Trial Information

A Phase II Study of 18F-Fluorodeoxyglucose (FluGlucoScan) in Patients Receiving a Treatment Planning Study of 3 Dimensional Conformal Radiation Therapy Guided by Breath Held CT and PET Imaging for Patients With Non-Small Cell Lung Cancer

Concurrent chemotherapy and 3-dimensional conformal radiation therapy (3D-CRT), using
computed-tomography (CT) simulation, is the current standard approach in the treatment of
inoperable non-small-cell lung cancer (NSCLC). Despite such therapeutic benefit, local
recurrence nonetheless remains a significant impediment to cure. Attempts to improve the
accuracy of CT-scanning in radiotherapy treatment planning have been increasingly studied.
One such approach is the attempted correlation of CT imaging temporally with the physiologic
breathing cycle, a process known as gating. By imaging the tumor only when the tumor is
immobilized, gating effectively eliminates the effect of motion, thus leading to typically
smaller visible tumor masses and the loss of motion-induced distortions. Lung-tumor
immobilization using self-gated breath-holding at extremes of inspiration has been validated
clinically, and is associated with improved lung-outcome predictors and normal tissue
complication probability overall. Several recent studies have demonstrated PET to be both
highly sensitive and moderately to highly specific in the staging of NSCLC, and even more
sensitive and specific than CT-scanning in the detection of mediastinal and distant
metastases from NSCLC. The co-registration of CT and PET images enables even greater
accuracy than either modality alone, while the functional imaging inherent in PET may better
facilitate the distinction between benign and malignant structures. Overall, the superior
tumor staging capability of PET (or PET-CT fusion) together with the improved dosimetry &
diminished normal-tissue toxicity associated with deep inspiration breath-hold (DIBH) is
expected to confer considerable clinical advantage to the use of gated PET in the
radiotherapeutic planning and treatment of NSCLC.

The first objective is to define the effect of respiratory-gating on PET-based radiotherapy
planning in comparison to the free-breathing condition for patients with NSCLC. The
endpoints here will be to quantify the variation of both PTV and normal-tissue complication
probability (NTCP) for certain relevant organs (lung, esophagus, heart) via a direct
analysis of calculated volumes.

The second objective is to identify the correlation between PET-based radiotherapy planning
volumes and CT-based planning volumes for respiratory-gated patients with NSCLC. The
endpoint for this objective will be to quantify the breath-held, PET-based PTVs and NTCPs in
comparison to the breath-held, CT-based PTVs and NTCPs.

This study will consider patients with locally advanced non-small-cell cancer of the lung
(NSCLC) who are eligible for radical (i.e. with curative intent) combined-modality therapy.
Patients will be accrued from the new patient lung clinic at the Cross Cancer Institute.
Following a complete clinical assessment comprising a thorough history and physical
examination, a thorough analysis of all available imaging, a consideration of all available
laboratory results and consideration of any ancillary test results (e.g. pulmonary function
testing), a decision will be made whether or not to offer a patient radical therapy. In the
case of any uncertainties, further tests, such as repeat CT scanning or diagnostic PET
scanning may be arranged to define eligibility.

Eligibility Criteria:

- Histologically-proven, unresected lung cancer of the following histologic types:
*squamous cell carcinoma, *adenocarcinoma, *undifferentiated large cell carcinoma,
*non-small cell, not otherwise specified (NOS, diagnosis on cytology alone)

- AJC Stage I-III disease (if all detectable tumor can be encompassed by radiation
therapy fields, including both the primary tumor and the involved regional lymph
nodes); patients with positive supraclavicular nodes (N3) are not eligible.

- Age > 18 and Karnofsky performance status > 70

- Measurable disease on the CT and PET images

- Patient must be deemed eligible for radical combined-modality therapy

- All patients must sign a study-specific informed consent form.

Ineligibility Criteria:

- M1 disease

- Karnofsky performance status < 70 and age < 18

- Patients who have undergone complete tumor resection

- Patients with post-resection intrathoracic tumor recurrence

- Evidence of small cell histology

- Prior or concurrent malignancy except non-melanomatous skin cancer (unless disease-free
for at least 5 years)

- Prior radiotherapy to the thorax or neck

- Prior chemotherapy

- Patients with myocardial infarction within the preceding 6 months or symptomatic heart
disease, including angina, congestive heart failure and uncontrolled arrhythmias

- Pregnant women; patients with childbearing potential must practice appropriate
contraception.

- Inability to maintain a state of deep inspiratory breath-hold for a minimum length of
time

Statistical Analysis: In a previous study comparing DIBH-gated CT-scanning to free-breathing
CT-scanning performed at this institution, it was found that a sample size of 10 patients
was appropriate to illustrate both a statistically significant reduction in PTV and a
statistically significant reduction in V20 (the volume of lung treated to a dose of =20Gy).
For the current study, given that the patient population is essentially the same as the last
one, and the fact that PET and CT are comparable imaging modalities for NSCLC in terms of
their sensitivity, a total sample size of 10 patients would be an appropriate number to
assess the difference between breath-held PET and free-breathing PET (i.e. the first
objective). This difference, in terms of both PTV and NTCP, will be assessed for
statistical significance with a paired Student's t-test.