bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic impact of chemoradiation-related lymphopenia in patients with locally advanced pancreatic cancer.
Authors: Kim Daniel W , Lee Grace , Weekes Colin D. , Ryan David P. , Parikh Aparna Raj , Allen Jill N. , Qadan Motaz , Ferrone Cristina R. , Fernandez-del Castillo Carlos , Hwang William L. , Hong Theodore S. , Wo Jennifer Y
Published: January 2021

439

Background: Chemoradiation (CRT) induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. The objective of this study was to evaluate the prognostic impact of lymphopenia in patients with nonmetastatic, unresectable pancreatic ductal adenocarcinoma (PDAC) treated by neoadjuvant FOLFIRINOX (5-fluorouracil [5FU]/leucovorin/irinotecan/oxaliplatin) followed by CRT. We hypothesized that severe lymphopenia would correlate with worse survival. Methods: The inclusion criteria for this single-institution retrospective study were: 1) biopsy-proven diagnosis of unresectable PDAC, 2) absence of distant metastasis, 3) receipt of neoadjuvant FOLFIRINOX followed by CRT, and 4) absolute lymphocyte count (ALC) available prior to and two months after initiating CRT. In general, CRT consisted of 5FU or capecitabine and RT with 58.8 Gy over 28 fractions. Lymphopenia was graded according to CTCAE v5.0. The primary variable of interest was lymphopenia at two months, dichotomized by ALC of < 0.5/μl (Grade 3 lymphopenia). The primary endpoint was overall survival (OS). Cox modeling and Kaplan-Meier methods were used to perform survival analyses. Results: A total of 138 patients were identified. Median follow-up for the entire cohort was 16 months. Median age was 65. Fifty-six percent were female, 86% were Caucasian, and 97% had ECOG ≤1. Median tumor size was 3.8 cm. Tumor location was pancreatic head in 63%, body in 22%, tail in 8%, and neck in 7%. Median baseline ALC for the entire cohort was 1.5 k/ul. Two months after initiating CRT, 106 (77%) had severe (Grade 3 or worse) lymphopenia. While there were no significant differences in baseline patient or disease characteristics, patients with severe lymphopenia received higher doses of RT with longer duration of treatment compared to those without severe lymphopenia. On multivariable Cox model, severe lymphopenia at two months was significantly associated with increased hazards of death (HR = 4.00 [95% CI 2.03-7.89], p < 0.001). Greater number of neoadjuvant FOLFIRINOX cycles received prior to CRT was associated with lower hazards of death (HR = 0.84 [95% CI 0.77-0.92], p < 0.001). The 12-month OS was 73% vs. 90% in the cohort with vs. without severe lymphopenia, respectively (log-rank p < 0.001). Conclusions: Treatment-related lymphopenia is common and severe lymphopenia may be a prognostic marker of poorer survival in locally advanced pancreatic cancer. Closer observation in high-risk patients and minimization of RT dose and duration are potential approaches to mitigating CRT-related lymphopenia. Our findings also suggest an important role of the host immunity in pancreatic cancer outcomes, supporting the ongoing efforts of immunotherapy trials in pancreatic cancer.
Gastrointestinal cancer mortality rate global trends over the last century.
Authors: Sidhu Ravina , Powar Perneet , Calla Ritu Priya , Vyas Dinesh
Published: January 2021

457

Gastrointestinal Cancer Mortality Rate Global Trends Over the Last Century Background: Global gastroenterology cancer mortality trends have drastically changed over past decades due to alterations in risk factors such as diet, populations, exposures, and medical advancements. This study investigates specifically how meat consumption, the biggest evolving risk factor for GI cancer mortality, has influenced various gastrointestinal incidence rates globally. Although the correlation between meat consumption and cancer risk has been investigated, a global temporal study investigating the national mortality rates of gastrointestinal cancers relating to meat production remains unexplored. We researched causes for the trends between meat production and GI cancer mortality in the USA, Canada, Japan, France, and Singapore. Methods: Cancer mortality data was collected from the WHO Cancer Mortality Database, specifically the IARC database. Meat consumption data was unavailable between the 1960s-2010, so meat production data was used and obtained from the FAOSTAT. Results: The pancreatic cancer mortality rate increased in each country except Canada. This spike is due to increased meat consumption, obesity, lack of screening modalities, poor prognosis, and late diagnosis of the disease. Canada’s 1% drop in mortality rate can be attributed to a decreased smoking rate amongst men (62% to 16% from 1965-2017) as well as a decline in meat consumption. The mortality rates of gastric and colorectal cancer (CRC) have decreased despite a meat production increase. Decreased H. pylori prevalence (Europe: 48.8% to 39.8%, North America: 42.4% to 26.6%, and Western Asia: 53.6% to 54.3%) , better food preservation, and improvement in environmental conditions have lowered gastric cancer incidence. The CRC mortality rate in the USA, Canada, Japan, and France decreased mostly due to colonoscopy screening measures, better treatment, and decreased red meat consumption. In Singapore, increased obesity and high caloric diets account for an increased CRC mortality rate despite decreased meat production. This rate is exacerbated by lower screening rates due to decreased CRC risk awareness. Conclusions: Gastric and CRC mortality rates decreased despite increased meat production, while pancreatic cancer incidence rates have increased. These trends are further investigated and necessary to understand to lower the mortality rates of GI cancers on a global scale.
Socioeconomic status (SES) and survival outcomes in patients with gastrointestinal (GI) cancers: An analysis of 1.4 million patients in the National Cancer Database (NCDB).
Authors: Salem Mohamed E. , Trufan Sally Jeanne , Symanowski James Thomas , Kadakia Kunal C. , Hartley Marion L. , Graves Kristi D , Musselwhite Laura W. , Kim Edward S. , Raghavan Derek , Hwang Jimmy J.
Published: January 2021

