Concordance of Two Endoscopic Procedures for Diagnosis of Carcinoma of the Upper Aerodigestive Tract

Brief Title

Concordance of Two Endoscopic Procedures for Diagnosis of Carcinoma of the Upper Aerodigestive Tract

Official Title

Accuracy of Endoscopic Diagnosis of Carcinoma of the UpperAerodigestive Tract: A Tandem Trial of Direct Rigid Endoscopy and Transnasal Flexible Endoscopy With Narrowband Imaging

Brief Summary

      This study will compare TNFE-NBI and biopsy, with DRE and biopsy for the diagnostic
      evaluation and staging of patients with suspicious UADT lesions. All patients enrolled in the
      study will undergo TNFE-NBI with biopsy of suspicious lesions prior to planned regular
      clinical care (DRE). Biopsies will be evaluated by standard clinical methods for patient
      diagnoses and care. As the current standard of care, if all biopsies for a given patient are
      non-malignant, a 3 month office visit will be arranged to evaluate and determine the need for
      further intervention. At the end of study enrollment both sets of biopsies will be
      re-evaluated in a blinded fashion by the surgical pathologist. Study assessment of malignant
      vs. non-malignant (benign) pathology will be used to see whether both tests tended to agree
      on diagnoses.
    

Detailed Description

      This is a single arm prospective study to evaluate the concordance between a standard-of-care
      diagnostic procedure and TNFE-NBI for diagnosing malignancy. The primary aim of this
      investigation is to determine whether the TNFE NBI procedure can detect and stage cancer in
      the head and neck as well as the standard DRE which requires general anesthesia.

      Patients who are pending direct laryngoscopy after presenting to the Department of
      Otolaryngology-Head and Neck Surgery at UCSF with UADT lesions will be asked to participate
      in the study provided all eligibility criteria are met. Under current standard-of-care for
      diagnostic evaluation and staging of UADT lesions, patients will undergo imaging studies
      including CT and/or MRI of the neck with contrast prior to direct laryngoscopy. Study
      participants will undergo both the TNFE NBI and DRE procedures.

      The study procedure TNFE NBI will be performed, followed 1-6 weeks later by DRE, the standard
      approach for diagnosis, without the surgeon having knowledge of the details of the first
      procedure. The sequence of examinations in this investigation is dictated by the need to
      minimize mucosal trauma during the first examination and allow for mucosal healing prior to
      the second examination, and thus cannot be randomized. TNFE-NBI produces much less mucosal
      trauma by avoiding direct blunt manipulation and through the smaller, 1.8mm, cupped biopsy
      forceps.

      Because it is possible that the TNFE NBI procedure might detect smaller tumors or lesions in
      different locations, the biopsy locations from the TNFE NBI procedure will be made known at
      the end of the DRE surgery to ensure that all needed areas are biopsied. Therefore, a
      secondary aim of this study will be to explore whether the TNFE NBI procedure may improve the
      detection of malignancy when added to the DRE surgery.

      Patients enrolling in the study will undergo TNFE-NBI with biopsy of suspicious lesions. The
      TNFE-NBI examinations will be digitally recorded. The examiner will describe, using standard
      language and diagrams, anatomic location of suspicious areas revealed during the procedure.
      Biopsy tissue will be labeled as to the area of origin.

      In the event that a participant does not tolerate TNFE-NBI, the study procedure will be
      aborted.

      At least one week and no more than 6 weeks after TNFE-NBI, patients will undergo standard of
      care direct rigid endoscopy. The intervening time to DRE is to allow for recovery of mucosal
      surfaces.

      Participants who did not tolerate TNFE-NBI will undergo DRE as standard of care.

