Brachytherapy, the use of radioactive isotopes placed directly on the desired target tissues during surgery or placed endoluminally, can be used for treatment of lung cancer. It offers several theoretic advantages when compared with traditional radiotherapy. Direct surgical placement of the radiation source allows for specific targeting and uniform delivery of the radiation minimizing the amount of normal lung in the radiation field. This potentially limits radiation side effects and ensures patient compliance which has been a major disadvantage of external beam radiation therapy.
Early Stage Lung Cancer
It has been established that lobectomy offers the best chance of cure for early-stage non–small-cell lung cancer. According to the Lung Cancer Study Group, sublobar or wedge resection is not as effective as lobectomy or pneumonectomy because it is associated with a high incidence of local recurrence.1 However, a large resection requires the patient to have a reasonable residual forced expiratory volume in 1 second (FEV1) of 0.8 to 1.2 L and a ventilation–perfusion scan corresponding to adequate breathing in other lung segments. Patients who have long histories of smoking commonly fail to have these advantageous characteristics. Techniques that combine sublobar resection with radiotherapy delivered intraoperatively or through the implantation of radioactive 125I seeds at the lung resection margin have shown promising results (see section “planar seed experience”). This procedure has been reported to reduce local disease recurrence and improve palliation of symptoms. Additionally, it provides a treatment option for patients who are not physically capable of undergoing lobectomy or pneumonectomy or who are considered high-risk surgical candidates consequent to other comorbidities.
Varying systems for radiation delivery are presently used in clinical practice. Three techniques have been described for use following sublobar resection all of which are compatible with thoracoscopy.
Planar Seed Implant Technique
There are several reports of wedge resection procedures for stage I tumors that have been performed in conjunction with planar 125I seed implants. This procedure has been reported to reduce local disease recurrence and improve local control.
After the wedge resection, the surgeon must measure the area at risk for length and width to determine the dimension of the implant. The implant is made of two components. The source material, called the Seed-in-Carrier, available through the Oncura Company (Plymouth Meeting, PA), consists of 125I seeds that are embedded in strands of absorbable Vicryl suture. A second isotope recently became commercially available, using 131Cs, from Isoray Medical (Richland, WA). There are 10 seeds in each strand, and each seed and strand is spaced 1 cm apart center to center. The individual seed measures 0.7 × 4 mm in dimension. The source material is attached to an absorbable mesh material made of either Dacron or Vicryl that is custom trimmed to fit the area at risk. Before trimming, 1 cm is added to the overall dimension to ensure an adequate margin for suturing. Parallel lines spaced 1 cm apart are drawn longitudinally on the mesh patch. The radioactive strands then are stitched to the mesh along these lines. The radioactive strands and suture should be handled with care using forceps only (Fig. 88-1). The source material is anchored on each side of the implant with a small staple, and any excess source material should be cut and disposed of properly in accordance with radiation disposal guidelines (Fig. 88-2). The custom mesh then is placed over the area of interest and sutured into place, using extreme care not to puncture the seeds (Fig. 88-3). Previously the mesh was prepared in the operating room; however, a prefabricated mesh construct is now available, in either 125I or 131Cs, which simplifies this step (Fig. 88-4). After the operation is concluded and the patient is stable (or at some future date), a postoperative CT scan is obtained over the area of interest to verify and document the final dose.
The source material is attached to Dacron or Vicryl absorbable mesh and trimmed to the treatment area. One centimeter is added to the overall dimension before trimming to leave an adequate margin for suturing. Intraoperatively, the custom mesh is placed over the treatment area and sutured in place, taking great care to avoid puncturing the radioactive seeds.
A novel technique of delivering radiation has also been developed at Brown University, where a 169Yb brachytherapy source delivery system has been developed which can be used in conjunction with commercially available surgical stapling instruments (Fig. 88-5). This includes a radioactive 169Yb seed sealed within titanium tube 0.28 mm in diameter and then capped and resealed by titanium wires laser welded to the tube to serve as legs of a tissue-fastening system. The use of these in patients is subject of future study.2
Santos et al.3 from Allegheny General Hospital published a large series using this technique. Their retrospective study of 101 patients with sublobar resection and planar seed implants at the suture line was compared with 102 similar patients with sublobar resection alone. Patients were surgically resected using video-assisted thoracic surgery (VATS) technique. The implants were made using Vicryl mesh. A planned dose of 100 to 120 Gy was delivered to a depth of 0.5 cm. The mesh then was sutured to the staple line. The local relapse rate was 2% for seeds (at 18 months) versus 18.6% for sublobar resection alone (at 24 months, p = 0.0001). Age and FEV1 were similar in each group, but the group with the implants had more stage IB patients (n = 23) than the group undergoing surgery alone (n = 0). Overall 4-year survival was 60% for surgery alone and 67% for surgery plus seed implants. The results were not statistically significant.
The New England Medical Hospital and Tufts University published a series of 33 patients who underwent a wedge resection (or segmental resection) with seed implants at the lung margins.4 The strands of seed in this series were implanted directly on the suture line without mesh. The planned dose was 125 to 140 Gy delivered to a depth of 1 cm. There was recurrence at the suture line in 2 of 33 (6%) patients (median follow-up 51 months), and the 5-year projected survival was 47%. The cancer-specific 5-year survival was 61%.
A multicenter retrospective study5 compared lobar and sublobar resection in stage I non–small-cell lung carcinoma and examined the use of adjuvant brachytherapy with sublobar resection. A total of 291 patients with T1N0 disease were evaluated, 124 treated with sublobar resection and 167 with lobectomy. Within the sublobar resection cohort, 60 out of 124 were treated with adjuvant Vicryl mesh brachytherapy with a significant decrease in local recurrence rate from 17.2% to 3.3% at a mean follow-up of 34.5 months in the mesh patient group. The American College of Surgeons Oncology Group (ACOSOG) has recently completed a phase III clinical trial ACOSOC Z4032 comparing sublobar resection alone and sublobar resection with adjuvant mesh brachytherapy. The early toxicity results for pulmonary function and dyspnea have been published.6,7 These show no significant change from baseline on either PFT or dypnea scores. The outcome results of this trial will provide the first prospective data for the use of brachytherapy to augment sublobar resection.
Stereotactic Ablative Body Radiotherapy (SABR) or stereotactic body radiation therapy (SBRT) has also emerged as an option for treatment in medically inoperable patients with early-stage lung cancer. Another prospective ACOSOG study, ACOSOG Z4099/RTOG1021, is specifically for high-risk operable patients and randomly assigns patients to either sublobar resection with mesh implant brachytherapy or SABR.
For patients unable to tolerate surgery, the seeds can be implanted directly in the tumor using a variation of this technique called volume implanting. Although this technique yields an inferior result to surgery, for inoperable patients, this may be an option for increasing the radiation dose. The radioactive seeds, usually 125I, are implanted in the tumor and any other area of gross disease. After the needle is inserted into the tumor, the seeds are deposited individually or in a line. The seeds are placed to cover a volume of disease, in contrast to the planar technique, which targets the resection cavity and margin. Clinicians at the Memorial Sloan Kettering Cancer Center of New York reported 65% locoregional control in their experience with volume implants.8 Another study from the Norris Cancer Center describes the volume implant technique used in 14 patients.9 All patients underwent surgical lymph node staging before the procedure. 125I seeds were used to implant the tumor. The local control rate was 71% with a 15-month median follow-up. All the relapses occurred in patients with stage III cancers. A dose of 80 Gy was delivered at the periphery, with a high dose of 200 Gy in the center of the tumor. There was no incidence of radiation pneumonitis.