bluuebunny/crossref_metadata_2025 huggingface dataset:
Weather in two climatic regions shapes the diversity and drives the structure of fungal endophytic community of bilberry (Vaccinium myrtillus L.) fruit
Authors: Nguyen Minh-Phuong , Lehosmaa Kaisa , Toth Katalin , Koskimäki Janne J. , Häggman Hely , Pirttilä Anna Maria
Published: January 2024

Background

Bilberry (Vaccinium myrtillus L.) is one of the most important economic and natural resources in Northern Europe. Despite its importance, the endophytic fungal community of the fruits has rarely been investigated. Biogeographic patterns and determinants of the fungal diversity in the bilberry fruit are poorly understood, albeit fungal endophytes can have a close relationship with the host plants. Here, we investigated the effect of climatic regions, and their weather conditions within growth season and soil properties on fungal endophytic communities of bilberry fruits collected from northern and southern regions of Finland using high-throughput sequencing technology targeting the internal transcribed spacer 2 ribosomal DNA region for fungi.

Results

Species richness and beta diversity (variation in community structure) were higher in the southern compared to the studied northern region. The weather condition of the growth season drove both fungal richness and community structure. Furthermore, abundance of the genera Venturia, Cladosporium, and Podosphaera was influenced by the weather, being different between the south and north regions.

Conclusions

We conclude that diversity and assembly structure of the fungal endophytes in bilberry fruits follow similar patterns as for foliar fungal endophytes, being shaped by various environmental factors, such as the climate and surrounding vegetation.
Dietary diversity and associated factors among women attending antenatal clinics in the coast region of Tanzania
Authors: Heri Rashidi , Malqvist Mats , Yahya-Malima Khadija I. , Mselle Lilian Teddy
Published: January 2024

Background

Antenatal care (ANC) is crucial for reducing maternal morbidity and mortality, especially in low-resource settings. During antenatal care, women are provided with resources for enhancing their dietary diversity, like nutrition education and counseling. Improved nutrition knowledge influences positive nutritional behavior change, like women’s improved dietary diversity, which may increase the likelihood of a healthier pregnancy and delivery experience.

Objective

This study aim was to assess dietary diversity and associated factors among pregnant women attending antenatal care in the Coast region of Tanzania.

Methods

The descriptive cross-sectional study design was used to assess dietary diversity and associated factors among 338 pregnant women. A semi-structured questionnaire collected information from pregnant women on social demographic characteristics, nutrition knowledge and dietary diversity. Women were classified as having a varied diet if they had consumed at least five of the ten food groups over the previous twenty-four hours. Multivariable logistic regression analyses were used to identify predictors of dietary diversity in pregnant women.

Results

Only 28% (95% CI: 23.5–33.1) (n = 95) of pregnant women met the minimum dietary diversity, and 18% (95% CI: 13.8–21.9) (n = 59) were considered to have a high level of nutrition knowledge. Living near a health facility (AOR = 1.77, CI 1.02, 3.06), having high nutrition knowledge (AOR = 2.58, 95% CI: 1.36, 4.89), and being pregnant for the first time (AOR = 2.44, 95% CI: 1.09, 5.44) were associated with adequate dietary diversity.

Conclusion

Pregnant women in the study were found to have low knowledge about nutrition and inadequate dietary diversity intake. The findings underscore the need to improve nutrition knowledge provision in antenatal clinics by emphasizing the importance of a diversified and high-quality diet. Healthcare providers in antenatal care clinics should consistently provide nutrition education and counseling to pregnant women and promote their diversified food consumption. Such knowledge may eventually promote healthier pregnancy and child development by curbing the nutritional deficiencies experienced during pregnancy.
Characterising concurrent pain experience and dietary patterns in people with chronic musculoskeletal pain: a feasibility study protocol
Authors: Ward Susan J. , Coates Alison M. , Baldock Katherine L. , Berryman Carolyn , Hill Alison M.
Published: January 2024

Introduction

Nutrition-related factors linked to pain chronicity and disability include weight status and dietary behaviours. Dietary patterns associated with concurrent pain episodes, however, remain poorly characterised. This paper outlines the protocol for a feasibility study that aims to characterise pain-related dietary and lifestyle behaviours in people experiencing chronic musculoskeletal pain.

Methods

The study will recruit participants who experience musculoskeletal pain on 5 or more days of the week for at least 3 months. Participants will attend two in-person clinic visits where physical measurements and a series of pain and lifestyle questionnaires will be completed. Visits will be conducted pre and post a 2-week self-monitoring period where participants will self-report concurrent diet, sleep, mood, and pain on four days and will wear a wrist-worn activity monitor (GENEActiv). Key feasibility metrics will evaluate participant recruitment, enrolment and retention rates, and compliance with the study data collection protocol.

Discussion

There remains a lack of evidence behind dietary advice as an adjunct pain management tool. Upon completion of the protocol, feasibility outcomes will identify challenges to guide the design and delivery of a dietary intervention for chronic musculoskeletal pain.
Financial markets implications of the energy transition: carbon content of energy use in listed companies
Authors: Mazzarano Matteo
Published: January 2024

Decarbonization is often misunderstood in financial studies. Furthermore, its implications for investment opportunities and growth are even less known. The study investigates the link between energy indicators and Tobin's Quotient (TQ) in listed companies globally, finding that the carbon content of energy presents a negative yet modest effect on financial performance. Furthermore, we investigated the effect carbon prices in compliance markets have on TQ for exempted and non-exempt firms, finding that Energy efficiency measures yield greater effects in the latter group. Conversely, it is also true that carbon prices marginally reduce TQ more in non-exempt firms. This implies that auction-mechanisms create burdens that companies are eager to relinquish by reducing emissions. However, reducing GHG yields positive effects on TQ only as long as it results in energy efficiency improvements.
The role of teacher assessment literacy in job stress and job burnout in EFL contexts: a mixed-methods investigation
Authors: Rezai Afsheen
Published: January 2024

