Neoplasms

Digestive System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Stomach Neoplasms

Atrophy

Gastritis, Atrophic

Gastritis

Pathological Conditions, Anatomical

Gastroenteritis

Gastrointestinal Diseases

Stomach Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Chronic Graft Versus Host Disease

Stomach Cancer

Corpus-dominant chronic atrophic gastritis was characterized by a PGI/PGII ratio of less than 3.

Healthy participants in the TwinGene cohort were included.

Metabolomic profiling using serum samples was performed based on Nightingale Blood Biomarker Analysis platform; Proteomic profiling will be performed by both Scanning SWATH and OLINK® Explore 384 Oncology panel.

Metabolomic profiling

The overall aim is to utilize multi-omics approach to identify novel etiopathogenesis and early detection biomarkers for stomach cancer precursor lesions. To achieve this aim, first the investigators will use stored serum samples to perform metabolomics profiling among 12,599 twin subjects, among whom 1034 were deemed to have chronic atrophic gastritis based on measured pepsinogen I and II levels. Logistic regression will be used to search for metabolites related to the risk of chronic atrophic gastritis. Second, the investigators will further measure serum proteome by using two quantitatively precise proteomics assays, among the above-mentioned twin subjects. Identified protein biomarkers will be combined with metabolomics biomarkers to create a prediction model for chronic atrophic gastritis. The results will hopefully improve our understanding of the etiological factors and provide promising early detection biomarkers for stomach cancer precursor lesions.

The study population is part of the Swedish Twin Registry (STR), which has since its establishment in the late 1950s collected questionnaire data from all twins born after 1886. The data in this specific study is a subset of the Screening Across the Lifespan (SALT) study within the STR, in which all twins born between 1911-1958 were interviewed between 1998-2002. The subcohort named TwinGene was set-up between the years 2004 and 2008 when participants were invited to respond to a questionnaire on common diseases and provide a blood sample. Samples were collected from 12,618 twins born 1958 or earlier, of which blood sample from 12,609 were available. After excluding 10 samples which were unable to link to the available environmental data, a total of 12,599 blood samples were analyzed. Corpus-dominant CAG was characterized by a PGI/PGII ratio of less than 3. Metabolomic profiling using serum samples has been performed based on Nightingale Blood Biomarker Analysis platform. Proteomic profiling will be performed by both Scanning SWATH and OLINK® Explore 384 Oncology panel. History of H. pylori infection is examined by measuring serum IgG antibodies against H. pylori, using ELISA. Detailed lifestyle information collected by questionnaires includes education, smoking, snuff dipping, alcohol drinking, drug use, diet, and height/weight, etc. Metabolites will be log transformed prior to analyses, due to its usually skewed distribution. For each metabolite, firstly, CAG patients will be compared with all the CAG-free controls. Wilcoxon-Mann-Whitney test or Kruskal-Wallis test will be used for comparing differences of protein expressions between CAG and non-CAG groups, and multiple comparisons will be adjusted using Bonferroni correction. Generalized estimation equation (GEE) models with the robust option will be fitted to estimate the odds ratios (ORs). Second, in the comparison with MZ co-twin controls and DZ co-twin controls, only complete twin pairs with discordant CAG will be included in the study. Specifically, conditional logistic regression models will be used to control for the matching within co-twin pairs. The investigators will further combine metabolomics and proteomics data, and try to build up a CAG prediction model. Covariates will include age, sex, H. pylori seropositivity, education level, smoking, snuff dipping, and alcohol drinking. Joint effects of different metabolites and interaction with other covariates will also be examined.

Participants from TwinGene provided blood samples.

Multi-omics Analyses on Etiology and Early Detection of Stomach Cancer Precursor Lesions

Multi-omics Approach for Identification of Etiopathogenesis and Early Detection Biomarkers of Stomach Cancer Precursor Lesions

Karolinska Institutet

Professor

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Adenocarcinoma

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Primary, adjuvant or salvage RT of the prostate (bed) without RT of the pelvic nodal regions in the small pelvis, according to local hospital guidelines and protocols.

Primary, adjuvant or salvage RT of the pelvic nodal regions in the small pelvis with possible additional RT of the prostate (bed), according to local hospital guidelines and protocols.

