Trial Information

A Prospective, Open, Single Center, Study of One-day Diagnostic Track for Lung Cancer Suspects From Chest X-ray Using PET-CT and Subsequent Multiple Endoscopic Investigations. (Including Bronchoscopy, EUS-FNA)

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.