458

Background: SES and access to care are factors that may impact patient outcomes. We examined the impact of SES on survival in patients (pts) with GI cancers. Methods: Data obtained from the NCDB were used to examine the association between SES and outcomes of GI cancer pts. Pts were categorized by income and education levels. Logistic regression, Cox proportional hazards models, and chi-square tests were used to examine the differences between the groups. Results: A total of 1,409,177 pts diagnosed with GI cancers between 2004 and 2016 were retrospectively studied (table). The majority of pts were male (54.3%), and 83.7% were white, 11.5% black, and 4.7% of other races. Of the entire cohort, 31% of pts lived in the highest income areas, whereas 18.3% were in the lowest and 50.6% in middle-income areas; 23% lived in the highest high school graduation rate (>93%) areas, whereas 17.4% lived in the lowest graduation rate (< 79%) areas; and 82.4% resided in metropolitan areas. Pts in the lowest compared to highest income areas were more likely to be black (OR: 6.5, 6.4-6.6), uninsured (2.9, 2.8-3.0), or have Medicaid (4.13, 4.04-4.22), and have a Charlson-Deyo score ≥ 1 (1.35, 1.33-1.36). In the multivariate analysis, cancer type, stage, tumor differentiation, income, education, insurance status, gender, race, Charlson-Deyo score, and type of treatment center were independent predictors for survival. After controlling for other factors, black pts had a 3% increased risk of death (HRadj = 1.03; 1.02-1.03; p < 0.001). Pts from lowest vs highest education areas had a 2% increased risk of death (HRadj = 1.02; 1.01-1.03; p < 0.001). Pts from the lowest income vs highest income areas had a 13% increased risk of death (HRadj = 1.13; 1.12-1.14; p < 0.001). Pts with Medicaid insurance had a 33% (HRadj: 1.33, CI 1.32-1.34, p < 0.001) and uninsured pts had 22% (HRadj: 1.22 (1.20-1.23, p < 0.001) increased risk of death compared to pts with private insurance. Pts from urban or rural areas vs metropolitan areas had a 1% increased risk of death (HRadj = 1.01; 1.00-1.02; p < 0.001). Conclusions: Low SES is associated with worse survival in pts with any GI cancer. Pts with low-income status and Medicaid or no health insurance had the highest risk of mortality. These stark inequities must be addressed with renewed efforts to identify, treat, and better support pts at highest risk for poor outcomes. [Table: see text]
Early detection and localization of multiple cancers using a blood-based methylation assay (ELSA-seq).
Authors: Gao Qiang , Li Bingsi , Cai Shangli , Xu Jiayue , Wang Chenyang , Su Jing , Fang Shuai , Qiu Fujun , Wen Xiaofang , Zhang Yuzi , Wang Guoqiang , Liu Hao , Zhang Zhihong
Published: January 2021

459

Background: Early detection of cancer can potentially offer clinical benefits, particularly for those without effective screening methods. The PREDICT study (pan-cancer early detection project, NCT 04383353) is a prospective, multi-center, longitudinal study that aims to identify multiple cancers non-invasively before symptoms become apparent. As a pilot project, the THUNDER (the unintrusive detection of early-stage cancer) study is designed for development and validation of ELSA-seq, a sensitive targeted methylation sequencing assay that interrogates epigenetic alterations from circulating cell-free DNA (cfDNA). Herein we report results from the second THUNDER sub study (THUNDER-II), which focused on malignancies developed in liver, colon/rectum, esophagus, pancreas, lung and ovary, of which four are gastrointestinal (GI) cancer types. Methods: THUNDER-II comprises four independent steps: marker discovery, model training, validation, and single-blind test. The marker discovery work was conducted by profiling 5.5 million CpG sites in 247 tissue samples (116 cancer, 131 normal/benign, 6 cancer types) using a SeqCap Epi CpGiant system (Roche). By combining data generated in-house and from public sources, a custom hybridization capture panel was designed to target 161,984 CpG sites. For cfDNA applications, 625 patients and 483 non-cancer controls were enrolled and divided into a training set (274 cancer and 195 non-cancer) and an independent validation set (351 cancer and 288 non-cancer). Results: The cancer patients and non-cancer controls were generally comparable with respect to age, gender, and smoking status. Various stages were represented in the cancer group, and 79.5% patients were diagnosed at early stages (I-III). At 99.5% training specificity (95%CI: 96.7-100%), the cross-validated sensitivity was 79.9% (95%CI: 74.6-84.4%). The results were consistent in the validation set, with 98.3% specificity (95%CI: 95.8-99.4%) and 80.6% (76.0-84.6%) sensitivity across stages and cancer types. In terms of tracking diseased organ(s), the classifier returned a tissue-of-origin (TOO) result in 98.6% cases, and 81.0% (95%CI: 77.2-84.3%) of these predictions were correct. Conclusions: Results from the THUNDER-II study demonstrated that early cancer signals could be identified by ELSA-seq with high specificity. This method also enabled accurate prediction of TOO, offering guidance for subsequent diagnostic work-up. Together these findings highlight the potential implementation of this sensitive and robust assay as a multi-cancer detection test.
Association of perioperative red blood cell transfusions with all-cause and cancer-specific death in patients undergoing surgery for gastrointestinal cancer.
Authors: Zuckerman Jesse , Coburn Natalie G. , Callum Jeannie , Mahar Alyson , Acuña Sergio A , Guttman Matthew P , Zuk Victoria , Turgeon Alexis F. , Martel Guillaume , Hallet Julie
Published: January 2021

