Prevention and Management of Radiation-induced Late Gastrointestinal Toxicity

Teo, Mark; Sebag‐Montefiore, David; Donnellan, Clare

doi:10.1016/j.clon.2015.06.010

Cited by 42 publications

(19 citation statements)

References 112 publications

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“…The high counts of Roseburia associating with CRO-stratified but not PRO-stratified late symptoms support that higher proportions of these bacteria relate to decreased symptom perception by patients in the presence of clinician-perceived disease. This hypothesis is consistent with the limited clinical effectiveness of oral or topical butyrate when treating radiation enteropathy (40). Although we acknowledge the low comparative proportions of these bacteria when compared with other SCFA producers such as Faecalibacterium, the trend of patients with radiation enteropathy having higher, but dynamically decreasing, SCFA production capacity (early cohort) and significantly decreased levels of homeostatic rectal mucosa cytokines involved in mucosal barrier maintenance and microbiota regulation (colonoscopy cohort) would support this assumption.…”

Section: Discussionsupporting

confidence: 77%

Microbiota- and Radiotherapy-Induced Gastrointestinal Side-Effects (MARS) Study: A Large Pilot Study of the Microbiome in Acute and Late-Radiation Enteropathy

Ferreira

Andreyev

Mohammed

et al. 2019

Clinical Cancer Research

137

145

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Purpose: Radiotherapy is important in managing pelvic cancers. However, radiation enteropathy may occur and can be dose limiting. The gut microbiota may contribute to the pathogenesis of radiation enteropathy. We hypothesized that the microbiome differs between patients with and without radiation enteropathy.Experimental Design: Three cohorts of patients (n ¼ 134) were recruited. The early cohort (n ¼ 32) was followed sequentially up to 12 months post-radiotherapy to assess early radiation enteropathy. Linear mixed models were used to assess microbiota dynamics. The late cohort (n ¼ 87) was assessed cross-sectionally to assess late radiation enteropathy. The colonoscopy cohort compared the intestinal mucosa microenvironment in patients with radiation enteropathy (cases, n ¼ 9) with healthy controls (controls, n ¼ 6). Fecal samples were obtained from all cohorts. In the colonoscopy cohort, intestinal mucosa samples were taken. Metataxonomics (16S rRNA gene) and imputed metataxonomics (Piphillin) were used to characterize the microbiome. Clinician-and patient-reported outcomes were used for clinical characterization.Results: In the acute cohort, we observed a trend for higher preradiotherapy diversity in patients with no self-reported symptoms (P ¼ 0.09). Dynamically, diversity decreased less over time in patients with rising radiation enteropathy (P ¼ 0.05). A consistent association between low bacterial diversity and late radiation enteropathy was also observed, albeit nonsignificantly. Higher counts of Clostridium IV, Roseburia, and Phascolarctobacterium significantly associated with radiation enteropathy. Homeostatic intestinal mucosa cytokines related to microbiota regulation and intestinal wall maintenance were significantly reduced in radiation enteropathy [IL7 (P ¼ 0.05), IL12/IL23p40 (P ¼ 0.03), IL15 (P ¼ 0.05), and IL16 (P ¼ 0.009)]. IL15 inversely correlated with counts of Roseburia and Propionibacterium.Conclusions: The microbiota presents opportunities to predict, prevent, or treat radiation enteropathy. We report the largest clinical study to date into associations of the microbiota with acute and late radiation enteropathy. An altered microbiota associates with early and late radiation enteropathy, with clinical implications for risk assessment, prevention, and treatment of radiation-induced side-effects. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):

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Section: Discussionsupporting

confidence: 77%

Microbiota- and Radiotherapy-Induced Gastrointestinal Side-Effects (MARS) Study: A Large Pilot Study of the Microbiome in Acute and Late-Radiation Enteropathy

Ferreira

Andreyev

Mohammed

et al. 2019

Clinical Cancer Research

137

145

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“…The cells in the bone marrow and gastrointestinal (GI) tract are the most sensitive to radiation damage, because these cells are highly proliferative and have a low sensitivity threshold to radiation, caused by fast cellular turnover (1,44,45). Along with hematopoietic injury, GI-ARS is a serious injury that causes various clinical manifestations, from those occurring in the mouth to those in the colon and rectum.…”

Section: Discussionmentioning

confidence: 99%

Mitigating Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on Hematopoietic Acute Radiation Syndrome after Total-Body Ionizing Irradiation in Mice

