Metastatic small bowel adenocarcinoma: role of metastasectomy and systemic chemotherapy

Bhamidipati, Deepak; Colina, Andreina; Hwang, Hyunsoo; Wang, H.; Katz, Matthew H.G.; Fournier, Keith F.; Serpas, V.; Thomas, J.; Sun, Ryan; Wolff, Robert A.; Raghav, Kanwal; Overman, Michael J.

doi:10.1016/j.esmoop.2021.100132

Cited by 12 publications

(20 citation statements)

References 29 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%

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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%

Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas

et al. 2023

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“…However, there is uncertainty about the benefit of metastasectomy in patients with advanced small intestine cancer. A large single institution study from MD Anderson showed that metastasectomy was associated with a better overall survival in well-selected patients with advanced small intestine adenocarcinoma [ 14 ]. Overall, 17% of patients with advanced disease underwent resection of the primary tumor and metastases.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported a benefit of palliative chemotherapy treatment in patients with advanced small intestine adenocarcinoma [ 14 , 16 , 26 , 27 , 28 , 29 ]. However, the benefit of chemotherapy treatment in early-stage disease (stage one–three) remains unclear [ 26 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Patients with Small Intestine Adenocarcinoma in a Canadian Province: A Retrospective Multi-Center Population-Based Cohort Study

Yanko

Mahmood

et al. 2022

Cancers

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Background: Small intestine adenocarcinoma is a rare cancer. The current study aims to determine the outcomes of patients with small intestine adenocarcinoma in a Canadian province. Methods: This retrospective population-based cohort study assessed patients with small intestine adenocarcinoma who were diagnosed from 2008 to 2017 in Saskatchewan. A Cox proportional multivariate regression analysis was performed to determine the correlation between survival and exploratory factors. Results: 112 eligible patients with a median age of 73 years and M:F of 47:53 were identified. Overall, 75% had a comorbid illness, and 45% had a WHO performance status >1. Of the 112 patients, 51 (46%) had early-stage disease and 61 (54%) had advanced-stage disease. The median overall survival (mOS) was as follows: stage one, 59 months; stage two, 30 months; stage three, 20 months; and stage four, 3 months (p < 0.001). The median disease-free survival of patients with stage three disease who received adjuvant chemotherapy was 26 months (95% CI:23.1–28.9) vs. 4 months (0.0–9.1) with observation (p = 0.04). Patients who received chemotherapy for advanced disease had a mOS of 10 months (3.5–16.5) vs. 2 months (0.45–3.6) without chemotherapy (p < 0.001). In the multivariate analysis, stage four disease, hazard ratio (HR), 3.20 (1.84–5.40); WHO performance status >1, HR, 2.22 (1.42–3.45); lack of surgery, HR, 2.10 (1.25–3.50); and a neutrophil:lymphocyte ratio of >4.5, HR, 1.72 (1.10–2.71) were significantly correlated with inferior survival. Conclusions: Most patients with small intestine adenocarcinoma were diagnosed with advanced-stage disease. Advanced-stage disease, poor performance status, lack of surgery and a baseline neutrophil:lymphocyte ratio >4.5 were correlated with inferior survival.

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“…The circumstances of chemotherapy-induced gastrointestinal toxicities involve inflammation and damage to mucosa, thus resulting in pain, nausea, vomiting, bloating, constipation, diarrhea and ulceration ( Eng, 2009 ). As an inhibitor of topoisomerase I (TOP1), irinotecan (CPT11) is one of the major agents used in the treatment of metastatic or advanced solid tumors (e.g., gastric ( Shintani et al, 2021 ), pancreatic ( Glassman et al, 2018 ), ovarian ( Mabuchi et al, 2019 ), colorectal ( Reita et al, 2019 ), and other tumors ( Bhamidipati et al, 2021 )). However, about 80% of patients receiving standard dose of CPT11 chemotherapy exhibit diarrhea-associated intestinal mucositis ( Gelibter et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Berberine Improves Irinotecan-Induced Intestinal Mucositis Without Impairing the Anti-colorectal Cancer Efficacy of Irinotecan by Inhibiting Bacterial β-glucuronidase

Yue

Gao

et al. 2021

Front. Pharmacol.

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Irinotecan (CPT11), a broad-spectrum cytotoxic anticancer agent, induces a series of toxic side-effects. The most conspicuous side-effect is gastrointestinal mucositis, including nausea, vomiting, and diarrhea. A growing body of evidence indicates that bacteria β-glucuronidase (GUS), an enzyme expressed by intestinal microbiota, converts the inactive CPT11 metabolite SN38G to the active metabolite SN38 to ultimately induce intestinal mucositis. We sought to explore the potential efficacy and underlying mechanisms of berberine on CPT11-induced mucositis. Our study showed that berberine (50 mg/kg; i. g.) mitigated the CPT11-induced loss of mucosal architecture, ulceration, and neutrophil infiltration. Meanwhile, berberine improved mucosal barrier function by increasing the number of globlet cells, protecting trans-endothelial electrical resistance (TEER), reducing permeability and increasing tight junction proteins expression. LC-MS analysis showed that berberine decreased the content of SN38 in feces, which correlated with decreases in both GUS activity and GUS-producing bacteria. Further molecular docking and Lineweaver-Burk plots analyses suggested that berberine functions as a potential non-competitive inhibitor against GUS enzyme. Of note, berberine maintained the anti-tumor efficacy of CPT11 in a tumor xenograft model while abrogating the intestinal toxicity of CPT11. Overall, we identified for the first time the remission effects of berberine on intestinal mucositis induced by CPT11 without impairing the anti-colorectal cancer efficacy of CPT11 partially via inhibiting bacterial GUS enzyme.

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Metastatic small bowel adenocarcinoma: role of metastasectomy and systemic chemotherapy

Cited by 12 publications

References 29 publications

Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas

Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas

Outcomes of Patients with Small Intestine Adenocarcinoma in a Canadian Province: A Retrospective Multi-Center Population-Based Cohort Study

Berberine Improves Irinotecan-Induced Intestinal Mucositis Without Impairing the Anti-colorectal Cancer Efficacy of Irinotecan by Inhibiting Bacterial β-glucuronidase

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