Feces, blood and urine: (1) shortly before, (2) during and (3) shortly after RT treatment, as well as (4) one-month post-RT

Collection of human biofluids

EORTC QLQ-C30, PR25: (1) shortly before and (2) shortly after RT treatment, as well as (3) one-month post-RT

Patient reported outcome measures

Piet Ost, MD, PhD

Radiotherapy (RT) of the abdomen and/or pelvis is known to cause acute and late gastrointestinal (GI) toxicities. While radiation dose and volume are known risk factors for developing such side effects, recent evidence suggests patterns of disturbance in the composition of the GI microbiota - so called "dysbiosis" - may also promote the host's susceptibility to GI toxicities through impaired intestinal barrier function and inflammation. The IMPRINT-study aims to expand the current knowledge on the role of intestinal bacteria and their metabolites involved in the pathophysiology of radiation-induced GI toxicities by longitudinally examining the microbiota composition (feces), the associated metabolome (blood, feces and urine) and bacterial extracellular vesicles (BEVs) (blood and feces).

The IMPRINT-study is a prospective biomarker study assessing the impact of different treatment field sizes and associated radiation doses on the patient's microbiome and metabolome, whereby the link with radiation-induced GI toxicities will be emphasized. Blood, urine and fecal samples will be longitudinally collected at 4 different time points: (1) shortly before, (2) during and (3) shortly after RT treatment, as well as (4) one-month post-RT. To our knowledge, this is the first clinical research project relating the impact of multiple radiation parameters on fecal-, urine- and blood-based biomarkers to risk of GI toxicities in a homogeneously defined study population.

Intestinal Microbiota in Prostate Cancer Patients as a Biomarker for Radiation-INduced Toxicity (IMPRINT)

Intestinal Microbiota in Prostate Cancer Patients as a Biomarker for Radiation-INduced Toxicity (IMPRINT): A Prospective Biomarker Study

Characterization of dynamic changes in the intestinal microbiota composition using 16S rRNA sequencing technology

Characterization of dynamic changes in the concentration of all small molecules (metabolites) in feces, blood and urine using ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS)

The identified microbiota and metabolite signatures will be investigated for association with incidence and severity of GI toxicities

GI and GU toxicities as per Common Terminology for Adverse Events (CTCAE) v4.0

Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients

Validated questionnaire assessing the health-related QOL of prostate cancer patients

BEVs in fecal and blood samples will be separated and analyzed through the orthogonal implementation of ultrafiltration, size-exclusion chromatography (SEC) and density-gradient centrifugation, followed by biochemical characterization

University Hospital, Ghent

Skin and Connective Tissue Diseases

Sarcoma

Osteosarcoma

Sarcoma, Ewing

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Ewing Sarcoma

Patients of \>= 12 years old (pediatric and adults) with new diagnosis of osteosarcoma and Ewing sarcoma will be included

* Localized and metastatic
* Male and female

Control cases matched by age, sex and italian geographic area

* Patients of \>= 12 years old (pediatric and adults) with new diagnosis of osteosarcoma and Ewing sarcoma will be included Localized and metastatic Male and female
* Control cases matched by age, sex, and geographic area

Anthropometric measurements (Body mass Index, Lean and fat body composition evaluation) and diet habits evaluation with EPIC-COS-FFQ

EPIC-COS Food Frequency Questionnaire diet Evaluation

At diagnosis before any treatment for bone sarcoma will be obtained :

1. a blood sample for metabolomics analyses
2. a stool sample for microbiota analysis
3. Lymphocyte subpopulations (CD3, CD4, CD8, NK) will be analyzed in blood samples

Metabolome, Microbiota, Lymphocytes subpopulations

Alessandra Longhi, MD

Inge Huybrechts, PhD

Giovanni Grignani, MD

Angela Tamburini, MD

Luca Coccoli, MD

Virginia Ferraresi, MD

Franca Fagioli, MD

Osteosarcoma and Ewing sarcoma treatment has not changed in the last 30 years.

