DR. CHEN: Good afternoon. I hope it is not too late after an open bar and dinner, for the radiation oncology talk. I would like to thank the committee that invited us to share our brachytherapy experience in lung cancer.

This is Pittsburgh where I come from, and this is the area surrounded by the three rivers. It is kind of neat to come to this. Our topic is brachytherapy and its clinical application with stage I non-small cell lung cancer that is high risk and unable to go for open surgical resection such as lobectomy.

This morning we talked about the increasing use of screening for early detection. So, there is an increase in the incidence of non-small cell lung cancer recently, and surgery is still most effective treatment for early stage disease. When we are talking about T1 lesions, five-year survival is around 68%, maybe higher, but more and more we are talking about how much of a resection we should do either with lobectomy or with wedge resection.

In the lung cancer study we have been showing the local recurrence with the lobectomy is about 6%, but wedge resection is about 22%. So, this is the first patient we had with a small nodule. This patient is about 70 years old, 10 years ago had head and neck cancer, had a laryngectomy and also had post-op radiation to the head and neck area. Now 10 years later presents with a second primary non-small cell stage I in the left side of the lung.

So, what do we do with this kind of patient? With the help of visual assist wedge resection we will be able to localize the lesion and be able to remove with thoracoscopy which is much safer. The patient with high risk of some co-morbid condition was unable to go through the open resection with the lobectomy. The thorascopic procedure is minimally invasive, utilizes muscle-sparing mini-thoracotomy to remove the lesion.

With this procedure we are able to assess lymph node environment and remove less normal tissue. There are fewer complications post-op and therefore it shortens the recovery time in the hospital. Unfortunately with wedge resection there are higher local recurrences. One option is post-op external beam radiation which Dr. Broka will address, but another way we can address that is maybe we can do intraoperative brachytherapy to decrease the local recurrence, which perhaps may translate into a survival benefit. With brachytherapy we can deliver high-dose radiation right in the tumor bed and the radiation dose falls off very quickly so we can spare the normal tissue. Also, brachytherapy can be performed during the surgery so there is no additional procedure needed to do the brachytherapy. The patient might not need external beam radiotherapy with which there is some disadvantage because in most of these high-risk patients their performance is limited, and they might not be able immobilization and to position the patient to be able to treat with external beam. Also, there is some uncertainty with localizing the tumor bed to be able to assess where we end the beam to the target. Also, with the lung changing position you might need to increase the margin and the field size. This would also require approximately 6 weeks of treatment.

We are looking at various radioactive sources to determine which one really is suitable for this visual assist thoracoscopy with intraoperative brachytherapy. The source we choose is iodine 125 because it is low energy. It is only 28 KeV. So, you can minimize the radiation hazard and also radiate with a very small pattern. It is about 4 or 5-millimeter pattern and the half-life is about 60 days. That means it will take about every 2 months 60 days the radioactivity will decay in half. So, they will decay all the radiation in approximately 1 year. These iodized seeds are commercially available and come in a sterile package. They come in 10 seeds of iodine in the vicryl suture with this stainless ring hosted the 10 seeds of iodine in a vicryl suture. There is protective radiation shielding to minimize radiation exposure and there is an attached needle so that we can sew into the mesh.

This is the procedure to prepare this iodine 125 vicryl mesh. This is a small piece of vicryl mesh we use and we use a marking pen to mark in the space depending on the activity we get from the iodine seed. So usually do about 1 to 1.5 centimeters in spacing and usually cover the tumor bed with a 2-centimeter margin.

So, this is the iodine 125 vicryl with the needle. We throw into this mesh and then we secure it with a staple or suture on the bow end.

So, after visual assist thoracoscopy and wedge resection the target volume with appropriate tumor bed and margin is determined, we usually will insure that we have a 2-centimeter margin. Like I said, iodine 125 vicryl mesh is prepared, this takes about 20 minutes. Then we insert the mesh into the thoracoscopy port with visual assistance. The mesh is over the tumor bed right on the staple line and is secured with suture on the corner of surgical drape. Usually we use about 40 or 50 seeds and the activity per seed running from about 0.4 to 0.6 millicurie for an entire radioactivity average of about 20 millicuries.

This is showing the mesh going into one of the keyholes. Then you revise it with a retractor with visual assist so we will be able to spread this mesh into the staple line of the wedge resection and secure the corner. After the procedure we survey for radiation safety and it usually is below requirement. That means the patient is not restricted. Usually after the procedure there is not any radiation safety issue for the patient. The most common sense instruction we give is that small babies and the pregnant ladies shouldn't stay with the patient for a long period of time, especially in the first 2 months after the procedure.

So, from January 1997 through April 2000 we had 53 patients treated at a single institution who were at high risk for open resection. We did the thoracostomy, wedge resection. There are 27 females, 26 males. The mean age is about 70 plus or minus 9 years. Twenty-seven patients underwent wedge resection and 26 patients underwent segmentectomy. All of the patients had a clear pathological margin, and mediastinal lymph node sampling was routinely performed.

After the patients recovered, we did an x-ray to confirm or to see that it is uniformly distributed and the dosimetry planning was done. We prescribed a dose initially of about 10,000 cGy and after several cases we increased it to 12,000 cGy to about 1-centimeter depth. Then we followed the patient with a physical examination, CT scan, pulmonary function test every 3 to 6 months.

So, there is some concern that the delivery of high-dose radiation might increase the incidence of radiation pneumonitis or fibrosis. Actually we had a CT scan repeated every 3-6 months. The computed tomography described a minimum degree of fibrosis or radiation pneumonitis. Another concern of the brachytherapy is the possibility of dislocation of seeds or radioactive source, so far we haven't had any patients with a seed dislocation. So, here are the results. We had 21 patients who were pathologic stage IA, and 32 patients who were IB. The mean hospital stay was about 9 day plus 4.8 days, two patients died after the surgery. The survival after 3 years by the Kaplan Meyer was 62.7% Fifteen patients developed mediastinal distant recurrence but so far in 17 months plus or minus approximately 10 months there have been no local recurrence.

Of the 12 patients who have died there were 7 who died due to regional or distant recurrence and 5 died due to progressive pulmonary failure. Pulmonary function tests done pre- and post-op are shown here, there is no affect by the brachytherapy on FEV-1 or FVC. Looking at these numbers there is not much change, maybe slightly better but not really any difference.

In conclusion, visual assist thoracoscopy wedge resection, either segmentectomy or wedge resection combined with intraoperative brachytherapy for the stage I patients who are high risk for open lobectomy is feasible and well tolerated.
So far there are no acute complication with brachytherapy, and there are no local recurrences. However, there are 15 patients who have developed regional and/or distant metastases.

Perhaps with the recent data we have been looking at our specimens for some molecular marker to suggest maybe we should add conformal external beam to the mediastinum or add chemotherapy for these high-risk patients. But longer follow-up and additional patients for this particular procedure are needed in order to determine the efficacy of local control and the translated survival benefits.
Thank you.

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