bluuebunny/crossref_metadata_2025 huggingface dataset:
Union Formation Among Youth in Sub-Saharan Africa: Does Early Sexual Debut Matter?
Authors: Somefun Oluwaseyi Dolapo , Odimegwu Clifford , Simo Fotso Arlette , Adebayo Kudus
Published: January 2019

Is early sexual debut a key determinant of union formation among young adults in sub-Saharan Africa (SSA)? Using a life-course perspective, this article analysed data from Demographic and Health Surveys of selected countries to examine the relationship between sexual behaviour measured by age at first sex and the likelihood of cohabitation or marriage. These associations were examined using binary and multinomial logistic regressions. Findings suggest that the decision for males to cohabit, get married, or remain single differs by age at sexual debut, although there is no similar evidence for females. While an understanding of the patterns revealed is significant for policy formulation on union formation of young people, it can help to reduce the reproductive health challenges among youth in SSA.
Statistical Analysis of Dependent Observations in the Orthopaedic Sports Literature
Authors: LeBrun Drake G. , Tran Tram , Wypij David , Kocher Mininder S.
Published: January 2019

Background:

Orthopaedic research may involve multiple observations from the same patient because of bilateral joint involvement, multiple disease sites, or recurrent disease episodes. These situations violate statistical independence and need to be accounted for via appropriate statistical techniques. Failing to account for nonindependence may lead to biased and overly precise effect estimates.

Purpose:

To determine the degree to which orthopaedic sports medicine studies analyze dependent observations and the proportion of these failing to account for nonindependence.

Study Design:

Cross-sectional study.

Methods:

Clinical studies published in The American Journal of Sports Medicine from 2012 to 2017 were reviewed. Studies reporting nonindependent observations because of multiple extremity involvement or multiple disease episodes were identified. Methods to account for nonindependence were recorded. Studies violating the assumption of independence were identified and stratified by study design, level of evidence, body part involved, and inclusion of a statistician coauthor. Univariate logistic regression was used to determine whether these factors were associated with violations of statistical independence.

Results:

After screening 1016 articles, 886 clinical studies were reviewed. A total of 135 (15%) studies analyzed dependent observations, and 111 (82%) of these failed to account for nonindependence. Relative to the knee, studies of the hip (odds ratio [OR], 0.21; P = .02) and the thigh or leg (OR, 0.03; P = .004) were less likely to violate statistical independence. Study design ( P = .03) was also associated with violations of statistical independence. Among studies that analyzed dependent observations, the median proportion of dependent observations relative to the total number of observations in each study was 0.07 (interquartile range, 0.04-0.12).

Conclusion:

The analysis of dependent observations is common in the orthopaedic sports literature, but most studies do not adjust for nonindependence in these situations. Investigators should be aware of incorrect inferences arising from nonindependence and how to statistically adjust for dependent data.
Statistical validation of utility of head-mounted display projection-based experimental impression evaluation for sequential streetscapes
Authors: Nishio Shoko , Ito Fumiko
Published: January 2019

This study compared the impression structure of streetscapes gained from field experiments with that from head-mounted display virtual reality experiments. The results were as follows: (1) the field experiment experience had a slight influence on the impressions reported from the head-mounted display experiment; (2) few items exhibited significant differences in impression values for the two experiments; (3) the impression structure comprised three factors—“Openness,” “Balance,” and “Activity”—in both experiments, and (4) no significant difference appeared between the two experiments relative to the subscale scores of these three factors. These results show that head-mounted display experiments can substitute field experiments.
Incorporating spatial autocorrelation and settlement type segregation to improve the performance of an urban growth model
Authors: Xu Chao , Pribadi Didit O , Haase Dagmar , Pauleit Stephan
Published: January 2019

As rapid urbanization and population growth have become global issues, urban growth modeling has become an essential tool for decision-makers to understand how urban growth works in overall dense environments and to assess the sustainability of current urban forms. However, in urban growth models (particularly when incorporating quantitative approaches to include driving factors of urban growth), spatial autocorrelation may influence the overall model performance. In this paper, an empirical study was conducted in the region of Munich, and an integrated urban growth model was tested to explain current urban growth. The modeling contributes to advances in the state of the art by combining a range of driving factors using autologistic regression with a transition probability matrix from the Markov chain method in a cellular automata model simulation. The autologistic regression employed here addresses the impact of spatial autocorrelation compared to ordinary logistic regression. Furthermore, this study compared modeling of overall settlement growth with modeling high- and low-density settlement types separately. Incorporating spatial dependency into the model through application of autologistic regression showed improvements when compared to the ordinary logistic regression model. The Kappa indexes were higher when separately modeling the two types of settlement density compared to modeling overall settlement growth since the driving factors of settlement growth of different densities might be different. From an urban planning perspective, this novel autologistic regression-Markov chain-based cellular automata model is a powerful tool that offers an opportunity for planners and government authorities to gain a more precise understanding of the different urban growth processes that might occur in an urban region similar to the one tested here. It should allow for a better assessment of the potential costs, benefits, and risks of corresponding planning strategies.
Development of shrink resistance cotton using fluorocarbon
Authors: Jain Anil Kumar , Tesema Addisu Ferede , Haile Adane
Published: January 2019

