bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel semi-empirical supervised model of vortex-induced vertical force on a flat closed-box bridge deck
Authors: Tian Xiaoxia , Yan Jingwen
Published: January 2019

This study presents a novel single-degree-of-freedom model of vortex-induced vertical force, which is based on supervised learning. There are three steps in the process of modeling. First, a hypothesis function based on the Taylor expansion is applied to describe the complicated of vortex-induced vertical force. Second, this hypothesis function is optimized by spectrum and correlation analysis. The terms in this function are deleted when they meet one of the following cases: the frequency amplitudes are close to 0; the correlation coefficients with the vortex-induced vertical force are less than 0.3; the correlation coefficients with other low-order terms are more than 0.8. Third, the validity and reliability of the optimized function are verified by comparative and residual analysis. The process of optimization makes the proposed model simple and well describes the main characteristics of vortex-induced vertical forces. Moreover, the maximum displacement is accurately predicted according to the proposed model. Simulation results show that the proposed model has a high coefficient of determination ( R2) compared with Scanlan’s and Zhu’s models, which means that the proposed model is more suitable to describe vortex-induced vertical forces.
Factors Associated With Patient Nonattendance in Rhinology Clinics
Authors: Hunter Benjamin N. , Cardon Brandon , Oakley Gretchen M. , Sharma Arun , Crosby Dana L.
Published: January 2019

Background

Nonattendance to clinical appointments is a global problem appreciated by clinicians with an ambulatory presence. There are few reports of nonattendance in otolaryngology clinics, and no reports on nonattendance for a single otolaryngology subspecialty.

Objective

To describe the no-show population in rhinology clinics.

Methods

A retrospective chart review was performed involving rhinology clinics from 2 academic medical centers in the United States. All patients who either attended their clinic appointment(s) or did not attend without previously cancelling from June 2016 to May 2017 were included. Data collected included patient demographics, appointment status, season and time of visit, insurance status, type of visit (new vs established), and provider seen.

Results

There were 2791 clinical appointments evaluated over a 12-month period at 2 rhinology clinics involving 4 fellowship-trained rhinologists. Ninety-two percent of patients kept their appointments, while 8% did not. Sex, season of visit, time of visit (am vs pm), type of visit, provider sex, provider location, or provider’s experience (<10 years vs ≥10 years) were not associated with patient’s attendance status. Univariate analysis showed that patient’s age ≤50 ( P = .001) and primary insurance type ( P < .001) were associated with nonattendance. Medicaid as the primary insurance type was associated with clinic nonattendance. Multivariable analysis showed that age ≤ 50 years, odds ratio (OR) 1.62 (95% confidence interval [CI] 1.14–2.30), P = .007, and primary insurance type (Medicaid: OR 3.75 [95% CI 2.58–5.45], P < .001) remained significant predictors of nonattendance.

Conclusion

Patients younger than 50 years and patients with Medicaid as the primary insurance types are associated with risk of missing rhinology clinic appointments. As a subspecialty, delivery of timely care and clinical efficiency could be improved by interventions directed toward improving attendance among this population.
Clinical and socio-demographic parameters contributing to treatment incompliance in Palestinian patients with diabetes
Authors: Salameh Basma , Salem Hiba , Abdallah Jihad M. , Batran Ahmad , Naerat Ehab Omar
Published: January 2019

Background:

This research study investigates the degree of medication-related satisfaction experienced by Palestinian patients with diabetes. In addition, this study further assesses the association between certain clinical and socio-demographic factors and the degree of satisfaction among the patients.

Methods:

This cross-sectional, descriptive study design consisted of 415 randomly selected patients from the Palestine Medical Complex (PMC), the Palestinian Ministry of Health Clinics, and from the Palestinian Diabetes Institute (also known as: Al-Bireh Medical Center). The Diabetes Medication Satisfaction (DiabMedSat) questionnaire measured patients’ satisfaction levels regarding their medications.

Results:

Odds ratios from binomial logistic analysis and the analysis of variance determined statistically significant correlations. The analysis has displayed the presence of significant associations between clinical and socio-demographic factors and treatment satisfaction. Significance was determined at p values < 0.05 and p values < 0.01.

Conclusion:

This research identified statistically significant associations between certain clinical and socio-demographic factors and diabetic patients’ satisfaction regarding their treatment. Addressing the concerns and difficulties experienced by the patients may impede treatment incompliance and hinder the development of complications, or at least postpone them.
Effect of nutritional status of pregnant women on birth weight of newborns at Butajira Referral Hospital, Butajira, Ethiopia
Authors: Woldeamanuel Gashaw Garedew , Geta Teshome Gensa , Mohammed Tesfaye Petros , Shuba Mulualem Belachew , Bafa Temesgen Abera
Published: January 2019

Back ground:

Maternal nutritional status influences the developmental environment of the fetus which consequently affects the birth weight of the newborn. However, the association between maternal nutritional factors and birth weight is complex and is not well characterized in Ethiopia.

Objective:

To assess the effect of maternal anthropometry and biochemical profile on birth weight of babies at Butajira Referral Hospital, Butajira, Ethiopia.

Methods and materials:

Laboratory-based cross-sectional study was conducted among 337 pregnant women at the hospital. Socio-demographic and obstetric characteristics were collected using pre-tested questionnaires. Blood sample was collected from each pregnant women for determination of total serum protein, total serum cholesterol and hemoglobin level. However, maternal dietary habits were not assessed in this study.