Reviewing the literature reveals that the role of teacher assessment literacy (TAL) in teacher job stress (TJS) and teacher job burnout (TJB) among English as foreign language (EFL) teachers in Iran has remained largely unexplored. As a result, this mixed-methods study investigated the association between TAL, TJS, and TJB in the Iranian EFL context. For the quantitative section, 413 EFL teachers, including 221 males and 192 females, were randomly selected. They completed the Teacher Assessment Literacy Questionnaire, the Teacher Job Stress Scale, and the Teacher Job Burnout Inventory, and the data was analyzed using structural equation modeling. For the qualitative part, 18 EFL teachers who joined the quantitative part participated in a focus group interview, and their responses were analyzed through a content analysis approach. Results indicated that TAL is a strong predictor of TJS and TJB. Specifically, the findings indicated that TAL was positively linked to all the sub-scales of TJS and TJB. Additionally, the complementary qualitative results yielded four themes: TAL promotes job productivity, TAL raises teachers’ social face, TAL enables teachers to manage the class efficiently, and TAL brings positive wash-back. The findings suggest that TAL, TJS, and TJB should be incorporated in pre-service and in-service teacher training courses in EFL education.
What rationale would work? Unfolding the role of learners’ attitudes and motivation in predicting learning engagement and perceived learning outcomes in MOOCs
Authors: Wei Xiaomei , Saab Nadira , Admiraal Wilfried
Published: January 2024

The aim of this study is to gain insight into the interplay between attitudes, motivation, learning engagement, and perceived learning outcomes in massive open online courses (MOOCs). An online survey was administered to 232 MOOC learners. This study provided comprehensive explanations for individual differences in learning engagement and perceived learning outcomes in MOOCs with a modified model of the expectancy-value theory of achievement motivation. The structural equation modeling revealed that attitudes served as a precursor of participation in MOOCs that significantly influenced self-efficacy, intrinsic value, and task effort cost; self-efficacy and intrinsic value were positively associated with both learning engagement and perceived learning outcomes, while attitudes toward MOOC learning was positively related to perceived learning outcomes only. Furthermore, the mediation analyses highlighted that intrinsic value was a powerful mediator, which positively influenced the effects of attitudes and self-efficacy on learning engagement and perceived learning outcomes. The moderation analyses discovered that task effort cost moderated the effects of attitudes on learning engagement and perceived learning outcomes. Curriculum designers and instructors could benefit from this study to understand what rationales drive individuals to be engaged in MOOC learning and to reach greater perceived learning outcomes in MOOCs.
Genetic expressions and evaluation of insecticidal activity of some essential oil and methomyl lannate 90% against Spodoptera frugiperda
Authors: Sadek Hanaa E. , Elbehery Huda H. , Mohamed Shereen Abdel-Hameed , El-wahab T. E. Abd
Published: January 2024

Background

Fall armyworm (FAW)Spodopterafrugiperdais regarded as a major pest of various economic crops, their caterpillars are a highly destructive and have a wide host range. The application of traditional pesticides is the main strategies used for its control, that resulting to number of negative impacts of pesticides on the environment and development of pesticide resistance.

Methods

This study’s goal was to assess the insecticide potency of three essential oils [rosemary (RosmarinusofficinalisL.), lemongrass (Cymbopogoncitratus) and Cinnamon (Cinnamomumzeylanicum)] and methomyl lannate 90% commercial insecticide to controlS.frugiperda(fall armyworm) and their effects on expression of caspase-8 and inhibitor of apoptosis protein genes and expression of acetylcholinesterase (AChE) gene in fall armyworm (FAW).

Results

The insecticidal activity against second larval instar of fall armyworm was evaluated with five concentrations (2.5%, 2%, 1.0%, 0.5% and 0.25%) for essential oil and four concentrations 0.4%, 0.2%, 0.15% and 0.05% for methomyl lannate 90%. The findings indicated that raising both essential oil concentrations and methomyl lannate 90% resulted in increased larval mortality at high concentration. The expression levels of Ache gene treated by low dose (0.3 µ/L) of methomyl lannate were increased (by 313%) significantly compared with the control but without significant differences.

Conclusions

The tested essential oils showed insecticidal activity against the second larval instar ofS.frugiperdadeath as a result of treatment with the tested oils having an effect on the genes that the pest uses to express critical processes (genes of apoptosis).
The osteogenic inducing potential of platelet-rich fibrin on stem cells derived from bone marrow and oral mucosa
Authors: Ibrahim Reham Mostafa , Halawa Ahmed , Soliman Nadia , Baraka Nuha , Aly Riham
Published: January 2024

Background

Recently, attention has been directed toward the use of osteoinductive biomaterials in combination with stem cells for possible application in repair of bony defects. Blood products, namely platelet-rich fibrin (PRF), have been widely used nowadays owing to their wide range of advantages. Gingival mesenchymal stem cells (GMSCs) also recently have been utilized and considered as a highly promising alternative source, eliminating a lot of the drawbacks faced by stem cells derived from the bone marrow. The present study aimed to compare the proliferative and osteogenic effect of PRF, on both GMSCs and BM-MSCs. BM-MSCs and GMSCs were cultured in osteogenic media in combination PRF for two weeks. Following culture, MTT assay was conducted to assess the proliferative capacity of both types of cells after subjection to PRF. Osteogenic differentiation was assessed by Alizarin red staining in addition to OSN and Runx2 gene expression by RT-qPCR.

