Radiation Enteritis Research Articles

Screening of biomarkers in acute radiation enteritis based on microbiome and clustering methods

BackgroundRadiation enteritis (RE) is a common complication of radiotherapy for abdominal and pelvic tumors, adversely affecting treatment outcomes and patients’ quality of life. Gut microbiome alterations may contribute to RE development, but the underlying pathogenic factors are not fully understood. This study aimed to characterize the intestinal microbial changes associated with RE and severe acute radiation enteritis (SARE) and to identify predictive biomarkers.MethodsWe enrolled 50 cervical cancer patients undergoing radiotherapy and 15 healthy women (controls). Stool samples were collected at the baseline and during weeks 2, 4, and 6 of radiotherapy, and then analyzed using 16 S rDNA sequencing and bioinformatics.ResultsAlthough the Bacteroidetes/Firmicutes (B/F) ratio was higher in patients with RE or SARE, it alone could not predict these conditions. Three enterotypes were identified based on dominant genera: Blautia (enterotype 1), Escherichia-Shigella (enterotype 2), and Faecalibacterium (enterotype 3). A decrease in Blautia and an increase in Escherichia-Shigella and Faecalibacterium were correlated with RE and SARE. Univariate logistic regression revealed that the Faecalibacterium enterotype at the baseline was associated with a 4.4-fold higher risk of developing SARE (odds ratio 5.400; P = 0.017). The Escherichia-Shigella enterotype was also linked to increased SARE incidence.ConclusionThese findings suggest that while single bacterial genera or the B/F ratio are insufficient predictors, enterotype classification may serve as a potential biomarker for predicting SARE in patients undergoing radiotherapy.

3D-printed brachytherapy in patients with cervical cancer: improving efficacy and safety outcomes

ObjectiveThis study aims to evaluate the efficacy and safety of 3D printing technology in brachytherapy for cervical cancer, comparing its outcomes with conventional free hand implantation brachytherapy.MethodsA total of 50 cervical cancer patients treated at the First Affiliated Hospital of Gannan Medical College from January 2019 to July 2023 were included in this study. Patients were divided into two groups: 25 patients received intensity-modulated radiotherapy (IMRT) combined with 3D-printed brachytherapy, and 25 patients underwent IMRT combined with free hand brachytherapy implantation. Key indicators analyzed included short-term therapeutic effects, survival outcomes, operation times, the number of CT scans, the number of needles inserted, dosimetric parameters, and complications.ResultsThe use of 3D-printed brachytherapy significantly improved the safety of radiation therapy operations, especially for large tumors (≥ 30 mm), by providing more precise dose distribution and reducing the radiation doses received by critical organs such as the bladder and rectum. Compared to the artificial implant group (88% prevalence), the 3D-printed brachytherapy group showed a significantly lower incidence of radiation enteritis (29.2% prevalence, p < 0.001). There were no significant differences in other complications between the two groups. For instance, the incidence of radiation cystitis was relatively high in the 3D-printed brachytherapy group (79.2% prevalence) compared to the artificial implant group (64% prevalence, p = 0.240). The median follow-up period in this study was 22.5 months [IQR 18–29]. Among the 49 patients included, 43 had cervical squamous carcinoma and 6 had cervical adenocarcinoma. Short-term therapeutic response rates were comparable, with no significant difference in overall survival observed between the two groups.Conclusion3D-printed brachytherapy offers a more effective and safer therapeutic option for patients with cervical cancer, particularly for those with large tumors or complex anatomical structures.