Results:

A total of 337 pregnant women were involved in the study. The mean (standard deviation) birth weight of the newborns was 3.14 ± 0.46 kg. After adjusting for different maternal factors, parity (p = 0.013), hemoglobin level (p = 0.046), pre-pregnancy body mass index (p < 0.001) and weight gain during pregnancy (p < 0.001) were positively associated with birth weight of the newborns, while the associations with total protein (p = 0.822) and total cholesterol (p = 0.423) were not significant.

Conclusion:

This study has shown that nutritional status of pregnant women as indicated by maternal anthropometry and hemoglobin level was associated with birth weight of the baby. Therefore, nutritional status of the pregnant women should be improved to reduce the risk of low birth weight.
The Longitudinal Association Between Social-Media Use and Depressive Symptoms Among Adolescents and Young Adults: An Empirical Reply to Twenge et al. (2018)
Authors: Heffer Taylor , Good Marie , Daly Owen , MacDonell Elliott , Willoughby Teena
Published: January 2019

Research by Twenge, Joiner, Rogers, and Martin has indicated that there may be an association between social-media use and depressive symptoms among adolescents. However, because of the cross-sectional nature of this work, the relationship among these variables over time remains unclear. Thus, in this longitudinal study we examined the associations between social-media use and depressive symptoms over time using two samples: 594 adolescents ( Mage = 12.21) who were surveyed annually for 2 years, and 1,132 undergraduate students ( Mage = 19.06) who were surveyed annually for 6 years. Results indicate that among both samples, social-media use did not predict depressive symptoms over time for males or females. However, greater depressive symptoms predicted more frequent social-media use only among adolescent girls. Thus, while it is often assumed that social-media use may lead to depressive symptoms, our results indicate that this assumption may be unwarranted.
Conferences, award ceremonies and the showcasing of ‘best practice’: A case study of the annual European Week of Regions and Cities in Brussels
Authors: Andersson Ida , Cook Ian R
Published: January 2019

This paper makes the case that conferences and award ceremonies are important means through which best practices are presented as being successful, transferable and transformative. To do this, it draws on the expanding literature on policy mobilities and a case study of the European Week of Regions and Cities conference and one of the centrepieces at the conference, the RegioStars awards ceremony. Organised by public bodies within the European Union and European Commission, these events take place annually in Brussels, and focus on best practice in regional and urban policy. The paper elaborates on its main argument in three ways. The first is that award ceremonies and conferences shape and are shaped by institutional, spatial and scalar dynamics. The second being that learning and educating are central to the performance of conferences, award ceremonies and the associated mobilisation of policies. The third argument is that such events have important consequences for those hosting the events.
Comment on “Shiatsu as an Adjuvant Therapy for Depression in Patients With Alzheimer’s Disease: A Pilot Study”
Authors: Lanza Giuseppe , Centonze Stella Silvia , Destro Gera , Vella Veronica , Bellomo Maria , Pennisi Manuela , Bella Rita , Ciavardelli Domenico
Published: January 2019

Recently, there has been increasing interest toward nonpharmacological approaches for dementia and associated clinical manifestations, such as depression, with the common goal to improve health and quality of life of both patients and caregivers. In this scenario, the role of Shiatsu is of clinical and research interest, although to date a definitive recommendation on a systematic use in clinical practice cannot be made. To overcome the heterogeneity of the previous studies, we tested Shiatsu as an add-on treatment for late-life depression in a dedicated community of patients with mild-to-moderate Alzheimer’s disease. We found a significant adjuvant effect of Shiatsu for depression in these patients and hypothesized a neuroendocrine-mediated action on the neural circuits implicated in mood and affect regulation. However, this finding must be considered preliminary and requires confirmation in larger-scale controlled studies, possibly extending the range of outcome measures and including predictors of response. Future investigations should also include an objective assessment of the hypothalamus-pituitary-adrenocortical axis functioning. Nevertheless, starting from this pilot study, we suggest that a customized protocol applied for an adequate period in a controlled sample will represent a non-invasive and feasible advance for promoting patients’ mood and, possibly, slowing cognitive decline.
Research on application of multimedia image processing technology based on wavelet transform
Authors: Sui Kun , Kim Hyung-Gi
Published: January 2019

With the development of information technology, multimedia has become a common information storage technology. The original information query technology has been difficult to adapt to the development of this new technology, so in order to be able to retrieve useful information in a large amount of multimedia information which has become a hot topic in the development of search technology, this paper takes the image in the multimedia information storage technology as the research object, uses the wavelet transform to divide the picture into the advantages of the low-frequency and high-frequency characteristics, and establishes the multimedia processing technology model based on the wavelet transform. The simulation results of face, vehicle, building, and landscape images show that different wavelet basis functions and different layers of images are decomposed, and the retrieval results and retrieval speed of images are different, When taking four layers of wavelet decomposition, the cubic b-spline wavelet as the wavelet basis function makes the classification result optimal, and the accuracy rate is 89.08%.
Advances in the treatment of traumatic scars with laser, intense pulsed light, radiofrequency, and ultrasound
Authors: Fu Xiujun , Dong Jiying , Wang Shen , Yan Min , Yao Min
Published: January 2019

Traumatic scarring is one of the most common complications after soft tissue injury caused by burns and trauma, which affects tens of millions of people worldwide every year. Traumatic scars diminish the quality of life due to disfigurement, symptoms of pain and itch, and restricted motion. The pathogenesis and pathophysiology of traumatic scar remain elusive. The management for traumatic scars is comprised of surgical and non-surgical interventions such as pressure therapy, silicone, corticosteroid, and radiotherapy, which are chosen by clinicians based on the physical examinations of scars. Recently, great progress in treating traumatic scars has been achieved by the development of novel technologies including laser, intense pulsed light (IPL), radiofrequency, and ultrasound. The aim of this review article was to summarize the advances of these technologies for traumatic scars intervention.
Do patients get better? A review of outcomes from a crisis house and home treatment team partnership
Authors: Butt Mohsin Faysal , Walls David , Bhattacharya Rahul
Published: January 2019