An attempt has been made to develop shrink resistance cotton textile by making it hydrophobic. The cotton fabric was made hydrophobic by treating with fluorocarbon resin emulsion at varying concentrations along with catalyst. The hydrophobicity was measured by carrying out water repellency test and also determining the water contact angle. The air permeability of cotton fabric was also determined and was not adversely affected. The untreated and treated cotton fabric was subjected to repeated domestic laundry condition and shrinkage was measured. In order to determine the impact of fluorocarbon treatment on fabric, the physical properties of treated and untreated cotton fabrics were compared. No adverse impact was observed in colour fastness properties. The tensile and tear strength showed good retention even at higher concentration of water repellent chemicals. This work finds wide use in home textiles and hotel industry. This work is of industrial interest as value added shrink resistance cotton textiles can fetch more export earnings.
Emotional branding speaks to consumers’ heart: the case of fashion brands
Authors: Kim Youn-Kyung , Sullivan Pauline
Published: January 2019

In this highly competitive market, fashion brands struggle to distinguish themselves to increasingly apathetic consumers. To become more competitive, fashion retailers employ emotional branding as a way to engage their customers, addressing the growing trend of consumers’ seeking emotional relationships with a brand. Although brand technicalities such as product attributes, features, and facts may be unmemorable, personal feelings and experiences better shape consumers’ evaluations of brands. This study illustrates why emotional branding is essential, especially to fashion brands, when developing brand strategies in a volatile marketplace. Trends that support a need for these strategies include consumers’ desires for positive experiences, expressing authentic self, achieving warm glow from helping others, and co-creating design or ideas with the brand. We propose a model for emotional branding strategies that focuses on sensory branding, storytelling, cause branding, and empowerment. The case studies we provide for each strategy describe how fashion brands can engage customers through emotional branding.
Carbonate and igneous rock characterization through reprocessing, FWI imaging, and elastic inversion of a legacy seismic data set in Brazilian presalt province
Authors: Penna Rodrigo , Araújo Sergio , Geisslinger Axel , Sansonowski Rui , Oliveira Leonardo , Rosseto João , Matos Marcilio
Published: January 2019

Recent discoveries made in the presalt carbonates of southeast Brazil are among the most important in the past decade. This province, especially Santos Basin, contains large accumulations of oil with excellent quality and high commercial value. The latest seismic processing technologies, along with elastic inversion, have been used for reservoir characterization and in identifying carbonates with high-permeability intervals to model flow behavior of the reservoirs. One challenge encountered is identifying the occurrence of igneous bodies within the reservoir interval and their correct characterization as input into the reservoir modeling. Igneous rocks encountered in the Brazilian presalt can be of both intrusive and extrusive origin. They may present a variety of permo-porous reservoir properties ranging from being flow barriers to acting as high-permeability corridors if fracturing is high enough. The presence of igneous rocks is not common in Brazilian presalt carbonates; therefore, specific methodologies must be used, both in seismic processing and quantitative interpretation, in order to map and predict those occurrences.
Geology differentiation: A new frontier in quantitative geophysical interpretation in mineral exploration
Authors: Li Yaoguo , Melo Aline , Martinez Cericia , Sun Jiajia
Published: January 2019

Geophysics aims to image subsurface geologic structure and identify different geologic units. While the former has dominated the interpretation of applied geophysical data, the latter has received much less attention. This appears to have persisted despite applications such as those in mineral exploration that inherently rely on the inference of geologic units from geophysical and geologic observations. In practice, such activities are routinely carried out in a qualitative manner. Thus, it is meaningful to examine this aspect and to develop a system of quantitative approaches to identify different geologic units. The development of geophysical inversions in the last three decades makes such interpretation tools possible. We refer to this newly emerging direction as geology differentiation and the resultant representation of geology model as a quasi-geology model. In this article, we will provide an overview of the historical background of geology differentiation and the current developments based on physical property inversions of geophysical data sets. We argue that integrating multiple physical property models to differentiate and characterize geologic units and work with the derived quasi-geology model may lead to a step change in maximizing the value of geophysical inversions.
Reviews
Authors: Rüger Andreas , Taylor Patrick , Saltus Rick
Published: January 2019

The Fracking Debate: The Risks, Benefits, and Uncertainties of the Shale Revolution, by Daniel Raimi, ISBN 978-0-231-18486-1, 2017, Columbia University Press, 280 p. Understanding the Bouguer Anomaly — A Gravimetry Puzzle, by Roman Pašteka, Ján Mikuška, and Bruno Meures, ISBN 978-0-12812-913-5, 2017, Elsevier, 142 p. Data Assimilation for the Geosciences, by Steven J. Fletcher, ISBN 978-0-128-04444-5, 2017, Elsevier, 976 p.
Randomized, open-label, phase II study comparing five-weekly S-1 plus cisplatin (SP) with tri-weekly capecitabine plus cisplatin (XP) in chemotherapy-naïve patients with HER2 negative advanced gastric cancer (AGC): OGSG 1105 HERBIS-4A trial.
Authors: Takeno Atsushi , Makari Youichi , Endo Shunji , Matsuyama Jin , Kawabata Ryohei , Sugimoto Naotoshi , Taniguchi Hirokazu , Nagai Kenichi , Tamura Shigeyuki , Nishijima Junichi , Ueda Shugo , Kimura Yutaka , Tamura Takao , Kobayashi Kenji , Kawakami HIsato , Fujitani Kazumasa , Sakai Daisuke , Shimokawa Toshio , Kurokawa Yukinori , Satoh Taroh
Published: January 2019