Differentiation of human umbilical cord mesenchymal stem cells into functional intestinal epithelial cells via conditioned medium co-culture

BackgroundThe induction of stem cell differentiation to generate intestinal epithelial cells (IECs) with absorptive functions offers significant therapeutic potential for treating conditions such as Crohn’s disease, ulcerative colitis, radiation enteritis, and other refractory intestinal epithelial injuries. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of differentiating into functional IEC-like cells. ObjectiveThis study aimed to induce the differentiation of hUC-MSCs into IECs using a conditioned medium co-culture method. MethodA culture medium derived from human IECs was used as the inductive medium to facilitate the differentiation of hUC-MSCs into IECs. The cellular morphology was assessed using inverted microscopy, and the expression of IEC markers, including Villin, CK20, CK8, and CK18 proteins, was analyzed via immunofluorescence staining. Furthermore, the expression levels of IEC markers, such as KRT18, were quantified using real-time quantitative PCR analysis. The functionality of the differentiated IECs in terms of sucrase secretion was assessed through sucrase activity assays. ResultsBy the 14th day of induction, hUC-MSCs exhibited a morphology similar to IECs and exhibited the expression of IEC markers, including the KRT18 gene and Villin, CK20, CK8, and CK18 proteins. Sucrase activity assays further confirmed that the differentiated cells demonstrated significant sucrase activity. ConclusionThe conditioned medium co-culture method effectively induced the differentiation of hUC-MSCs into functional IECs.

Important practical aspects in the management of patients with shot bowel syndrome and intestinal failure

Short bowel syndrome is a gastrointestinal disorder resulting from massive resection of the small intestine. The most common causes of resection are acute mesenteric ischemia, Crohn’s disease, abdominal trauma, adhesive intestinal obstruction, intestinal malignancies, and radiation enteritis. Short bowel syndrome with intestinal failure is characterized by severe malabsorption-m aldigestion accompanied by abdominal pain, diarrhea, dehydration, and progression of protein-energy malnutrition. Many patients with SBS develop long-term clinical complications over time due to altered bowel anatomy and physiology or various therapeutic interventions such as parenteral nutrition and central venous catheterization. This review focuses on the most important aspects of diagnosis, treatment, and prevention of several complications that can occur in this patient population, including macronutrient and micronutrient imbalances, diarrhea, fluid and electrolyte imbalances, metabolic bone disease, biliary disorders, bacterial overgrowth in the small intestine, and complications related to venous access. The main therapeutic strategies for SBS with intestinal failure are: special diet, enteral nutritional support with semi-elemental mixtures, parenteral nutrition, oral rehydration, antimicrobal and antidiarrheal drugs, enzymes. Administration of glucagon-like peptide 2 analog, teduglutide, is clinically effective in reducing dependence on parenteral nutrition and improving quality of life. Management of patients with SBS with intestinal failure is a complex long-term process which requires dynamic clinical and laboratory monitoring.

Clinical efficacy and safety of neoadjuvant chemotherapy with paclitaxel and cisplatin in combination with concurrent chemoradiotherapy for locally advanced cervical cancer: a systematic review and meta-analysis.

The meta-analysis was to evaluate the therapeutic benefits of neoadjuvant chemotherapy (NACT), primarily consisting of platinum-based regimens in conjunction with paclitaxel, when integrated with concurrent chemoradiotherapy (CCRT) for individuals afflicted with locally advanced cervical cancer (LACC). The outcomes were determined by overall survival (OS), progression-free survival (PFS), complete response rate (CRR), objective response rate, recurrence rate and adverse events. The assessment of these outcomes was based on the relative risk (RR) accompanied by its 95% confidence interval (CI). Eight articles were included for analysis. LACC patients who underwent treatment with paclitaxel combined with cisplatin (TP)-based NACT in conjunction with CCRT demonstrated improved OS at 2 (RR: 1.11, 95% CI: 1.07, 1.16, P < 0.001), 3 (RR: 1.30, 95% CI: 1.23, 1.37, P < 0.001) and 5years (RR: 1.20, 95% CI: 1.10, 1.32, P < 0.001), as well as PFS at 1 (RR: 1.03, 95% CI: 1.00, 1.06, P =0.035), 2 (RR: 1.21, 95% CI: 1.04, 1.40, P = 0.012), 3 (RR: 1.26, 95% CI: 1.17, 1.34, P < 0.001) and 5 (RR: 1.39, 95% CI: 1.25, 1.55, P < 0.001) years, when compared with patients who received CCRT alone. Moreover, the TP-based NACT in conjunction with CCRT achieved a higher CRR and exhibited a lower rate of disease recurrence (RR:1.28, 95% CI:1.08, 1.50, P = 0.003). No significant differences in the risk of adverse effects including anemia, leukopenia, thrombocytopenia, radiocystitis and radiation enteritis between the group treated with TP-based NACT combined with CCRT and the group treated with CCRT alone were observed. The combination of TP-based NACT and CCRT demonstrates superior clinical efficacy than CCRT alone. This study may contribute to reducing the burden of LACC by using TP-based NACT plus CCRT.