464

Background: Perioperative anemia and red blood cell (RBC) transfusions are common in patients undergoing gastrointestinal cancer surgery. To adequately balance the risks and benefits of transfusion, clinicians must understand the potential effect of transfusions on long-term outcomes. Methodologic issues have limited previous studies exploring the association between RBC transfusion and survival in this specific patient population. Our objective was to determine, among patients who have undergone gastrointestinal cancer resection, if perioperative RBC transfusions are associated with higher risk of all-cause and cancer-specific death. Methods: In this population-based retrospective cohort study, we used administrative datasets containing routinely collected data from Ontario, Canada. Patients who underwent gastrointestinal cancer resection between January 1, 2007 and March 31, 2019 and survived at least 90 days postoperatively were eligible for inclusion. All-cause death from the ninetieth post-operative day was compared between groups using Kaplan-Meier methods and Cox proportional hazards models. Cancer-specific death was compared using competing risk methods. Regression adjusted for potential confounders. Sensitivity analyses, including the E-value, evaluated the robustness of estimates. Results: We identified 74,962 patients (mean age, 67.7 years; 55.4% male; 79.7% colorectal cancer) who underwent resection for gastrointestinal cancer and survived at least 90 days after surgery. Over a median follow-up of 4.1 years (interquartile range 1.9-5.0 years), patients who received RBC transfusions demonstrated increased hazards of all-cause and cancer-specific death relative to patients who were not transfused (hazard ratio: 1.39, 95% confidence interval 1.34 to 1.44; cause-specific hazards ratio: 1.36, 1.30 to 1.43). The adjusted risk of all-cause death was higher in early follow-up intervals (3-6 months post-operatively) but remained elevated in each subsequent interval over 5 years. Conclusions: RBC transfusion among patients with gastrointestinal cancer is associated with increased all-cause death; this persisted over time suggesting a long-term effect of perioperative transfusion. These findings should help clinicians balance the risks and benefits of transfusion and highlight the need for well-designed, multicenter randomized trials to determine if aggressive transfusion avoidance protocols could improve patient survival after gastrointestinal cancer surgery.
Feasibility of using a computerized food frequency questionnaire (FFQ) to assess dietary patterns in patients with advanced gastrointestinal (GI) malignancies.
Authors: Jain Rishi , Denlinger Crystal S. , Handorf Elizabeth A. , George Roshan , Lewis Bianca , Hunt Alexandra , Stromberg Kara , Astsaturov Igor A. , Dotan Efrat , Hall Michael J. , Vijayvergia Namrata , Fang Carolyn Y
Published: January 2021

465

Background: Identification of poor dietary patterns is important for the optimal management of patients with metastatic GI malignancies who suffer from high rates of malnutrition and sarcopenia which are associated with increased rates of treatment-related toxicity and worsened survival. Dietary records or recall methods and FFQs are available but have high patient burden and are seldom utilized in oncology settings outside of formal nutritional consultations. Thus, we evaluated the feasibility of conducting serial assessments of dietary patterns using a novel computerized FFQ technology. Methods: Assessments of diet using the computerized FFQ, nutritional status (NUTRISCORE), QOL and anorexia/cachexia burden (FAACT), anxiety/depression (HADS) and taste burden were done at the time of initiation of first-line chemotherapy (baseline) and 3 months later. The FFQ was done independently either at home on personal computer after visit or via iPad in infusion room. Dietary quality was defined by the Healthy Eating Index 2010 (HEI) score, which was automatically calculated by the computerized FFQ software. Feasibility was defined as at least 70% of patients completing baseline and 3-month assessments. Spearman’s correlations were used to determine associations between measures. Results: 29 patients with advanced (metastatic or unresectable) GI cancers were enrolled and 23 completed the baseline FFQ (8 colorectal, 5 pancreas, 5 gastroesophageal, 5 other). Median age was 58 (20-78) with M:F ratio of 10:13. The overall completion rate of baseline and 3-month assessments was 81.8%, meeting the pre-defined feasibility criteria. The mean baseline HEI score was 65 (range 38-88). Of patients who completed both baseline and 3-month assessments, the mean HEI score remained stable at 58 with changes in specific HEI components including a 20% decline in the seafood and plant protein score and a 13% decline in the whole grain score and small improvements in other areas (e.g. empty calories, dairy). There were no significant correlations between baseline HEI score and other assessments. Conclusions: It is feasible to use a computerized FFQ to assess for longitudinal changes in eating patterns and dietary quality in patients with advanced GI cancers, particularly when patients can complete the assessments during chemotherapy infusions. Preliminary findings also suggest that the FFQ can be helpful for highlighting areas in which diet quality could be improved. Additional analysis of other computerized FFQ data (e.g. macro/micronutrient consumption) is ongoing.
Incidence, mortality and hospital resource utilization in patients with gastrointestinal cancer and malnutrition: A nationwide analysis.
Authors: Katiyar Vatsala , Vohra Ishaan , Lingamaneni Prasanth , Baral Binav , Kumar Rohit
Published: January 2021