Results

PRF proved to have a positive proliferative effect, especially on GMSCs, compared to BM-MSCs. PRF also demonstrated a positive osteogenic inductive effect on both stem cell types, but its effect seemed to be more pronounced when combined with GMSCs.

Conclusions

PRF proved to be a promising and potent inducer of proliferation and osteogenesis when used in combination with stem cells, especially when combined with GMSCs.
Predictors of mortality in heart failure patients with reduced or mildly reduced Ejection Fraction: The CASABLANCA HF Study
Authors: Couissi Abdessamad , Haboub Meryem , Hamady Siyam , Ettachfini Taha , Habbal Rachida
Published: January 2024

Background

Heart failure (HF) poses a significant public health challenge throughout the world and Morocco. Our objective was to delineate the epidemiological characteristics of Moroccan patients living with chronic heart failure and to identify prognostic factors correlated with CHF mortality.

Results

A total of 1344 patients participated in this study, with survival rates at 3, 6, and 10 years recorded at 75.2%, 60%, and 34%, respectively. During the follow-up, 886 patients succumbed, representing a mortality rate of 65.9%. A Cox regression model, utilizing baseline candidate variables, was developed to predict cardiovascular (CV) mortality. Predictors all of which had a P value less than 0.05 included age, left ventricular ejection fraction (EF) at commencement (< 35%), hypertension, male sex, anemia, creatinine levels, and the number of hospitalizations due to HF decompensation. Notably, the frequency of hospitalizations emerged as the most potent predictor of mortality, with an HR of 2.5 (95% CI [2–2.9]). Almost 90% of patients with three or more readmissions for HF decompensation experienced mortality by the follow-up’s conclusion.

Conclusions

This study offers valuable insights into risk factors and clinical outcomes in HF patients in Morocco. Factors such as male gender, advanced age, a history of hypertension, lower systolic blood pressure, rehospitalizations for HF decompensation, low left ventricular ejection fraction, anemia, and elevated creatinine levels were associated with increased mortality. Medical and health services managers should be aware of the substantial burden and future challenges posed by HF in Morocco, prompting the adoption of multidisciplinary strategies for its management and care.
Pulmonary metastatectomy in pediatric cancer patients at National Cancer Institute, Egypt: prognostic factors and outcome
Authors: Hamoda Asmaa , Elattar Inas , Mahmoud Heba , Abdelrahman Mohamed , Ebied Emad
Published: January 2024

Background

Metastatic tumors account for 80% of all lung tumors in children. Wilms tumour and osteosarcoma are the most tumors of childhood that produce lung metastases. The aim of the current study is to assess the prognostic factors of pulmonary metastatectomy in pediatric solid tumours as age, number, size, site,laterality, resectability of pulmonary nodules, and number of Thoracotomies. Calculate overall survival among patients who underwent pulmonary metastatectomy.

Methods

It is a retrospective study including all pediatric patients with metastatic solid tumors to lungs treated at pediatric oncology department, National Cancer Institute, Cairo University from 2008 to 2014. Fifty-five patients were included, 43 (78.2℅) patients of them had Osteosarcoma.

Results

Thirty (54.5℅)patients were male. The mean age was 15 years ranging from (4.5- 23) years. The site of primary disease was at lower limbs in 43 (78.2%) patients. All patients underwent complete surgical resection of the primary disease with negative margin, 22(51.1%) of the osteosarcoma patients did amputation with tumor necrosis less than 90%. All patients received chemotherapy and only 9 received radiation therapy. The patients were classified into four groups according to time of diagnosis of pulmonary metastasis: at time of diagnosis in 13 (21.8%) patients, within treatment in 16 (30.9%) patients, within first year follow up in 18 (32.7%) patients and detected late in 8 (14.5%) patients. Bilateral lung metastasis diagnosed by CT chest were detected in 42 (76.4%) patients. Size of metastatic nodules was ranging from (0.5 to 10 cm) with mean 3.4 cm. Number of metastatic nodules was ranging from (1 to 28) median 4.Metastatic complications were detected in 19 patients. 5-year OS was 74.8% in the study group, and 68% in osteosarcoma patients. Effect of prognostic factors as sex, time of respectability, laterality, tumor necrosis of the 1ry disease, Timing of lung metastasis, size and site of the primary, Surgical approach of metastatectomy, postoperative complications on overall survival of the studied patients was done with significant P-value of tumor necrosis of the 1ry disease and Timing of lung metastasis 0.017, 0.001 respectively.

Conclusion

Resection of pulmonary metastases of pediatric solid tumours is a safe and effective treatment that offers better survival.
Oncologic safety of transverse colon cancer surgery without central vessel ligation.
Authors: Lee Kyung-ha , Kim Ji Yeon , Yang In Jun , Yoon Seung-Hwan
Published: January 2024