S3805 Complexities in Managing Hemorrhagic Radiation Enteritis: An Endoscopist's Perspective and Case Report

S3805 Complexities in Managing Hemorrhagic Radiation Enteritis: An Endoscopist's Perspective and Case Report

Clinical characteristics, treatment strategy, and clinical outcomes in type 2 intestinal failure

Objective: To evaluate the characteristics, clinical management and clinical outcomes of type 2 intestinal failure (IF). Methods: A descriptive case-control study was carried out. The inclusion criteria were as follows: (1) the diagnosis of IF was performed according to the European Society for Parenteral and Enteral Nutrition (ESPEN) consensus statement. (2) using a requirement for parenteral nutrition (PN) of 28 days or more as surrogate marker. (3) a multidisciplinary team (MDT) included surgeons, nutritionist, pharmacist, stoma therapists, and critical care physicians. (4) complete laboratory data. Patients with type 1 and type 3 IF and those who do not cooperate with follow-up. All the data of 67 type II IF were collected from the database in Sir Run Run Shaw Hospital from Jan 2016 to Dec 2023. The pathophysiology, clinical management, and outcomes of type II IF were analyzed. Results: A total of 67 type II IF were included. The median age was 54 (15-83) with 43 males and 24 females. The body mass index was (17.5±3.8) kg/m2, the incidence of malnutrition was 67.2% (45/67), the incidence of sarcopenia was 74.6% (50/67), the median number of previous surgeries was 2.0 (1-13), and the median duration time of PN was 2.1 (1-12) months. The underlying disease of type 2 IF included 36 Crohn`s disease, 2 ulcerative colitis, 3 radiation enteritis, 2 intestinal Behcet's disease, 4 mesenteric infarction, 1 aggressive fibromatosis, 5 abdominal cocoon syndrome, 5 gastrointestinal perforation, 1 hernia, 4 intestinal dysmotility, and 4 other reasons (gastrointestinal tumor, trauma, and non-Hodgkin's lymphoma). According to the pathophysiology of IF, there were 33 intestinal fistula, 12 intestinal dysmotility, 6 mechanical obstruction, 13 short bowel syndrome, and 3 extensive small bowel mucosal disease. After treatment with MDT, 67 patients with type 2 IF received nutritional support therapy for intestinal rehabilitation treatment, of which 36 patients recovered with oral diet or enteral nutrition, 31 patients underwent reconstructive surgery after intestinal rehabilitation treatment failure. The median duration time of reconstructive surgery was 2.7 (1-9) months. 24 patients recovered intestinal autonomy after surgery, with 7 deaths, including 6 deaths due to abdominal infections and 1 case of intestinal dysmotility with abiotrophy and liver failure. Conclusion: Standardized multidisciplinary treatment plays an important role in type II intestinal failure, and it promotes patients with intestinal failure regain enteral autonomy.

Colonic long-term retention and colonization of probiotics by double-layer chitosan/tannic acid coating and microsphere embedding for treatment of ulcerative colitis and radiation enteritis

