Telomere Biology in Early Adenocarcinoma of the Lung

Brief Title

Telomere Biology in Early Adenocarcinoma of the Lung

Official Title

Prospective Cohort Study of Telomere Biology Among Patients With Early Adenocarcinoma of the Lung

Brief Summary

      Early adenocarcinoma of the lung has an excellent five-year survival after resection.
      However, its clinical and radiologic presentation is highly variable. Traditional means for
      preoperative diagnosis such as Positron Emission Tomography (PET-CT) and trans-thoracic
      needle biopsy demonstrate unacceptable false positive and negative rates.

      Telomere biology is activated aberrantly is most lung cancers but has not been studied in
      early stages to the best of our knowledge.

      The objective of this study is to evaluate telomere length and activity with suspected early
      stage adenocarcinoma of the lung.
    

Detailed Description

      Bronchoalveolar carcinoma has been traditionally used to refer to a subset of adenocarcinoma
      distinguished by its peripheral location, typical "lepidic" growth pattern and tendency for
      both bronchogenic and lymphatic spread. For the purpose of this discussion and consistency
      with the revised 2011 criteria, BAC subtypes will be collectively referred to as early
      adenocarcinoma.

      The clinical presentation of early adenocarcinoma subtypes is highly variable ranging from a
      small solitary nodule to extensive lobar consolidation. Many peripheral lesions have a
      characteristic ground glass opacity appearance on Chest CT, which may correlate with an
      improved prognosis. The reported five-year disease-free survival after resection for isolated
      lesions may approaches 100%.

      Preoperative diagnosis of such lesions is complicated by several limitations. First, the
      differential diagnosis is broad including an extensive number of inflammatory and infectious
      processes. Second, positron emission tomography (PET), which identifies regions of increased
      metabolic activity, may be falsely negative due to the slow growth of early adenocarcinoma
      lesions. Transbronchial needle biopsy is also unreliable to confirm or exclude disease in
      non-solid type lesions.

      The proportion of lung cancers classified as adenocarcinoma has steadily increased and now
      comprises nearly ½ of cases. However, the proportion of adenocarcinoma in situ is uncertain.
      Previous reports range from 5-10% in a large series to as high as 24% in the large
      Surveillance, Epidemiology and End Results database. Thus, these early adenocarcinoma lesions
      may represent a disproportionately large number of lung cancers which are PET negative yet
      carry an excellent prognosis after early resection. The early adenocarcinoma subtypes
      represent a clinical entity requiring further characterization to distinguish lesions more
      likely to be malignant from benign.

      Telomerase is activated aberrantly in most lung cancers and mutations in telomerase
      components predispose to solid malignancies. For patients with non-small cell lung cancer,
      numerous studies correlate increased tumor telomerase activity with increased likelihood of
      Stage IIIB and Stage IV disease and/or reduced survival. Furthermore, telomerase inhibition
      is currently being studied in clinical trials of patients with advanced non-small lung
      cancer.

      Problem:

      The semi-solid lung lesion may represent early stage adenocarcinoma which has an excellent
      prognosis upon early diagnosis and prompt surgical resection. However, the semi-solid lesion
      has a broad differential diagnosis and preoperative features characteristic of adenocarcinoma
      are needed to distinguish malignant from benign lesions.

      Objective:

      To study telomere length and telomerase activity in patients with suspected early
      adenocarcinoma of the lung whom are referred for surgical biopsy of lung lesions.
    

Study Type

Observational

Primary Outcome

Telomere Capture Percentage

Condition

Adenocarcinoma of the Lung

Study Arms / Comparison Groups

 Suspected Adenocarcinoma of the Lung

Description:  Patients with suspected adenocarcinoma of the lung referred for surgical lung biopsy after multi-disciplinary team recommendation.

Publications

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

Estimated Enrollment

100

Start Date

September 2014

Completion Date

September 2017

Primary Completion Date

September 2016

Eligibility Criteria

        Inclusion Criteria:

        Patients referred by a multi-disciplinary team meeting recommendation for surgical lung
        biopsy due to suspected adenocarcinoma of the lung and agree to a one-time peripheral blood
        sample for telomere analysis as described.

        Exclusion Criteria:

        Patients whom were not evaluated by the multi-disciplinary team discussion prior to
        referral for surgical lung biopsy.

        Patients with other chronic inflammatory disease requiring immunosuppressive therapy or
        known extra-pulmonary malignancy.
      

Gender

All

Ages

18 Years - 90 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

, +972-3-52-603-5410, [email protected]

Location Countries

Israel

Location Countries

Israel

NCT ID

NCT02239432

Organization ID

0067-14-MMC

Responsible Party

Sponsor

Study Sponsor

Meir Medical Center

Study Sponsor

, , 

Verification Date

September 2014