Magnifying NBI for Occult NPC

• ClinicalTrials.gov Identifier: NCT04593186
• Recruitment Status: Recruiting
• First Posted: October 19, 2020
• Last Update Posted: July 28, 2021
• Sponsor: Chinese University of Hong Kong
• Information provided by (Responsible Party): Hon Chi Yip, Chinese University of Hong Kong

Study Description

Brief Summary:

Diagnosis of nasopharyngeal carcinoma (NPC) is currently made by trans-nasal endoscopy and biopsy. The small caliber endoscope provides only a limited view of the nasopharynx and may not be able to provide a thorough assessment of the nasopharynx. The investigators have developed a novel endoscopic approach to access the nasopharynx by using a trans-oral high definition endoscope with magnification and image enhancement function. In this cohort study, we aim to investigate the efficacy of diagnosing NPC by applying the novel technique in a high risk patient group with elevated plasma EBV DNA but with negative screening with conventional trans-nasal endoscopy.

Condition or disease	Intervention/treatment	Phase
Nasopharyngeal Carcinoma	Procedure: Trans-oral magnifying endoscopy with NBI	Not Applicable

Detailed Description:

Nasopharyngeal carcinoma (NPC) is endemic in our region and is the 9th most common cancer in Hong Kong. Traditionally diagnosis has been through a nasoendoscopic examination of the nasopharynx with white light followed by a biopsy of suspicious lesions for a confirmatory diagnosis. However, given the geometry of the anatomy of the nasopharynx, with its inherent crevices and varying amounts of lymphoid tissues, lesions are not always easily identified leading to potential missed lesions. The non-specific aspect of white light also leads to excessive biopsies that are not without risk and of some discomfort to patients. Recent advances in liquid biopsies have also allowed for the detection of earlier and smaller lesions that are not always easily identified on nasoendoscopy but rather are seen on Magnetic Resonance Imaging (MRI).

An alternative imaging technique is the use of Narrow Band Imaging (NBI) to view the vasculature of the mucosa to identify suspicious lesions for pre-malignancy and malignancy that has been popularized in the gastrointestinal tract. In NPC, NBI with the flexible nasoendoscopes has been used in the diagnosis of NPC with varying success. Researchers at Chinese University of Hong Kong has found that in NPC NBI has limitations arising from a lack of consensus on vascular findings on NBI that constitute malignancy, lack of magnification and long focal length of current nasoendoscopes1. Flexible endoscopy using conventional esophago-gastroscopy endoscope (OGD) with NBI and magnification power up to 80x overcome the limitations of current nasoendoscopes. The passage of the endoscope through the mouth and retroflexion at oropharynx could visualize the nasopharynx clearly and detailed assessment is feasible.

Here in this study the investigators will seek to use a trans-oral magnifying endoscopy with NBI and retroflexion into the nasopharynx to view the nasopharynx to evaluate the feasibility in the diagnosis of occult nasopharyngeal carcinoma.

The aim of this study is to investigate the clinical usefulness of trans-oral magnifying endoscopy with NBI as a screening tool for patients at increased risk of nasopharyngeal carcinoma (NPC).

The investigators hypothesize that with the use of magnifying NBI trans-oral endoscopy, the nasopharynx could improve the diagnostic yield of NPC in high risk patients with negative test on conventional investigations. As a result, such endoscopic screening tool could be used routinely to identify early NPC in patients deemed at risk.

Study Design

This study is a prospective single arm study designed to evaluate the diagnostic yield of trans-oral magnifying NBI endoscopic assessment of nasopharynx in patients who are deemed elevated risk of NPC but with negative traditional endoscopic and radiological screening.

In a previous study conducted by the Department of Chemical Pathology and Otorhinolaryngology, screening of 20000 asymptomatic individuals was performed using plasma Epstein Barr Virus DNA analysis. The presence of plasma EBV DNA consisting of short DNA fragments released by NPC cells helped identify NPC patients. In the published results, 34 NPC was identified in 300-screened positive individuals. In the rest of the cohort, NPC was not identified with initial nasoendoscopy and biopsy. A few more cancers was subsequently identified on Magnetic Resonance Imaging upon follow-up at 3 years and was confirmed with repeated endoscopic biopsies. In the current study the investigators would invite patients with persistently positive screening on plasma EBV-DNA analysis and no cancer found on usual diagnostic tests to undergo the novel screening endoscopy.

Individuals would be screened for eligibility at the clinic follow-up at the Department of Otorhinolaryngology. Study consent would be taken if they agree to participate in the current study.

Endoscopic procedures would be performed by endoscopists with expertise on performing magnifying NBI endoscopy at the Combined Endoscopy Center, Prince of Wales Hospital. It would be conducted at the Combined Endoscopy Center, Prince of Wales Hospital. Topical local anaesthetic will be applied to the oropharynx and nasopharynx. In addition, intravenous sedation by use of Midazolam and Fentanyl would be given. Endoscopes with magnification and NBI function would be used (GF-H290Z, Olympus Medical Corporations, Tokyo, Japan). A soft black hood would be attached to the tip of the endoscope for better focal length adjustment.