466

Background: Malignancies are associated with a high prevalence of cachexia, protein energy malnutrition (PEM) and failure to thrive. We analyzed the National inpatient Sample database (NIS) to understand the temporal trends and differences between gastrointestinal cancers (GIC) patients with and without malnutrition. Methods: All adults admitted with GIC including esophageal, gastric, pancreatic, hepatic, gall bladder, small and large intestine and anal cancers from 2012-2016 were identified from the NIS using the ICD 9 and ICD 10 codes. We analyzed the temporal trends of mortality and resource utilization. Multivariable logistic regression was used to evaluate the risk factors for malnutrition in patients with GIC. Results: There were 2,645,285 GIC inpatient admissions between 2012-2016, out of which 6.1% patients died. 11.1% (±0.22) patients had PEM and three most common GIC associated with PEM were Esophageal (19.7±0.24%), gastric (16.5±0.22%) and small intestine (15.2±0.41%). On multivariate analysis, PEM was more common in male gender (OR: 1.07, 95% CI:1.05-1.08, P<0.01), African- American race (OR:1.14, 95% CI: 1.10-1.17, P<0.01) and Charlson comorbidity index >=2(OR:1.5, 95% 1.42-1.51, P<0.01). Malnourished patients were often terminally ill (48.8% vs 39.8%), in intensive care unit (7.89% vs 3.75%), were more likely to be seen by palliative care team (17.6 % vs 9.8%) and were more likely to die (9.6% vs 5.70%, OR-1.76; p <0.01). The incidence, mortality, and total charge of PEM in patients with GIC significantly increased from 2012 to 2016 as shown in the table below. Conclusions: Malnourished patients with GIC tend to have more advanced disease and have an increased mortality as compared to patients with adequate nutritional status. Optimization of their nutritional status can greatly improve outcomes and curb healthcare costs. [Table: see text]
Beyond BRCA? clinical utility of homologous recombination deficiency in gastrointestinal cancers.
Authors: Tsang Erica S , Csizmok Veronika , Williamson Laura , Pleasance Erin D. , Topham James T. , Karasinska Joanna , Titmuss Emma , Schrader Kasmintan A , Cafferty Fergus , Yip Stephen , Tessier-Cloutier Basile , Mungall Karen , Sun Sophie , Lim Howard John , Loree Jonathan M. , Laskin Janessa J. , Marra Marco A. , Jones Steven J. M. , Schaeffer David F. , Renouf Daniel John
Published: January 2021

472

Background: There is emerging evidence about the predictive role of homologous recombination deficiency (HRD) in multiple cancers. The clinical utility of HRD is less well defined in gastrointestinal (GI) malignancies. Methods: We reviewed the whole genome (WGS) and transcriptomic (RNA-Seq) data of patients with advanced GI cancers between 2012-2018 in the Personalized Oncogenomics trial (NCT02155621). Scores were calculated as the sum of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions scores. HRD was defined as a score ≥34. Mutational analysis was performed to determine the presence of mutational signature 3, which is usually strongly associated with BRCA status. Retrospective chart review was conducted to extract treatment and survival outcomes. Overall survival (OS) from initiation of first-line systemic therapy and time to progression on platinum therapy (TTPp) were calculated. Linear and multivariable regression analyses were conducted. Results: Of 154 patients with GI primaries, 56% were male and 105 (68%) were exposed to a platinum agent in the metastatic setting. Primary sites included upper GI (N=20, 9%), pancreas (N=35, 16%), colorectal (N=74, 33%), and other GI primary (N=25, 11%). Ten patients (6%) had a BRCA1/2 mutation, 20 (13%) had a high HRD score, and 11 (7%) had a high signature 3 score (>0.05). Six patients had both high HRD and high signature 3 scores (Table). On linear regression, high HRD scores and mutational signature 3 were independently associated with longer TTPp (β=4.17, 95% CI 0.15-8.19, p=0.04; β=8.03, 95% CI 2.87-13.18, p<0.05, respectively). On multivariable linear regression, after adjusting for HRD score, BRCA1/2 status, and tumor site, only cases with a mutational signature 3 retained significance ( p<0.05). HRD status was not prognostic for OS (HR 1.02, 95% CI 0.65-1.62, p=0.92). Conclusions: Within a cohort of patients with GI malignancies characterized by WGS and RNA-Seq, mutational signature 3 was more strongly associated with TTPp compared to HRD score. These data highlight potential predictive implications of Signature 3 to complement HRD and BRCA status in identifying patients who may benefit from exposure to platinum therapy. [Table: see text]
The impact of immunotherapy education on GI cancers.
Authors: Parikh Kinjal , Lucero Katie , Warren Charlotte , Van Laar Emily Sherene , Kugel Patrick , Kadkhoda Haleh
Published: January 2021