For other types of cancer the epidemiologic and prognostic correlations between dietary behavior, lifestyle and metabolic alterations (i.e.obesity, insulin-resistance) are well known (breast cancer, prostate cancer, colon cancer). However, no epidemiological or prognostic data are available about the metabolic profile and lifestyle behaviors in patients with osteosarcoma and Ewing'sarcoma and only few preclinical studies are available. An in vitro study showed a higher glucose and glutamine consumption from metastatic osteosarcoma cells compared to primary tumor osteosarcoma cells. The effect of the intestinal microbiota into the metabolism of nutrients, drugs, inflammation, epigenetic and immune response was found not only correlated to gastrointestinal tumors but also to other tumors outside gastrointestinal system as well The aim of this study is to investigate if there are differential dietary habits, metabolome, microbiota or immune profile in patients with bone sarcoma compared to a control population in a 1:2 multicenter study.

MATERIALS \& METHODS A population of 270 patients of \>12 yrs old (pediatric and adults) with new diagnosis of osteosarcoma and Ewing sarcoma will be included. A detailed dietary intake assessment will be done with EPIC-COS food frequency questionnaire (FFQ) and anthropometric measures (Weight, Height, body fat/lean mass composition) will be taken at diagnosis before treatment and compared to 540 controls matched by age, sex, and italian geographic area.

In addition, inside this main study a pilot study of 55 patients and 110 controls of same age, sex, geographic area will be performed for analysis of metabolome, microbiota, and immune profile.

At diagnosis, before any treatment , a blood sample will be obtained for metabolomics analyses (untargeted approach with over 100.000 of metabolites, (Mass Spectrometry method) and to evaluate lymphocyte subpopulations (CD3, CD4, CD8, NK) in blood. Microbiota will be analyzed in donated stool samples using the S16 method. All data will be analyzed for inter-correlations among the different parameters and to investigate putative associations with EPIC-COS Food Frequency questionnaires and anthropometric data .

STATISTICAL ANALYSIS Conditional logistic regression analyses will be used to calculate odds ratio (OR) and 95% confidence interval (CI) to investigate associations between dietary habits and bone sarcoma risk in the case control study. An odds ratio of 1.6 with a potency of 85% was considered in the sample size calculations, leading to a target sample size of 270 cases with 540 matched healthy controls.

For the pilot cohort samples of 55 cases and 110 controls will be analyzed for metabolome, microbiota and immune profile. According to the results of this pilot study further cases among the population of FFQ study will undertake further analysis of metabolome and/or microbiota and/or lymphocyte subpopulation to confirm the results of pilot study.

OBJECTIVES OF THE STUDY

1. Compare the diet habits and anthropometric measures in bone sarcoma patients at diagnosis with matched controls
2. Pilot study: in the first 55 pts and their matched 110 healthy voluntary controls will be explored:

   1. the occurrence of altered or more recurrent metabolites in patients' blood compared to controls
   2. different microbiota diversity and composition between patients and case controls
   3. different lymphocytes subpopulations composition.

Bioinformatics analysis will be performed to investigate these objectives

Inside this main study (270:540) a pilot study of 55 patients and 110 controls of same age, sex, geographic area (1:2) will be performed for analysis of metabolome, microbiota, and immune profile.

At diagnosis before any treatment a blood sample will be obtained for metabolomics analyses (untargeted approach with over 100.000 of metabolites, (Mass Spectrometry method) and to evaluate lymphocyte subpopulations (CD3, CD4, CD8, NK) in blood. Microbiota will be analyzed in donated stool samples using the S16 method. All data will be analyzed for inter-correlations among the different parameters and to investigate putative associations with Food Frequency questionnaires and anthropometric data.

Dietary Habits, Metabolome, Immune Profile and Microbiota in Patients With Bone Sarcoma

Evaluation of Dietary Habits, Metabolome, Immune Profile and Microbiota in Patients With Bone Sarcoma

Diet habits from osteosarcoma and Ewing sarcoma patients will be compared with diet habits from a control population. The diet habits data will be evaluated EPIC COS FFQ( European Prospective Investigation Into Cancer and Nutrition Case Only Study Food Frequency Questionnaire) which report:

the food consumptions in the last 12 months

- Main food groups (water and other drinks, grain products, fruits and vegetables, legumes, meat and fish products, dairy products, sweets and savory snacks)

FFQ-EPIC COS can be accessed on PubMed (PMID: 12484126 and PMID: 12484120).