108

Background: Transverse colon cancers (TCC) have mixed embryological and molecular characteristics of right and left colon cancers and they are difficult to classified to right or left colon cancer due to the ambiguity of their location. Therefore, there is a lack of research about TCC alone, and it tended to be excluded in previous large clinical trials. Also, the optimal surgical procedure for each TCC varies depending on the location and stage of the tumor and anatomic structure of the patient. Consequently, standardization of surgery for TCC has not been established, and the oncologic benefits of central vessel ligation (CVL) with complete mesocolic excision and D3 dissection are unclear yet. The aim of the study is to evaluate oncologic safety of TCC surgery without CVL of middle colic artery. Methods: It is a retrospective, observational study. The clinical, surgical, and pathological characteristics were investigated retrospectively and statistical analyses were performed using chi-square test, independent samples T-test, and Kaplan-Meier analysis. Mid TCC was defined as tumor arising in the middle third of transverse colon and determined by intraoperative exploration. Hepatic and splenic flexure colon cancer, which were defined as tumor is adjacent to liver or spleen, were excluded. Radical resection was conducted along the embryological surgical plane, following D2 or D3 dissection. Central vessel ligation was defined as ligation of root of middle colic artery. Results: The numbers of proximal, mid, and distal TCC were 48 (45.3%), 32 (30.2%), and 26 (24.5%), respectively. The numbers of right hemicolectomy, transverse colectomy and left hemicolectomy were 57 (53.8%), 28 (26.4%) and 21 (19.8%). The numbers of No CVL group and CVL group were 47 (44.3%) and 59 (55.7%). The numbers of stage I, II and III were 24 (22.6%), 45 (42.5%), 37 (34.9%), and 49 patients underwent adjuvant treatment. The most frequent organ of recurrence was peritoneum (N=6, 5.6%). There was no statistically significant difference of stage, mean number of retrieved lymph node (24.12 vs. 22.36 p=0.464), mean number of metastatic lymph node (1.53 vs. 0.74, p=0.163), mean proximal margin (19.2 cm vs. 16.7 cm, p=0.139), mean distal margin (9.6 cm vs. 9.9 cm, p=0.753), adjuvant chemotherapy, and the rate of recurrence with lymph node metastasis. Also, there was no statistically significant difference of 6-year DFS survival and OS in stage II and III. Conclusions: When following oncologic plane and adequate lymph node dissection, resection without CVL for TCC is considered to have equal surgical and oncologic outcomes comparing to resection with CVL. Therefore, it is considered that CVL would not be always mandatory for TCC surgery, and a branch of middle colic artery could be preserved, if necessary.
A first-in-human, open-label, phase I trial of daily oral zelenirstat, an NMT inhibitor, in patients with relapsed/refractory advanced cancer including gastrointestinal cancers.
Authors: Spratlin Jennifer L. , Sangha Randeep S. , Jamal Rahima , Beauchamp Erwan , Berthiaume Luc G. , Mackey John Robert
Published: January 2024

129

Background: Myristoylation catalyzed by N-myristoyltransferases (NMT) 1 and 2 regulates membrane-bound signaling important in cancer, including Src and Src-family tyrosine kinases. Zelenirstat is a potent oral small molecule pan-NMT inhibitor. Transcriptomic analysis of zelenirstat treated cell lines identified an expression signature that predicts cancers most likely to be responsive to NMT inhibition; high sensitivity scores were seen in colorectal carcinomas and diffuse large B-cell lymphoma. The objectives of this phase I study were to determine the safety, tolerability, and maximum tolerated dose (MTD) of zelenirstat monotherapy in patients (pts) with refractory cancers. Methods: Pts with advanced solid malignancies or relapsed/refractory B-cell lymphomas were dose escalated with daily oral zelenirstat in 28-day cycles until progressive disease or dose-limiting toxicity (DLT). Results: Between September 2021 and July 2023, pts received 28-day cycles of zelenirstat ranging from 20 mg/d to 280 mg/d. In 21 evaluable patients, DLT was not observed up to and including the 210 mg/d cohort. Gastrointestinal DLTs were seen in the 280 mg/d cohort, establishing 210 mg/d to be the MTD. In doses up to and including 210 mg/d, gastrointestinal adverse events were the most common, reported in 29% of pts; these were primarily Gr 1 or 2 diarrhea, nausea or vomiting. Transient Gr 2 thrombocytopenia was seen in 3 pts. Zelenirstat did not induce neuropathy, alopecia, or prolong QT intervals. Plasma concentrations peaked between 1h and 4 h, terminal half-lives were 6.7 to 12 h, and steady state was achieved by day 8. Proton pump inhibitors lowered exposure and were prohibited in the higher dose cohorts. At 100 mg/d and higher, trough plasma concentrations exceeded the levels predicted to be therapeutic. Stable disease as best response was seen in 5 (30%) of 17 evaluable pts, including 1 patient with advanced refractory colon cancer who received 6 cycles of therapy at 140 mg daily dosing prior to PD. Another colon cancer patient with 5 prior lines of therapy continues 210 mg/d dosing after > 5 cycles of therapy, with non-RECIST criteria reductions of approximately 50% in CEA and tumor volumes. Conclusions: Zelenirstat was well-tolerated on a continuous daily oral schedule at doses as high as 210 mg/d, establishing the MTD to be 210 mg. The absence of severe toxicities, attainment of plasma concentrations highly active in preclinical models, and early evidence of clinical benefit in patients with refractory colon cancer warrant further trials. Updated data will be presented. Clinical trial information: NCT04836195 .
Fruquintinib with PD-1 inhibitors versus fruquintinib monotherapy in late-line mCRC: A retrospective cohort study based on propensity score matching.
Authors: An Tianqi , Lian Yugui , Zhou Quanbo , Zhao Chao , Wang Zheng , Zhao Ruihua
Published: January 2024