479

Background: Gastrointestinal (GI) cancers are a heterogeneous group of cancers with varying underlying pathophysiology and distinct treatment paradigms. Immunotherapy (IO) is unique in each of the subtypes and biomarkers utility varies. With the expansion of IO in each cancer subtypes, education remains essential to optimize patient outcomes through integration of the latest evidence-based data at point of care. Through the partnership between Medscape Oncology and the Society for Immunotherapy of Cancer, 2 educational activities were designed to increase the knowledge and competence of oncologists surrounding the role of IO in patients with advanced GI cancers. Methods: The 2 educational activities included a text based online activity with 3 chapters focused on gastroesophageal cancers, colorectal cancers, and hepatocellular carcinoma (HCC) and a 30-minute online, video discussion with 3 faculty and synchronized slides on HCC. Educational effectiveness was assessed with repeated paired pre/post assessment where learners served as their own controls. A chi-square test was used to identify statistical significance in proportion of correct responses. The first activity launched 11/27/2019 and the second activity launched on 5/8/20. Data were collected and reported through 8/25/2020. Results: A total of 8433 learners, including 1543 oncologists, participated from 11/2019 through 8/2020. Participation in education resulted in significant relative improvements among oncologist learners on IO in GI cancers in (n = 641): 110%: role or eligibility of immune checkpoint inhibitors (ICIs) (p < .001) 38%: clinical trial data of ICIs (p < .001) Subsequent education on unresectable HCC demonstrated a significant relative improvement in both knowledge and competence for oncologist learners (n = 902): 19%: regarding clinical trial data in unresectable HCC (p = .073) 19%; competence identifying role of ICIs in unresectable HCC (p < .05) 59%: competence managing irAEs in unresectable HCC (p < .001). Conclusions: These 2 online CME-certified educational activities resulted in statistically significant gains in oncologist knowledge surrounding the use of IO in advanced GI cancers Follow-up education on HCC demonstrated the value and benefit of multi-modal and sequential activities on improving competence among oncologists caring for patients with unresectable HCC There remains a need for continuous education as more oncologists utilize IO in their practice while the understanding and availability of clinical data continues to expand and evolve in the varying GI cancer subtypes. More than 50% of learners continued to demonstrate a need in understanding the clinical trial data or role of IO in metastatic GI cancers with more than 40% of the learners demonstrating continued need on clinical trial data or role of IO in HCC specifically.
Adherence to clinical practice guidelines for adjuvant chemotherapy for colorectal cancer in Uruguay: A population-based study.
Authors: Fontes Santiago , Marín-Jiménez Ana , Berry Megan , Cuello Mauricio , Sánchez Juan Carlos , Reyes Graciela , Krygier Gabriel David
Published: January 2021

53

Background: Despite surgery, the 5-year risk of systemic recurrence of colorectal cancer (CRC) in the absence of any further therapy is approximately 50 % for those with lymph node involvement and 20 ─ 30 % if the lymph nodes are negative. Adjuvant chemotherapy contributes to improved disease-free and overall survival for node-positive (stage III) or high-risk node negative (stage IIB) colon cancer. Similar benefits are observed for adjuvant chemoradiotherapy in rectal cancer. Previous research shows varied rates of adherence to published adjuvant chemotherapy Clinical Practice Guidelines (CPGs) for CRC, although population-based data is scarce. Purpose: The aim of this analysis was to assess adherence rates to adjuvant chemotherapy prescription within 16 weeks of surgery according to local and international CPGs for CRC patients treated with curative intent between 2008 and 2019 at the Uruguayan National Cancer Institute. Data regarding factors associated with chemotherapy receipt beyond 16 weeks from surgery and chemotherapy non receipt was also retrieved and analysed. Methods: We retrospectively reviewed medical and pathology reports of 833 patients diagnosed with CRC at our institution. Patients with stages IIB or III CRC who underwent curative-intent surgery were identified and included in the present analysis. A 16-week benchmark timeline for treatment initiation from date of surgery was considered. Fisher’s exact test was used to determine factors independently associated with receipt of chemotherapy and meeting the 16-week benchmark (p 0.05). Results: A total of 400 patients were identified of which 72% had peritoneal colorectal tumors and 28% had sub-peritoneal rectal tumors. Approximately 70% of the latter group received neoadjuvant chemo-radiotherapy. Considering the total cohort, 61% received adjuvant chemotherapy. Factors predicting chemotherapy receipt in the peritoneal colorectal group were age ≤ 70 and stage III disease. In the sub-peritoneal rectal group no significant effect was found. The 16-week benchmark was met in 72% (175) of those receiving chemotherapy and 70.6% (167) completed 6 months of systemic adjuvant treatment. A total of 156 patients (39%) did not receive adjuvant chemotherapy. The factors predicting chemotherapy non receipt were age > 70 and stage IIB in the peritoneal colorectal group. Conclusions: This analysis of adherence to CPGs identified several factors associated with chemotherapy non receipt and chemotherapy receipt outside of timeline benchmarks from date of curative-intent surgery in Montevideo, Uruguay. The two main factors significantly associated with chemotherapy non receipt were advanced age and lower disease stage. To our knowledge, our data is the first to elucidate these specific factors in the Uruguayan CRC patient population.
Clinician perspectives on preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies.
Authors: Lau-Min Kelsey S. , Varughese Lisa A. , Nelson Maria N. , Cambareri Christine , Reddy Nandi J. , Oyer Randall A. , Teitelbaum Ursina R. , Tuteja Sony
Published: January 2021

54

Background: Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice. Methods: We conducted a multi-site mixed-methods study to understand clinician attitudes toward PGx testing and to identify facilitators and barriers to using preemptive testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a demographic survey and semi-structured interview informed by the Consolidated Framework for Implementation Research. Interviews were analyzed using a modified grounded theory approach. Results: A total of 16 medical oncologists and 9 oncology pharmacists from one academic medical center and two community hospitals participated. Fifteen (60%) participants reported feeling comfortable or very comfortable with interpreting PGx test results. While clinicians expressed generally favorable attitudes toward PGx testing, many were hesitant to use it to preemptively guide chemotherapy dosing due to a perceived lack of evidence for this practice. They cited a lack of consensus chemotherapy dosing recommendations in response to PGx test results, as well as concerns about decreased drug efficacy, especially in patients treated with curative intent. Additional barriers included 1) a low prevalence of actionable PGx variants; 2) lengthy PGx test turnaround time; 3) concerns about testing costs and lack of insurance coverage; and 4) burdensome integration of PGx testing into clinical workflows. The electronic health record emerged as a potential tool for the unobtrusive integration of PGx testing into clinical practice–suggested applications included default PGx test orders for eligible patients, discrete reporting of PGx variant results, and clinical decision support to guide subsequent chemotherapy dosing. Conclusions: Successful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multi-level effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study. The electronic health record should be explored as a tool to integrate PGx testing into routine practice.
ALTER-C-001: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC—A single-arm, multicenter, phase Ⅱ clinical trial.
Authors: Yan Jin , Zhang Li , Jin Yongdong , Han Yunwei , Sun Hao
Published: January 2021

