakamura Rieko , Wada Norihito , Kitagawa Yuko
Published: January 2019

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Background: The sentinel node (SN) concept is safely applied and validated in early gastric cancer. Gastric lymph nodes are divided into five basins with the main gastric arteries. The suprapyloric lymph nodes (No. 5) and the anterosuperior lymph nodes with the common hepatic artery (No. 8a) are classified in the right gastric artery (r-GA) basin, and the subpyloric lymph nodes (No. 6) are classified in the right gastroepiploic artery (r-GEA) basin. The aim of this study is to analyze the lymphatic flows between these lymph nodes and basins. Methods: Five hundred and fourty-nine patients with cT1N0 or cT2N0 gastric cancer underwent SN mapping. We used technetium-99 tin colloid solution and blue dye as a tracer. Results: We detected SN No. 5 in 36 (6.6 %) patients. In these patients, we detected SN No. 5 with SNs that belonged to the left gastric artery (l-GA) basin (69 %), r-GA basin (14 %), and r-GEA basin (44 %). No. 6 was detected as SN significantly more frequently with SN No. 5. We detected SN No. 6 in 100 (18.2 %) patients. In these patients, we detected SN No. 6 with SNs that belonged to the l-GA basin (42 %), left gastroepiploic artery (l-GEA) basin (4 %), r-GA basin (28 %), and r-GEA basin (41 %). No. 4d, No. 5 and No. 8a were detected as SNs significantly more frequently with SN No. 6. We detected SN No. 8a in 43 (7.8 %) patients. In these patients, we detected SN No. 8a with SNs that belonged to the l-GA basin (65 %), l-GEA basin (7 %), r-GA basin (21 %), r-GEA basin (58 %), and posterior gastric artery (p-GA) basin (7 %). No. 6 and No. 9 were detected as SNs significantly more frequently with SN No. 8a. SN No. 5 and No. 8a were tend to be detected with not SNs that belonged to the r-GA basin but No. 6, and SN No. 6 was detected significantly more frequently with No. 4d, No. 5 and No. 8a. Conclusions: Our findings show that lymphatic flows exist not only between lymph nodes which are belonged to the same basin, but also between No. 5 and No.6, and No.6 and No. 8a. On the other hand, the lymphatic flows between No. 5 and No. 8a seem to be limited. Our results suggest that the lymph node dissection of No. 6 given lymphatic flows from lesser curvature side and retroperitoneal side is important for surgery of gastric cancer.
Potentially curable gastric adenocarcinoma (GAC) patients treated without surgery.
Authors: Mizrak Kaya Dilsa , Nogueras-Gonzalez Graciela M. , Estrella Jeannelyn , Harada Kazuto , Ghazanfari Amlashi Fatemeh , Lin Quan , Blum Murphy Mariela A. , Lee Jeffrey H , Weston Brian , Bhutani Manoop S. , Matamoros Aurelio , Sagebiel Tara L. , Devine Catherine E , Patnana Madhavi , Minsky Bruce D. , Das Prajnan , Badgwell Brian D. , Ajani Jaffer A.
Published: January 2019

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Background: Surgery is the best option to cure localized GAC. When surgery is not possible due to comorbidities or patient refusal, definitive chemoradiation is an option. We report on one of the largest cohorts of GAC patients who did not have surgery. Methods: We identified 71 patients with localized GAC who received chemo/chemoradiation therapy but did not have surgery. We assessed various endpoints (overall survival [OS] and recurrence-free survival [RFS]). Clinical complete response (cCR; negative post therapy biopsy and no evidence of cancer by imaging) was also assessed. Results: The median follow-up time was 1.8 years (range; 0.4-10.6). Most of the patients were men (64.8%) and the median age was 73 years (range; 30-96). Reason for not having surgery included comorbidities in 34 (47.9%), poor performance status 14 (19.7%), and patient refusal 23 (32.4%). Most of the patients (80.3%) received chemoradiation and 14 (19.7%) could receive only chemotherapy. Of all 71 patients, 32 (45.1%) achieved to a cCR. For the entire cohort, the median OS was 2.1 years (95% Cl 0.98-1.02). The estimated OS rates at 2 and 5 years were 46.5% and 11.3%, respectively. The median OS and the median RFS for patients with cCR were 2.3 and 1.8 years (95% Cl 0.97-1.01), respectively. Female gender (HR 0.47, 95% Cl 0.25-0.91, p = 0.024) and chemoradiation (HR 0.36, 95% Cl 0.16-0.85; p = 0.019) were independently associated with longer OS in the multivariate analysis. Histologic grade and the presence of signet ring cell had no effect on OS. Conclusions: Our data show that patients with localized GAC who do not undergo surgery have a low but measurable 5-year OS rate of 11.3%.
Fluoropyrimidine (F) alone versus F plus platinum (P) as first-line chemotherapy in patients (pts) with advanced gastric cancer (AGC) and severe peritoneal metastasis (SPM): A multicenter observational study.
Authors: Arai Hiroyuki , Iwasa Satoru , Boku Narikazu , Kawahira Masahiro , Yasui Hirofumi , Masuishi Toshiki , Muro Kei , Hironaka Shuichi , Fukuda Naoki , Takahari Daisuke , Nakajima Takako Eguchi
Published: January 2019