102

Background: This phase II study aimed to investigate the safety and efficacy of XP compared to SP in the first-line treatment of HER2 negative AGC. Methods: Patients were randomly assigned to receive either SP (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/ m2 on day 8, every 5 weeks) or XP (capecitabine 1,000 mg/m2 twice daily for 14 days plus cisplatin 80 mg/m2 on day 1, every 3 weeks). Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), and adverse events. Results: 84 eligible patients were randomly assigned to receive SP ( N = 41) or XP ( N = 43). No statistical difference was observed in overall RR between the SP and XP groups [51.2% (95% CI, 35.1% to 67.1%) vs. 53.5% (95% CI, 37.7% to 68.8%), P = 1.000]. Despite not significant, however, SP vs. XP showed a trend toward better PFS [median, 5.9 months vs. 4.1 months; hazard ratio (HR), 0.763; 95% CI, 0.462 to 1.259; P = .284] and OS (median, 13.5 months vs. 10.0 months; HR, 0.776; 95% CI, 0.485 to 1.244; P = .290). This trend in the SP vs. XP comparison was more pronounced in TTF (median, 4.5 months vs. 3.1 months; HR, 0.651; 95% CI, 0.421 to 1.006; P = .052). Common grade 3 to 4 hematological toxicities were neutropenia and anemia (SP group, 23% and 23%; XP group, 35% and 28%). Grade 3-4 anorexia and hyponatremia were more frequently seen in the XP group (31% and 16%) compared to the SP group (13% and 5%). Treatment-related deaths occurred in one patient (2.3%) in the XP group. Conclusions: XP failed to demonstrate the superior efficacy over SP. Higher incidence of severe toxicities by XP suggests SP as the standard 1st line chemotherapy for HER2 negative AGC in Japan. Clinical trial information: UMIN000006755.
Recombinant humanized anti-PD-1 monoclonal antibody (JS001) as salvage treatment for advanced gastric adenocarcinoma: Preliminary results of an open-label, multi-cohort, phase Ib/II clinical study.
Authors: Xu Rui-hua , Wang Fenghua , Xu Nong , Shen Lin , Dai Guanghai , Yuan Xianglin , Shi Jianhua , Yang Shujun , Feng Ji Feng , Hu Xi-Chun , Zhang Qingyuan , Chen Ye , Lin Xiaoyan , Ba Yi , Liu Yunpeng , Jiang Yi , Yongqian Shu , Li Qi , Li Wei , Yao Sheng
Published: January 2019

108

Background: Patients with gastric adenocarcinoma (GC) or gastroesophageal junction cancer (GEC) often present with advanced or metastatic 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 GC. (Clinical trial ID: NCT02915432) Methods: Refractory/metastatic GC 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, 48 GC pts (74.5% 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, 25 GC pts have been evaluated for clinical efficacy. 5 PR (partial response) and 10 SD (stable disease) were observed (ORR 20% and DCR 60%). The PD-L1 expression positivity (defined as positive staining ³1% on Tumor Cell or on Immune Cell by SP142) in EC tumor was 14.3% (7/48). 3/5 (60%) PD-L1+ patients and 2/20 (10%) PD-L1 negative patients achieved partial responses. Conclusions: JS001 showed a promising preliminary clinical activity in heavily pre-treated metastatic GC pts with a manageable safety profile. Of the 25 evaluable GC patients by 9/11/2017, 5 PR and 10 SD were observed (ORR 20% and DCR 60%). Among PD-L1 positive patients (n=5), ORR was 60% and DCR 80%. Pts will be continuously monitored for safety and efficacy upon JS001 treatment. Clinical trial information: NCT02915432.
Patterns of chemotherapy (CT) use in a U.S.-wide cohort of patients (pts) with metastatic gastric cancer (MGC).
Authors: Abrams Thomas Adam , Meyer Gary , Hess Lisa M. , Zhu Yajun , Zhang Sui , Liepa Astra M. , Meyerhardt Jeffrey A. , Schrag Deborah , Enzinger Peter C. , Fuchs Charles S.
Published: January 2019

112

Background: MGC is associated with poor survival outcomes. Despite multiple therapeutic options, there is no clearly defined standard-of-care (SOC) CT algorithm. Assessing MGC treatment trends of CT utilization is of critical import. Few population studies have examined the frequencies and temporal trends of MGC CT regimens. This study was designed to address this knowledge deficit. Methods: Eligible pts had biopsy-proven MGC diagnoses and received CT between Jan 2005 and Dec 2016 at academic, private or community hospital practices using IntrinsiQ, a US-wide CT order entry system that captures pt, provider and CT data. Temporal trends were analyzed in the context of SOC changes during the study’s observational period. Results: Among 4,333 MGC pts, median age was 64; 74% were male. In 1st-line CT, 26% received fluoropyrimidine [FU] + oxaliplatin (FOLFOX), 15% received epirubicin + platinum + FU [ECF/EOX], 15% received docetaxel (D) + cis/carboplatin (C) + FU [DCF], 13% received C + paclitaxel, 10% received C + FU [CF], 5% received taxane [TAX] monotherapy. FOLFOX use has increased steadily to 41% in 2015 while DCF use dropped from 29% in 2007 to below 10% by 2015. Biologics were used in 11% of all 1st-line starts and 24% of all 2nd-line starts. Trastuzumab represented 72% of 1st line biologic use (with or without CT backbones), overall use increased from 0% in 2008 to 16% of 1st line in 2015 In 2nd line, no single treatment regimen was used in more than 7% of patients in 2005, but the use of newer treatments has increased over time: trastuzumab use increased from 0% in 2008 to a peak of 22% in 2016 and ramucirumab use increased from 0% in 2012 to its peak in 2015 of 26%. Conclusions: This population-based study provides insight into US MGC treatment patterns and recent trends with the availability of novel agents. [Table: see text]
Ramucirumab treatment in patients with gastric cancer/gastroesophageal junction adenocarcinoma: Secondary analysis of efficacy and safety results of 4 dosing regimens in the phase II trial I4T-MC-JVDB.
Authors: Ajani Jaffer A. , Udrea Anghel Adrian , Sarosiek Tomasz , Schenker Michael , Morgan Carys , Pikiel Joanna , Joseph Mano , Salek Tomas , Tournigand Christophe , Ferry David Raymond , Zhang Yawei , Long Amanda , Kuo Wen-Ling , Gao Ling , Russo Francesca , Mansoor Wasat
Published: January 2019