70

Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is considered as the standard first-line therapy for metastatic colorectal cancer (mCRC), and maintenance treatment is proven to be a promising and controversial therapeutic strategy which is mainly involved bevacizumab or capecitabine. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib is a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously. Previous studies indicated that anlotinib demonstrated clinical benefits for patients with mCRC. This study aimed to evaluate the efficacy and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib maintenance therapy for mCRC. Methods: ALTER-C-001 trial was an open label, single-arm, multicenter phase II study. A calculated sample size of 53 patients with previously untreated mCRC, ranging from 18-75 years old and an ECOG performance status ≤ 1 were planned to recruit. Eligible patients were treated with capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) for 6 cycles followed by maintenance therapy of anlotinib (12mg, po, d1~14, q3w) until disease progression or intolerable adverse events (AEs). The primary endpoint was progression-free survival (PFS). Secondary endpoints were ORR, DCR, DOR and safety. Results: From January 2020 to September 2020, a total of 9 patients were enrolled, 6 patients were available for efficacy assessment. In best overall response assessment (all confirmed), there were 66.7% PR (4/6), 16.7% SD (1/6) and 16.7% PD (1/6). The preliminary ORR and DCR of the 6 patients was 66.7% (95% CI, 22.3-95.7%) and 83.3% (95% CI, 35.9-99.6%), respectively. The median PFS was not reached. Most treatment-related adverse events (TRAEs) were grade 1-2. Grade 3 or above TRAEs were as follows: hypertriglyceridemia (33.3%), hypertension (16.7%), neutropenia (16.7%) and lipase elevated (16.7%). No grade 5 AEs were observed. Conclusions: The preliminary results indicated that anlotinib plus XELOX regimen followed by anlotinib monotherapy as first-line treatment exhibited antitumor efficacy and manageable toxicity for patients with mCRC. The study is still ongoing and the data will be updated subsequently. Clinical trial information: ChiCTR1900028417.
Neoadjuvant chemoradiotherapy with capecitabine in locally advanced rectal cancer: Analysis of prognostic factors.
Authors: Romero Jesus , Sánchez Sofía , Sánchez Arsenio , Alonso Isabel , Benlloch Raquel , Córdoba Sofía , Zapata Irma , Gil Beatriz , López Marta , Hernández María , Pastrana Miguel , Herreros Alberto , Ruíz Casado Ana , Obeso Jorge , Engel Olga
Published: January 2021

92

Background: Capecitabine-based neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer (LARC). The objective of this retrospective study is to analyze overall survival (OS), local relapse free-survival (LRFS), distant metastases free-survival (DMFS) and prognostic factors. Methods: Between 2009 and 2018, 207 patients(p) with LARC has been treated in our hospital with neoadjuvant CRT. Clinical characteristics: Mean age: 65 y (41-87); male:129, female:78; TNM: cT2: 12p, cT3: 176p, cT4: 19p, cN0: 59p, cN1: 106p, cN2: 42p. Treatment: pelvic radiotherapy (45Gy, 1.8Gy/day) plus concomitant capecitabine (852mg/sqm/12h for 28 days). Surgery (mesorectal excision) was carried out 6-8 after the end of CRT. Statistics:Kaplan-Meier and Log-rank test. Results: Mean follow-up: 43 months. Downstaging:104/192 (54%). Pathological complete response:31/192 (16%). Sphincter preservation rate was 82%. Five-year OS, LRFS and DMFS were 89.9%, 93.3% and 81.7%, respectively. Factors predicting shorter 5-y OS were: cT4 (69% vs 91% and 91% for cT1 and CT2, respectively; p=0.027), pT3-4 (85% and 64% vs 100%, 100% and 98% for pT0, pT1 and pT2, respectively; p=0.008), pathological involved nodes (pN+) (77% vs 96%; p=0.001), perineural invasion (PNI) (78% vs 95%; p=0.041), LVI (p<0.001), Ryan 3 (p<0.001), resection margin R1 (67% vs 94% for R0; p<0.001), no pCR (p=0.027) and absence of downstaging (73% vs 97%; p=0.001). Factors associated with poor 5-y DMFS were:pT3-4 ( 70% and 0% vs 96%,88% and 98% for pT0,pT1 and pT2, respectively; p<0.001), pN+ (68% vs 88% for pN0: p<0.001), PNI (64% vs 85%; p=0.036), Ryan 3 (49% vs 96%, 85% and 85% for Ryan 0, 1 and 2, respectively; p<0.001), R1 (33% vs 86% for R0; p<0.001) and absence of downstaging (50% vs 71%; p<0.001). CTCAE 4.0 grade 3 toxicity: 1%. No grade 4 toxicity was seen. Conclusions: CRT with capecitabine provides high rates of survival and sphinter preservation with excellent tolerance. Patients with adverse pathological factors (pT4, pN+, PNI, Ryan 3, R1 and absence of downstaging) have a higher risk of distant metastasis and are more likely to benefit from adjuvant chemotherapy.
Effect of a Multifactorial Intervention on Fracture in Patients With Type 2 Diabetes: Subanalysis of the J-DOIT3 Study
Authors: Sasako Takayoshi , Ueki Kohjiro , Miyake Kana , Okazaki Yukiko , Takeuchi Yasuhiro , Ohashi Yasuo , Noda Mitsuhiko , Kadowaki Takashi
Published: January 2021

Aims

To evaluate the effects of an intensified multifactorial intervention and patient characteristics on the incidence of fractures comorbid with type 2 diabetes.