Aims and method

The Tower Hamlets Crisis House (voluntary sector), in partnership with the local home treatment team, offers a brief residential alternative to psychiatric hospital admission. Here, we review clinician-reported (Health of the Nation Outcome Scales; HoNOS) and patient-reported (DIALOG) outcome scores collected from successive admissions between June 2015 and December 2016, to assess the effectiveness of the service model. We identified 153 successive admissions, and of these, 85 (55.6%) and 91 (59.5%) patients completed both admission and discharge DIALOG and HoNOS questionnaires, respectively. We analysed ten out of twelve HoNOS domains and eight patient-reported outcome measure DIALOG domains.

Results

We found a statistically significant improvement in nine out of ten domains of HoNOS and three out of eight domains of DIALOG.

Clinical implications

A partnership between a home treatment team and crisis house can result in positive outcomes for patients, as determined by both clinicians and patients.

Declaration of interest

None.
Survival outcomes comparable between endoscopic resection and surgical resection for T1b esophageal adenocarcinoma.
Authors: Datta Samit Kumar , Belini Geoffrey , Singh Maharaj , Papenfuss Wesley Allan , Hernandez Lyndon , Sanchez Federico Augusto , Weese James L. , Chevinsky Aaron , Guda Nalini
Published: January 2019

100

Background: Current guidelines recommend esophagectomy for submucosal T1b esophageal cancer. Data regarding efficacy of endoscopic resection (ER) of T1b esophageal cancer are limited. Our goal was to compare survival outcomes of ER as opposed to conventional surgical resection (SR) in a large cohort of patients with T1b cancers from a large national database. Methods: Data were obtained from the large national database maintained by the Commission on Cancer. Patients with T1b esophageal cancers with clinical stage 1A and 1B who underwent ER and SR between 2010 and 2014 were identified using the American Joint Committee on Cancer (AJCC Version 7). Patients undergoing ER and SR were identified. Patients who underwent neoadjuvant therapy or had incomplete survival data were excluded. The primary outcome was survival for age and Deyo-Charlson comorbidity index. We also evaluated 30-Day and 90-Day Mortality outcomes. Results: There were 1071 patients with T1b esophageal cancer with complete mortality data. After selecting and excluding patients above, 141 patients were identified who underwent EET and 286 who underwent esophagectomy. Average age was 71.5 years in the ER group and 64.5 years in the SR group (p < 0.001). In the group, 30-Day mortality after surgery was 1/134 (0.8%, 7 missing) compared to surgery with 30-Day mortality of 6/283 (2.1%, 3 missing) (P = 0.308). 90-Day mortality after surgery for the ER group was 3/134 (2.2%, 7 missing) compared with the surgery with 90-Day mortality of 11/281 (3.9%, 5 missing) (P = 0.377). Adjusted for age and Deyo-Charlson comorbidity index, there was a HR of 1.051 (95% CI 0.695-1.589, p = 0.815) for mortality associated with surgery compared with ER. Mean follow-up of 42.6 months for the ER group and 55.7 months for surgery group. Conclusions: Based on the data from a large national cancer data base ER seems to be comparable to SR in terms of short term (30 day and 90 day) mortality. Overall survival seems to be similar in both groups Prospectively done randomized studies comparing ER versus SR are desirable.
Endoscopic submucosal dissection versus surgery for undifferentiated-type early gastric cancer: A meta-analysis.
Authors: Kim Byung-Wook , Ma Dae Won , Kim Joon Sung
Published: January 2019

111

Background: It is still controversial to treat undifferentiated early gastric cancer by endoscopic submucosal dissection (ESD). Therefore, we aimed to perform a meta-analysis to investigate long-term outcomes of ESD and surgery for undifferentiated early gastric cancer. Methods: PubMed, Cochran Library, and EMBASE were used to search for relevant researches comparing endoscopic submucosal dissection and surgery for undifferentiated early gastric cancer. The methodological quality of the included publications was evaluated using the Risk of Bias Assessment tool for Non-randomized Studies. The overall survival rate, recurrence rate, adverse event rate, and complete resection rate were explored, and the odds ratio (OR) and 95% confidence interval (CI) were estimated. Results: This meta-analysis enrolled five studies, with 376 and 1148 participants undergoing ESD and surgery, respectively. Overall survival rate did not show significant difference between ESD and surgery group (OR 0.57, 95% CI 0.18 – 1.83, P = 0.34). However, ESD was associated with higher recurrence rate (OR 11.57, 95% CI 5.07 – 26.39, P < 0.001) and lower complete resection rate (OR 0.03, 95% CI 0.01 – 0.11, P < 0.001). Adverse event rate was similar between two groups (OR 0.95, 95% CI 0.46 – 1.96, P = 0.88). Conclusions: Despite higher recurrence rate and lower complete resection rate, ESD demonstrated similar overall survival rate and adverse event rate in the treatment of undifferentiated early gastric cancer compared to surgery.
The efficacy of splenic hilar lymph node dissection in advanced gastric cancer.
Authors: Toriumi Tetsuro , Makuuchi Rie , Kamiya Satoshi , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori
Published: January 2019

