Fast-track Diagnosis for Lung Cancer Suspects With PET-CT and EUS
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Study type: Observational

Summary: 
      Patients who are admitted to the outpatient pulmonology department by a general practitioner
      or specialist with a chest X-ray suspicious for lung cancer with an age between 18 and 80
      years are suitable for participation. The X-ray and referral are studied by a chest physician
      (by phone or fax ). Selected patients are invited to enter the study after answering a
      questionnaire by phone (p. 31). The questionnaire screens patients' interest, co-morbidity
      and medication use. Informed consent forms, patient information forms and a time table for
      the diagnostic day are provided by mail or E-mail in cases where time gets short. Waiting
      time to enter the study will be no longer than one week.

      Hundred patients will be recruited by means of informed consent. Patients will be admitted at
      the pulmonary ward for the study day and will be accompanied by nurses. All patients will get
      PET-CT scanning in the morning of the study day. Depending on the location of lesions seen on
      PET-CT, further invasive diagnostic procedures will be planned for the afternoon.

      Mediastinal and adjacent structures will be analysed with EUS-FNA. Mediastinal staging will
      be done with bronchoscopy alone for central located tumors, peripherally located lesions will
      be analysed with EUS-FNA or bronchoscopy.

      The percentage of patients in which this diagnostic track leads to a diagnosis and tumor
      stage in one day will be determined. The number of tests and diagnostic procedures needed to
      obtain a diagnosis, including tumor stage (especially final stage NSCLC) and function tests,
      will be compared with a historical matched study group. This historical study group is chosen
      from an era before the availability of integrated PET-CT and ultrasound guided endoscopic
      tools and meets the same inclusion and exclusion criteria as the patients in this study. The
      timelines from initial chest X-ray to diagnostic day to informing the patient to start of
      treatment will be determined. These figures will be compared with the historical study group.
    

Detailed description: 
      Background of the study:

      Patients have to pass different diagnostic phases in their analysis of a chest X-ray
      suspicious for lung cancer. Long waiting times with uncertainty about the outcome are a waste
      of time and unacceptable for the patient. Hospital visits as a consequence of this are a
      financial burden. Important reasons for physicians to shorten diagnostic tumor analysis.
      Shortening and intensifying the diagnostic track by combining diagnostic and staging
      procedures would preclude unnecessary tests and procedures, lowering the total hospital costs
      per patient and may lead to more satisfaction for patient and physician.

      PET-CT is the most important imaging tool for lung cancer analysis and better than CT or
      FDG-PET alone, but not optimal for determination of tumour invasion in mediastinal or other
      adjacent structures. MRI is more suitable for this purpose, but is limited available. EUS-FNA
      (carinal lymph nodes), eventually in combination with CT or FDG-PET and EBUS-TBNA (right
      mediastinal lymph nodes), superior to TBNA alone, are novel imaging techniques with a high
      accuracy. Bronchoscopy provides information on tumour type and resectability of centrally but
      not peripherally located tumours. Mediastinal staging can be performed by adding TBNA to
      bronchoscopy with high accuracy. PET-CT, as a superior imaging mode, could direct for the
      best subsequent endoscopic technique for obtaining a tissue diagnosis as well as leading to a
      more comprehensive staging of patients with suspected lung cancer.

      False negative findings could be caused by sampling errors or false interpretations by the
      cytopathologist of specimens with tumour cell poverty. A more sensitive immune histochemical
      analysis could modify EUS-FNA and EBUS-TBNA results.

      Objective of the study:

        1. to study feasibility of a fast one-day diagnostic track including PET-CT and subsequent
           diagnostic/ staging investigation depending on PET-CT findings.

           to determine:

        2. the percentage of patients in which the one-day track is sufficient for diagnosis and
           staging needing no more further investigations.

        3. the time-spans needed for diagnosis (including staging and function tests) of the
           patients in comparison to a historical study group.

        4. the amount of investigations needed to obtain the diagnosis compared with a historical
           study group.

        5. the effect of immuno-histochemical analysis on the sensitivity of data of diagnostic
           procedures.

      Study design:

      A Prospective, open, single center, study.

      Patients who are admitted to the outpatient pulmonology department by a general practitioner
      or specialist with a chest X-ray suspicious for lung cancer with an age between 18 and 80
      years are suitable for participation. The X-ray and referral are studied by a chest physician
      (by phone or fax ). Selected patients are invited to enter the study after answering a
      questionnaire by phone ( p. 31).

      The questionnaire screens patients' interest, co-morbidity and medication use. Informed
      consent forms, patient information forms and a time table for the diagnostic day are provided
      by mail or E-mail in cases where time gets short. Waiting time to enter the study will be no
      longer than one week.