Methods

Fracture events were identified and analyzed among adverse events reported in the J-DOIT3 study, a multicenter, open-label, randomized, parallel-group trial that was conducted in Japan, in which patients with type 2 diabetes were randomly assigned to receive conventional therapy for glucose, blood pressure, and lipids (targets: HbA1c < 6.9%, blood pressure <130/80 mm Hg, LDL-cholesterol <120mg/dL) or intensive therapy (HbA1c < 6.2%, blood pressure <120/75 mm Hg, LDL-cholesterol <80mg/dL) (ClinicalTrials.gov registration no. NCT00300976).

Results

The cumulative incidence of fractures did not differ between those receiving conventional therapy and those receiving intensive therapy (hazard ratio (HR) 1.15; 95% CI, 0.91-1.47; P = 0.241). Among the potential risk factors, only history of smoking at baseline was significantly associated with the incidence of fractures in men (HR 1.96; 95% CI, 1.04-3.07; P = 0.038). In contrast, the incidence of fractures in women was associated with the FRAX score [%/10 years] at baseline (HR 1.04; 95% CI, 1.02-1.07; P < 0.001) and administration of pioglitazone at 1 year after randomization (HR 1.59; 95% CI, 1.06-2.38; P = 0.025).

Conclusions

Intensified multifactorial intervention may be implemented without increasing the fracture risk in patients with type 2 diabetes. The fracture risk is elevated in those with a history of smoking in men, whereas it is predicted by the FRAX score and is independently elevated with administration of pioglitazone in women.
Changes in Ghrelin and Glucagon following a Low Glycemic Load Diet in Women with PCOS
Authors: Hoover Sarah E , Gower Barbara A , Cedillo Yenni E , Chandler-Laney Paula C , Deemer Sarah E , Goss Amy M
Published: January 2021

Context

Altered satiety hormones in women with polycystic ovarian syndrome (PCOS) may contribute to obesity. Diets with a low glycemic load (GL) may influence appetite-regulating hormones including glucagon and ghrelin.

Objective

To test the hypothesis that following a 4-week, eucaloric low vs high GL diet habituation, a low vs high GL meal will increase glucagon and decrease ghrelin to reflect greater satiety and improve self-reported fullness.

Methods

Secondary analysis of a randomized crossover trial.

Participants

Thirty women diagnosed with PCOS.

Intervention

Participants were provided low (41:19:40% energy from carbohydrate:protein:fat) and high (55:18:27) GL diets for 8 weeks each. At each diet midpoint, a solid meal test was administered to examine postprandial ghrelin, glucagon, glucose, insulin, and self-reported appetite scores.

Results

After 4 weeks, fasting glucagon was greater with the low vs high GL diet (P = .035), and higher fasting glucagon was associated with lesser feelings of hunger (P = .009). Significant diet effects indicate 4-hour glucagon was higher (P < .001) and ghrelin was lower (P = .009) after the low vs high GL meal. A trending time × diet interaction (P = .077) indicates feelings of fullness were greater in the early postprandial phase after the high GL meal, but no differences were observed the late postprandial phase.

Conclusion

These findings suggest after low GL diet habituation, a low GL meal reduces ghrelin and increases glucagon in women with PCOS. Further research is needed to determine the influence of diet composition on ad libitum intake in women with PCOS.
Synthesis of Alkaline-soluble Triazine-based Poly(phenylene sulfide)s with Single/Double Pendant Carboxylic Acid Moieties and Their Application to Refractive Index Contrast Materials
Authors: Higashihara Tomoya , Fu Mao-Chun , Hatakeyama Kouji , Ando Shinji , Takahashi Ryosuke , Ueda Mitsuru
Published: January 2021

The design, synthesis, and optical characterization of refractive-index-contrast (RIC) triazine-based poly(phenylene sulfide)s (PPSs) are investigated. Indeed, novel PPSs with two pendant groups, either tert-butyl (tBu) ester or carboxylic acid groups, at each monomer repeating unit (PPS-2E or PPS-2CA, respectively) were successfully synthesized. PPS-2CA showed high refractive index (n) values of 1.6964 (633 nm) and 1.6714 (940 nm) as well as high δn (increase in the n value by the deprotection of PPS-2E) values of +0.062 (633 nm) and +0.058 (940 nm).
Social development and public debt sustainability
Authors: Vavoura Chara , Vavouras Ioannis
Published: January 2021

The issue of public debt sustainability is of exceptional importance in the case of Greece. As a rule, the relevant analysis is limited to the examination of the fiscal policy measures reported to contribute to reducing public debt leaving out the investigation of the factors that caused the country’s debt crisis. The objective of the present paper is to explore the determinants of Greece’s debt crisis and the strategy required to address it. Our work highlights the issue of social development, which is found to be a necessary condition for ensuring the long run sustainability of the country’s public debt.
The use of internet and domestic violence offenders behaviours in Greece
Authors: Chatzifotiou Sevaste , Filippidis George , Fotou Eleni , Koutsoukis Spiros
Published: January 2021