112

Background: Total gastrectomy with splenectomy for splenic hilar lymph node (No.10 LN) dissection had been a standard treatment for proximal advanced gastric cancer in Japan. The efficacy of No. 10 LN dissection with splenectomy for advanced gastric cancer without the greater curvature invasion was denied by a randomized controlled trial, JCOG0110. However, JCOG0110 did not include the patients with greater curvature invasion. Therefore, we aimed to clarify the role of No. 10 LN dissection in patients with proximal advanced gastric cancer invading the greater curvature. Methods: A total of 273 patients with proximal advanced gastric cancer who underwent curative total gastrectomy with splenectomy from 2002 to 2013 were included. We reviewed esophagogastroduodenoscopy and upper gastrointestinal series for evaluation of clinical tumor localization and classified the patients into with greater curvature invasion group (G group, n = 108) or without invasion group (NG group, n = 165). The incidence and therapeutic value index (TVI) of No. 10 LN were compared between the groups. Results: Patients in the G group had more advanced T stage, undifferentiated histology, and larger tumor size than those in the NG group. However, there was no difference in survival between the groups; 5-year overall survival (5-OS) was 66.3% in the G group and 69.1% in the NG group (p = 0.570). The incidence of No.10 LN metastasis was significantly higher in the G group (10.2%) than that in the NG group (3.0%) (p = 0.028). TVI for No.10 LN dissection was higher in the G group (5.6) than that in the NG group (0.6). The survival of the patients with No.10 LN metastasis tended to be better in the G group, although it did not reach statistical significance (5-OS: 54.5% in G group vs. 20.0% in NG group, p = 0.336). Conclusions: It is suggested that splenic hilar LN dissection has a favorable effect on survival in patients with proximal gastric cancer invading the greater curvature.
Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: A retrospective real world study.
Authors: Chen Yang , Dai Guanghai
Published: January 2019

113

Background: Although the clinical trial WJOG7112G was failed to prove weekly paclitaxel with trastuzumab in patients with HER2-positive gastric or gastro-esophageal junction (GEJ) cancer refractory to trastuzumab is better than paclitaxel alone, there are limited data concerning efficacy of continuing trastuzumab beyond first-line progression in the real world. Methods: This retrospective study included all consecutive patients with HER2-positive advanced gastric or GEJ adenocarcinoma who received a chemotherapy with trastuzumab in first-line, or second-line, or third-line therapy between 2010 and 2016 in Chinese People’s Liberation Army General Hospital. Progression-free survival (PFS) and overall survival (OS) were estimated from the initial chemotherapy. Results: A total of 67 patients (median age, 59 years; male, 71.6%) with HER-2 positive advanced gastric or GEJ adenocarcinoma treated with chemotherapy plus trastuzumab initially in first (n = 50), second (n = 13), or third (n = 4) line of therapy were included. The median OS of trastuzumab for initial first-line, second-line, or third-line treatment was 16.7 months, 14.2 months, and 13.2 months, respectively (P = 0.83). In patients initially using trastuzumab in first-line therapy, the continuation (n = 19) versus discontinuation (n = 31) of trastuzumab beyond first-line progression was significantly associated with an improvement of median PFS (3.4 versus 1.9 months; P = 0.02), but not OS (19.0 versus 16.4 months; P = 0.13). In the multivariate analysis including the ECOG PS, number of metastatic sites and chemotherapy regimen, the continuation of trastuzumab beyond progression remained significantly associated with longer PFS (HR, 0.77; 95% CI, 0.41-0.93; P = 0.04), but not OS (HR, 0.85; 95% CI, 0.56-1.22; P = 0.24). Conclusions: This study suggests that HER-2 positive advanced gastric or GEJ adenocarcinoma patients could benefit from trastuzumab no matter when they start receiving trastuzumab. The continuation of trastuzumab beyond progression has clinical benefit in patients with HER2-positive advanced gastric cancer for PFS, but not for OS. Large scale prospective randomized validation is warranted.
The preventive effect of neoadjuvant therapy on poor long-term outcomes of postoperative complications in patients with esophageal squamous cell carcinoma: A retrospective cohort study.
Authors: Takeuchi Masashi , Kawakubo Hirofumi , Mayanagi Shuhei , Irino Tomoyuki , Fukuda Kazumasa , Nakamura Rieko , Wada Norihito , Kitagawa Yuko
Published: January 2019

120

Background: Postoperative complications have a negative impact on overall survival after esophagectomy because systemic inflammation may induce residual cancer cell growth. A solution that could suppress micrometastasis is neoadjuvant therapy; however, to date, no study has shown that neoadjuvant therapy suppresses the proliferation of cancer cells due to postoperative complications after esophagectomy. To investigate the preventive effect of neoadjuvant therapy on poor long-term outcomes of postoperative complications in patients with esophageal squamous cell carcinoma. Methods: In total, 509 patients who underwent esophagectomy for primary esophageal squamous cell carcinoma were included in this retrospective cohort study. We investigated the relationship between complications, such as pneumonia, and long-term oncologic outcomes with and without neoadjuvant therapy. Results: Among all the patients, the 3-year overall survival (OS) rate was 68.4% and the disease-free survival (DFS) rate was 58.1%. The patients were categorized into two groups: the neoadjuvant therapy (+) group (n = 227) and the neoadjuvant therapy (−) group (n = 282). Among patients not undergoing neoadjuvant therapy, the patients with pneumonia, atrial fibrillation, pyothorax, or chylothorax had significantly poorer OS and DFS than patients without these complications. However, among patients undergoing neoadjuvant therapy, there were no significant differences in long-term outcomes, regardless of the presence of complications. In multivariate analyses, pneumonia (p = 0.014) and chylothorax (p = 0.006) were identified as predictors of death in the neoadjuvant therapy (−) group. Conclusions: In patients with esophageal squamous cell carcinoma, the negative impact of postoperative complications can be reduced by performing neoadjuvant therapy.
Pre-treatment pulmonary function testing as a predictor of cardiopulmonary toxicity in esophageal cancer patients treated with trimodality therapy.
Authors: Smith Na Lu , Hallemeier Christopher Leigh , Spears Grant M. , Halfdanarson Thorvardur Ragnar , Neben-Wittich Michelle A. , Harmsen William S. , Mahipal Amit , Blackmon Shanda H , Haddock Michael G. , Merrell Kenneth
Published: January 2019