139

Background: Immune checkpoint inhibitors (ICIs) are highly effective in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). However, the population of MSI-H/dMMR only accounts for 5% of mCRC. And most of the remaining microsatellite stable or proficient mismatch repair (MSS/pMMR) mCRC patients appeared not to benefit from mere immunotherapy. Fruquintinib, as the standard third-line regimen for mCRC, is an oral small-molecule anti-angiogenic tyrosine kinase inhibitor. Studies demonstrated that fruquintinib combined with programmed death receptor-1 (PD-1) inhibitors (FP) can reverse the immunosuppression and achieve promising efficacy. However, due to the lack of the research comparing the efficacy between fruquintinib monotherapy (FM) and FP, it remains unclear if FP can bring extra benefit. Methods: This is a retrospective cohort study conducted in the First Affiliated Hospital of Zhengzhou University. Patients (pts) with MSS/pMMR mCRC who had received at least the 2nd line treatment were eligible. Propensity score (PS) would be calculated to balance the baseline characteristics of two cohorts. Progression-Free survival (PFS) was set as the primary endpoint. The Kaplan–Meier method and Cox proportional hazard model was used to evaluate PFS and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: From Apr 2020 to Jan 2023, 83 eligible pts in total were enrolled. According to the treatment received, 47 and 36 pts were respectively allocated into FP cohort and FM cohort. With a global median follow-up of 16.5 mo, the crude PFS was 6.8 (95% CI: 4.3-11.3) mo in FP cohort vs. 3.9 (3.1-4.7) mo in FM cohort. The HR of FP was 0.58 (95% CI: 0.34-0.98, FM as reference). Multivariate Cox regression showed that the adjusted HR was 0.49 (95% CI: 0.26-0.93), which was adjusted with sex, age greater than 65 yr, ECOG-PS, RAS mutation, BRAF mutation, location of lesion (left or right), surgery history, metastases (liver and lung), prior medication (bevacizumab and cetuximab), and current line (3 or later). With PS, we performed three statistical methods, namely inverse probability weighting, PS matching (the sample size was 37 vs. 29 after matching), and additional adjustment for propensity score with multivariate cox regression. The HR of FP were 0.49 (95% CI: 0.26-0.94), 0.40 (95% CI: 0.21-0.77), and 0.46 (95% CI: 0.24-0.90), respectively. Conclusions: Pts in FP cohort showed a significantly greater PFS than those in FM cohort. And with further analysis, FP indicated robustly lower HRs than FM. Our study suggests FP could provide additional benefits to pts with MSS/pMMR mCRC, and warrants further investigations in a large cohort.
Tumor genomics and sidedness to predict outcomes in metastatic colorectal cancer (mCRC).
Authors: Boland Patrick M , Quintanilha Julia , Li Gerald , Clark Allison , Carlson Erik , Morley Samantha , Aboosaiedi Ali , Mitchell Jerry W. , Ross Jeffrey S. , Graf Ryon , Deming Dustin A. , Lieu Christopher Hanyoung
Published: January 2024

207

Background: Tumor sidedness is a prognostic factor and predictive parameter for EGFR monoclonal antibody (mAb) treatment in mCRC. Sidedness is believed to be a surrogate for genomic differences. This study aimed to evaluate genomics vs. tumor sidedness in anticipating outcomes in mCRC. Methods: We included patients (pts) with microsatellite stable mCRC tested by Foundation Medicine tissue comprehensive genomic profiling assay. Patient data was obtained by the US-based de-identified Flatiron Health-Foundation Medicine real-world clinico-genomic database (FH-FMI CGDB), originating from approximately 280 US cancer clinics (1/2011–3/2023). Genomic alterations (GA) in 324 genes were compared between right and left side tumors using Fisher’s exact test, adjusted for multiple comparisons. Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared by Cox proportional hazard models adjusted for prognostic features in pts receiving 1st line chemotherapy (chemo) + EGFR mAb or bevacizumab (bev). Multivariable analyses including prognostic features, sidedness and GA were performed. Comparisons of the explanatory power of genomics vs. sidedness were performed by the likelihood ratio test (LRT). Results: 3845mCRC pts (2584 left and 1261 right) were included. GA in APC, TP53, ARID1A, and FBXW7 were more prevalent in left side, while GA in BRAF, KRAS, AMER1A, PIK3CA, RNF43, BCOR, PTEN, SMAD4, MAP2K1, and BCOR in right side. 2109 pts received chemo + EGFR mAb or bev. Multivariable analyses identified BRAF, KRAS, MAP2K1, and APC as independently associated with outcomes. Pts were classified as having GA in RAS pathway (RASalt: KRAS/NRAS, BRAF, or MAP2K1), APC (APCalt), both RAS pathway and APC (APC/RASalt), and none. RASalt group had less favorable outcomes while APCalt group had more favorable outcomes, regardless of treatment received and sidedness. LRT indicated that when genomics was added to the sidedness evaluation, there was an improvement in outcome prediction (p<0.001), but not when sidedness was added to genomics. Conclusions: Tumor genomics better explains differences in outcomes than sidedness in 1st line treatment in mCRC. [Table: see text]
Association of circulating tumor DNA (ctDNA) molecular disease (MRD) detection with lymph node metastasis after local excision of pathological T1 colorectal cancer: First results from DENEB, a CIRCULATE-Japan GALAXY substudy.
Authors: Miyo Masaaki , Kato Takeshi , Nakamura Yoshiaki , Mishima Saori , Bando Hideaki , Yukami Hiroki , Ando Koji , Watanabe Jun , Akazawa Naoya , Yokota Mitsuru , Kagawa Yoshinori , Jurdi Adham A , Liu Minetta C. , Oba Koji , Taniguchi Hiroya , Kotani Daisuke , Oki Eiji , Takemasa Ichiro , Mori Masaki , Yoshino Takayuki
Published: January 2024