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Background: The standard 1st-line chemotherapy for AGC pts with SPM has not been established. F alone is generally used for their treatment because of difficulty of hydration for dosing of cisplatin (CDDP) in pts with massive ascites, and has shown limited efficacy. It is unclear whether a combination of F and P (CDDP or oxaliplatin): FP improves their clinical outcome. We therefore investigated the efficacy and safety of FP in comparison with F alone. Methods: This retrospective study comprised of AGC pts with SPM and HER2 negative or unknown tumors who received FP or F as 1st-line chemotherapy between Jul 2010 and Sep 2016 at 6 institutions in Japan. SPM was defined as having massive ascites and/or inadequate oral intake requiring intravenous nutrition support. Overall survival (OS), progression-free survival (PFS), response rate of ascites, improvement rate of oral intake, and safety were compared between two treatment groups. Results: A total of 129 pts (64 in FP group, 65 in F group) were included. Patient characteristics (FP vs F) were as follows: median age, 62 vs 67; PS 0/1/2/3/4 (%), 6/64/25/3/2 vs 8/42/42/8/0; massive ascites/inadequate oral intake/both (%), 61/25/14 vs 35/29/35; number of metastatic sites 1-2/3-5 (%), 77/23 vs 78/22; median serum albumin level (g/ml), 3.1 vs 3.1. OS was significantly longer in FP group than F group (median, 9.0 vs 5.0 months; HR 0.56, 95%CI 0.39-0.82; log-rank p < 0.01); it remained significant upon multivariate analysis adjusting for prognostic variables (HR 0.48, 95% CI 0.32-0.73, p < 0.01). Pts in FP group had significantly better PFS in both uni- and multivariate analyses (median, 4.3 vs 2.3 months; HR 0.44, p < 0.01 and HR 0.40, p < 0.01, respectively). Response rate of ascites (51% vs 17%) and improvement rate of oral intake (64% vs 43%) also were better in FP group (p < 0.01 and p = 0.09, respectively). Toxicities were tolerable in both groups, but grade ≥3 neutropenia was more frequent in FP group (36% vs 11%). Conclusions: FP showed significantly better efficacy than F alone, and it could be a promising option as 1st-line treatment for AGC pts with SPM.
Comparison of bimodality versus trimodality therapy for esophageal or gastroesophageal junction (GEJ) cancer: Experience from the Princess Margaret Cancer Centre.
Authors: Natori Akina , Sim Hao-Wen , Chan Bryan Anthony , Sun Peiran , Moignard Stephanie , Yokom Daniel , Lim Charles Henry , Jiang Maria , Ma Lucy Xiaolu , Chen Eric Xueyu , Liu Geoffrey , Knox Jennifer J. , Darling Gail Elizabeth , Yeung Johnathan Chi-Wai , Wong Rebecca , Hafezi-Bakhtiari Sara , Conner James , Rogalla Patrik , Jang Raymond Woo-Jun , Elimova Elena
Published: January 2019

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Background: There are no phase 3 trials comparing definitive chemoradiation (bimodality) versus. perioperative chemoradiation (trimodality) for locoregional esophageal/GEJ cancer. Methods: A retrospective analysis (2011-2015) compared bimodality and trimodality therapy in patients (pts) with locoregional esophageal/GEJ cancer treated with curative intent. Overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis. Uni- and multivariable Cox proportional hazards regression adjusted for patient and disease factors. Results: Of 108 patients, 82 (76%) were male. Mean ages were 69.5 ± 11.0 years (bimodality; N = 41) and 60.5 ± 11.1 years (trimodality; N = 67). For bimodality pts, 37% had adenocarcinoma and 63% had squamous cell carcinoma (SCC). For trimodality pts, 79% had adenocarcinoma and 21% had SCC (p < 0.0001). Bimodality pts received a higher radiation dose compared to trimodality pts (50.1 ± 6.7 vs. 45.2 ± 6.4 Gy). Median follow-up was 49.3 months. We found no significant OS difference between bimodality (27.0 months) and trimodality therapy (29.8 months) in the overall cohort (p = 0.57) (4 year OS rate: 42% vs. 38%). In the subgroup with adenocarcinoma histology, trimodality therapy significantly improved OS and DFS compared to bimodality (OS: 31.8 vs. 10.4 months, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.18-0.66, p = 0.001; DFS: 15.0 vs. 6.7 months; HR 0.39, 95%CI 0.21-0.73, p = 0.003). In the SCC subgroup, median OS and DFS were similar (OS: not reached vs. 29.2 months, p = 0.48; DFS: 27.0 vs. 24.0, p = 0.96). Using multivariable regression with AIC backward selection, the only retained prognostic factors were treatment modality (p = 0.06) and histology (p = 0.01). Conclusions: Our findings support preferential use of trimodality therapy for pts with adenocarcinoma histology given superior OS and DFS, whereas bimodality and trimodality therapy appeared comparable in pts with SCC histology. Pending confirmation in a larger series with longer follow-up, these findings suggest differential treatment algorithms for locoregional esophageal and GEJ cancer based on tumor histology.
Updated results of MSCMCC gastric cancer cohort: Indirect comparison between adjuvant chemoradiation and perioperative chemotherapy in gastric cancer patients.
Authors: Mydlowska Magdalena , Rybski Sebastian , Guzel Zuzanna , Kokoszyńska Katarzyna , Wyrwicz Lucjan
Published: January 2019