Oral probiotics can alleviate enteric inflammations but their rapid transit through the gut limits their retention and colonization in the colon. Here, a novel strategy integrating the bacterial double-layer coating and hydrogel microsphere embedding techniques was used to highly enhance the colonic retention and colonization efficiency of Lactobacillus rhamnosus GG (LGG). LGG was coated by the double layers of chitosan (CS) and tannic acid (TA), and then embedded in calcium alginate (CA) hydrogel microspheres to form LGG@CT@CA. The microspheres resisted gastric liquids, improving LGG safe transit through the stomach to reach the colon. LGG@CT was rapidly released in the colon due to the good swelling of hydrogel microspheres. More importantly, LGG exhibited long-term retention up to 7 days in the colon and colonized the deep site of the colonic mucosa. LGG@CT@CA had a high therapeutic efficiency of ulcer colitis with the long colon and the low intestinal permeability of colonic tissues. LGG@CT@CA also alleviated the small intestinal damage induced by irradiation and the survival rates were improved. The mechanisms included local ROS decrease, IL-10 increase, and ferroptosis reduction in the small intestine. The oral colon-targeted system holds promise for oral probiotic therapy by the long-term retention and colonization in the colon.

Endoscopic Diagnosis and Treatment of Benign Small Bowel Stricture

Benign small bowel strictures can occur in association with various conditions, including small bowel Crohn’s disease, nonsteroidal anti-inflammatory drug-induced enteritis, ischemic enteritis, intestinal tuberculosis, radiation enteritis, postoperative adhesions, and anastomotic strictures. Benign small bowel strictures are classified into two categories, low-grade and high-grade. Low-grade small bowel strictures involve a partial reduction of the internal diameter of the small intestine, causing slight obstruction of the passage of food and digestive fluids without significant bowel obstruction symptoms. By contrast, high-grade small bowel strictures involve a severe narrowing of the intestinal lumen, leading to marked obstruction of the passage of food and digestive fluids and pronounced bowel obstruction symptoms. Small bowel strictures can be diagnosed using various methods, including abdominal plain radiography, abdominal computed tomography, computed tomography enterography, magnetic resonance enterography, balloon-assisted enteroscopy, and abdominal ultrasound. Each diagnostic method has unique advantages and disadvantages as well as differences in diagnostic specificity and sensitivity. Therefore, even if small bowel strictures are not observed using a single imaging technique, their presence cannot be completely excluded. A comprehensive diagnosis that combines clinical information from multiple diagnostic modalities is necessary. Therapeutic approaches for managing small bowel strictures include medical therapy, endoscopic balloon dilation using balloon-assisted enteroscopy, and surgical methods such as strictureplasty and segmental resection. Endoscopic balloon dilation, in particular, can help reduce complications associated with repeated surgeries for strictures.

Comparison of 3D-printed multichannel non–co-planar vaginal applicators and single-channel vaginal applicators for brachytherapy with positive or close surgical margins in cervical cancer

OBJECTIVEThis study was conducted to compare the differences between 3D-printed multichannel non-coplanar vaginal applicators and single-channel vaginal applicators in cervical cancer patients with positive or close surgical margins. METHODSBetween January 2015 and June 2023, 104 cervical cancer patients who underwent radical surgery with positive or close surgical margins were enrolled to receive concurrent intensity-modulated chemoradiotherapy combined with 3D-printed multichannel non-coplanar vaginal applicators (3D-printed group, 41 patients) or single-channel vaginal applicators (single-channel group, 63 patients) guided brachytherapy. The dosimetric parameters, 5-year local control (LC), progression-free survival (PFS), overall survival (OS) of two groups were retrospectively analyzed. RESULTSThe high-risk clinical target volume (D90, D100) and high-dose volume fraction (V150) in 3D-printed group were significantly higher than those in single-channel group (p<0.05), and the homogeneity index (HI) and conformal index (COIN) were equally better in 3D-printed group. In 3D-printed group, the D2cc, D1cc, and D0.1cc of the bladder and rectum were significantly lower than those of the single-channel group (p<0.05). The 3D-printed group had significantly superior 5-year LC (70.0% vs. 51.3%, P=0.041) and PFS (63.0% vs. 44.2%, P=0.045), but OS were not significantly different between treatment groups (75.4% vs. 59.7%, P=0.112). The incidence of radiation enteritis and cystitis was lower in the 3D-printed group than in the single-channel group, but no statistical difference was noted. CONCLUSIONSThe 3D-printed multichannel non-coplanar vaginal insertion applicators shows the advantage of target dose, improve the LC and PFS in patients with positive or close surgical margins after cervical cancer surgery. Thus, the popularization of this method and its application may be of value.