      Hundred patients will be recruited by means of informed consent. In a narrow logistic scheme
      the study subjects will undergo a diagnostic work up to a maximum of 3 patients per study day
      (p. 32). Patients will be admitted at the pulmonary ward for the study day and will be
      accompanied by nurses. All patients will get PET-CT scanning in the morning of the study day.
      Depending on the location of lesions seen on PET-CT, further invasive diagnostic procedures
      will be planned for the afternoon, according to a scheme outlined on page 33. In the
      meanwhile, routine blood tests, EKG and pulmonary function tests are done. The invasive
      diagnostic procedure to be chosen, has to provide ideally a diagnosis and stage at one time.

      Mediastinal and adjacent structures will be analysed with EUS-FNA or EBUS-TBNA. EBUS-TBNA
      will be used for right mediastinal lymph nodes. Carinal lymph nodes are biopsied with
      EUS-FNA. Mediastinal staging will be done with bronchoscopy alone for central located tumors,
      peripherally located lesions will be analysed with EUS-FNA or bronchoscopy in combination
      with EBUS-TBNA.

      When enough material is available, cytologic specimen will be stored in cell casts fixed in
      agar. In case of negative biopsies, surgical verification follows. When this verification
      proves that cytologic biopsies were false negative, immune histochemical analysis on the agar
      imbedded material will be done retrospectively.

      When patients are recovered from their diagnostic procedure, they will leave the hospital
      with an appointment for a visit one week later to be informed about their diagnosis and
      treatment. Additive appointments will be made on a term as short as possible and necessary
      when extra diagnostic tests are needed like MRI, exercise tests, perfusion tests or
      evaluation by other consultants.

      The percentage of patients in which this diagnostic track leads to a diagnosis and tumor
      stage in one day will be determined. The number of tests and diagnostic procedures needed to
      obtain a diagnosis, including tumor stage (especially final stage NSCLC) and function tests,
      will be compared with a historical matched study group. This historical study group is chosen
      from an era before the availability of integrated PET-CT and ultrasound guided endoscopic
      tools and meets the same inclusion and exclusion criteria as the patients in this study. The
      timelines from initial chest X-ray to diagnostic day to informing the patient to start of
      treatment will be determined. These figures will be compared with the historical study group.

      Finally, patients will be asked to fill in a patient satisfaction questionnaire concerning
      the one-day diagnostic program track, the informative visit and after an eventual successive
      treatment start (p. 31).

      Study population:

      Hundred patients with suspicion of lung cancer on X ray with an age between 18-85 years
      admitted to the pulmonologist by their general practitioner or specialist.

      Intervention (if applicable):

      One-day diagnostic track using PET-CT eventually with bronchoscopy, EUS-FNA , EBUS-TBNA and
      ultrasound guided transcutaneous biopsies.

      Primary study parameters/outcome of the study:

        1. Number of patients that will have a definitive diagnosis and final stage NSCLC in one
           day.

        2. Time between chest X-ray with suspicion on lung cancer and the first visit to the
           outpatient clinic.

        3. Time between the first outpatient clinical contact and informing patient about definite
           diagnosis.

        4. Time from the definite diagnosis until the initiation of therapy.

      Secundary study parameters/outcome of the study (if applicable):

        1. Number of patients able to have all diagnostic tests in one-day.

        2. Number of tests and procedures that have been performed.

        3. Patient satisfaction with the one-day procedure.

        4. Sensitivity of EUS-FNA and EBUS-TBNA when immunohistochemical analysis is added to
           investigate false negative procedures.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness (if applicable):

      There are no different adverse effects due to the diagnostic program. Patients in the one-day
      diagnostic track will undergo the same diagnostic interventions as patients outside the
      study. The risk of bleeding and infection due to the EUS and EBUS procedures must be
      mentioned, although patients would be undergo these biopsies even if they would not
      participate to this trial; there is no 'additive risk'.

      The burden is that the whole diagnostic program could lead to psychological distress because
      of the several investigations within a relatively short period. Patients with claustrophobia
      might be anxious during the PET-CT. The expected benefits are a patient satisfaction due to
      short diagnostic timeframes, lesser diagnostic procedures and faster decision making in
      therapeutic options.
    

Intervention name(s): fast track diagnosis; conventional diagnosis
Intervention type(s): Procedure; Procedure
Intervention description(s): fast-track diagnosis, PET-CT, bronchoscopy; out-patient diagnosis
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients suspected of lung cancer
      
Keywords: fast-track diagnosis; PET-CT; endoscopic techniques; lung cancer