For advanced disease, brachytherapy sometimes can be used to convert an unresectable or marginally resectable tumor into a lesion that is acceptable for oncologic resection. After maximal resection by the surgeon, the area at risk (close or positive margin) is noted by the radiation oncologist and surgeon. The area is measured, usually adding 0.5 to 1 cm to all dimensions for a radiation dosimetric margin. The area typically is a rectangle, but can be any shape. This area then is treated with brachytherapy. One way to clear this margin is to place a permanent planar implant.
Planar Seed Experience for Locally Advanced Disease
Dana-Farber Cancer Institute published their experience of patients with a total of 48 implants.10 The implant model we used consisted of 125I seeds in suture that were then sutured to a mesh patch and implanted in high-risk surgical beds. The mean follow-up in our series was 21 months. Local control was maintained in 81%. There were three patients (6%) with grade 3 to 4 toxicity, one with a tracheoesophageal fistula, one with esophageal perforation, and one with persistent pneumothorax. Both patients with esophageal problems had partial-thickness resection of their esophagus with seeds placed on the surgical bed.11
A retrospective series from the Memorial Sloan Kettering Cancer Center demonstrated that stage III patients with mediastinal involvement exhibited similar median (16 vs. 17 months) and 5-year survival (15%) for complete resection versus incomplete resection plus brachytherapy. These results were superior to brachytherapy alone without resection and neither resection nor brachytherapy.12 The Memorial Sloan Kettering Cancer Center reported another series of patients with all lung cancer stages. This series had a 50% increase in median survival (8–12 months) with brachytherapy after incomplete resection compared with no surgery.13 This was compared with a 17-month median survival for complete resection. New York Hospital looked at this technique in a prospective study.14 Twelve patients with stage III non–small-cell lung cancer who had gross or microscopically positive margins after resection were implanted using the planar technique. The implants were composed of either 125I or 103 Pd embedded in a Gelfoam plaque. The dose prescribed was a 1-cm margin around the area of positive margins. All patients received either preoperative or postoperative external beam radiation at a dose range of 45 to 60 Gy. The results showed 82% local control with addition of brachytherapy for positive margins after surgery. The 2-year overall and cancer-specific survivals were 45% and 56%, respectively. In another series, the Memorial Sloan Kettering Cancer Center also reported 75% locoregional control with partial resection and implant compared with 86% locoregional control with full resection.15
Intraoperative Radiation Therapy (IORT) and Afterloading Catheters
Radiation delivered intraoperatively also can be used for treating close and positive resection margins. Two methods can be used: afterloading and IORT. Afterloading is delivered by placing hollow blind-ended plastic catheters along the area at risk, after which the radiation is loaded into the catheters. The catheters are spaced 1 cm apart in parallel lines. The open end of the catheter is directed out of the skin. Care must be taken to prevent kinking or sharp angles, which would prevent loading. The patient is permitted to stabilize for a period and then sent to the radiation department for loading. IORT is delivered more conventionally using a mobile accelerator in a specially equipped operating room (OR).
Afterloading can be delivered by a low-dose-rate (LDR) or high-dose-rate (HDR) method. With the LDR method, radioactive sources on a string are loaded into the catheters, where they remain for several days. During the interval, the patient must remain isolated in a radiation-safe room with full radiation precautions. After an appropriate interval, the catheters are removed and radiation precautions are withdrawn. A newer version of this technique, HDR afterloading, uses a remote-control device. Catheters are placed, as with the LDR method. However, the radiation is delivered using a single computer-controlled source that can be placed at various positions and dwell times. This flexibility permits greater dose conformation, termed dose optimization. All treatments are delivered in a shielded room, which reduces incidental dose exposure to the technical staff. Both techniques are considered radiobiologically equivalent. The Memorial Sloan Kettering Cancer Center has used the afterloading technique (LDR) in the mediastinum with good local control and 2-year actuarial survivals of 76% and 51%, respectively, for N2 disease. Another group from Seattle also demonstrated good local control with the addition of brachytherapy.16
Intraoperative Radiation Therapy
Specialized equipment is needed for IORT. The radiation can be delivered using a mobile accelerator in a shielded OR or in the radiation department, where the radiation vault is also a functional OR. After surgical resection, the area at risk must be demarcated by the surgeon. The normal tissue can be moved out of the field or shielded with thin strips of lead. The cone from the linear accelerator is inserted into the patient, or applicators for HDR brachytherapy are placed. All personnel must leave the room when the radiation is delivered, which usually takes several minutes.