      The DRE examiner will be blinded as to which areas were biopsied during the TNFE-NBI
      procedure until completion of the standard of care DRE examination and tissue biopsy
      selection. In the investigator's experience, areas of prior biopsy will not be apparent to
      the DRE examiner as mucosal recovery will occur during 1-6 weeks elapsing between TNFE-NBI
      and DRE. Upon completion of the standard of care DRE examination and tissue biopsy selection,
      the DRE examiner will open the TNFE-NBI examiner's note describing the areas deemed
      suspicious during TNFE-NBI. Additional areas may then be examined and biopsied with DRE based
      on the TNFE-NBI note. Records will be kept as to which anatomic areas were:

        1. identified by both procedures,

        2. identified by DRE only after prompting by the TNFE-NBI note

        3. identified by DRE only (not previously identified by TNFE-NBI).

      A diagnosis of carcinoma in situ or invasive squamous cell carcinoma will be considered
      positive for malignancy. If a diagnosis of malignancy is made after the initial endoscopy,
      regardless of which test was positive, the patient will be contacted immediately so that
      appropriate treatment can be pursued. For diagnoses of dysplasia and other non-malignant
      conditions such as polyp, lymphoid tissue, papilloma, etc., the patient will be scheduled for
      follow-up.

      Routine follow-up of benign lesions includes a routine head and neck examination, including
      indirect laryngoscopy with a fiberoptic endoscope 2-3 months after biopsy. New or enlarging
      lesions will be assessed in the operating room with DRE per standard of care. Lesions
      initially diagnosed as non-malignant that are stable or not visualized at follow-up will not
      need re-biopsy per standard of care.

      At the conclusion of study enrollment, all biopsy specimens will be de-identified, batched,
      and evaluated by a pathologist blinded to the type of endoscopy. A diagnosis of carcinoma in
      situ or invasive squamous cell carcinoma will be considered positive for malignancy.

      If patients with non-malignant diagnoses of study pathology (both TNFE-NBI and DRE) have been
      diagnosed with malignancy at or before routine follow-up, the study evaluation will be
      considered a false negative. If no malignancy developed within three months of the biopsy
      procedures, the study evaluation will be considered a true negative. (This design represents
      a compromise in evaluating patients with a negative endoscopy. By necessity a negative
      diagnosis is one of exclusion, given that complete pathologic evaluation of every patients'
      upper aerodigestive tract is neither ethical, practical, nor feasible in clinical practice.
      Precedent for this design can be found in Smith-Bindman, Chu et al. 2005)
    


Study Type

Interventional


Primary Outcome

Agreement between TNFE-NBI and DRE

Secondary Outcome

 Agreement of TNFE-NBI and DRE on tumor stage and location

Condition

Upper Aerodigestive Tract Lesions

Intervention

Direct Rigid Endoscopy


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Device

Estimated Enrollment

0

Start Date

July 2010



Eligibility Criteria

        Inclusion Criteria:

          -  Age eighteen years or older

          -  Patients who are pending operative direct laryngoscopy as standard clinical care

          -  Presence of upper aerodigestive tract (UADT) (oropharyngeal, hypopharyngeal and/or
             glottic mucosal) lesion(s) suspicious for diagnoses including but not limited to:
             squamous cell carcinoma, carcinoma in situ, squamous dysplasia, papilloma, OR presence
             of diagnosed metastatic squamous cell carcinoma in the neck with an unidentified
             primary lesion

          -  Ability to give written informed consent and willingness to comply with the
             requirements of the protocol

        Exclusion Criteria:

          -  Patients who are not medically able to undergo TNFE

          -  Allergy to topical anesthesia

          -  Active lymphoma

          -  Lesion inaccessibility to TNFE: oral cavity (anterior 2/3 tongue, buccal mucosa)

          -  Coagulopathy: INR ≥ 1.5

          -  Any condition that compromises compliance with the objectives and procedures of this
             protocol, as judged by the principal investigator such as anxiety or narrow nasal
             passage way.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Mark S. Courey, MD, , 



Administrative Informations


NCT ID

NCT01175499

Organization ID

10-00166

Secondary IDs

10201

Responsible Party

Sponsor

Study Sponsor

University of California, San Francisco


Study Sponsor

Mark S. Courey, MD, Principal Investigator, UCSF Helen Diller Family Comprehensive Cancer Center, Otolaryngology, Head & Neck Surgery


Verification Date

August 2014