117

Background: Ramucirumab (RAM) is approved for treatment of advanced gastric cancer or gastroesophageal junction adenocarcinoma with disease progression after prior platinum and/or fluoropyrimidine chemotherapy at 8 mg/kg every 2 weeks (Q2W). Previous phase 3 trials indicated that efficacy of RAM correlated with exposure. While the primary objectives of the open-label RAM monotherapy JVDB study were pharmacokinetics and safety, a secondary analysis was conducted on efficacy and safety of the 3 higher exposure regimens vs. the standard regimen. Methods: Patients ( n = 164) were randomized 1:1:1:1 to 4 treatment arms: 8 mg/kg Q2W (Arm 1), 12 mg/kg Q2W (Arm 2), 6 mg/kg every week (Arm 3), and 8 mg/kg Days 1 and 8 (D1D8) every 3 weeks (Q3W) (Arm 4). Treatment-emergent adverse events (TEAEs) were graded by NCI CTCAE v4.0. Tumor response was assessed by RECIST 1.1. Results: Median (months) progression-free survival (PFS) of the 3 arms and overall survival (OS) of 2 arms was increased compared to the standard regimen (Table). Best overall response was partial response (Arm 2, n = 4; Arm 3, n = 2). The majority of patients experienced ≥1 TEAE (81.4%); 39.1% had ≥1 Grade ≥3 event and 26.7% had ≥1 serious event. The most frequent Grade ≥3 events were fatigue (5.6%), abdominal pain (5.05%), hypertension (5.0%), anemia (4.3%), and vomiting (3.7%). Conclusions: Although the study was not powered for statistical comparisons, some trends toward improved efficacy vs. the standard regimen were observed; the greatest median PFS months and OS improvement was 1 month (Arm 2 vs. Arm 1; PFS = 2.50 vs. 1.45; OS = 6.74 vs. 5.68). Despite higher RAM exposures with the experimental regimens, the safety profile is similar to the standard dose regimen, and no unexpected safety findings were observed. Clinical trial information: NCT02443883. [Table: see text]
A comparison of doublet versus triplet chemotherapy regimens for esophagogastric adenocarcinoma (EGC): Is more always better?
Authors: Felismino Tiago , Alves Ana Caroline , Oliveira Audrey , Costa Wilson Luiz da , Coimbra Felipe José Fernandez , Jesus Victor Hugo Fonseca , Camandaroba Marcos Pedro Guedes , Mello Celso Lopes
Published: January 2019

124

Background: Recent data showed that a taxane-containing triplet regimen (FLOT) was superior to an anthracycline-containing regimen (ECX/ECF). However, there is no comparison between more costly and toxic triplet (T) regimens versus doublets (D) in the perioperative setting (periCT) of EGC. Methods: A retrospective analysis of patients (pts) with newly diagnosed EGC was carried out at AC Camargo Cancer Center from 2007 to 2015. Pts received either a D with a fluopyrimidine and platin or T with addition of epirubicin or docetaxel. Variables used in the Cox model were age, site, TNM, Lauren subtype and periCT (T versus D). The selection between T and D was at physician's choice. Endpoints were Relapse Free Survival (RFS) and Overall Survival (OS). Results: A total of 128 pts were included. Median age was 59.5y (56.5y for T and 67y for D, respectively). Male/female ratio was 82/46. Sixty-six received T (DCF 26 pts, EOX 28, ECX 8, 4 others) and 62 received D (FOLFOX 47 pts, CF 13, 2 others). Primary site: gastric in 93 pts and 35 EGJ. Main clinical staging cT3 N = 81 (63.3%), cN+ 84 (65.4%). Lauren subtype: intestinal N = 48, diffuse N = 54. Regarding surgery: 114 pts were resected and median lymph nodes removed 30. Pathologic complete response was seen in N = 9 (14.5%) and N = 4 (6.1%) considering D and T regimens, respectively (p = 0.14). In multivariate analysis there was no advantage of T over D regarding RFS (HR = 1.65, 0.87 – 3.11, p = 0.12) or OS (HR = 1.29, 0.65 – 2.57, p = 0.45). The 3y RFS rate was 63.2% for D and 40.6% for T and the 3y OS was 69.4% for D and 56.1% for T. Conclusions: In our analysis outcomes of pts treated with T regimen was not superior to D. Our main T was DCF and D was FOLFOX. We consider that doublet regimens may still have a role in periCT in EGC and could be an option for frail or elderly pts. Future trials are needed to confirm our data.
Extended outcomes of intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastases.
Authors: Chan Dexter Yak Seng , Syn Nicholas , Neogh Cui Ting , Phua Niam Sin , . Elya , Ho Jinghsan , Sundar Raghav , Tan Chee Seng , Ngoi Natalie , Chee Cheng Ean , Shabbir Asim , So Jimmy , Yong Wei-Peng
Published: January 2019