121

Background: We evaluated the role of pre-treatment pulmonary function testing (PFT) in predicting the likelihood of cardiac and/or pulmonary toxicity for esophagus cancer patients receiving trimodality therapy. Methods: From 2007 to 2013, 64 patients with esophageal cancer received trimodality therapy at a single tertiary center with pre-treatment PFTs. The odds ratio of pre-treatment PFT as a predictor of cardiopulmonary toxicity was assess with univariate analysis (UVA). FEV1 (forced expiratory volume in 1 second) and DLCO (diffusion capacity for carbon monoxide) were assessed per 0.5-unit decrease. Percent FEV1 and DLCO predicted were assessed per 10% decrease. Results: The median age was 62 years (range, 41-79) with 88% male patients. A total of 70% of patients had adenocarcinoma with 66% having stage 3 disease. Most patients were former (43%) or current smokers (32%) and 18% had COPD. One or more cardiac comorbidities were observed in 54% of patients. The median RT dose was 50 Gy and the most frequent concurrent chemotherapy was cisplatin/5FU (53%). The median pre-treatment FEV1 and DLCO was 2.8 liters (range, 1-4.9) and 22.5 mL/min/mmHg (range, 17.2-25.5), respectively. This correlated to a median percent predicted value for FEV1 and DLCO of 85% (range, 30-124%) and 81.5% (range, 49-119%), respectively. The overall rate of any cardiac and pulmonary toxicity was 35% and 50%, respectively. Percent predicted value of both FEV1 and DLCO was statistically associated with pulmonary but not cardiac toxicity (Table). Conclusions: Patients with compromised pre-treatment pulmonary function are at higher risk of developing post-treatment pulmonary toxicities. Pulmonary function testing should be routinely performed prior to initiation of trimodality therapy for patient risk stratification. [Table: see text]
Comparative effectiveness of nivolumab (NIVO) relative to standard of care (SOC) for advanced/metastatic (adv/met) gastric or gastroesophageal junction cancer (GC/GEJC): A simulated treatment comparison (STC).
Authors: Chau Ian , Ayers Dieter , Goring Sarah , Keeping Sam , Goulding Rebecca , Cope Shannon , Chamot Eric , Le Hannah , Xu Yanqing , Abraham Pranav , Korytowsky Beata
Published: January 2019

128

Background: The prognosis of adv/met GC/GEJC among patients receiving third and later lines (L) of therapy is poor, and effective treatment options are limited. The study objective was to estimate the relative effect of NIVO versus SOC for overall survival (OS), in the US among adv/met GC/GEJC patients who received ≥ 3L therapy. Methods: A STC was performed using individual patient data from the single-arm CheckMate 032 (CM032) trial, and the Flatiron Health (FH) database. Eligible patients had adv/met GC/GEJC and received NIVO (CM032) or SOC (FH) as ≥ 3L therapy; all patients met CM032 eligibility criteria. A regression model of OS was fit to CM032 data using prognostic factors and treatment effect modifiers identified through a systematic literature review. The regression model was used to predict OS for NIVO, using Flatiron patient characteristics as covariates, and to estimate the expected outcome if NIVO had been available in the Flatiron population. The observed and predicted OS for NIVO was compared against the observed OS for SOC to generate naïve and adjusted hazard ratio comparisons of NIVO vs SOC. Results: In total, 42 and 43 patients were included from CM032 and Flatiron, respectively. In the Cox model, 19 prognostic factors were considered and the final model adjusted for 6, based on data availability across the two sources: ECOG, alkaline phosphatase (ALP) and hemoglobin, sex, prior surgery, and tumor location. Median OS was 8.97 months in the NIVO group and 5.61 months in the SOC group. The STC adjustment yielded a hazard ratio of 0.66 (95% CI: 0.41 to 1.06) for NIVO vs SOC compared to the naïve estimate of 0.64 (0.40 to 1.03). Sensitivity analyses confirm this result. Conclusions: In the absence of head-to-head data, this study suggests that NIVO may confer a benefit in terms of OS versus SOC for patients with GC/GEJC in ≥ 3L therapy in the US setting. Despite the inherent limitations of using non-randomized comparisons of clinical trial data and real-world evidence, these findings provide insight into the potential benefit of novel agents such as NIVO.
Phase I/II study of ramucirumab plus nivolumab in patients in second-line treatment for advanced gastric adenocarcinoma (NivoRam study).
Authors: Hara Hiroki , Shoji Hirokazu , Takahari Daisuke , Esaki Taito , Machida Nozomu , Nagashima Kengo , Aoki Kazunori , Honda Kazufumi , Miyamoto Takahiro , Boku Narikazu , Kato Ken
Published: January 2019