Diet quality index from osteosarcoma and Ewing sarcoma patients will be compared with diet habits from a control population. Data will be accessed with EPIC COS FFQ( European Prospective Investigation Into Cancer and Nutrition Case Only Study Food Frequency Questionnaire )

- Diet quality index will be calculated to compare adherence to dietery guidelines and it will be expressed in percentage

Body Mass Index (BMI) measure will be achieved in patients and controls by impedance Tanita scale model BC545 based on height (in centimeters) and weight (in Kilograms) expressed in subjects \>18yrs as 1) underweight if \<18.5, 2) normal weight 18.5 to 25,3)overweight 25-30 and 4) obese \>30.

BMI measure will be achieved by impedance Tanita scale model BC545 in study patients at diagnosis and compared with a control subjects.

Lean mass and fat mass will be calculated via impedance Tanita scale model BC545 as a percentage of total weight .Lean body mass is the difference between total body weight and body fat weight, expressed as percentage (%)

Concentration of untargeted blood metabolites obtained via mass spectometry SANIST technique from blood of 55 patients and from 110 control subject blood. Metabolome will be analyzed in order to determine if there is an occurrence of altered or more recurrent metabolites in patients' blood compared to controls.

Microbiota will be analyzed with S16 method. Microbiota diversity and composition between patients and controls will be analyzed and expressed as alpha and beta diversity

Concentrations of (CD3,CD4.CD8,NK) lymphocytes subpopulation will be detected onceat diagnosis before any treatment for sarcoma and they will beexpressed as total number.

The lymphocytes subpopulation will be measured once at diagnosis in study patients and matched controls.

Fatty acids triglycerids(mg/dL), total cholesterol (mg/dL), HDLcholesterol (mg/dL) and LDL cholesterol (mg/dL), glucose (mg/dL) will be measured once in blood at diagnosis in study patients and control subjects

International Agency for Research on Cancer

Istituto Ortopedico Rizzoli

Principal Investigator

Uterine Cervical Neoplasms

Endometrial Neoplasms

Urinary Bladder Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

No intervention: Questionnaires, food diaries and stool sample.

Caroline Henson, MBBS FRCP PhD

Eight in ten patients will develop bowel problems during radiotherapy, eg diarrhoea, pain and incontinence, half will develop difficult long-term bowel problems. It is not known why some people get bowel problems and others do not and there is no test to predict who will develop bowel problems following their treatment.

There is a link between the changes in the number and type of gut bacteria (the microbiome) in some bowel conditions and it is possible to test for these different bacteria in a simple stool sample using genetic testing. Also gut bacteria produce different gases in the stool called "volatile organic compounds" (VOCs), which can be measured in stool samples. Specific VOC patterns have been seen in other bowel conditions and small studies suggesting that there are specific VOC and gut bacteria patterns in the stool of those undergoing pelvic radiotherapy which may help to identify people who will get difficult bowel problems. Diet can change the microbiome/VOCs so diet change could improve bowel symptoms after radiotherapy.

The investigators would like to test stool samples of patients with womb, cervix or bladder cancer having pelvic radiotherapy to see if there are differences in the number/type of gut bacteria and VOCs between those who get severe bowel symptoms compared to those with mild bowel symptoms. They also want to see whether these differences in VOCs or gut bacteria can tell who will develop severe bowel symptoms during or after radiotherapy and determine the effect of diet.

The first step is to run the study on a small scale to confirm that a larger study would work. This will make sure the investigators can recruit and consent people safely and will test the best ways of measuring bowels symptoms using several questionnaire options. They will collect the information needed to work out how many people would be needed in a large trial to fully test the theory. Ultimately, the investigators would like to use differences in the number/type of gut bacteria and VOCs to find ways to better prevent and treat bowel problems after pelvic radiotherapy.

