Diagnostic Power Comparison Between VOCs and CTCs

The Diagnostic Power of VOCs Compared With CTCs for Cancer

Early diagnosis of malignant tumors is pivotal for improving their prognoses. Circulating tumor cells (CTC) in peripheral blood and Volatile organic compounds (VOCs) in exhaled breath are newly developed diagnosis method. Due to the low percentage of CTCs in peripheral blood of cancer patients and the surface structure of lymphocytes (especially megakaryocytes) is often confused with tumor cells, CTC has a high false positive and negative rate. In recent years, the detection of volatile organic compounds (VOCs) in exhaled breath as a simple and noninvasive method has shown broad application prospects in the diagnosis of various diseases. A series of studies of VOCs diagnosing solid tumors the investigators had conducted in the past decade show that VOCs can not only distinguish different types of tumors, but also can make a distinction between different stages. This study was to compare CTC and VOCs with clinical samples. Predictive models will be built employing discriminant factor analysis (DFA) pattern recognition method. Sensitivity and specificity will be determined using leave-one-out cross-validation or an independent blind test set.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Gastric Cancer; Diagnoses Disease; Circulating Tumor Cell; Volatile Organic Chemicals
• Intervention / Treatment: Diagnostic test: Circulating tumor cells, Volatile organic compounds

Detailed Description

200 patients with definitive diagnoses will be enrolled and the alveolar exhaled breath samples and peripheral venous blood will be collected. Two blood samples and two breath samples will be collected from each patient. One blood sample will be send to CTC tests for a blind test and the other will be used for headspace VOCs analyses. One breath sample was used for analysis with the Nano-sensors array, and the other was used for gas chromatography coupled with mass spectrometry (GC-MS) analysis. The VOCs samples were collected using sorbent tubes at a total flow through sorption trap of 200ml/min, then will be send to Israel Institute of Technology for further test.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Chuyang Bao, MD; Phone Number: +86 18555039598; Email: des_mond@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

200 patients or volunteers who undergo Gastroscopy or breast surgery in Anhui Provincial cancer hospital, Hefei, China

Description

Inclusion Criteria:

• 18-75 years
• Definitive diagnosis of gastric cancer, breast cancer,benign breast disease and gastric lesions
• ECOG(Eastern Cooperative Oncology Group) scores ≤ 2

Exclusion Criteria:

• Other palliative chemotherapy and radiotherapy for this cancer
• Other cancer
• Diabetes, Fatty liver
• Autoimmune disease
• Pulmonary ventilation dysfunction

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Gastric cancer; patients with definitive diagnosis of gastric cancer by pathology	Diagnostic test: Circulating tumor cells, Volatile organic compounds; Alveolar exhaled breath samples and peripheral venous blood(10ml) will be collected from each patients
Breast cancer; patients with definitive diagnosis of breast cancer by pathology	Diagnostic test: Circulating tumor cells, Volatile organic compounds; Alveolar exhaled breath samples and peripheral venous blood(10ml) will be collected from each patients
Benign gastric diseases; Gastritis or gastric ulcer	Diagnostic test: Circulating tumor cells, Volatile organic compounds; Alveolar exhaled breath samples and peripheral venous blood(10ml) will be collected from each patients
Benign breast diseases; Hyperplasia of mammary glands or mastitis	Diagnostic test: Circulating tumor cells, Volatile organic compounds; Alveolar exhaled breath samples and peripheral venous blood(10ml) will be collected from each patients
Normal; healthy volunteers	Diagnostic test: Circulating tumor cells, Volatile organic compounds; Alveolar exhaled breath samples and peripheral venous blood(10ml) will be collected from each patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Discrimination between Malignant and Benign Gastric/Breast Lesions and normal group with each diagnostic method (Na-nose/GC-MS/CTC)	Exhaled breath samples and peripheral venous blood collected will be used to build predictive models employing discriminant factor analysis (DFA) and thereafter examine the sensitivity and specificity of model identification.	From June 15,2019 to June 1,2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comprehensive diagnostic model of VOCs and CTCs	Organize predictive models of VOCs/CTCs and establish Comprehensive Diagnostic Model.	From June 1,2020 to Dec 31,2020

Collaborators and Investigators

• Sponsor: Anhui Medical University
• Collaborators: Technion, Israel Institute of Technology
• Investigators: Principal Investigator: Hu Liu, MD, Anhui Provincial Cancer Hospital

Publications and helpful links

General Publications

• Nakhleh MK, Amal H, Jeries R, Broza YY, Aboud M, Gharra A, Ivgi H, Khatib S, Badarneh S, Har-Shai L, Glass-Marmor L, Lejbkowicz I, Miller A, Badarny S, Winer R, Finberg J, Cohen-Kaminsky S, Perros F, Montani D, Girerd B, Garcia G, Simonneau G, Nakhoul F, Baram S, Salim R, Hakim M, Gruber M, Ronen O, Marshak T, Doweck I, Nativ O, Bahouth Z, Shi DY, Zhang W, Hua QL, Pan YY, Tao L, Liu H, Karban A, Koifman E, Rainis T, Skapars R, Sivins A, Ancans G, Liepniece-Karele I, Kikuste I, Lasina I, Tolmanis I, Johnson D, Millstone SZ, Fulton J, Wells JW, Wilf LH, Humbert M, Leja M, Peled N, Haick H. Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules. ACS Nano. 2017 Jan 24;11(1):112-125. doi: 10.1021/acsnano.6b04930. Epub 2016 Dec 21.
• Amal H, Leja M, Broza YY, Tisch U, Funka K, Liepniece-Karele I, Skapars R, Xu ZQ, Liu H, Haick H. Geographical variation in the exhaled volatile organic compounds. J Breath Res. 2013 Dec;7(4):047102. doi: 10.1088/1752-7155/7/4/047102. Epub 2013 Nov 1.
• Barash O, Zhang W, Halpern JM, Hua QL, Pan YY, Kayal H, Khoury K, Liu H, Davies MP, Haick H. Differentiation between genetic mutations of breast cancer by breath volatolomics. Oncotarget. 2015 Dec 29;6(42):44864-76. doi: 10.18632/oncotarget.6269.
• Amal H, Shi DY, Ionescu R, Zhang W, Hua QL, Pan YY, Tao L, Liu H, Haick H. Assessment of ovarian cancer conditions from exhaled breath. Int J Cancer. 2015 Mar 15;136(6):E614-22. doi: 10.1002/ijc.29166. Epub 2014 Sep 5.
• Leja MA, Liu H, Haick H. Breath testing: the future for digestive cancer detection. Expert Rev Gastroenterol Hepatol. 2013 Jul;7(5):389-91. doi: 10.1586/17474124.2013.811033. No abstract available.
• Amal H, Ding L, Liu BB, Tisch U, Xu ZQ, Shi DY, Zhao Y, Chen J, Sun RX, Liu H, Ye SL, Tang ZY, Haick H. The scent fingerprint of hepatocarcinoma: in-vitro metastasis prediction with volatile organic compounds (VOCs). Int J Nanomedicine. 2012;7:4135-46. doi: 10.2147/IJN.S32680. Epub 2012 Jul 30.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 15, 2019
• Primary Completion (ANTICIPATED): June 1, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: May 20, 2019
• First Submitted That Met QC Criteria: May 20, 2019
• First Posted (ACTUAL): May 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 3, 2019
• Last Update Submitted That Met QC Criteria: May 30, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Gastric cancer; Breast cancer; CTCs; VOCs; diagnoses
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Neoplasm Metastasis; Stomach Neoplasms; Neoplastic Cells, Circulating
• Other Study ID Numbers: DPCVC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No