Gastroprotective and microbiome-modulating effects of ubiquinol in rats with radiation-induced enteropathy

Radiation enteritis is a frequently encountered issue for patients receiving radiotherapy and has a significant impact on cancer patients' quality of life. The gut microbiota plays a pivotal role in intestinal function, yet the impact of irradiation on gut microorganisms is not fully understood. This study explores the gastroprotective effect and gut microbiome-modulating potential of ubiquinol (Ubq), the reduced form of the powerful antioxidant CoQ-10. For this purpose, male albino rats were randomly assigned to four groups: Control, IRR (acute 7 Gy γ-radiation), Ubq_Post (Ubq for 7 days post-irradiation), and Ubq_Pre/Post (Ubq for 7 days pre and 7 days post-irradiation). The fecal microbiomes of all groups were profiled by 16S rRNA amplicon sequencing followed by bioinformatics and statistical analysis. Histopathological examination of intestinal tissue indicated severe damage in the irradiated group, which was mitigated by ubiquinol with enhanced regeneration, goblet cells, and intestinal alkaline phosphatase expression. Compared to the irradiated group, the Ubq-treated groups had a significant recovery of intestinal interleukin-1β, caspase-3, nitric oxide metabolites, and thio-barbituric reactive substances to near-healthy levels. Ubq_Pre/Post group displayed elevated peroxisome proliferator-activated receptor (PPAR-γ) level, suggesting heightened benefits. Serum insulin reduction in irradiated rats improved post-Ubq treatment, with a possible anti-inflammatory effect on the pancreatic tissue. Fecal microbiota profiling revealed a dysbiosis state with a reduction of bacterial diversity post-irradiation, which was re-modulated in the Ubq treated groups to profiles that are indistinguishable from the control group. These findings underscore Ubq's gastroprotective effects against radiation-induced enteritis and its potential in restoring the gut microbiota’s diversity and balance.

Progress on the effects and underlying mechanisms of evodiamine in digestive system diseases, and its toxicity: A systematic review and meta-analysis

BackgroundEvodiamine (EVO) is one of the primary components of Evodia rutaecarpa and has been found to have a positive therapeutic effect on various digestive system diseases. However, no systematic review has been conducted on the research progress and mechanisms of EVO in relation to digestive system diseases, and its toxicity. PurposeThis study aimed to provide a reference for future research in this field. Study designA systematic review and meta-analysis of the research progress, mechanisms, and toxicity of EVO in the treatment of digestive system diseases. MethodsFive electronic databases were utilized to search for relevant experiments. We conducted a comprehensive review and meta-analysis of the pertinent literature following the guidelines of Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). ResultsEVO's animal experiments in digestive system diseases primarily focus on colorectal cancer, gastric ulcers, liver cancer, liver fibrosis, ulcerative colitis, colitis-associated cancer, and functional gastrointestinal disorders. EVO also has positive effects on pancreatic cancer, radiation enteritis, gastric cancer, tongue squamous cancer, hepatitis B, oral cancer, and esophageal cancer in vivo. EVO's in cellular experiments primarily focus on SGC7901, HT29, HCT-116, and HepG2 cells. EVO also exhibits positive effects on SW480, LoVo, BGC-823, AGS, COLO-205, MKN45, SMMC-7721, Bel-7402, QGY7-701, PANC-1, SW1990, BxPC-3, HSC4, MC3, HONE1, and CNE1 cells in vitro. The potential common pathways include TGF-β, PI3K-AKT, Wnt, ErbB, mTOR, MAPK, HIF-1, NOD-like receptor, NF-κB, VEGF, JAK-STAT, AMPK, Toll-like receptor, EGFR, Ras, TNF, AGE-RAGE, Relaxin, FoxO, IL-17, Hippo, and cAMP. The mechanisms of EVO on ulcerative colitis, gastric cancer, and HCT116 cells are still controversial in vivo. EVO may have a bidirectional regulatory effect on functional gastrointestinal disorders through calcium signaling. The mechanisms of EVO on HCT116, HT29, SW480, AGS, COLO-205, and SW1990 cells are still controversial in vitro. The question of whether EVO has obvious toxicity is controversial. ConclusionIn both cellular and animal experiments, EVO has demonstrated positive impacts on digestive system diseases. Nevertheless, additional in vivo and in vitro research is required to confirm the beneficial effects and mechanisms of EVO on digestive system diseases, as well as its potential toxicity.