Background 80% of patients develop GI-toxicity during pelvic radiotherapy and half develop chronic GI-toxicity. This manifests as diarrhoea, pain, bleeding and incontinence. Unlike many diseases, the triggering event, i.e. radiotherapy, is known, enabling the identification of specific pathophysiological changes. The metabolomic and microbiomic profile of patients undergoing pelvic radiotherapy and the link with GI-toxicity has not been fully explored. Studies suggest radiation alters the gut microbiome, altering microbial diversity. Higher pre-radiotherapy diversity has been seen in those with no GI symptoms with reducing diversity as GI-toxicity increases and an association between low microbial diversity and severity of chronic GI-toxicity. Dietary change can alter microbial composition. Faecal VOCs are chemicals that exist in the gaseous phase at ambient temperature and form the faecal metabolome, the result of the interaction between the gut microbiota and cell metabolism. VOCs can be identified using established techniques and unique VOCs patterns have been identified in specific GI diseases. Early data suggest differences in VOCs between patients with high vs low levels of GI-toxicity. Metabolomic and microbiomic profiling and manipulation has the potential to advance understanding of disease-related pathways to predict, prevent and treat GI-toxicity.

Rationale GI-toxicity is a significant cause of morbidity both during and after pelvic radiotherapy to the extent that it adversely affects quality of life. There is a paucity of research into this condition. The metabolomic and microbiomic profile of patients undergoing pelvic radiotherapy and the link with GI-toxicity has not been fully explored. Studies suggest radiation alters the gut microbiome, altering microbial diversity. Higher pre-radiotherapy diversity has been seen in those with no GI symptoms with reducing diversity as GI-toxicity increases and an association between low microbial diversity and severity of chronic GI-toxicity. Dietary change can alter microbial composition. Unique VOCs patterns have been identified in specific GI diseases. Early data suggest differences in VOCs between patients with high vs low levels of GI-toxicity. Metabolomic and microbiomic profiling and manipulation has the potential to advance understanding of disease-related pathways to predict, prevent and treat GI-toxicity.

By comparing samples collected pre and post radiotherapy the investigators aim to identify potential biomarkers. They are going to integrate metadata indicating a negative GI response to the therapy, i.e. GI toxicity symptoms from validated questionnaires, with microbial community data and VOCs data in order to identify markers (VOCs or bacteria) that increase with symptoms. They will also identify which species make patients more susceptible to negative outcomes by analysing the community pre-treatment.

Previous literature using culture based methods showed an increase in E. coli and Staphylococcus spp. and the investigators will determine whether they can confirm this. In terms of VOCs, they will look for markers of inflammation, e.g. aldehydes. It has been proposed that there are similarities between radiation-induced GI-toxicity and IBD, particularly Crohn's disease, therefore it would be interesting to see whether there is a similar dysbiosis of the microbial community and VOCs profile to that observed in Crohn's disease, i.e. whether decreased species diversity, increased Bacteroides species and Enterobacteriaceae coupled with a decrease in Faecal bacterium are also observed in patients with severe GI toxicity symptoms.

Potential interventions to modify the gut microbiome, e.g. diet, pre/probiotics, synthetic faecal microbiota transplantation, are in wide clinical research use currently in other related clinical areas, e.g. inflammatory bowel disease, and would be the types of interventions that may be indicated by information from this work and the subsequent definitive study.

The objectives of the subsequent definitive study are as follows:

1. Determine the differences in VOC profile/microbiome in patients with the most severe vs least severe GI-toxicity at 4 weeks and 6 months.
2. Determine the differences in VOC profile/microbiome at baseline in patients who develop the most severe vs least severe GI-toxicity at 4 weeks and 6 months.
3. Characterise disease-related pathways for GI-toxicity to identify potential therapeutic targets, including dietary.

Effect of Pelvic Radiotherapy on the Intestinal Microbiome and Metabolome

Investigating the Effect of Pelvic Radiotherapy on the Intestinal Microbiome and Metabolome to Improve the Detection and Management of Gastrointestinal (GI) Toxicity.

Obtain initial data regarding microbiome (diversity or composition) associated with risk of GI-toxicity and that is associated with greater severity of GI-toxicity in response in response to radiotherapy in the acute and chronic phases

Obtain initial data (peak area/metabolite(VOC)/sample) regarding VOCs profile associated with risk of GI-toxicity and that is associated with greater severity of GI-toxicity in response in response to radiotherapy in the acute and chronic phases.

To use metabolomic profiling to further understand the pathophysiology of GI-toxicity to identify potential therapeutic targets for treatment and/or prevention, including dietary targets

To use microbiomic profiling ( data table containing number of reads/species/sample) to further understand the pathophysiology of GI-toxicity to identify potential therapeutic targets for treatment and/or prevention, including dietary targets

Recruitment rates: can we achieve sufficient recruitment to the study? Are patients willing to participate?