125

Background: Peritoneal metastasis is common in gastric cancer. It is difficult to treat and carries a grave prognosis. Studies have shown increased drug concentration in the peritoneal cavity when chemotherapy is administered intraperitoneally (IP). We had previously published early results on IP paclitaxel plus XELOX for such patients and now present our longer term data. Methods: Patients with unresectable and/or recurrent gastric adenocarcinoma with peritoneal dissemination and/or positive peritoneal washing cytology, not previously-treated or received prior systemic therapy > 180 days ago and ECOG ≤2 are eligible. Patients were treated with 8 cycles of paclitaxel 40 mg/m2 IP on days 1 and 8, oxaliplatin 100 mg/m2 IV on day 1 and capecitabine 1000 mg/m2 b.i.d. PO for 2 weeks followed by 1 week of rest. The primary endpoint is 1-year overall survival rate and the secondary endpoints are safety, response rate and peritoneal cytological response. Patients who subsequently have no distant metastases, with stable or reduced peritoneal disease and 2 consecutive negative peritoneal cytology would be eligible for conversion gastrectomy. Results: 34 patients have been enrolled and received at least one cycle at the time of reporting. Median no. of cycles is 8 (range: 1–8) and median follow-up is 30.2 months. Median OS is 16.4 months (IQR: 10.1–27.2) and 1-year survival rate is 64.9% (95% CI: 45.5%–78.9%). Of 30 evaluable patients, 1 achieved CR (3.3%), 6 (20.0%) achieved PR, 16 (53.3%) achieved SD and 7 (23.3%) experienced PD. Peritoneal cytology turned negative in 17 of 32 (53.1%) patients. Severe (grade ≥ 3) AE were neutropenia ( N= 7), febrile neutropenia ( N= 3), diarrhoea ( N= 3), hand-foot syndrome ( N= 2), bacterial peritonitis ( N= 2) and hypokalaemia ( N= 4) and tumour perforation ( N= 1). One death occurred due to neutropenic sepsis. 8 patients had conversion gastrectomy with no additional morbidity, with a 1-year survival of 87.5% with a median OS of 18.8 months. Conclusions: XELOX + IP paclitaxel appears to be a well-tolerated and active regimen in gastric cancer with peritoneal metastases, and may offer survival benefits. Finally, conversion gastrectomy may be considered in patients with favourable response. Clinical trial information: NCT01739894.
Outcomes for advanced HER2-positive gastroesophageal cancer by anatomical location: Experience from the Princess Margaret Cancer Centre.
Authors: Lim Charles Henry , Yokom Daniel , Jiang Di Maria , Ma Lucy Xiaolu , Sun Peiran , Sim Hao-Wen , Natori Akina , Chan Bryan Anthony , Moignard Stephanie , Knox Jennifer J. , Chen Eric Xueyu , Liu Geoffrey , Swallow Carol Jane , Darling Gail Elizabeth , Brar Savtaj Singh , Hafezi-Bakhtiari Sara , Conner James , Elimova Elena , Jang Raymond Woo-Jun
Published: January 2019

131

Background: The landmark ToGA trial established trastuzumab (T) based therapy as the standard of care for advanced HER2+ gastric and gastroesophageal junction cancer. However, outcomes for T based therapy for HER2+ esophageal cancer have not been well characterized. Methods: We conducted a retrospective analysis of patients (pts) with HER2+ gastroesophageal cancer receiving T based therapy at our institution from 2011-2016. Distal esophagus ( < 35 cm) and Siewert type I/II tumours were defined as esophageal (E). Siewert type III and stomach tumours were defined as gastric (G). Trained abstractors collected pt demographics and treatment details. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of first T treatment. Chi-square tests, t-tests and Cox proportional hazards models were applied where appropriate. Results: We identified 87 pts with advanced HER2+ disease. 62% (n = 54) had de novo metastatic (M1) disease. 57 patients were treated with T based therapy, with median age 57 years (IQR 48-67), 91% baseline performance status 0-1, 19% female, and 7% Asian. 63% (n = 36) had E and 37% (n = 21) had G primary tumours. 67% (n = 38) presented with M1 disease. 33% (n = 19) underwent surgery with curative intent and received T based therapy at recurrence. Baseline characteristics were balanced between the E and G groups. Survival data were available for 51 patients. The E and G groups did not have significant differences in PFS (median 9.5 vs. 9.1 months, HR 0.89 (95% CI 0.44-1.80), p = 0.74) or in OS (median 15.8 vs. 14.2 months, HR 0.88 (95% CI 0.42-1.82), p = 0.73). 63% (n = 36) were treated with subsequent systemic therapy after progression on T, with 23 receiving one line, 9 receiving two lines and 4 receiving three additional lines of treatment. The number subsequent therapies received was similar between E and G groups. Conclusions: Although patients with distal esophagus tumours were not included in the ToGA trial, our analysis suggests that patients with E and G tumours had similar outcomes. Our contemporary cohort had comparable survival outcomes relative to patients receiving T in the ToGA trial (median PFS = 6.7 months, median OS = 13.8 months).
Can recurrence patterns after curative resection for gastric adenocarcinoma (GCa) inform the selection of adjuvant treatment?
Authors: Luu Shelly , Swett-Cosentino Jossie , Shan Shubham , Tung Stephanie , Siddiqui Mina , Ringash Jolie , Brar Savtaj Singh , Coburn Natalie , Swallow Carol Jane
Published: January 2019