23

Background: Patients with pathological T1 (pT1) colorectal cancer (CRC) at high risk for lymph node metastasis (LNM) after complete local resection are recommended to receive additional intestinal resection along with lymph node dissection. However, the existing pathological criteria for risk stratification of LNM are inadequate, such that ~90% of patients without LNM are exposed to potentially unnecessary treatment. Based on the CIRCULATE-Japan platform, we launched DENEB, a new prospective substudy within the GALAXY observational study, to explore the ability of predicting LNM using circulating tumor DNA (ctDNA) detection compared to the standard pathological criteria. Methods: This study included patients with pT1 CRC who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk-stratification criteria for LNM. The additional surgery was indicated for patients meeting any of the following criteria: (1) depth of submucosal invasion (>1000µm); (2) lymphovascular invasion; (3) poorly differentiated adenocarcinoma, signet-ring cell carcinoma, or mucinous carcinoma; and (4) high-grade tumor budding (BD2/3) at the site of deepest invasion according to the Japanese guideline. ctDNA was analyzed from plasma samples collected within 4 weeks before the additional intestinal resection using a personalized, tumor-informed assay (Signatera bespoke multiplex-PCR NGS assay). The study assessed the diagnostic concordance rate between ctDNA detection and the occurrence of LNM. Results: Of 208 CRC patients enrolled between July 2021 and May 2023 in DENEB, 166 patients met the inclusion criteria. Of these, 22 (13.3%) were ultimately diagnosed with pStage III due to the presence of LNM in additional intestinal resection. Among the 166 patients, 6 patients tested ctDNA-positive; all 6 had LNM, yielding a positive predictive value of 100.0%. On the other hand, 160 patients had ctDNA-negative results, 144 of whom did not have LNM, resulting in a negative predictive value of 90.0%. The overall diagnostic concordance rate for ctDNA in detecting LNM was 90.4% (95% confidence interval, 84.8% to 94.4%). All 6 patients with a ctDNA-positive result and LNM had left-sided colorectal cancer and a tumor diameter greater than 13 mm. Conclusions: This analysis showed that ctDNA testing has the potential to improve risk stratification of LNM in patients with pT1 CRC who underwent complete local resection. Clinical trial information: UMIN000039205 .
SKYSCRAPER-08: A phase III, randomized, double-blind, placebo-controlled study of first-line (1L) tiragolumab (tira) + atezolizumab (atezo) and chemotherapy (CT) in patients (pts) with esophageal squamous cell carcinoma (ESCC).
Authors: Hsu Chih-Hung , Lu Zhihao , Gao Shegan , Wang Jun-Ye , Sun Jong-Mu , Liu Tianshu , Fan Qingxia , Cai Jun , Ge Feijiao , Li Sijing , Zhang Li , Cha Edward , Shen Lin
Published: January 2024

245

Background: Inhibition of TIGIT, a novel checkpoint inhibitor, may further amplify immune responses by complementing the PD-L1/PD-1 pathway. Anti-tumor activity has been demonstrated with cancer immunotherapy in ESCC. SKYSCRAPER-08 (NCT04540211) is evaluating the efficacy and safety of tira (anti-TIGIT) + atezo (anti-PD-L1) in combination with CT compared with placebo + CT as 1L treatment (tx) in an Asian population with unresectable locally advanced (LA), unresectable recurrent, or metastatic (R/M) ESCC. Methods: Eligible pts (confirmed LA or R/M ESCC; ECOG PS 0–1; no prior systemic tx) were randomized 1:1 to receive tira 600mg + atezo 1200mg + CT (paclitaxel 175mg/m2 + cisplatin 60–80mg/m2, local standard of care) or placebo + CT on Day 1 of each 21-day cycle (cycles 1–6); followed by tira + atezo or placebo maintenance until loss of clinical benefit/unacceptable toxicity. Primary endpoints: independent review facility (IRF)-assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints: investigator (INV)-assessed PFS, objective response rate (ORR), duration of response (DoR), and safety. Results: Overall, 461 pts were randomized (tira + atezo + CT, n= 229; placebo + CT, n=232). Pt characteristics were generally balanced between arms. As of 15 June 2022 (minimum survival follow-up 6.5 months [mo]; PFS primary analysis), median IRF-assessed PFS was 6.2 mo for tira + atezo + CT vs 5.4 mo for placebo + CT (HR 0.56; 95% CI: 0.45, 0.70; P<0.0001). As of 13 Feb 2023 (minimum survival follow-up 14.5 mo; OS final analysis), median OS was 15.7 mo for tira + atezo + CT vs 11.1 mo for placebo + CT (HR: 0.70; 95% CI: 0.55, 0.88; P= 0.0024). INV-assessed PFS, IRF-assessed ORR and DoR are presented in Table. Treatment-related adverse events (TRAEs) occurred in 98.2% of pts (both arms); Grade 3/4 TRAEs in 59.6% (tira + atezo + CT) and 56.4% (placebo + CT) of pts; Grade 5 TRAEs in 2.6% (tira + atezo + CT) and 0.9% (placebo + CT) of pts. Conclusions: The study met both primary endpoints of IRF-assessed PFS and OS, demonstrating statistically significant and clinically meaningful improvements in PFS and OS for tira + atezo + CT over placebo + CT. Generally consistent benefit was observed across subgroups, including PD-L1 status. The safety profile was consistent with the known risks of the individual tx. Clinical trial information: NCT04540211 . [Table: see text]
Prevalence of modifiable risk factors of Hispanic adult patients admitted with gastric cancer in the US.
Authors: Nieto Dominguez Alejandro , Eichinger Sarah Elizabeth , Guifarro Rivera Daniel
Published: January 2024

