13C-uracil breath test to predict 5-fluorouracil toxicity in gastrointestinal cancer patients

e13008 Background: Up to 30% of patients on 5-fluorouracil (5FU) experience severe toxicity. Dihydropyrimidine-dehydrogenase (DPD) deficiency explains 36-61% of cases. Predicting toxicity is an unmet challenge. Uracil breath test (UraBT) consists of measuring 13CO2 in exhaled breath after ingestion of 2-13C-uracil to evaluate pyrimidine (and 5FU) catabolism. Methods: We studied 33 gastrointestinal cancer patients previously exposed to 5FU: thirteen had grade 3-4 and 20, grade 0-1 toxicity. Groups were well-balanced regarding: age (median, 57 years); gender (males, 35%); primary (colorectal, 90%); ethnicity (Caucasians, 55%); chemotherapy (Mayo clinic regimen, 75%). Main toxicities were febrile neutropenia, diarrhea and stomatitis. Tests used to evaluate pyrimidine catabolism: (1) sequencing of three exons of DPYD; (2) plasma dihydrouracil/uracil ratio (UH2/U); (3) UraBT. We tested the performance of UraBT to discriminate patients who had grade 0-1 toxicity versus grade 3-4 toxicity and patients with and without proven DPD-deficiency. DPD-deficients were defined as having had grade 3-4 toxicity plus either UH2/U < 1.8 or deleterious mutation. Results: 4/13 grade 3-4 toxicity patients proved to be DPD-deficient: three had deleterious mutations (IVS14+1G>A in one; SNP 2846A>T in two), and one had low UH2/U ratio. Mean delta over baseline in 50 minutes (DOB50) significantly differed between groups. DOB50 ≤ 161.4 discriminated individuals with grade 3-4 versus grade 0-1 toxicity (sensitivity= 61.5%; specificity= 85%) and DPD-deficient versus non DPD-deficient (sensitivity= 75%; specificity= 85%). Conclusions: UraBT is a non-invasive and easy to perform method with promising accuracy in discriminating individuals with severe toxicity to 5FU, comparing favorably to most tests available to predict 5FU toxicity. [Table: see text]

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Clinical Association between Phospho-AKT Expression with Clinicopathological Characteristics of Gastrointestinal Cancer Patients: A Meta-Analysis

Critical Reviews in Eukaryotic Gene Expression ◽

10.1615/critreveukaryotgeneexpr.2020028658 ◽

2020 ◽

Vol 30 (4) ◽

pp. 299-309

Author(s):

Hossein Abdeahad ◽

Afsane Bahrami ◽

Majid Khazaei ◽

Gordon A. Ferns ◽

Marjan Erfani ◽

...

Keyword(s):

Cancer Patients ◽

Gastrointestinal Cancer ◽

Meta Analysis ◽

Clinicopathological Characteristics

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Identification of cluster of differentiation molecule-associated microRNAs as potential therapeutic targets for gastrointestinal cancer immunotherapy

The International Journal of Biological Markers ◽

10.1177/17246008211005473 ◽

2021 ◽

pp. 172460082110054

Author(s):

Hanyu Zhang ◽

Mingxing Li ◽

Parham Jabbarzadeh Kaboli ◽

Huijiao Ji ◽

Fukuan Du ◽

...

Keyword(s):

Cancer Immunotherapy ◽

Cancer Patients ◽

Gastrointestinal Cancer ◽

Therapeutic Targets ◽

Microrna Expression ◽

The Cancer Genome Atlas ◽

Gastrointestinal Cancers ◽

Almost All ◽

Cluster Of Differentiation

Background: Cluster of differentiation molecules are markers of immune cells that have been identified as a potential immunotherapeutic target for cancer treatment. MicroRNAs are small non-coding RNAs that act as tumor suppressors or oncogenes whose importance in diagnosis, prognosis, and treatment of gastric and colorectal cancers has been widely reported. However, their association with cluster of differentiation molecules in gastrointestinal cancers has not been well studied. Therefore, our study aimed to analyze the relationship between microRNAs and cluster of differentiation molecules in gastrointestinal cancers, and to identify cluster of differentiation molecule-associated microRNAs as prognostic biomarkers for gastrointestinal cancer patients. Methods: Targetscan, Starbase, DIANA microT, and miRDB were used to investigate microRNA profiles that might be correlated with cluster of differentiation molecules in gastrointestinal cancers. Moreover, The Cancer Genome Atlas data analysis was used to investigate the association between cluster of differentiation molecules and microRNA expression in patients with gastric, colon, rectal, pancreatic, and esophageal cancers. The Kaplan–Meier plotter was used to identify the association between overall survival and cluster of differentiation molecule-associated microRNA expression in gastrointestinal cancer patients. Results: miR-200a, miR-559, and miR-1236 were negatively associated with CD86, CD81, and CD160, respectively, in almost all types of gastrointestinal cancers, which were further verified in the in vitro studies by transfecting microRNA mimics in gastric cancer, colon cancer, pancreatic, and esophageal cell lines. Conclusion: Our study showed that miR-200a, miR-1236, and miR-559 are identified as cluster of differentiation-associated microRNAs in gastrointestinal cancers, providing a novel perspective to identify new therapeutic targets for cancer immunotherapy in gastrointestinal cancer patients.

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Changes in the palliative performance scale may be as important as the initial palliative performance scale for predicting survival in terminal cancer patients

Palliative & Supportive Care ◽

10.1017/s1478951520001248 ◽

2021 ◽

pp. 1-5

Author(s):

Guk Jin Lee ◽

Ji Hyun Gwak ◽

Myoung Sim Kim ◽

Mi Yeong Lee ◽

Seo Ree Kim ◽

...

Keyword(s):

Cancer Patients ◽

Gastrointestinal Cancer ◽

Poor Prognosis ◽

Accurate Estimation ◽

Terminal Cancer ◽

Hospice Patients ◽

Terminal Cancer Patients ◽

Group A ◽

Group B ◽

Performance Scale

Abstract Objective The accurate estimation of expected survival in terminal cancer patients is important. The palliative performance scale (PPS) is an important factor in predicting survival of hospice patients. The purpose of this study was to examine how initial status of PPS and changes in PPS affect the survival of hospice patients in Korea. Method We retrospectively examined 315 patients who were admitted to our hospice unit between January 2017 and December 2018. The patients were divided based on the PPS of ≥50% (group A) and ≤40% (group B). We performed survival analysis for factors associated with the length of survival (LOS) in group A. Based on the hospice team's weekly evaluation of PPS, we examined the effect of initial levels and changes in group A on the prognosis of patients who survived for 2 weeks or more. Results At the time of admission to hospice, 265 (84.1%) patients were PPS ≥50%, and 50 (15.9%) were PPS ≤40%. The median LOS of PPS ≥50% and PPS ≤40% were 15 (2–158 days) and 9 (2–43 days), respectively. Male, gastrointestinal cancer, and lower initial PPS all predicted poor prognosis in group A. Male, gastrointestinal cancer, and a PPS change of 10% or greater, compared with initial status 1 week and 2 weeks of hospitalization, were all predictors of poor prognosis in group A patients who survived for 2 weeks or longer. Significance of results Our research demonstrates the significance of PPS change at 1 week and 2 weeks, suggesting the importance of evaluating not only initial PPS but also change in PPS.

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