Acceptability of recruitment process to patient cohort measured using internally generated non-validated questionnaire led by the research nurse

Experience of the study process by patient cohort measured using internally generated non-validated questionnaire led by the research nurse

Practicality and acceptability of obtaining stool samples for patient cohort measured using internally generated non-validated questionnaire led by the research nurse

Rate of patient leaving the study before completing

Reason for patient leaving the study before completing

Acceptability of questionnaires and food diaries to patient cohort measured using internally generated non-validated questionnaire led by the research nurse

Proportion of patients who complete the study eg rate of attrition of patients and rate of missing data items

To identify microbiome (diversity or composition) or VOCs profile that confers risk of GI-toxicity and that is associated with participants greater severity of GI-toxicity in response in response to radiotherapy in the acute and chronic phases

To use metabolomic and microbiomic profiling to further understand the pathophysiology of GI-toxicity to identify potential therapeutic targets for treatment and/or prevention, including dietary targets

University of Liverpool

University of Manchester

Wythenshawe Hospital

The Christie NHS Foundation Trust

Carcinogenesis

Cell Transformation, Neoplastic

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplastic Processes

The HPV integration status will be checked by GWAS.

A multi-omics analysis including genome-wide association study, whole exome sequencing, transcriptomics and metabolomics.

A multi-omics analysis

Lei Li, M.D.

Lei Li, MD

This study aims to analyze the multi-omics results between uterine cervical adenocarcinoma patients with and without human papillomavirus (HPV) infections. The multi-omics profiles include genome wide association study (GWAS), whole exome sequencing, analysis of transcriptomics and metabolomics. The HPV integration status is interpreted by GWAS. A comprehensive multi-omics will reveal the role of HPV integration in the molecular mechanism of tumorigenesis and prognosis of uterine cervical adenocarcinoma.

An 8 ml peripheral venous blood, and 50 μL cancer tissue and tissue adjacent to cancer will be collected from eligible patients.

HPV Integration and Tumorigenesis of Uterine Cervical Adenocarcinoma

A Multi-omics Study on the Human Papillomavirus Integration and Tumorigenesis of Uterine Cervical Adenocarcinoma

All data will be available to all researchers.

The differences of frequencies of somatic driving mutations will be compared between patients with and without HPV integration.

The alteration of patterns of RNA expression, including mRNA, miRNA, and lncRNA, will be compared between patients with and without HPV integration.

The alteration of patterns of protein expression and signal pathway will be compared between patients with and without HPV integration.

Progression-free survival between patients with differential expressed multi-omics will be compared.

Lei Li

Nervous System Diseases

Nutritional and Metabolic Diseases

Recurrence

Glioma

Glioblastoma

Brain Neoplasms

Astrocytoma

Ketosis

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Hypoglycemic Agents

All Drugs and Chemicals

Metformin

Insulin

Insulin, Globin Zinc

Biguanides

Partial brain re-irradiation combined with metabolic intervention (low carbohydrate diet and/or metformin treatment)

Partial brain re-irradiation to a dose of 30-35Gy delivered over 2 weeks (10 fractions).

Partial brain re-irradiation.

Different cohorts will receive no, low dose or higher dose metformin.

Under close supervision of a dietician, patients will receive a low carbohydrate diet, enriched as necessary with medium chain triglyceride (MCT) supplements.

low carbohydrate diet

Yaacov R Lawrence, MBBS MA MRCP

Hila Gnessin, Bsc

Yaacov R Lawrence, MA MBBS MRCP

Recurrent brain tumours are extremely aggressive and despite optimal treatment, median survival is less than two years. One of the standard treatment options in this situation is radiation therapy. Currently there is intense scientific interest concerning the abnormal energy metabolism in cancer cells. All cells require energy in order to function, obtaining 'fuel' molecules such as glucose and fatty acids from the blood stream. Brain tumours exhibit "metabolic reprogramming", meaning that their energy requirements and utilization of fuel molecules are quite different from normal cells. Brain tumour cells are exquisitely dependant on glucose as a source of energy. Animal studies have shown that when these tumours are deprived of glucose they are very sensitive to radiation therapy.