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Background: More than 19% of the US population is comprised of Hispanic individuals. For decades, cancer incidence has been increasing in this population, including cancers associated with infection (gastric, hepatic, cervical) and resulting from delayed screening (colorectal, cervical and breast). Risk factors associated with gastric cancer include H. pylori, obesity, alcohol, and tobacco use. However, ethnicity has not been a commonly reported risk factor despite the fact that studies have shown increasing incidence of gastric cancer in Hispanics at a younger age. Methods: We used the 2016-2019 National Inpatient Sample (NIS) database to stratify patients with gastric cancer by age, ethnicity, and comorbidities. Results: There were 77,745 adults with gastric cancer. Of these, 578 (7.45%) were ages 18-44 (group 1), 28,370 (36.47%) 45-64 years old (group 2), and 43,590 (55.08%) were over 65 (group 3). Group 1 was comprised of 29.4% White, 34.3% Hispanic, 14.5% Black, and 21.8% Asian or Pacific Islander patients. Group 2 consisted of 46.7% White, 19.7% Hispanic, 17.4% Black, and 16.2% Asian or Pacific Islander individuals. Group 3 had the highest percentage of White patients (56.0%) and lowest percentage of Hispanic individuals (12.9%). Group 3 also consisted of 15.1% Black and 16.0% Asian or Pacific Islander patients. In Hispanics with gastric cancer, there was a predominance of H. pylori among younger patients (8.6% in group 1 vs 3.6% and 2.1% in groups 2 and 3 respectively) (p = 0.00). Incidence of smoking increased with age (19.9% in group 1, 28.1% in group 2 and 31.1% in group 3) (p = 0.00) as did incidence of diabetes (8.1% in group 1, 26.4% in group 2 and 36.0% in group 3) (p = 0.00). Alcohol use was 3.0% in group 1, 4.3% in group 2 and 2.3% in group 3 (p = 0.035). The differences between all groups for gastric ulcer, gastric polyp and obesity were not statistically significant. Conclusions: Gastric cancer accounts for approximately 1.5% of all new cancers diagnosed in the US, with a high incidence in older White populations. However, this study demonstrates that there is a large proportion of young Hispanics with gastric cancer who have higher associated instances of H. pylori. This suggests the need for further research to determine if there is utility in screening for H. pylori in asymptomatic young Hispanics to decrease the burden of gastric cancer in this population. [Table: see text]
Esophageal cancer in Hispanics: A propensity score matched analysis of the National Cancer Database.
Authors: Meredith Kenneth Lee , Huston Jamie , Shridhar Ravi
Published: January 2024

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Background: Hispanics are the fastest-growing minority and largest ethnic group accounting for 19.1% of the US population. The American Cancer Society estimated 21,560 new cases of esophageal cancer (EC) in the US in 2023. Hispanics are reported to be at high risks for EC. We sought to interrogate the demographic patterns of esophageal cancer in Hispanics. Additionally, we sought to examine evidence of socioeconomic disparities and differential therapy. Methods: We identified Hispanic vs Non-Hispanic (NH) patients in the National Cancer Database with esophageal cancer between 2005–2018. Variables compared were age, sex, tumor data, surgical intervention, type of treatment, insurance status, income, residence area, and Charlson/Deyo score. Pearson’s Chi-square test was used to compare categorical variables. Groups were statically equated with propensity score-matched analysis (PSM). Survival analysis was estimated by the Kaplan-Meier method and associated log-rank test. Significance was considered at p-value ≤0.05. Results: We identified 66,335 patients with a median age of 63 years (18-90). Hispanics represented 4.2% (2,786) of the entire patient cohort. In this US population we identified significant disparities between Hispanic and NH groups. Differences among Hispanics included higher prevalence of squamous EC (22% vs 19%) p<0.001, higher likelihood of stage IV disease (40.7% vs. 34.8%) p<0.001, younger age p<0.001, higher uninsured status (10.3% vs 3.3%) with income < $40,227 (27.5% vs 16.9%) p<0.001 when compared to NH. However, Hispanics were less likely to have surgical intervention (20.5% vs 27.5%) p<0.001, receive neoadjuvant therapy (61.8% vs 72%) and overall, less likely to receive any type of treatment (30.1% vs 26.1%) when compared to NH p<0.001. Time to treatment was delayed in those Hispanics who were uninsured 37 weeks (22-55) compared to those with private insurance 31 weeks (20-47) p<0.001. Multivariate analysis revealed that any treatment, insurance status, and lower income were all predictors of survival. Treated Hispanics demonstrated no difference in survival then their treated non-Hispanic counterparts (median survival 18.5 vs 18.7 months) with overall 5 year survival at 24% and 25% respectively (p=0.66). Conclusions: Despite lower prevalence, there is a disproportionately higher number of metastatic and untreated cases of esophageal cancer among Hispanics. This disparity may be explained by Hispanics' limited access to medical care exacerbated by their socioeconomic and insurance status. Our findings warrant further clinical and epidemiologic research to reveal other factors impacting these health and health care disparities.
Real-world comparison of treatment outcomes between advanced esophagogastric junction adenocarcinoma and gastric adenocarcinoma.
Authors: Kadono Toru , Hirose Toshiharu , Hirano Hidekazu , Shoji Hirokazu , Okita Natsuko Tsuda , Takashima Atsuo , Kato Ken
Published: January 2024

