Temporal Variation in Exhaled Volatile Organic Compounds in Esophageal Cancer Patients

Temporal Variation in Exhaled Volatile Organic Compounds in Response to Therapeutic Intervention in Esophageal Cancer Patients

The purpose of this study is to investigate whether exhaled breath can be used to detect and monitor esophageal cancer.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Other: Exhaled VOC breath test

Detailed Description

Esophageal cancer ("EG cancer") affects over half a millions people worldwide every year. Early esophageal cancer typically has non-specific symptoms that are often mistaken for benign (non-cancer) conditions. As a result, patients are often referred for further investigations only when they have more prominent symptoms that are typically associated with advanced incurable disease. As a consequence, 7 out of 10 new cases of EG cancer diagnosed are considered to be at an advanced stage, with less than 1 in 3 patients eligible for potentially curative therapy. Better ways of diagnosing esophageal cancer earlier are therefore needed. An ideal test for esophageal cancer would be non-invasive, simple to administer in the community, and cost effective.

The investigators' approach to this clinical challenge is to establish a non-invasive test for the detection of esophageal cancer that is based upon the unique signature of small molecules within exhaled breath. In this study that is being conducted in collaboration with researchers in the United Kingdom (UK), the investigators would like to measure the levels of these small molecules within the breath of patients with esophageal cancer at different times during their treatment: (i) at diagnosis; (ii) after chemoradiotherapy, and; (iii) after surgery. By studying how the small molecules contained within the breath change as a result of esophageal cancer and its treatment, the investigators hope to learn new information that can help develop a new test for this disease.

The investigators will also measure the small molecules within saliva and urine samples collected at the same time as breath in order to study if there are any important differences between these three samples. The investigators will also attempt to measure different bacteria

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W2 1NY
    • Imperial College London
• United States
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18-90 years
• Newly-diagnosed, treatment naïve patients with esophageal and/or gastroesophageal junctional cancer
• Planning to undergo curative treatment, including neoadjuvant chemoradiotherapy and surgical resection

Exclusion Criteria:

• Pregnant females
• Without malignant esophageal disease
• Malignancy at a secondary site other than the esophagus
• Undergoing palliative treatment for esophageal cancer
• Not receiving neoadjuvant chemoradiotherapy and surgical resection for esophageal cancer
• Inability or unwillingness to provide written informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Investigate whether exhaled breath can be used to detect and monitor esophageal cancer.; The procedures will include collecting participant's personal information and samples of participant's exhaled breath, urine, and saliva.	Other: Exhaled VOC breath test; To determine longitudinal variation in exhaled VOC concentrations during intended curative therapy for EC cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exhaled breath and urinary VOC concentrations as biomarkers of esophageal cancer	The composition and concentration of volitile organic compounds (VOC) in exhaled breath and urinary samples will be assessed to establish a VOC signature of esophogeal cancer	Before commencing treatment for esophageal cancer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in VOC concentrations that occur in response to therapeutic intervention	VOC concentrations in exhaled breath and urinary samples will be assessed longitudinally to assess how VOC concentrations change in response to therapeutic intervention	(i) Before commencing treatment for esophageal cancer, (ii) About 4 - 6 weeks after neoadjuvant therapy, (iii) About 3 - 5 days after surgical resection (but before hospital discharge), (iv) At routine follow up (6 - 12 months after surgery)
Linkage of longitudinal VOC data to predominant upper gastrointestinal bacterial species	Bacterial RNA will be extracted from saliva samples to identify bacterial composition. Bacterial composition will then be correlated with breath and urinary VOC levels	(i) Before commencing treatment for esophageal cancer, (ii) About 4 - 6 weeks after neoadjuvant therapy, (iii) About 3 - 5 days after surgical resection (but before hospital discharge), (iv) At routine follow up (6 - 12 months after surgery)
Patient acceptability of breath test	Study subjects will be asked to complete a short survey designed to assess their understanding and opinions regarding breath testing	Before commencing treatment for esophogeal cancer

Collaborators and Investigators

• Sponsor: Benaroya Research Institute
• Collaborators: Imperial College London
• Investigators: Principal Investigator: Donald E Low, MD, Virginia Mason Medical Center

Publications and helpful links

General Publications

• Antonowicz S, Bodai Z, Wiggins T, Markar SR, Boshier PR, Goh YM, Adam ME, Lu H, Kudo H, Rosini F, Goldin R, Moralli D, Green CM, Peters CJ, Habib N, Gabra H, Fitzgerald RC, Takats Z, Hanna GB. Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma. Nat Commun. 2021 Mar 5;12(1):1454. doi: 10.1038/s41467-021-21800-5.
• Kamal F, Kumar S, Edwards MR, Veselkov K, Belluomo I, Kebadze T, Romano A, Trujillo-Torralbo MB, Shahridan Faiez T, Walton R, Ritchie AI, Wiseman DJ, Laponogov I, Donaldson G, Wedzicha JA, Johnston SL, Singanayagam A, Hanna GB. Virus-induced Volatile Organic Compounds Are Detectable in Exhaled Breath during Pulmonary Infection. Am J Respir Crit Care Med. 2021 Nov 1;204(9):1075-1085. doi: 10.1164/rccm.202103-0660OC.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: March 11, 2024
• First Submitted That Met QC Criteria: June 10, 2024
• First Posted (Actual): June 12, 2024

Study Record Updates

• Last Update Posted (Actual): August 27, 2024
• Last Update Submitted That Met QC Criteria: August 25, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: CRP19015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD is not required for analysis. Study ID used to represent study participants.

Drug and device information, study documents

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