Kim¹,

Jeong

Shin

et al. 2019

Radiation Research

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Acute radiation syndrome (ARS) occurs as a result of partial-or whole-body, high-dose exposure to radiation in a very short period of time. Survival is dependent on the severity of the hematopoietic sub-syndrome of ARS. In this study, we investigated the mitigating effects of a lipid molecule, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), on the kinetics of hematopoietic cells, including absolute neutrophil count (ANC), red blood cells (RBCs) and platelet counts, in mice after gamma-ray total-body irradiation (TBI). Male and female BALB/c mice (11 weeks old) received a LD 70/30 dose of TBI. PLAG significantly and dosedependently attenuated radiation-induced mortality (P ¼ 0.0041 for PLAG 50 mg/kg; P , 0.0001 for PLAG 250 mg/kg) and body weight loss (P , 0.0001 for PLAG 50 and 250 mg/ kg) in mice. Single-fraction TBI sharply reduced ANC within 3 days postirradiation and maintained the neutropenic state (ANC , 500 cells/ll) by approximately 26.8 6 0.8 days. However, administration of PLAG attenuated radiationinduced severe neutropenia (ANC , 100 cells/ll) by effectively delaying the mean day of its onset and decreasing its duration. PLAG also significantly mitigated radiationinduced thrombocytopenia (P , 0.0001 for PLAG 250 mg/kg) and anemia (P ¼ 0.0023 for PLAG 250 mg/kg) by increasing mean platelet and RBC counts, as well as hemoglobin levels, in peripheral blood. Moreover, delayed administration of PLAG, even at 48 and 72 h after gamma-ray irradiation, significantly attenuated radiation-induced mortality in a time-dependent manner. When compared to olive oil and palmitic linoleic hydroxyl (PLH), only PLAG effectively attenuated radiation-induced mortality, indicating that it has a distinctive mechanism of action. Based on these preclinical observations, we concluded that PLAG has high potential as a radiation countermeasure for the improvement of survivability and the treatment of hematopoietic injury in gamma-rayinduced ARS.

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“…One more source of contact with myelosuppressive factors is radiation therapy, which is routinely used in oncology (up to 70% of patients with malignant tumors are treated with) as well as anti-cancer chemotherapy with cytostatics [6][7][8]. Medical use of radiation accounts for 98% of the population dose contribution from all artificial sources and represents approximately 20% of the total exposure.…”

Section: Introductionmentioning

confidence: 99%

Sorption Detoxification as an Addition to Conventional Therapy of Acute Radiation Sickness and Iatrogenic Leukopenia

Шевчук¹,

Snezhkova²,

Bilous³

et al. 2020

Cells of the Immune System

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Leukopenia is an essential part of the clinical course of acute radiation sickness and is a side effect of anti-cancer treatment. In both situations, the main factors which determine the survival are the degree of bone marrow suppression and gastrointestinal tract damage due to the presence of a large pool of fast-dividing cells. Leuko-and neutropenia are main limiting factors which may contribute to chemotherapy failure. Hematopoietic cytokines the part of conventional therapy in this field, but their effects require boosting. That is why the use of means and methods of adsorption therapy is considered promising. Sorption therapy creates a basis for sorption detoxification, a doctrine of curative measures directed to the removal of toxic endogenous or exogenous compounds from body fluids. The most widely used types are the purification of blood or its components (hemosorption), oral administration of sorption materials (enterosorption) and application-sorption therapy of wounds and burns. In this chapter, the results of early and recent research and prospects for the use of carbon adsorption therapy for the treatment of acute radiation sickness and cytostatic myelosuppression are discussed.

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Prevention and Management of Radiation-induced Late Gastrointestinal Toxicity

Cited by 42 publications

References 112 publications

Microbiota- and Radiotherapy-Induced Gastrointestinal Side-Effects (MARS) Study: A Large Pilot Study of the Microbiome in Acute and Late-Radiation Enteropathy

Microbiota- and Radiotherapy-Induced Gastrointestinal Side-Effects (MARS) Study: A Large Pilot Study of the Microbiome in Acute and Late-Radiation Enteropathy

Mitigating Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on Hematopoietic Acute Radiation Syndrome after Total-Body Ionizing Irradiation in Mice

Sorption Detoxification as an Addition to Conventional Therapy of Acute Radiation Sickness and Iatrogenic Leukopenia

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