129

Background: Nivolumab (Nivo) showed a survival benefit in salvage line of advanced gastric cancer (AGC) patients in ATTRACTION-2 trial. Based on synergistic anti-tumor effects by simultaneous blockade of PD-1 and VEGFR-2, this phase 1/2 study was conducted to investigate the safety and efficacy of Nivo plus ramucirumab (Ram) in the second line chemotherapy for AGC. Methods: AGC patients with measurable lesions, PS 0-1, disease progression on first line chemotherapy containing platinum were eligible. Patients received Nivo (3mg/kg, Q2W) and Ram (8mg/kg, Q2W) until unacceptable toxicity or disease progression. After feasibility was evaluated in six patients (phase 1 part), additional 40 patients were required in a phase 2 part with the primary analysis (expected 6-months progression-free survival (PFS) rate of 36%, threshold of 18%, one-sided alpha level of 10%, power of 90%). Secondary endpoints included overall response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and safety. Results: 46 AGC patients (median age 66 years, PS 1 40%) were enrolled. No dose limiting toxicities were observed in the phase 1 part. With median follow up time of 10.2 month, 6-month PFS rate was 37.4% (90% confidential intervals: 25.7-49.2%), which met the primary endpoint of the phase 2 part. ORR/DCR were 26.7%/62.2%. Median PFS/OS were 2.9/9.0 months. Among all enrolled patients, grade 3 or 4 treatment related adverse events were hypertension (n = 2), diarrhea (n = 2), perforation at jejunum (n = 1), hemorrhage (n = 1), colitis (n = 1), pancreatitis (n = 1), liver dysfunction (n = 1), cholangitis (n = 1), hematoma (n = 1), neutropenia (n = 1) and proteinuria (n = 1). There were no treatment-related deaths. Conclusions: Combination of Nivo and Ram showed promising antitumor activity and mild toxicity profile for second line AGC, which is worth evaluating in a further confirmatory study. Clinical trial information: NCT02999295.
Impact of peripheral neuropathy induced by platinum in first-line chemotherapy on second-line chemotherapy containing paclitaxel for advanced gastric cancer.
Authors: Otsuka Ryo , Iwasa Satoru , Yanai Takako , Shoji Hirokazu , Honma Yoshitaka , Okita Natsuko , Takashima Atsuo , Kato Ken , Hashimoto Hironobu , Makino Yoshinori , Sekiguchi Masatoshi , Ishizone Yoshimasa , Boku Narikazu , Yamaguchi Masakazu
Published: January 2019

132

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of platinum and paclitaxel (PTX) persisting for long time. In the Gastric Cancer Treatment Guideline (Japanese Gastric Cancer Association, 2018), first-line chemotherapy with fluoropyrimidine plus platinum followed by taxane based chemotherapy is recommended. It is not well known how much CIPN by platinum in the first-line chemotherapy affect the tolerability of second-line chemotherapy containing PTX (second-PTX). Methods: The subjects were advanced gastric cancer patients who received second-PTX after the platinum-containing first-line chemotherapy between March 2015 and June 2018. Patients were divided into two groups according to prior platinum: oxaliplatin (prior L-OHP) and cisplatin (prior CDDP) groups. CIPN was graded according to CTCAE ver.4. Severity of CIPN, dose reduction and discontinuation due to CIPN during the second-PTX were compared between the two groups. Results: 109 patients (50 prior L-OHP group and 59 prior CDDP group) were included in this retrospective study. The severity of CIPN just before second-PTX was 46% for grade 1 and 12% for grade 2 in the prior L-OHP group, and 8.5% and 0% in the prior CDDP group. The initial dose of PTX was reduced in 59 % of the prior L-OHP and in 39 % of the prior CDDP group. The worst grade of CIPN during second-PTX was 40% for grade 1, 34% for grade 2, 14% for grade 3 in the prior L-OHP group, and 33.9%, 20.3%, 0% in the prior CDDP group. Median time to grade 2 neuropathy during second-PTX was 2.5 months in the prior L-OHP group and 8.6 months in the prior CDDP group (p = 0.0004). CIPN-related dose reduction of PTX were 12.0% in the prior L-OHP group and 3.4% in the prior CDDP group (p = 0.177). Discontinuation of second-PTX due to CIPN were 10.0% in the prior L-OHP group and 5.1% in the prior CDDP group (p = 0.541). Conclusions: The severity of CIPN and tolerability of the second-PTX may be affected by prior platinum, L-OHP or CDDP, in the first-line chemotherapy for advanced gastric cancer.
Tislelizumab in combination with chemotherapy for the treatment of Chinese patients (pts) with esophageal squamous cell carcinoma (ESCC): Results from one cohort of an ongoing phase 2 study.
Authors: Xu Nong , Yuan Xianglin , Wang Buhai , Bai Yu-Xian , Li En Xiao , Li Yanyan , Wang Huanli , Xu Jianming
Published: January 2019