Acupuncture therapies on radiotherapy-induced radiation enteritis: A systematic review and meta-analysis

Acupuncture therapies on radiotherapy-induced radiation enteritis: A systematic review and meta-analysis

Investigating the relationship between postoperative radiotherapy and intestinal flora in rectal cancer patients: a study on efficacy and radiation enteritis.

This study aimed to investigate the impact of radiation therapy and radiation enteritis on intestinal flora, providing insights for treatment and prevention. Fecal samples were collected from 16 patients undergoing pelvic radiotherapy at Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital). Samples were collected before and after radiotherapy (27-30Gy), and analyzed using DNA sequencing and biostatistical methods. Patients with radiation enteritis showed increased α-diversity and β-diversity of intestinal flora compared to those without radiation enteritis. Differences in flora composition were observed, with higher abundance of secondary pathways such as amino acid metabolism, carbohydrate metabolism, cofactors and vitamins metabolism, and lipid metabolism. The study revealed that patients developing radiation enteritis during pelvic radiation therapy had increased diversity and abundance of intestinal flora compared to those who did not develop radiation enteritis. Additionally, patients without radiation enteritis showed significantly higher diversity and abundance of intestinal flora post-radiation compared to pre-radiation.

T Cell-Derived Apoptotic Extracellular Vesicles Hydrolyze cGAMP to Alleviate Radiation Enteritis via Surface Enzyme ENPP1.

Radiation enteritis is the most common complication of pelvic radiotherapy, but there is no effective prevention or treatment drug. Apoptotic T cells and their products play an important role in regulating inflammation and maintaining physiological immune homeostasis. Here it is shown that systemically infused T cell-derived apoptotic extracellular vesicles (ApoEVs) can target mice irradiated intestines and alleviate radiation enteritis. Mechanistically, radiation elevates the synthesis of intestinal 2'3' cyclic GMP-AMP (cGAMP) and activates cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) proinflammatory pathway. After systemic infusion of ApoEVs, the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) enriches on the surface of ApoEVs hydrolyze extracellular cGAMP, resulting in inhibition of the cGAS-STING pathway activated by irradiation. Furthermore, after ApoEVs are phagocytosed by phagocytes, ENPP1 on ApoEVs hydrolyzed intracellular cGAMP, which serves as an intracellular cGAMP hydrolyzation mode, thereby alleviating radiation enteritis. The findings shed light on the intracellular and extracellular hydrolysis capacity of ApoEVs and their role in inflammation regulation.

Network Pharmacology and Bioinformatics Analysis identify potential therapeutic effects of Berberine on Colon Cancer complicated with Radiation Enteritis

Background: Patients with colon adenocarcinoma (COAD) who undergo radiation therapy develop radiation enteritis (RE). The predictive value of RE in COAD is yet to be established. Berberine, an active compound derived from the traditional Chinese medicinal plant, Coptis chinensis, has notable anti-inflammatory properties and offers protection to the intestinal mucosa. This study aimed to evaluate the possible therapeutic effect and mechanism of berberine as a treatment for COAD complicated with RE (COAD&amp;RE). Methods: Relevant genetic features of diverse COAD&amp;RE populations were analyzed using bioinformatics and the Cox proportional hazards regression model. The therapeutic targets of berberine were predicted using network pharmacology and molecular docking. In vivo and in vitro experiments were conducted to validate the core genes identified using molecular docking. Results: RE has a certain impact on the prognosis of COAD and berberine may play an important role in the treatment of COAD&amp;RE. In addition, we identified five core therapeutic targets of berberine by network pharmacology and molecular docking: CCND1, MYC, AR, LEP, and CYP19A1. In vivo experiments showed that berberine increased short-term survival rate, body weight, and intestinal epithelial cell recovery in mice after radiation. In an in vitro study, berberine promoted the proliferation of human intestinal epithelial cells and enhanced the radiosensitivity of HT29 cells after radiation, and the relative mRNA expression levels of CCND1 and MYC closely correlated with these effects. Conclusions: This study predicted the potential therapeutic effects of berberine on COAD&amp;RE and verified the relevant mechanisms, which may provide insights and suggestions for the clinical treatment of COAD&amp;RE.