This paper seeks to investigate the correlations between the use of communication technology and intimate partner violence, in terms of manifestations of aggressive behaviours, changes in modus operandi, stalking behaviours and the use of coercive control through communication technology. The subjects of the study are courtmandated offenders (n=21) who are enrolled in a therapeutic program specifically designed for domestic violence offenders. Finally, recommendations for future research and policy and practice are offered.
Ανδρέας Φερώνας Κοινωνικός Αποκλεισμός και Κοινωνική Αλληλεγγύη στην Ελλάδα της Κρίσης, Αθήνα: Διόνικος, 2019
Authors: Οικονόμου Χαράλαμπος
Published: January 2021

no abstract
The Social Accounting Matrix, the reduction of borrowing through the reduction of government consumption and its effect on the Greek economy
Authors: Economidis Charalampos
Published: January 2021

The aim of this paper is to calculate the impact of the reduction or elimination of net borrowing on the Greek economy. The assumption made for this calculation is that a reduction of net borrowing leads to a reduction of government consumption. The effects on the Greek economy of reducing borrowing are calculated by using the Social Accounting Matrix. The results show that a reduction of borrowing must be replaced by a significant increase in production and the resulting reductions relate primarily to sectors in which the state has sizeable participation, such as education, health, security, public administration and defence services.
With and Against the Powers of Contingency: an Introduction
Authors: Dimakopoulou Stamatina
Published: January 2021

Introduction
“The ever-dissolving image of deceptively tranquil antiquity”: Classical Myth and Literature in the Prose and Poetry of Laura Riding
Authors: Theodorakopoulos Elena
Published: January 2021

This essay discusses the poet, critic and novelist Laura (Riding) Jackson (1901-1991), and her engagement with classical myth and literature. The focus is on her poetry and on the novel A Trojan Ending. The aim of the essay is to establish Riding as a significant voice in the reception and interpretation of classical myth and literature during the 1920s and 30s.
The ‘Classics’ in India: Unseen Presence, Cloaked Authority
Authors: Trivedi Harish
Published: January 2021

The classics were taught not only in the West but also all over the colonised world –except in India, probably because India was acknowledged to have foundational classics of its own written in a language which was proclaimed by Western scholars to be fully a match of Greek and Latin. However, an earlier connection between Greece and India that began in 326 BCE with the aborted attempt by Alexander the Great to conquer India left enduring cultural traces which have been explored by creative writers and scholars alike. In the hey-day of British rule in India, the British governors and civil servants, who were themselves steeped in classical education, often fashioned themselves on the model of Pax Romana, so that the absence in India of a direct classical education was still not exempt from a pervasive classical penumbra.
Perspectives of different stakeholders on data use and management in public health emergencies in sub-Saharan Africa: a meeting report
Authors: Munung Nchangwi  Syntia , Chi Primus Che , Abayomi Akin , Afolabi Muhammed O. , Ambe Jennyfer , Bonarwolo Korlia , Kajoleh Francis Kombe , Staunton Ciara , Ujewe Samuel , Yusuf Kabba , Tangwa Godfrey B.
Published: January 2021

During public health emergencies (PHEs), data are collected and generated from a variety of activities and sources, including but not limited to national public health programs, research and community-based activities. It is critical that these data are rapidly shared in order to facilitate the public health response, epidemic preparedness, as well research during and after the epidemic. Nonetheless, collecting and sharing data during PHEs can be challenging, especially where there are limited resources for public health and research-related activities during a PHE. In a symposium that brought together different stakeholders that were involved in the 2013-2016 Ebola outbreaks in West Africa, meeting attendees shared their perspectives on the values and management of data during PHEs in sub-Saharan Africa. Key factors that could inform and facilitate data management during PHEs in sub-Saharan Africa were discussed, including using data to inform policy decisions and healthcare; a coordinated data collection and management scheme; identifying incentives for data sharing; and equitable data  governance mechanism that emphasise principles of reciprocity, transparency and accountability rather that trust between stakeholders or collaborators. Empirical studies are required to explore how these principles could inform best practices for data management and governance during PHE in sub-Saharan Africa.
Contribuições da Psicanálise Existencial à Prática Clínica: Indicações Teóricas e Metodológicas
Authors: Castro Fernando Gastal de , Resende André Diogo , Gabriel Mariana
Published: January 2021

Tem-se como objetivo desse artigo aportar contribuições teóricas e metodológicas da psicanálise existencial à prática clínica a partir do existencialismo e da fenomenologia de Jean-Paul Sartre. Em um primeiro momento, esboçaremos os contornos principais da psicanálise existencial em comparação com a perspectiva freudiana, focando nos conceitos de desejo, projeto, repressão e situação, sustentando a psicanálise existencial como uma clínica de situações. Em um momento seguinte, nos dedicamos à exposição de um caso clínico, com a finalidade de tornar mais concreta as contribuições metodológicas do método progressivo-regressivo e da reflexão purificadora. Buscaremos mostrar, nesse sentido, a pertinência de uma perspectiva metodológica que alcance o vivido singular, atravessado pelas múltiplas formas de violências do universo social produtoras de situações traumáticas, bem como as possibilidades de metamorfose do projeto existencial. Em nossas considerações finais, destacamos os desafios de uma prática clínica em se ocupar da dialética entre o universo social, no qual recrudescem formas de violência, e a singularidade do projeto existencial em luta contra suas determinações e desejoso por transformar-se.