14

Background: Tislelizumab, a humanized IgG4 mAb with high affinity and specificity for PD-1, is specifically engineered to minimize binding to FcγR on macrophages, thereby abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti-PD-1 therapy. This phase 2 study assessed the safety and tolerability of tislelizumab combined with chemotherapy as first-line therapy in pts with gastric cancer and ESCC; the results of the ESCC cohort are presented here. Methods: Chinese pts with inoperable, locally advanced ESCC were treated with tislelizumab (200 mg IV Q3W), cisplatin (80 mg/m² IV Q3W for up to six cycles), and fluorouracil (800 mg/m²/d, days 1-5 IV Q3W for up to six cycles). Safety/tolerability of the combination regimen was assessed by monitoring adverse events (AEs) per NCI-CTCAE v4.03 criteria. Results: As of 13 June 2018, 15 pts (median age, 61 yrs; male/female, 14/1) were enrolled. The median treatment duration was 108 days (range 21-201). The mean (Q1, Q3) dose intensity was 0.92 (0.91, 0.97) for tislelizumab, 0.91 (0.90, 0.98) for cisplatin, and 0.78 (0.72, 0.97) for 5-FU. Among 15 pts, AEs occurring in > 2 pts reported to be related to chemotherapy and/or tislelizumab are detailed in the table. One pt experienced grade 5 hepatic dysfunction (possibly from progressive disease and underlying hepatitis) which was possibly related to study treatment, according to the investigator. Four pts discontinued study treatment due to AEs (grade 3 tracheal fistula, grade 3 lung infection, grade 2 pneumonitis, and grade 3 increase in aspartate aminotransferase). The antitumor activity data remain unmatured and may be updated later. Conclusions: Tislelizumab combined with chemotherapy was generally well tolerated in pts with advanced ESCC. Clinical trial information: NCT03469557. [Table: see text]
Neoadjuvant nivolumab plus concurrent chemoradiation in stage II/III esophageal/gastroesophageal junction cancer.
Authors: Kelly Ronan Joseph , Smith Kellie Nicole , Anagnostou Valsamo , Thompson Elizabeth , Hales Russell K. , Battafarano Richard J. James , Voong K Ranh , Yang Stephen C. , Feliciano Josephine Louella , Shin Eun Ji , Hu Chen , El Asmar Margueritta , Chan Hok Yee , Velculescu Victor E. , Sears Cynthia , Pardoll Drew M. , Amjad Ali Imran , Guerrieri Patrizia , Jobe Blair Anderson , Zaidi Ali Hussainy
Published: January 2019

142

Background: Neoadjuvant chemoradiation (cRT) prior to surgical resection in stage II/III esophageal/gastroesophageal junction (E/GEJ) cancer results in a complete pathologic response rate (pCR) of 20-30%. The appearance of favorable microenvironment features (enhanced tumor infiltrating lymphocytes, perivascular lymphocytes and tertiary lymphoid structures) after induction therapy in resected EC suggest early stage tumors may respond favorably to immune based therapy and in particular to PD-1 blockade when combined with cRT. Methods: In this pilot study, we administered 2 cycles of induction nivolumab (N) q2 weekly prior to standard of care carboplatin/paclitaxel/radiation plus 3 additional cycles of N on week 1, 3 and 5 of cRT. An Ivor-Lewis esophagectomy (E/MIE) was performed 6-10 weeks after the last IO dose. The primary endpoints of the study were safety and feasibility. We also evaluated the pCR, survival and temporal dynamics of T cell receptor clonotypes. Results: Between August 2017 and July 2018, 16 patients were enrolled on study. Induction N and neoadjuvant N combined with cRT in stage II/III E/GEJ cancers has an acceptable toxicity profile and was not associated with delays in surgery. Toxicities of note include steroid responsive grade 3 dermatitis (1/16), grade 3 hepatitis (1/16) and no cases of pneumonitis. To date, 10 patients with E adenocarcinoma have had an E/MIE and the pCR is 4/10 (40%). T cell receptor sequencing of the tumor bed and serial peripheral blood T cells revealed high peripheral representation of tumor-associated T cells. In one notable case, the highest-frequency intratumoral clone decreased in frequency in the peripheral blood upon treatment and rapidly increased after surgical resection, potentially signifying trafficking to the tumor site. Conclusions: Induction N and N combined with cRT has limited side-effects, did not result in surgical delay or enhanced surgical morbidity/mortality and induced a pCR of 40% in stage II/III E/GEJ cancers. Additional efficacy data on the full cohort and more in depth correlative studies will be presented to validate systemic activation of anti-tumor T cell responses. Clinical trial information: NCT03044613.
Impact of antibiotic use on response to treatment with immune checkpoint inhibitors.
Authors: Khan Uqba , Peña Cristian , Brouwer Julianna , Hoffman Katherine , Choudhury Arindam Roy , Zhang Chao , Thakkar Prashant , Betel Doron , Sarkar Sandipto , Sonnenberg Gregory , Saxena Ashish , Shah Manish A.
Published: January 2019

143

Background: There is an emerging evidence that the gut microbiome may influence anti-tumor immune response during treatment with checkpoint inhibitors (CPIs). A number of factors can cause gut microbiome dysbiosis including the use of antibiotics (ABX). We hypothesized that the use of ABX during immunotherapy can adversely affect the efficacy of CPIs. We explored the prevalence of ABX use amongst patients (pts) using CPIs, and whether the use of ABX influences the response to CPIs. Methods: We performed an institutional retrospective review of all the pts treated with CPIs from 2/2015-3/2018. A patient was considered to have used ABX if he or she was prescribed ABX within 6 months before or after, initiating CPIs. Statistical analysis was done using logistic regression with overall response rate (ORR) (CR, PR and SD) as the outcome. 9 separate analyses were done: one for each temporality (30 days, 60 days, 6 months) and use-order (before, after, neither) combination. Odds ratios for ORR as univariate analysis, and adjusted for age and sex; and adjusted for age, sex, and tumor type were calculated. Results: Out of 242 pts, 111 were lung, 36 bladder, 35 renal, 16 gastrointestinal and 44 other cancers. 50% (121) pts received nivolumab, 28% (68) pembrolizumab and 21% (52) atezolizumab. 75%, 46% and 32% of the pts received ABX within 6 months, 60 days and 30 days of starting CPIs. Only ABX use in the first 30- or 60-days following CPI initiation was associated with inferior ORR (OR 0.42 [95% CI:0.23,0.76] p = 0.005 for 60-days). ABX use prior to initiation of CPI at any time point, or ABX use in the first 6 months of CPI use did not impact CPI efficacy, Table 1. Conclusions: ABX use within the first 60 days of starting CPI therapy is prevalent (32%). This study suggests that the use of ABX within 60 days following initiation of CPIs significantly negatively impacts the ORR. Unnecessary usage of ABX should be avoided, especially during the early phase of starting CPIs. [Table: see text]
Timing after neoadjuvant therapy predicts mortality in patients undergoing esophagectomy.
Authors: Maramara Taylor , Huston Jamie , Shridhar Ravi , Meredith Kenneth L
Published: January 2019