136

Background: Despite improvements in multidisciplinary care and surgical technique, ≈40% of patients recur after curative resection for GCa. Adjuvant treatment decisions should be informed by the expected timing and site of failure, but accurate data are limited. The aim of our study was to describe and analyze the patterns of recurrence at our center. Methods: Patients who underwent curative intent margin-negative resection from 2006-16 were identified from a prospective GCa database. Date of first detection and site of recurrence were determined. Survival curves were calculated by the KM method. Univariate and multivariable analyses (MVA) were performed to identify predictive variables. Significance was set at p < 0.05. Results: Of 123 patients who met inclusion criteria, median age was 70 yrs, 37% were female, and median follow-up after resection was 24 mos (IQR 11-40). Five-year OS was 72% and RFS 69%. In 34 of 36 patients who recurred, recurrence was detected within 2 yrs. Receipt of adjuvant therapy (Macdonald or MAGIC) was associated with better 5-year OS and RFS than surgery alone (79% vs. 60%, 77% vs. 60%) and delayed time to recurrence (median 10.4 vs. 7.1 mos). Receipt of CRT by the Macdonald protocol appeared to lower the risk of locoregional recurrence vs. surgery alone (see Table) despite routine D2 lymphadenectomy. On MVA, recurrence at any site was predicted by age £ 60y (OR 3.8), male gender (4.0), and AJCC stage > II (4.6). Peritoneal recurrence was predicted only by age £ 60y (3.2). Conclusions: Recurrence after curative resection occurred within 2 yrs of resection. Locoregional recurrence was uncommon in patients who received postoperative CRT. Peritoneal recurrence, which might be abrogated by prophylactic HIPEC at the time of resection, is not well explained by clinicopathologic variables, and novel molecular predictors are required. [Table: see text]
Phase 1b/2 study of margetuximab (M) plus pembrolizumab (P) in advanced HER2+ gastroesophageal junction (GEJ) or gastric (G) adenocarcinoma (GEA).
Authors: Catenacci Daniel V.T. , Park Haeseong , Lockhart A. Craig , Gold Philip Jordan , Enzinger Peter C. , Nordstrom Jeffrey L. , Hong Sam , Hochster Howard S. , Kelly Ronan Joseph , Uronis Hope Elizabeth , Bendell Johanna C. , Oh Sang Cheul , Park Se Hoon , Kim Yeul Hong , Kang Yoon-Koo , Lee Keun-Wook , Ng Matthew CH , Wigginton Jon M. , Davidson-Moncada Jan Kenneth , Bang Yung-Jue
Published: January 2019

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Background: Trastuzumab (T) + chemotherapy (ctx) is standard for 1st line advanced HER2+ GEA, yet subsequent targeted options are lacking. M is an anti-Her 2 monoclonal antibody with an optimized Fc domain to increase affinity for activating CD16A Fc-receptors (FcR) on NK cells. Outcomes for T-treated patients (pts) carrying the low-affinity CD16A-F allele are generally worse than pts homozygous for the high-affinity V allele. M is designed to be FcR genotype independent. Evidence of clinical activity of M alone has been seen in HER2+ GEA pts post T, while P has demonstrated durable activity. Loss of HER2 amplification may occur after T failure in a subset of initially HER2+ GEA pts. Preclinical studies suggest that engagement of innate and adaptive immunity with the combination of anti-HER-2 antibodies and T-cell checkpoint inhibition could achieve greater antitumor activity than either agent alone. Methods: Advanced HER2+, PD-L1-unselected GEA pts post T failure were eligible. Dose escalation evaluated 10 and 15 mg/kg M and 200 mg P for 2nd line or higher pts. Cohort expansion evaluates safety and objective response rate (ORR) by RECIST v1.1 in 2nd line pts. M + P is given every 21 days; response assessed every 6 weeks. HER2 amplification status was assessed in a subset of pts by plasma circulating tumor (ct) DNA analysis prior to Cycle 1 of M+P. Results: Dose escalation enrolled 9 pts; cohort expansion 48 pts at 15 mg/kg M: 30 in North America (NA) and 18 in Asia (A). Treatment was well tolerated, with 1 drug-related serious adverse event. Of 38 evaluable pts to date in expansion (24 NA and 14 A), the best overall responses include 7 pts (18.4%) with PR (4 confirmed and 3 unconfirmed) and 11 (28.9%) with SD. Higher ORR trends were observed in A vs NA (35.7% vs 8.3%) and G vs GEJ (31.6% vs 5.3%). Of 25 pts with ctDNA results, HER2 amplification detection was higher in GC than GEJ (80% vs 53%). Responses were independent of FcR genotype; CD16A genotype for evaluable pts with PR: 1 V/V, 2 V/F, 2 F/F with similar allelic distribution among non-responders. Conclusions: M+P is a well-tolerated ctx-free regimen that has shown preliminary antitumor activity in 2nd line pts with advanced/metastatic GEA. Clinical trial information: NCT02689284.
Patterns of recurrence and outcomes after curative resection of locally advanced HER2-positive gastroesophageal cancer (HPGEC).
Authors: Jiang Di Maria , Lim Charles Henry , Ma Lucy Xiaolu , Sun Peiran , Sim Hao-Wen , Natori Akina , Chan Bryan Anthony , Yokom Daniel , Moignard Stephanie , Chen Eric Xueyu , Liu Geoffrey , Knox Jennifer J. , Swallow Carol Jane , Darling Gail Elizabeth , Brar Savtaj Singh , Hafezi-Bakhtiari Sara , Conner James , Jang Raymond Woo-Jun , Elimova Elena
Published: January 2019

