Prognostic implications of thymidylate synthase gene polymorphisms in patients with advanced small bowel adenocarcinoma treated with first-line fluoropyrimidine-based chemotherapy

Yhim, Ho‐Young; Cho, Sang‐Hee; Kim, Sam Yong; Cho, In Sung; Lee, Kyu Taek; Lee, Won Sup; Lee, Soon Il; Park, Moo Rim; Park, Sang-Gon; Han, Hye‐Suk; Choi, Yoon Seok; Chung, Ik‐Joo; Shim, Hyungbo; Lee, Na-Ri; Song, Eun-Kee; Kim, Hee Sun; Yim, Chang-Yeol

doi:10.3892/or.2015.3954

Cited by 4 publications

(10 citation statements)

References 33 publications

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“…After full-text revision, 57 studies were included, with a total of 35 176 patients. Among the 57 studies, 6 studies 27 , 28 , 29 , 30 , 31 , 32 were prospective cohort studies or phase 2 trials, and 51 studies 1 , 3 , 4 , 17 , 19 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 were retrospective in nature ( Table ; eTables 1 and 2 in…”

Section: Resultsmentioning

confidence: 99%

“…Studies in the palliative setting commonly studied all SIA localizations. Twenty-six studies 3 , 17 , 27 , 28 , 29 , 30 , 32 , 33 , 35 , 44 , 46 , 48 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 68 , 70 , 72 , 74 , 75 , 76 , 77 (65.0%) specified the chemotherapy regimens. Targeted agents were investigated in 7 studies, 31 , 60 , 61 , 63 , 64 , 71 , 76 of which most assessed bevacizumab.…”

Section: Resultsmentioning

confidence: 99%

“…Of 57 studies, 23 studies 3 , 17 , 27 , 29 , 30 , 31 , 32 , 33 , 36 , 38 , 44 , 49 , 50 , 51 , 58 , 60 , 62 , 63 , 70 , 71 , 73 , 74 , 77 (40.4%) were subject to serious risk of bias due to the lack of multivariable analyses and selection bias (eTable 3 in Supplement 1 ). Thirty-three studies 1 , 4 , 19 , 28 , 34 , 35 , 37 , 39 , 40 , 41 , 42 , 43 , 45 , 46 , 47 , 48 , 52 , 53 , 54 , 55 , 56 , 57 , 59 , 61 , 64 , 65 , 66 , 67 , 69 , 72 , 75 , 76 , 78 (57.9%) had medium or low risk of bias.…”

Section: Resultsmentioning

confidence: 99%

“… 87 , 88 For cisplatin combinations, our study suggested a smaller survival benefit compared with other regimens. The 2 studies 59 , 74 that demonstrated a higher mOS and mPFS for cisplatin compared with oxaliplatin combinations included mainly duodenal adenocarcinomas (80%), which might be sensitive to cisplatin-based treatment due to their anatomical proximity to the pancreas and stomach. 89 , 90 …”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas

et al. 2023

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ImportanceAlthough small intestinal adenocarcinomas (SIAs) are rare, they have a poor prognosis, and the optimal treatment strategies are largely unknown. Because of the lack of high-quality evidence, guidelines for colorectal cancer are often followed in the treatment of SIAs.ObjectiveTo review the current evidence regarding survival benefit of systemic therapies, including chemotherapy, targeted agents, and immunotherapy, for patients with SIAs.Data SourcesFollowing the Preferred Reporting Items for Systematic Reviews and Meta-analyses, MEDLINE and Embase were searched for articles published from January 1, 2005, until June 1, 2022.Study SelectionRetrospective cohort studies and prospective phase 2 or 3 trials describing survival after systemic therapies for patients with SIAs were eligible for inclusion. Assessment of study eligibility was blinded and performed by 3 reviewers.Data Extraction and SynthesisThe reviewers independently extracted data. Random effects, inverse variance, pairwise meta-analyses were performed.Main Outcomes and MeasuresPrimary outcomes were overall survival (OS) and progression-free survival (PFS) of patients with SIAs after systemic therapies. Measures of interest included hazard ratios for survival and median survival times.ResultsOverall, 57 retrospective cohort and phase 2 studies of 35 176 patients were included. Adjuvant chemotherapy, generally fluoropyrimidine-based, was associated with increased OS in stage I to III SIAs (hazard ratio [HR], 0.60; 95% CI, 0.53-0.68), especially in stage III tumors (HR, 0.55; 95% CI, 0.48-0.64), irrespective of tumor localization. Palliative chemotherapy was also associated with an OS benefit (HR, 0.48; 95% CI, 0.40-0.58). Fluoropyrimidine-oxaliplatin combinations were superior to other regimens (OS: HR, 0.54; 95% CI, 0.30-0.99; PFS: HR, 0.46; 95% CI, 0.30-0.71). Furthermore, bevacizumab added to chemotherapy compared with chemotherapy alone was associated with significantly prolonged PFS (HR, 0.62; 95% CI, 0.43-0.89). Immunotherapy showed a 50% overall response rate in previously treated defective mismatch repair tumors.Conclusions and RelevanceIn this systematic review and meta-analysis, adjuvant and palliative chemotherapy were both associated with improved survival of patients with SIAs, especially fluoropyrimidine-based regimens and fluoropyrimidine-oxaliplatin combinations. Adding bevacizumab to chemotherapy appears to prolong PFS and deserves further investigation. Immunotherapy seems beneficial and should be considered for patients with defective mismatch repair tumors. International collaborations should be undertaken to confirm and improve efficacy of systemic therapies for patients with SIAs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas

et al. 2023

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“…[7] As a consequence, polymorphisms affecting TS and MTHFR levels are presumed to be determinants of 5-FU clinical response, but indeed their clinical utility is still controversial. [17–26]…”

Section: Introductionmentioning

confidence: 99%

Pre-treatment assay of 5-fluorouracil degradation rate (5-FUDR) to improve prediction of 5-fluorouracil toxicity in gastro-esophageal cancer

et al. 2016

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Background5-fluorouracil (5-FU) based chemotherapy is the most common first line regimen used in gastric and gastroesophageal junction cancer, but development of severe toxicity is a main concern in the treatment. The present study is aimed to evaluate a novel pre-treatment assay, known as the 5-FU degradation rate (5-FUDR), as a predictive factor for 5-FU toxicity.MethodsPre-treatment 5-FUDR and gene polymorphisms related to 5-FU metabolism (DPYDIVS14+1G>A, MTHFRA1298T or C677T, TMYS TSER) were characterized in gastro-esophageal cancer patients. Association with toxicities was retrospectively evaluated, using multivariate logistic regression analysis.Results107 gastro-esophageal cancer patients were retrospectively analyzed. No relation between gene polymorphisms and toxicity were detected, while low (< 5th centile) and high (> 95th centile) 5-FUDRs were associated with development of grade 3-4 toxicity (OR 11.14, 95% CI 1.09-113.77 and OR 9.63, 95% CI 1.70-54.55, p = 0.002).ConclusionsCompared to currently used genetic tests, the pre-treatment 5-FUDR seems useful in identifying patients at risk of developing toxicity.

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Clinical practice guidelines for duodenal cancer 2021

et al. 2022

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Duodenal cancer is considered to be a small intestinal carcinoma in terms of clinicopathology. In Japan, there are no established treatment guidelines based on sufficient scientific evidence; therefore, in daily clinical practice, treatment is based on the experience of individual physicians. However, with advances in diagnostic modalities, it is anticipated that opportunities for its detection will increase in future. We developed guidelines for duodenal cancer because this disease is considered to have a high medical need from both healthcare providers and patients for appropriate management. These guidelines were developed for use in actual clinical practice for patients suspected of having non-ampullary duodenal epithelial malignancy and for patients diagnosed with non-ampullary duodenal epithelial malignancy. In this study, a practice algorithm was developed in accordance with the Minds Practice Guideline Development Manual 2017, and Clinical Questions were set for each area of epidemiology and diagnosis, endoscopic treatment, surgical treatment, and chemotherapy. A draft recommendation was developed through a literature search and systematic review, followed by a vote on the recommendations. We made decisions based on actual clinical practice such that the level of evidence would not be the sole determinant of the recommendation. This guideline is the most standard guideline as of the time of preparation. It is important to decide how to handle each case in consultation with patients and their family, the treating physician, and other medical personnel, considering the actual situation at the facility (and the characteristics of the patient).

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Prognostic implications of thymidylate synthase gene polymorphisms in patients with advanced small bowel adenocarcinoma treated with first-line fluoropyrimidine-based chemotherapy

Cited by 4 publications

References 33 publications

Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas

Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas

Pre-treatment assay of 5-fluorouracil degradation rate (5-FUDR) to improve prediction of 5-fluorouracil toxicity in gastro-esophageal cancer

Clinical practice guidelines for duodenal cancer 2021

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