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Background: In the western world gastric cancer patients are either treated with peri-operative chemotherapy or adjuvant chemoradiation and no direct comparisons of these two treatment strategies are available. In our referral gastric cancer center (MSCMCC) we have changed in January 2013 the treatment protocol from adjuvant chemoradiation (like in INT-0116 study) to peri-operative chemotherapy (ECF or CF regimen). Here we report the updated results of single institution indirect comparison of two treatment strategies in the treatment of gastric cancer patients. Methods: 139 consecutive pts who underwent gastrectomy between 2009-2015 treated at MSCMCC were identified in a cohort manner (2009-2012 radiochemotherapy: 60 pts; 2013-2015- peri-operative chemotherapy: 79 pts). The patients’ clinical characteristics were collected from medical records. All patients were followed for relapse and survival with median observation time of 57 and 17 months for chemoradiation and peri-operative chemotherapy respectively. Results: The patients’ characteristics were similar in two groups including, age, sex, ECOG status and Lauren-classification types. DFS was similar in both arms with 47% of patients in radiochemotherapy and 63% of peri-operative chemotherapy patients without relapse at 2 years cut-off (p=0.17). OS was not significantly different between the groups (p=0.783). The toxicity profile was similar in two cohorts, with only leukopenia reported more often in the chemoradiation group (grade 3-4: 43.3% vs 12.3%. p<0.001) and low platelet count (grade 3-4: 6.7% vs 3.7%; p=0.19).There was a trend for excessive mucositis (p=0.067) and diarrhea (p=0.051) in the chemoradiation group. Vomiting more often observed in the peri-operative chemotherapy group (grade 3-4: 29.6% vs 13.3%, p=0.032). Notable, no differences were reported for neutropenia, fatigue and weigth loss. Conclusions: This indirect comparison suggests that results of two modalities are similar in terms of RFS. Further follow up is needed to assess the impact on survival. The toxicity profile favours the peri-operative chemotherapy.
Safety and efficacy of apatinib in elderly patients with advanced or metastatic gastric cancer in the post-marketing phase IV study: Subgroup analysis by age (Ahead-G201).
Authors: Wen Lu , Qin Shukui , Li Jin , Deng Wenying , Wang Junsheng , Zhang Guifang , Zhong Haijun , Jia Tongfu , Ba Yi , Bai Yuxian , Lin Xiaoyan , Wang Mei , Wang Lin , Liu Likun , He Yifu , Tao Min , Xie Congying , Ye Feng , Wu Xiang-yuan , Yang Jianwei
Published: January 2019

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Background: Old age is a potential negative predictor, and thus is of interest. Data from the ongoing post-marketing Phase IV trial were collected to assess the effect of age on apatinib treatment in 2000+ patients (pts) with chemotherapy-refractory advanced or metastatic gastric cancer. Methods: This subgroup analysis was stratified by age (<65 or ≥65 yrs). Both incidence of adverse events (AEs) and clinical outcomes were compared. Results: 725 pts <65 yrs and 312 pts ≥65 yrs were enrolled (data cut-off 2017/7/10). Differences in gender, ECOG PS, BMI, disease duration and metastatic sites were observed. 68.6% and 39.7% of pts aged ≥65 yrs experienced AEs of any grade and grade ≥3, which were not different with 70.2% and 40.0% of pts aged <65 yrs. The common AE profile was similar, but elderly pts had a higher incidence of hypertension, diarrhea and bilirubin increase (Table). Pts ≥65 yrs showed a higher objective response rate (12.2% vs. 9.9%) and longer overall survival (7.82 vs. 6.05 mos); however, there was no statistical difference. The disease control rate (79.6% vs. 65.4%; p=0.002) and progression free survival (PFS) (5.71 vs. 3.22 mos; p<0.001) of pts ≥65 yrs were significantly superior to pts <65 yrs. Multivariate Cox regression model confirmed that age ≥65 yr was a positive prognostic factor for PFS independent of baseline and treatment characteristics (HR: 0.67 [95%CI, 0.50–0.88]). Conclusions: Pts ≥65 yr is not at increased risk of overall AEs, but hypertension, diarrhea and bilirubin increase should be closely monitored. The PFS benefit in elderly pts will be validated. Clinical trial information: NCT02426034. [Table: see text]