In this clinical trial the investigators combine radiation therapy with a low-carbohydrate diet, in patients with recurrent brain tumours. In addition, subjects will receive medication with metformin, a drug usually used to treat diabetes. Metformin inhibits glucose metabolism within cancer cells, and additionally has reported intrinsic anti-cancer activity. Subjects will undergo advanced imaging and hormonal studies before, during and after the trial in order to obtain maximal translational-scientific impact.

The hypothesis:

The metabolic changes induced by the combination of a moderately-low carbohydrate diet combined with supplementary MCT and metformin therapy will selectively starve tumor cells. While normal brain cells are capable of deriving energy from ketone bodies during glucose restriction, tumor cells remain largely glucose-dependent for energy due to oncogene induced down-regulation of oxidative phosphorylation. While the tumor cells are in this 'vulnerable' state they will be less able to repair the damage induced by ionizing radiation.

Short-term implementation of the metabolic intervention (i.e. combined diet and metformin therapy) prior to, during, and after hypofractionated (2 week) radiation therapy is expected to increase tolerability, increase compliance and avoid the chronic metabolic complications associated with extreme carbohydrate restriction diets.

Treatment of Recurrent Brain Tumors: Metabolic Manipulation Combined With Radiotherapy

Improving the Response of Recurrent Glioma to Radiation Therapy Through Metabolic Intervention

The investigators will track adverse events in order to determine the safety of the intervention.

We will track patient compliance in order to determine the tolerability of the intervention.

We will assess plasma levels of glucose, insulin and other relevant hormones before, during and after the intervention.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Multi-omics Analyses on Etiology and Early Detection of Stomach Cancer Precursor Lesions	NCT06267703	Chronic Atrophi...	Metabolomic pro...	46 Years - 97 Years	Karolinska Institutet
Multi-omics Analyses on Etiology and Early Detection of Stomach Cancer Precursor Lesions	NCT06267703	Chronic Atrophi...	Metabolomic pro...	46 Years - 97 Years	Karolinska Institutet
Intestinal Microbiota in Prostate Cancer Patients as a Biomarker for Radiation-INduced Toxicity (IMPRINT)	NCT04638049	Prostate Cancer Prostate Adenoc... Prostatic Neopl...	Collection of h... Patient reporte...	18 Years -	University Hospital, Ghent
Dietary Habits, Metabolome, Immune Profile and Microbiota in Patients With Bone Sarcoma	NCT04735289	Osteosarcoma Ewing Sarcoma	EPIC-COS Food F... Metabolome, Mic...	12 Years -	Istituto Ortopedico Rizzoli
Intestinal Microbiota in Prostate Cancer Patients as a Biomarker for Radiation-INduced Toxicity (IMPRINT)	NCT04638049	Prostate Cancer Prostate Adenoc... Prostatic Neopl...	Collection of h... Patient reporte...	18 Years -	University Hospital, Ghent
Dietary Habits, Metabolome, Immune Profile and Microbiota in Patients With Bone Sarcoma	NCT04735289	Osteosarcoma Ewing Sarcoma	EPIC-COS Food F... Metabolome, Mic...	12 Years -	Istituto Ortopedico Rizzoli
Effect of Pelvic Radiotherapy on the Intestinal Microbiome and Metabolome	NCT04995809	Urinary Bladder... Uterine Cervica... Endometrial Neo...		18 Years -	The Christie NHS Foundation Trust
HPV Integration and Tumorigenesis of Uterine Cervical Adenocarcinoma	NCT03742869	Cervical Adenoc... Human Papilloma... Genome-wide Ass... Whole Exome Seq... Transcriptome Metabolome Tumorigenesis Prognosis	A multi-omics a...	-	Peking Union Medical College Hospital
Treatment of Recurrent Brain Tumors: Metabolic Manipulation Combined With Radiotherapy	NCT02149459	Brain Neoplasms	Partial brain r... Metformin low carbohydrat...	18 Years -	Sheba Medical Center

Spots Global Cancer Trial Database for metabolome

Every month we try and update this database with for metabolome cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for metabolome

Every month we try and update this database with for metabolome cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for metabolome cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.