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Background: Literature on recurrence and outcomes of HPGEC is scarce. The aim of this study was to determine pattern of recurrence and outcomes after curative intent surgery for locally advanced HPGEC. Methods: A retrospective database was used to identify consecutive patients with gastroesophageal adenocarcinomas undergoing curative intent resection between 2011 and 2016 at the Princess Margaret Cancer Centre. Clinico-demographic data were extracted from the electronic health record. Patterns of relapse are classified as nonvisceral (defined as recurrences in the bone, peritoneal or both), visceral (not nonvisceral, including the brain), or both. Time to relapse (TTR) and overall survival (OS) were calculated from date of histologic diagnosis. Results: Of 45 patients with HPGEC, 78% were male, and 91% were non-Asian. Median age was 64.4 years (interquartile range [IQR] 53, 70); 60% were gastroesophageal junction, 24% were gastric, and 16% were esophageal adenocarcinomas; 31% were poorly differentiated tumors while 68% had clinical or pathological node positive disease. Complete R0 resection occurred in 93%, and 84% had received perioperative therapy (31% with perioperative chemotherapy; 40% with pre-operative chemoradiation; 9% with post-operative chemoradiation). With a median follow-up time of 26.0 months. relapse rate of HPGEC at last follow-up was 78%. Among first relapses, 94% were distant, while 6% were local recurrences. Among distant relapses, visceral recurrences occurred in 85%, nonvisceral in 3%, and 12% patients had both visceral and nonvisceral recurrences. None had peritoneal only recurrence. Median TTR was 12.2 months (IQR 8.8, 23.5), while median post-recurrence survival was 9.7 months (IQR 4.7, 16.3). Of the entire cohort, 2-year OS was 53% and 3-year OS was 26%. Conclusions: More than three-quarters of patients with HPGEC experienced recurrence after curative intent multimodality therapy. Our results suggest that HPGEC rarely relapse with peritoneal only disease or local recurrence, thereby calling into question the utility for aggressive surveillance, pending verification from larger cohorts.
Robotic-assisted (RAMIE) x thoracoscopic esophagectomy (MIE): Comparison on safety and lymph nodal dissection in 181 cases.
Authors: Sallum Rubens Antonio Aissar , Takeda Flavio Roberto , Santo Marco Aurelio , Cecconello Ivan
Published: January 2019

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Background: Robotic-assisted esophagectomy (RAMIE) gained evidence among the major oncological procedures due possibilities on lymph nodal dissection. The concept of esophagectomy and extensive lymphadenectomy with low morbidity boosted by the videothoracoscopic esophagectomy(MIE) is now focused on the robotic approach. Methods: The first 37 cases of RAMIE were studied. The thoracic field performed in the prone position with three robotic arms and abdominal field idem, as performed in the upper GI robotics procedures. Conversion to open or laparoscopic procedures, morbidity and mortality as well as the length of the lymphadenectomy were evaluated. These data were compared to the first 154 cases of MIE operated by the same surgical team in those early results. Also the late survival of the MIE group is presented. Results: All except 2 RAMIE cases were Siewert I or II Adenocarcinoma, 32 post neoadjuvancy: MAGIC (7) or CROSS (25). There was no conversion to lap or open procedures. No patient received blood transfusion. One complication was observed: a partial rotation of gastroplasty in the thorax, that required thoracoscopic approach in the day 7. Mortality (90 days) was zero. Mean resected lymph nodes was 42.5 (30-76). In the MIE group, complications were: respiratory (26.2%), infectious (8.4%), cervical fistula (17.7%), vocal cord palsy (8.4%). 30 and 90 days mortality were one (0.93%) and 3 (2.8%). Mean dissected lymph nodes = 31.6 (± 14.3), 1:57 positives (± 3.21) and RAD 00:05 (± 0:09). The overall five-year survival was 69% (95% CI: 57% - 83%), 75% in stage 0 / I / II and 42% in III/IV. Conclusions: RAMIE with these technical proposal, seams to be safe without mortality. Lymph nodal achieved was equal to greater than the practiced through MIE. After those cases we started a randomized prospective trial on this issue (NCT02292914).
HER-2 overexpression in gastroesophageal junction (EGJ) adenocarcinoma as a predictor of prognosis in patients treated with perioperative chemotherapy.
Authors: Felismino Tiago , Oliveira Audrey , Alves Ana Caroline , Jesus Victor Hugo Fonseca , Costa Wilson L. , Coimbra Felipe José Fernandez , De Barros E. Silva Milton Jose , Riechelmann Rachel Pimenta , Begnami Maria Dirlei , Rodrigues Newton Augusto Ferreira , Mello Celso Lopes
Published: January 2019

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Background: Approximately 15% of all gastroesophageal adenocarcinomas overexpress HER-2. This is more common in intestinal subtype and proximal tumors. HER-2 status is associated with poor prognosis in non-metastatic patients, but its prognostic impact on the outcomes of pts treated with perioperative chemotherapy (CT) is unclear. Methods: The aim of this study was to retrospectively analyze the influence of HER-2 status on the overall survival (OS) and Relapse Free Survival (RFS) of pts with locally advanced gastroesophageal adenocarcinoma treated with perioperative CT. HER-2 positive tumors were defined by 3+ immunohistochemical staining or fluorescence in situ hybridization positivity. Independent variables used in the Cox model were: Lauren's subtype, clinical staging, and a combination of primary site and HER-2 status. Results: A total of 97 patients were included: median age was 62y, 62 (63.9%) were male; N = 57 (58.8%) had cT3 tumors and 60 (60.1%) had cN+. Lauren’s subtype was intestinal in N = 35 (36.1%), and diffuse in N = 44 (45.4%). CT regimens were mainly FOLFOX (46.4%), EOX (23.7%) or DCF (13.4%). Regarding primary site and HER-2 status: gastric HER-2 negative N = 61, Gastric HER-2 positive N = 8, GEJ HER-2 negative N = 23, GEJ HER-2 positive N = 5. In a Cox multivariate analyses for OS and RFS, EGJ HER-2 positive pts had higher chance of recurrence (HR = 3.57, 1.08 – 11.77, p = 0.03) and death (HR = 6.14, 1.83 – 20.60, p = 0.003). EGJ HER-2+ 3y RFS was zero and 3y OS was 20%. Conclusions: EGJ HER-2+ tumors carried a dismal prognosis and had little benefit from conventional perioperative CT strategies. Although further studies are needed to confirm our data, we believe that a different approach, possible combining anti-HER-2 drugs, should be tested in this scenario.
Efficacy of cytotoxic agents after progression of anti-PD-(L)1 antibody for pretreated metastatic gastric cancer.
Authors: Kato Kyoko , Narita Yukiya , Mitani Seiichiro , Honda Kazunori , Masuishi Toshiki , Taniguchi Hiroya , Kadowaki Shigenori , Ura Takashi , Ando Masashi , Tajika Masahiro , Muro Kei
Published: January 2019

