Cesium-131 Seed Brachytherapy Plus Subtotal Resection for Lung Cancer Patients
Cesium-131 Seed Brachytherapy Plus Subtotal Resection for Lung Cancer Patients
The primary curative treatment of lung cancer patients is surgery, chemotherapy and/or
 radiation therapy (either or all depending on the extent of disease). Surgical resection
 usually requires removal of a lobe of the lung (lobectomy). 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 worse local control of cancer with wedge resection. Therefore,
 localized disease wedge resection is considered an inadequate operation. This inadequacy can
 be compensated if radiation seeds are added to the site of wedge resection. Iodine-125
 (I-125) is the most commonly used radiation seed for this purpose. I-125, however,
 unfortunately has a relatively long half life (time taken for activity to become half) of 2
 months. Therefore, the patient is technically 'radioactive' for an average of 6 months to 1
 year. This can seriously compromise quality of life.

 Cesium-131 is another radiation seed that may more effectively treat lung cancer patients.
 Cs-131 has been previously used in prostate cancer successfully. Cs-131 has similar energy to
 I-125 but has a much shorter half life (9days as compared to 60 days for I-125). Patients who
 receive Cs-131 radiation seeds are expected to be radioactive for 30 days (1 month) as
 compared to 180 days (6 months) with I-125. The objective of this study is the use Cs-131
 radiation seeds in lung cancer patients who are planning to undergo a wedge resection for
 localized disease and follow the patients for cancer control and toxicity. These results will
 be compared to pre-existing data for I-125 treatment outcomes in lung cancer patients who
 have had a wedge resection for localized disease.
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.
Inclusion Criteria:

 1. Patients must have suspicious lung nodule for clinical stage I/recurrent Lung Cancer

 2. Mass Tumor size < 7 cm

 3. Patient must have a CT scan of the chest with upper abdomen within 90 days prior to
 date of pre-registration.

 4. Patient must have ECOG/Zubrod performance status 0,1, or 2.

 5. Resected lung cancers with positive margins

 Exclusion Criteria:

 1. Patient has already received high dose radiation to the area

 2. Cancerous nodule is very close to the esophagus or spinal chord, thereby increasing
 the risk of radiation treatment

 3. Pregnancy or unwillingness to practice a form of birth control (i.e. abstinence, oral
 contraceptives, etc.)