A prospective double-blind clinical study: Effect of probiotics and thalidomide on radiation enteritis in patients with pelvic cancer undergoing concurrent chemoradiotherapy.

e23013 Background: Radiation induced diarrhea (RID) is one of the commonest and most distressing side effects during and after radiotherapy predominantly in patients whose irradiation region is pelvis. Thalidomide reduces severity as well as the frequency indicated in RID but mechanism of action is not elucidated. Probiotics are beneficial microorganisms that may regulate flora of intestines to increase immunity and have a protective effect on RID. This pilot study was designed to ascertain effects of thalidomide and probiotics on RID in patients being subjected to pelvic irradiation. Methods: A double-blind, single-center, randomized pilot study was conducted. Patients were classified into two groups as thalidomide plus probiotics (Lactobacillus rhamnosus + Probio-M9, ) group (TP group) or plus placebo group (P group).Incidence of grade 3/4 diarrhea, was a primary endpoint of the study. Other secondary endpoints analyzed were rates and severity of diarrhea, antibiotics use, body weight, albumin, and lymphocyte changes. 31 patients undergoing pelvic radiotherapy with or without concurrent chemotherapy were randomly selected from government tertiary general hospital. Results: The incidence of grade 3/4 diarrhea was 9.5% (95% CI: 0 to 24.5%) in TP, which was significantly different from historical data of 30% to 60%. The incidence of grade 3/4 diarrhea in group P was 19.8% (95% CI: 0~41.3%). The frequency and severity of diarrhea in group TP were little less than in group P. There is no significant difference between them. Basically, the time for antibiotic use in groups P and TP was the same, with a slightly longer time from first antibiotic exposure in group TP as compared to group P. The moment of first antibiotics have been prescribed in our study patients, this was better than that of a clinical routine treatment experience and other research data according to the literature. The changes in body weight, albumin level, and lymphocyte at different stages before and after radiotherapy in group TP were not statistically significant, and the level of body weight and albumin in group P was slightly reduced compared with before radiotherapy but increased compared with group TP after radiotherapy. Furthermore, there were no severe adverse effects regarding thalidomide as well as probiotics reported among patients who participated in this study. Conclusions: The combined treatment with thalidomide and probiotics is beneficial to ameliorate RID in patients receiving pelvic radiotherapy, yet this study can't represent whole conclusion due to small size of patients. We will also need larger, multicenter double-blind placebo-controlled trials to confirm exact efficacy and safety of this combined treatment. Clinical trial information: NCT05059613 .

Cannabidiol mitigates radiation-induced intestine ferroptosis via facilitating the heterodimerization of RUNX3 with CBFβ thereby promoting transactivation of GPX4

Radiation enteritis remains a major challenge for radiotherapy against abdominal and pelvic malignancies. Nevertheless, there is no approved effective therapy to alleviate irradiation (IR)-induced gastrointestinal (GI) toxicity. In the current study, Cannabidiol (CBD) was found to mitigate intestinal injury by GPX4-mediated ferroptosis resistance upon IR exposure. RNA-sequencing was employed to investigate the underlying mechanism involved in the radio-protective effect of CBD, wherein runt-related transcription factor 3 (RUNX3) and its target genes were changed significantly. Further experiment showed that the transactivation of GPX4 triggered by the direct binding of RUNX3 to its promoter region, or by stimulating the transcriptional activity of NF-κB via RUNX3-mediated LILRB3 upregulation was critical for the anti-ferroptotic effect of CBD upon IR injury. Specially, CBD was demonstrated to be a molecular glue skeleton facilitating the heterodimerization of RUNX3 with its transcriptional chaperone core-biding factor β (CBFβ) thereby promoting their nuclear localization and the subsequent transactivation of GPX4 and LILRB3. In short, our study provides an alternative strategy to counteract IR-induced enteritis during the radiotherapy on abdominal/pelvic neoplasms.