157

Background: Neoadjuvant therapy (NT) prior to esophagectomy has dramatically improved survival in patients with esophageal cancer. Currently, most surgeons will allow 6-12 weeks after NT prior to recommending esophagectomy. Given that complete pathologic response (pCR) correlates to an improvement in survival, some have advocated a longer interval should be entertained to increase the pathologic response. The impact of an expanded NT-surgery timing is not currently well understood. Methods: Utilizing the National Cancer Database, we identified patients with esophageal cancer who underwent NT followed by esophagectomy. Patients were divided into 4 time intervals: < 6 wks, 6-12 wks, 3-6 mo, and > 6 mo. Mann-Whitney U, Kruskal Wallis, and Pearson’s Chi-square test were used as appropriate. Survival analyses were performed using the Kaplan-Meier method and p < 0.05 was considered significant. Results: We identified 9,256 patients who received NT followed by esophagectomy. There were 8,053 (87%) adenocarcinomas and N = 1203 (13%) squamous cell carcinomas. 7,858 (84.9%) were male and 1,398 (15.1%) female with a median age was 62 (24-88). R0 resections decreased as the NT-Surgery interval increased: < 6 wks, 6-12 wks, 2-6 mos, and > 6 mos at 93%, 94.1%, 94.1%, and 86.2% respectfully p = 0.004. Additionally, the median lymph nodes harvested decreased as timing increased: 12, 12, 10, and 9 p < 0.001 and the median nodes positive decreased as timing increased 1.5, 1.3, 1.1, and 2.4 p = 0.01. The complete response rates increased as timing increased 15.5%, 20.1%, 22.7%, and 25.8% p < 0.001. However, this improvement in pCR did not translate into an increase in median survival: < 6 wks 40.9 mos, 6-12 weeks 38.5 mos, 3-6 mos 34.8 mos, and > 6 mos 39.8 mos of survival, p = 0.94 90-day mortality increased as the timing from neoadjuvant therapy increased: 6.4%, 7.9%, 9.4%, and 16.0%, respectively p = 0.001. Conclusions: Our data demonstrates that patients who have a prolonged NT- esophagectomy interval will have a substantial increase in 90-day mortality. While there was an increase in pathologic complete response rates, this did not translate into an improvement in survival. The current recommendations of a NT-surgery timing of 6-12 weeks should remain.
Which is the best procedure for the treatment of gastric cancer in the upper stomach?
Authors: Sato Reo , Tokunaga Masanori , Watanabe Masahiro , Sugita Shizuki , Tonouchi Akiko , Tanaka Yuri , Akimoto Eigo , Ono Takeshi , Kameyama Akira , Kaito Akio , Kinoshita Takahiro
Published: January 2019

159

Background: The incidence of upper-third early gastric cancer (EGC) has been increasing in East Asia. Although total gastrectomy (TG) has been a standard treatment for upper-third EGC, proximal gastrectomy (PG) or distal gastrectomy (DG) can be indicated for some selected patients. Theoretically, the more we preserve stomach volume, the better postoperative quality of life will be. However, this issue is not fully investigated. The aim of this study was to clarify the most suitable procedure for upper-third EGC. Methods: This study included 187 patients who underwent TG (n = 20), PG (n = 138), or DG (n = 29) for cT1N0 upper-third gastric cancer between 2009 and August 2017. Surgical outcomes, including bodyweight change one year after the surgery, were retrospectively compared among surgical procedures. DG was generally selected if the distance between the esophagogastric junction (EGJ) and proximal margin of the tumor was more than 20 mm. PG was chosen if at least the distal half of the stomach could be preserved. Otherwise, TG was performed. Results: Background characteristics and proportion of laparoscopic approach were not different among the groups. The duration of surgery was not significantly different, but intraoperative blood losswas significantly less in DG than PG (19 vs. 39 g, p = 0.02). The incidence of Clavien-Dindo classification grade IIIa or more anastomosis-related complications was less frequent in DG (3.4%) than in PG (15.9%, p = 0.13) or TG (10%, p = 0.56), although the differences were not statistically significant. Albumin and hemoglobin levels one year after surgery were not significantly different among the groups. Bodyweight loss one year after surgery was less in DG (11.1%) than in PG (14.6%, p = 0.03) or TG (16.6%, p < 0.01). Conclusions: DG was a safe procedure with less bodyweight loss, and thus preservation of the EGJ should be considered for all patients with tumors at least 2 cm apart from the EGJ. If the distance between EGJ and tumor is less than 2 cm, PG or TG will be indicated. However, surgical outcomes between PG and TG in this study were not different, and therefore, further investigations including long term quality of life are necessary.