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Background: The efficacy of anti-PD-1 antibody for metastatic gastric cancer (mGC) was revealed. In non-small cell lung cancer (NSCLC), it was reported that overall response rate (ORR) in patients (pts) treated with chemotherapy (CTx) after immunotherapy exposure was higher than historical data from the pre-anti-PD-(L)1 era. The purpose of this retrospective study was to evaluate whether CTx improved efficacy outcomes after exposure anti-PD(L)1 antibody in mGC. Methods: We investigated retrospectively clinical characteristics at baseline of mGC pts who received CTx after progression of anti-PD-(L)1 antibody between April 2014 and August 2017. Anti-PD-(L)1 antibody was adapted as third- or later-line therapy. Pts fulfilled following criteria: histologically proven adenocarcinoma; ECOG PS 0-2; adequate organ functions; and received CTx including fluoropyrimidines (FU), platinum, and taxane or irinotecan. We evaluated efficacy outcomes, including ORR, disease control rate (DCR), time to treatment failure (TTF), and overall survival (OS). Results: Out of 40 treated with anti-PD-(L)1 antibody, 15 pts were included. Patient characteristics were as follows: median age (range), 67 (46-83) years; male/female, 13/2; ECOG PS (0/1/2), 5/8/2; HER2 positive, 8; histology (differentiated/undifferentiated), 10/5; metastatic lesions (peritoneum/liver/lung), 4/8/3; number of metastatic sites (1/≥2), 2/13; number of prior CTx regimens (3/4/5), 2/9/4; median period (range) from first line CTx, 30.7 (12.7-68.1) months; and CTx regimens (FU+oxaliplatin/taxane/irinotecan), 10/3/2. ORR, DCR, median TTF, and OS were 33% (95% CI, 15.2-58.3), 87% (95% CI, 62.1-96.3), 3.5 (95% CI, 1.6-4.4) months, and 7.6 (95% CI, 4.4-8.5) months, respectively. There were no predictive and prognostic factors associated with ORR, TTF, and OS on univariate analysis. At the beginning of CTx, 4 pts had immune-related adverse events (irAEs), but these were manageable and no new irAEs appeared during CTx. Conclusions: Our data support further evaluation of the use of CTx after progression of anti-PD-L 1 antibody, even in heavily pretreated mGC pts. Updated results will be presented.
Systemic chemotherapy for gastric cancer with early recurrence after adjuvant S-1 monotherapy: A multicenter retrospective study.
Authors: Hasegawa Hiroko , Mitani Seiichiro , Wakatsuki Takeru , Hara Hiroki , Hirao Motohiro , Takahari Daisuke , Chin Keisho , Kadowaki Shigenori , Muro Kei
Published: January 2019

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Background: S-1 monotherapy is one of the standard adjuvant treatments for stage II or III gastric cancer patients (pts). Early recurrence after adjuvant therapy has a poor prognosis and the optimal regimen remains to be established. This study aimed to clarify the treatment outcomes of systemic chemotherapy and explore encouraging regimens for gastric cancer pts with early recurrence. Methods: We retrospectively reviewed gastric cancer pts at four institutions who underwent curative gastrectomy followed by adjuvant S-1 monotherapy and identified pts who developed recurrence during the adjuvant therapy or within 6 months after completion between 2005 and 2015. Other main eligibility criteria were Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2, adequate organ function and no massive ascites. The Cox proportional hazards model was used to evaluate the survival outcomes, adjusting for relevant factors. Results: A total of 112 pts were included. Pts characteristics were as follows: median age (range), 62 (29-83) years; male/female, 84/28; ECOG-PS 0/1/2, 39/63/10; diffuse/intestinal, 73/39; HER2 status positive/negative/unknown, 17/46/49; metastatic site liver/peritoneum, 32/44; and number of metastatic sites 1/≥2, 94/18. The taxane-based regimens were as follows: weekly paclitaxel (PTX) (38), nab-PTX (4), trastuzumab (Tmab) + PTX (4), S-1 + PTX (3), and the others (4). The platinum-based regimens were irinotecan + cisplatin (IP) (31), capecitabine + cisplatin (XP) (7), S-1 + cisplatin (5), Tmab + XP (4), and the others (2). For all pts, the median PFS and OS were 3.7 months (M) and 11.4 M, respectively. After excluding HER2-positive pts, there were no statistically significant differences between the taxane-based and platinum-based regimens in survival outcomes (median OS, 7.6 M vs. 12.2 M; adjusted HR = 0.93, 95% CI 0.58-1.49), nor between IP and the other platinum-based regimens (median OS, 11.8 M vs. 13.3 M; adjusted HR = 0.64, 95% CI 0.28-1.46). Multivariate analysis showed treatment regimen was not a prognostic factor. Conclusions: The regimens so far selected for gastric cancer with early recurrence resulted in similar, poor prognosis.