Upon insertion through a mouthpiece, the scope will then be retroflexed into the nasopharynx and the lateral walls into the Fossa of Rosenmuller and the posterior nasopharyngeal wall will be systematically examined with white light and NBI. Target suspicious areas would be examined by use of magnification with the power up to 80X. Biopsy would be taken if suspicious lesion is identified during the procedure.

In addition, non-contrast Magnetic Resonance Imaging (MRI) of the nasopharynx would be performed if the participants have not received a similar scan in recent 6 months and have no contra-indications to MRI. The MRI finding would be correlated with the endoscopic and histological findings.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 246 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Trans-oral magnifying endoscopy with Narrow Band Imaging assessment of nasopharynx
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: Trans-oral Magnifying Endoscopy With Narrow Band Imaging for Screening of Nasopharyngeal Carcinoma
• Actual Study Start Date: April 15, 2021
• Estimated Primary Completion Date: October 31, 2022
• Estimated Study Completion Date: November 30, 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: Trans-oral magnifying endoscopy with NBI; Transoral magnifying endoscopy with High Definition Upper Endoscope with Narrow Band Imaging enhancement (Olympus GIF-H290Z)

Procedure: Trans-oral magnifying endoscopy with NBI; Endoscopic procedures would be performed by endoscopists with expertise on performing magnifying NBI endoscopy. Topical local anaesthetic will be applied to the oropharynx and nasopharynx. In addition, intravenous sedation by use of Midazolam and Fentanyl would be given. Endoscopes with magnification and NBI function would be used (GF-H290Z, Olympus Medical Corporations, Tokyo, Japan). A soft black hood would be attached to the tip of the endoscope for better focal length adjustment. Upon insertion through a mouthpiece, the scope will then be retroflexed into the nasopharynx and the lateral walls into the Fossa of Rosenmuller and the posterior nasopharyngeal wall will be systematically examined with white light and NBI. Target suspicious areas would be examined by use of magnification with the power up to 80X. Biopsy would be taken if suspicious lesion is identified during the procedure.

Outcome Measures

Primary Outcome Measures :

1. Rate of Newly diagnosed Nasopharyngeal cancer [ Time Frame: 1 month ]
   Newly diagnosed nasopharyngeal cancer with the novel endoscopic approach

Secondary Outcome Measures :

1. Rate of Adverse event - overall [ Time Frame: 7 days ]
   Rate of Adverse event related to the endoscopic procedure
2. Rate of adverse event - haemorrhage [ Time Frame: 7 days ]
   Rate of haemorrhage related to the endoscopic procedure
3. Rate of adverse event - perforation [ Time Frame: 7 days ]
   Rate of perforation related to the endoscopic procedure
4. Rate of adverse event - infection [ Time Frame: 7 days ]
   Rate of infection related to the endoscopic procedure
5. Rate of adverse event - aspiration pneumonia [ Time Frame: 7 days ]
   Rate of aspiration pneumonia related to the endoscopic procedure
6. Stage of the newly diagnosed nasopharyngeal cancer [ Time Frame: 1 month ]
   TNM stage distribution of the newly diagnosed NPC
7. Duration of the endoscopic procedure [ Time Frame: 1 day ]
   Duration from scope insertion to scope withdrawal

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male, age ≥ 18 years old
2. Positive result on plasma EBV-DNA analysis
3. No cancer identified on conventional investigations including nasoendoscopy and MRI

Exclusion Criteria:

1. History of nasopharyngeal, oropharyngeal cancer
2. Patients on anticoagulation (Including warfarin and other direct oral anti-coagulants)
3. Bleeding tendency (International Normalized Ratio (INR) > 1.5 or Platelet < 50 x109/L)
4. Trismus, unable to pass oral endoscope
5. Allergic to local anaesthetic agents (Lignocaine)
6. Failure of vital organ (heart, lungs, liver, or kidneys) function
7. Other conditions deemed unsuitable for endoscopy
8. Refusal to participate, or inability to sign consent for study

Contacts and Locations

Contacts

Contact: Hon Chi Yip, MBChB, FRCSEd; 35052956; hcyip@surgery.cuhk.edu.hk

Locations

Hong Kong

Prince of Wales Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Hon Chi YIP, FRCSEd 35052627 hcyip@surgery.cuhk.edu.hk

Sponsors and Collaborators

Chinese University of Hong Kong

Investigators

• Principal Investigator: Hon Chi Yip, MBChB, FRCSEd; Chinese University of Hong Kong

More Information

• Responsible Party: Hon Chi Yip, Associate consultant, Chinese University of Hong Kong
• ClinicalTrials.gov Identifier: NCT04593186
• Other Study ID Numbers: CRE-2020.426
• First Posted: October 19, 2020
• Last Update Posted: July 28, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hon Chi Yip, Chinese University of Hong Kong:

nasopharyngeal carcinoma, Narrow band Imaging, Magnifying endoscopy

Additional relevant MeSH terms:

Carcinoma; Nasopharyngeal Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases