Trial Information

Cesium-131 Seed Brachytherapy Plus Subtotal Resection for Lung Cancer Patients Who Are Not Candidates for Lobectomy or Patients With High Risk of Local Recurrence

A lobectomy (removal of a full lobe of the lung or removal of ¼ - 1/5 of the entire lungs)
is a part of the primary curative treatment for people with lung cancer. There are, however,
some patients who are unable to have a lobectomy. There are several reasons why a patient
should not have a lobectomy including prior operations in the same area of the lung or poor
lung functions. Sub-lobe operations (less than a full lobectomy), are alternatives for these
patients. Types of sub-lobe operations include wedge resection or segmentectomy.

However, a randomized trial in early stage lung cancer patients that compared lobectomy
versus wedge resection showed that cancer was not controlled as well in individuals who had
the wedge resection. Localized disease wedge resection alone is therefore considered an
inadequate operation. This inadequacy, however, can be compensated for if radiation seeds
are implanted (added) to the site of wedge resection.

Iodine-125 radiation seeds are currently the most common radioactive material implanted in
the operative bed after wedge resection. However, I-125 has a half-life of 60 days. This
causes the patient to be "radioactive" for 6 months to 1 year. When an individual is
radioactive they must take necessary precautions that result in a significantly compromised
quality of life. These precautions are 1) no continuous close contact (less than 3 feet) for
a significant duration of time (more than 15 minutes), 2) no close contact with pregnant
women and children, 3) adequate precautions especially during air travel and 4) risk of
radioactive seed displacement several months.

The local control of cancer with this treatment is >95%_ %. Cesium-131 is a novel radiation
seed that has the same energy as I-125 but has a much shorter half life (9days). That means
that Cs-131 seeds give off all their radiation at a faster rate. When a radioactive seeds
gives off all of its radiation it is no longer radioactive and the dangers of radioactivity
no longer exist. With a half life of 9 days, Cs-131 gives off all of its radiation in 1
month. This significantly reduces the time when the patient is 'radioactive'. Therefore,
Cs-131 has less of a negative affect on quality of life than I-125.

In addition, because of Cs-131's significantly faster rate of radiation dissemination,
faster growing cancers (especially lung cancer) cells should be killed more efficiently
thereby increasing cancer control rates. In addition, the lesser total radiation time may
result in reduced short term and long term side effects.

Cs-131 is FDA approved and has been used mostly for prostate cancer. Our experience with
Cs-131 in prostate cancer has shown it to be a very well tolerated treatment with excellent
cure rates.

The primary study endpoint is to assess local control of localized lung cancers after
limited resection (wedge resection or segmentectomy) and Cs-131 seed placement in comparison
to previously assessed local control of localized lung cancers after limited resection and
I-125 seed placement. The primary objective is to assess local control after a wedge
resection and Cs-131 implant. The secondary objective is to assess quality of life (as
related to side effects) of Cs-131 seed placement after limited surgical resection in lung
cancers and compare it to already existing data on I-125 tolerability.

Procedures that are part of regular cancer care and may be done whether a patient enrolls in
the research study or not include:

1. CT scans of patient chest

2. Medistinoscopy (only if the surgeon is suspicious that there is cancer in the patient's
lymph nodes),

- If the cancer has spread to the lymph nodes, patients will no longer be eligible
for the study as the classification of their disease would no longer be NSCLC.
Patients would alternately receive appropriate, and standard treatment

Standard procedures being done only because the patient is part of the study;

1) Quality of life questionnaires

Follow-up Patients will be monitored for local recurrence, regional recurrence and distant
recurrence and progression for three years.

Local recurrence: recurrence within the same lobe or hilum (N1 nodes), or at the staple line
after treatment effects such as scarring have subsided.

Regional recurrence: recurrence within another lobe or pleura on the same side as the
resection, or the ipsilateral mediastinal (N2) nodes.

Distant recurrence: recurrence within contralateral lobe, contralateral mediastinal (N3)
nodes or distant metastatic disease (other organs).

Patients also will be monitored for additional primaries and regional recurrence, with
histological confirmation whenever possible. Autopsy reports will be obtained whenever
possible. A copy of the death certificate will also be obtained.

Protocol follow-up will be performed at 3, 6, 12, 18, 24, and 36 months and yearly to 5
years. The yearly follow-up visits for Years 4 and 5 will consist of either a phone call or
clinical visit (at investigator's discretion) for vital status only. These follow-up visits
will occur + 60 days from the yearly anniversary date of the resection.

A CT scan will be performed pre-operatively and at 3, 6, 12, 18, 24, 30 and 36 months.

QoL using the SF36 and UCSD Shortness of Breath Questionnaire will be obtained
pre-operatively and at 3, 12 and 24 months.

Post-operative adjuvant chemotherapy may be given at the discretion of the treating
physician. Postoperative adjuvant radiation therapy will never be performed.

Evaluation of Outcomes

Local Recurrence (primary endpoint)

Local recurrence is indicated when a follow-up examination shows growth of primary tumor or
abnormality in the resected lobe on CT scan. Since scarring may occur adjacent to the
brachytherapy site, a CT scan will be obtained at 3 months. This will form the baseline
study that local recurrence will be judged against. Increased parenchymal opacification (by
25% or more) adjacent to the staple line/mesh line will be considered suspicious for local
recurrence. The repeated CT scans should allow any significant changes to be observed even
if there is a slight image artifact from the metal seeds which may interfere with
interpretation of the CT scan.

Any suspicious areas will be confirmed by a needle biopsy.

Scans for Disease Relapse Unconfirmed by Biopsy If biopsy of suspicious areas is not
feasible, then a PET scan is required. Copies of the PET scan, the 3- month (baseline) CT
scan and the most current CT scan.

Quality of Life As a secondary outcome, patient-centered quality of life (QoL) data will be
measured using the SF36 and dyspnea will be measured using the UCSD Shortness of Breath
Questionnaire. [Eakin, 1998] These are ill patients with significant pulmonary morbidity. It
will be important to quantify any changes in overall health and pulmonary-specific symptoms
in this population. Each patient will act as his or her own control. These validated
instruments have been used in many trials of patients with severe lung disease. Measurements
will be undertaken before and at 3, 12 and 24 months after surgery.