Clinical trial NCT04735289: Dietary Habits, Metabolome, Immune Profile and Microbiota in Patients With Bone Sarcoma
Official title: Evaluation of Dietary Habits, Metabolome, Immune Profile and Microbiota in Patients With Bone Sarcoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Osteosarcoma
Ewing Sarcoma
Keywords: Metabolome
Microbiota
Bone sarcoma
Immune profile
Dietary habits
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
Collaborators: name: International Agency for Research on Cancer
First posted: 2021-02-03
Enrollment: 810
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * Patients will be selected from the central and satellite centers
* Control group will be selected from the same age, sex, geographic area of the recruited patients

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* Osteosarcoma and Ewing sarcoma first diagnosis
* No previous chemotherapy treatment
* ≥ 12 years old
* Able to understand the questionnaire
* No malignant tumor diagnosis for the last 5 years
* Control case should have a range of +/- 2 years old for patients \>= 21 years old. For patients between 12 and 21 years old the difference should be +/- 1 years.

Exclusion Criteria:

* Other tumor type
* Not able to understand the questionnaire
* Patient diagnosed for malignant tumor during the last 5 years

Primary outcomes:
measure: Diet habits in patients versus case controls measured by EPIC COS FFQ
timeFrame: At diagnosis, up to 4 years
measure: Diet Quality Index -
timeFrame: At diagnosis, up to 4 years
measure: Number of patients overweight and obese measured by Body mass index (BMI compared to controls)
timeFrame: At diagnosis, up to 4 years
measure: Body composition
timeFrame: At diagnosis, up to 4 years
Secondary outcomes:
measure: Concentration of blood metabolites - Metabolome
timeFrame: At diagnosis, up to 4 years
measure: Microbiota
timeFrame: At diagnosis, up to 4 years
measure: Concentrations of lymphocytes subpopulation
timeFrame: At diagnosis, up to 4 years
measure: Lipid profile and Glucidic profile
timeFrame: At diagnosis, up to 4 years
Other outcomes:
Locations:
city: Candiolo
country: Italy
facility: IRCCS Candiolo Cancer Institute
state: Torino
city: Bologna
country: Italy
facility: Rizzoli Orthopedic Institute - Bologna
city: Firenze
country: Italy
facility: Ospedale pediatrico Meyer - U.O. Pediatric Oncoematology
city: Milano
country: Italy
facility: IRCCS Istituto Nazionale Tumori - U.O. Pediatric Oncology
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - U.O. Pediatric Oncoematology
city: Roma
country: Italy
facility: Regina Elena Cancer Center
city: Torino
country: Italy
facility: Ospedale Regina Margherita - U.O. Pediatric Oncoematology
Study officials:
affiliation: Istituto Ortopedico Rizzoli - Bologna
name: Alessandra Longhi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Garrett WS. Cancer and the microbiota. Science. 2015 Apr 3;348(6230):80-6. doi: 10.1126/science.aaa4972.
citation: Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med. 2016 Dec 15;375(24):2369-2379. doi: 10.1056/NEJMra1600266. No abstract available.
citation: Soldati L, Di Renzo L, Jirillo E, Ascierto PA, Marincola FM, De Lorenzo A. The influence of diet on anti-cancer immune responsiveness. J Transl Med. 2018 Mar 20;16(1):75. doi: 10.1186/s12967-018-1448-0.
citation: Fritsche-Guenther R, Gloaguen Y, Kirchner M, Mertins P, Tunn PU, Kirwan JA. Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source Dependencies. Cancers (Basel). 2020 May 27;12(6):1371. doi: 10.3390/cancers12061371.
citation: Albini A, Briga D, Conti M, Bruno A, Farioli D, Canali S, Sogno I, D'Ambrosio G, Consonni P, Noonan DM. SANIST: a rapid mass spectrometric SACI/ESI data acquisition and elaboration platform for verifying potential candidate biomarkers. Rapid Commun Mass Spectrom. 2015 Oct 15;29(19):1703-10. doi: 10.1002/rcm.7270.