Phase II study of tislelizumab combined with concurrent chemoradiotherapy for locally advanced cervical cancer.

e17523 Background: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer (LACC). However, local recurrence and distant metastasis are the main modes of treatment failure in LACC, especially for patients with stage IIIA ~IVA as well as patients with large masses (&gt;4cm) and regional lymph node metastasis. This study aimed to evaluate the efficacy and safety of tislelizumab (anti-PD-1 antibody) combined with concurrent chemoradiotherapy for locally advanced cervical cancer. Methods: Eligible patients were age 18-75 years, ECOG performance status of 0-1 and untreated cervical cancer (2018 FIGO stage IIIA, IIIB, IVA, or cervical tumor diameter &gt; 4cm with regional lymph node metastasis, or paracervical invasion with regional lymph node metastasis). All patients received CRT plus tislelizumab 200mg Q3W for 1 year or disease progression or intolerable toxicity. The CRT includes at least 4 cycles of cisplatin 40mg/m2 QW + EBRT 45~50Gy/25f then BT 28~30Gy/4~5f. The primary endpoint was tumor regression ratio before brachytherapy. Secondary endpoints were 3-month and 6-month objective response rate (ORR), 1-year and 3-year OS and PFS, safety. Results: From August 24, 2022 to February 4, 2024, 30 patients were enrolled. 25 patients completed CRT and were available for evaluation. The median age was 59 years (range 40-75). The tumor regression ratio before brachytherapy was 90.6%. The ORR at 3 and 6 months were 100%, The OS and PFS rate at 1 year were 100%. The main adverse effect was neutropenia (36% for grade 3-4 and 20% for grade 1-2). Radiation enteritis incidence was 64% and were grade 1-2. Other adverse effect such as nausea, vomiting, and dizziness occurred during CRT and could be alleviated after symptomatic treatment. No immune-related adverse events were observed. Conclusions: Our results suggest that Tislelizumab combined with concurrent chemoradiotherapy showed valuable antitumor activity and controllable safety in LACC. We will keep strictly implementing our study protocol for further PFS and OS. Clinical trial information: NCT05588219 .

The Effect of Probiotics on Radiation Enteritis in Endometrial Cancer Patients Undergoing Radiotherapy

Introduction: Radiation enteritis is damage to the small and large intestines caused by radiation therapy for regional cancer treatment. The incidence is around 90% in patients undergoing radiation in the pelvic and abdominal regions. This study aimed to report the effect of probiotics on radiation enteritis in endometrial cancer patients. Case presentation: A 57-year-old morbidly obese woman diagnosed with endometrial cancer underwent chemoradiation therapy. On the 21st out of 25 radiation sessions and the 2nd chemotherapy session, the patient visited the nutrition clinic at the Radiation Oncology Therapy Center with a complaint of diarrhea for the past 5 days. The diarrhea occurred approximately 10 times a day, with each bowel movement being approximately 50 ml and yellow in color. The patient was then treated with anti-diarrheal therapy, probiotics (Lactobacillus acidophilus, Bifidobacterium longum, and Streptococcus thermophilus) 2 times a day, zinc 20 mg once a day, and prescribed a low-fat and lactose-free diet. After monitoring on the 21st day, the frequency of liquid bowel movements decreased to 2 times a day, and the appetite improved. Conclusion: Patients with radiation enteritis who are given probiotics may experience a reduction in symptoms of acute diarrhea. Direct administration of probiotics increases beneficial bacteria in the digestive tract.