Several series have used this technique. The largest series in the literature is from the University Clinic of Navarra, Pamplona, Spain.17 Calvo and colleagues retrospectively reported findings in 104 patients treated between 1984 and 1993, all of whom had stage IIIA or IIIB cancers. Between 1984 and 1989, 22 patients had surgery and IORT followed by endobronchial brachytherapy (EBRT). Between 1989 and 1993, 82 patients had neoadjuvant chemotherapy. Responders (46 patients) had surgery, IORT, and EBRT; nonresponders had chemoradiation, surgery, with IORT as a final boost. Their technique used a dose of 10 to 15 Gy (18–20 Gy unresectable). The series reported local control rates for patients with microscopic residual disease of 66% (33 of 50) and 35% (15 of 42) for patients with macroscopic residual disease. The best results were observed with Pancoast tumors, which demonstrated a local control rate of 92% (11 of 12) and 100% (5 of 5) for microscopic and macroscopic disease, respectively. The most common toxic event was grade III–IV esophagitis in 25%. Other reported toxicities were symptomatic pneumonitis, transient neuropathy, and lung fibrosis. Other series are listed in Table 88-1.
Table 88-1Published Experience with Intraoperative Radiation Therapy (IORT) ||Download (.pdf) Table 88-1Published Experience with Intraoperative Radiation Therapy (IORT)
|INSTITUTION ||NUMBER OF PATIENTS ||RADIATION SCHEME ||RESULTS |
|NCI18 || 4 ||IORT 0, 20, 30, 40 Gy ||25% 5-yr OS, toxicity over 25 Gy |
|Graz University19 ||14 ||IORT 10–20 Gy + EBRT 46–56 Gy ||5-yr OS 15%, recurrence-free 5 yr 53% |
|Montpellier20 ||17 ||IORT 10–20 GY + 45 Gy EBRT ||Actuarial survival at 11 yrs 18%, median survival 36 mo |
|Allegheny University17 ||21 ||IORT 10 Gy + EBRT 45–59.4 Gy |
(pre or postop)
|5-yr actuarial survival 33% |
|Instituto Madrileno21 (Madrid, Spain) ||18 ||IORT +EBRT (per or postop) ||5-yr actuarial survival 22%, cause-specific 33% |
Complications from any of these techniques are similar and minimal compared with the surgery itself. Poor wound healing or abscess formation can occur but is very rare. The most concerning toxicity is fistula formation. Care must be used to avoid placing the seeds directly on any injured organ, such as the esophagus or blood vessels.11 Intact tissue can tolerate very-low-dose-rate (VLDR) radiation well; however, any injury to the organ, whether caused by the tumor or as a consequence of the surgery, can predispose to a fistula. This complication can be avoided when implantation is necessary by adding another layer of luminal protection for the blood vessels of the esophagus using biologic or artificial technique. However, if there has been extensive dissection in the subcarinal space or partial esophageal wall resection, we do not recommend permanent seed implantation because of the predisposition to fistula formation, necessitating further surgery. We have reported two cases of mediastinal carcinoid tumors in patients who had been treated previously with chemoradiation. In both instances, the tumor was adherent to the esophageal muscularis, and an esophageal fistula developed, necessitating additional surgical repair.22
Tumor recurrence or metastasis can be treated with brachytherapy. Brachytherapy has the advantage that it can be used for patients and tumors that have already received radiation. Care must be taken in reirradiating the heart, spinal cord, or esophagus; the other organs can tolerate reirradiation with brachytherapy. Depending on the location and surgical resection, any of the previously described techniques can be used, from permanent seeds, to afterloading catheters, to IORT. Sometimes seed implants are preferred because of their slower rate of delivery. The slower the rate, the larger is the dose of reirradiation the patient can tolerate. LDR and VLDR techniques are better tolerated than HDR techniques in certain risky organs.