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Background: The characteristics of esophagogastric junction adenocarcinoma (EGJA) differ from those of gastric adenocarcinoma (GA). Although chemotherapy for advanced GA has been adapted for advanced EGJA, its efficacy remains unknown. This study aims to elucidate the effectiveness of chemotherapy for advanced EGJA in real-world practice. Methods: This retrospective study compared treatment outcomes between advanced GA and EGJA in patients with performance status (PS) 0 to 2 who received doublet or triplet chemotherapy, including platinum agents, as first-line treatment at our hospital between 2010 and 2020. Patients with non-curative resection factors limited to positive peritoneal cytology, or those who relapsed during adjuvant chemotherapy or within 6 months after its completion, were excluded. Results: Out of the total 825 patients, 765 had GA and 60 had EGJA. The baseline characteristics of the GA and EGJA groups were as follows, respectively: median age 65.0 and 59.5 years (p = 0.02); PS 0, 35.9% and 33.3%; PS 1, 57.5% and 65.0%; PS 2, 6.5% and 1.7% (p = 0.28); HER2 positive, 16.1% and 26.7% (p = 0.06); diffuse histology, 52.7% and 26.7% (p < 0.01); lymph node metastasis, 74.0% and 93.3% (p < 0.01); peritoneal metastasis, 66.4% and 25.0% (p < 0.01); liver metastasis, 26.4% and 40.0% (p = 0.03); lung metastasis, 6.5% and 16.7% (p < 0.01). The proportions of fluoropyrimidine, taxanes, and irinotecan in all treatment lines did not differ between the two groups (fluoropyrimidine, 99.7% vs. 100%; taxanes, 70.1% vs. 73.3%; irinotecan, 23.0% vs. 23.3%). However, the EGJA group used ramucirumab, trastuzumab, and immune checkpoint inhibitors (ICIs) significantly more frequently than the GA group (ramucirumab, 27.8% vs. 43.3%, p = 0.02; trastuzumab, 15.4% vs. 26.7%, p = 0.03; ICIs, 21.0% vs. 41.7%, p < 0.01). Overall survival did not differ between the two groups (median, 14.8 months vs. 18.5 months, HR 0.80; 95% CI, 0.59-1.10, p = 0.17). Moreover, multivariate analysis revealed that EGJA and GA had a comparable prognosis (HR 1.23; 95% CI, 0.87-1.72, p = 0.24). HER2 positivity was a favorable prognostic factor in multivariate analysis, whereas diffuse histology, poor PS, lymph node metastasis, liver metastasis, and the presence of peritoneal metastasis were poor prognostic factors. There was no difference in time-to-treatment failure between the two groups for first-line (median, 6.1 vs. 4.9 months, HR 0.96; 95% CI, 0.73-1.28, p = 0.80), second-line (median, 2.9 vs. 3.5 months, HR 0.99; 95% CI, 0.73-1.34, p = 0.93), and third-line treatment (median, 1.9 vs. 2.7 months, HR 0.78; 95% CI, 0.53-1.13, p = 0.62). Conclusions: In real-world practice, the efficacy of chemotherapy for advanced EGJA was comparable to that for advanced GA.
Real-world experience with trastuzumab deruxtecan among patients with gastric cancer: 4 month-interim analysis of an all-patient post-marketing surveillance study in Japan.
Authors: Kawakami Hisato , Uchino Kazuhiro , Hashimoto Wataru , Muro Kei
Published: January 2024

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Background: Interstitial lung disease (ILD) is an important identified risk in the Japanese risk management plan of trastuzumab deruxtecan (T-DXd). In Japan, all-patient post-marketing surveillance (PMS) is underway to investigate the risk of ILD among patients with gastric cancer treated with T-DXd in a real-world setting. We present an interim analysis of the large-scale all-patient PMS. Methods: This is an observational, multicenter, all-patient PMS (jRCT2001200001) with an observation period of 12 months that enrolled all patients treated with T-DXd for HER2-positive unresectable advanced or recurrent gastric cancer between Sep 2020 and Dec 2021. This interim analysis is based on safety data from the first 4 months of all enrolled patients. All potential ILD (identified based on the pre-specified list of AE terms) reported by physicians were adjudicated by an independent ILD adjudication committee (ILD-AC). The incidence of ILD was calculated from adjudicated drug-related ILD. Results: The interim analysis set included 1074 patients with median age of 70 years (range: 23-100). Of the 1074 patients, 1051 (97.9%) received T-DXd as third-line or later treatment. One hundred and eight patients (10.1%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) 2 or greater, and 32 (3.0%), 3 (0.3%), and 23 (2.1%) patients had severe renal impairment (15≤ creatinine clearance (CL) <30 mL/min), end-stage renal disease (CL <15 mL/min), and ILD/radiation pneumonitis at baseline, respectively (all of which were defined as exclusion criteria in clinical trials of T-DXd). Median initial dose of T-DXd was 6.4 mg/kg (range: 3.1-6.4). Median treatment duration of T-DXd was 4.0 months (range: 0.7-4.0). During the first 4 months from the initial treatment, T-DXd was discontinued in 50.9% (547/1074) of patients. The most common reasons for treatment discontinuation were disease progression (n=390, 71.3%), adverse events other than ILD (n=76, 13.9%), and ILD (n=56, 10.2%). All potential ILD that occurred during the first 4 months were adjudicated by ILD-AC, and the incidence of all grades, grade ≥3, and grade 5 adjudicated drug-related ILD were 5.2% (n=56), 1.5% (n=16) and 0.7% (n=7), respectively. Of the 56 patients with adjudicated drug-related ILD, 54 (96.4%) discontinued T-DXd. The incidence of adjudicated drug-related ILD by time from initial treatment of T-DXd were 0.7% (7/1074) at ≤ 1 month, 2.0% (19/949) at 1-2 months, 2.7% (22/829) at 2-3 months, and 1.2% (8/652) at 3-4 months. Conclusions: The interim analysis revealed patient experiences and treatment profiles of T-DXd and the incidence of ILD during the first 4 months since initial treatment in a real-world setting in Japan. The final analysis including a risk factor analysis for ILD of the ongoing PMS is planned.