Permanent Iodine-125 Interstitial Planar Seed Brachytherapy for Close or Positive Margins for Thoracic Malignancies

Int. J. Radiation Oncology Biol. Phys., Vol. 76, No. 4, pp. 1114–1120, 2010 Copyright Ó 2010 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/10/$–see front matter

doi:10.1016/j.ijrobp.2009.02.067

CLINICAL INVESTIGATION

Lung

PERMANENT IODINE-125 INTERSTITIAL PLANAR SEED BRACHYTHERAPY FOR CLOSE OR POSITIVE MARGINS FOR THORACIC MALIGNANCIES SUBHAKAR MUTYALA, M.D.,* ALEXANDRA STEWART, D.M., M.R.C.P., F.R.C.R.,y ATIF J. KHAN, M.S., M.D.,z ROBERT A. CORMACK, PH.D.,x DESMOND O’FARRELL, M.SC.,x DAVID SUGARBAKER, M.D.,{ AND PHILLIP M. DEVLIN, M.D., F.A.C.R.x * Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine in Bronx, New York, New York; y St. Luke’s Cancer Centre, Royal Surrey County Hospital, Guildford, England; z Department of Radiation Oncology, Cancer Institute of New Jersey, New Jersey; x Department of Radiation Oncology and { Department of Thoracic Surgery, Dana Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts Purpose: To assess toxicity and outcome following permanent iodine-125 seed implant as an adjunct to surgical resection in cases of advanced thoracic malignancy. Methods and Materials: An institutional review board-approved retrospective review was performed. Fifty-nine patients were identified as having undergone thoracic brachytherapy seed implantation between September 1999 and December 2006. Data for patient demographics, tumor details, and morbidity and mortality were recorded. Results: Fifty-nine patients received 64 implants. At a median follow-up of 17 months, 1-year and 2-year KaplanMeier rates of estimated overall survival were 94.1% and 82.0%, respectively. The 1-year and 2-year local control rates were 80.1% and 67.4%, respectively. The median time to develop local recurrence was 11 months. Grades 3 and 4 toxicity rates were 12% at 1 year. Conclusions: This review shows relatively low toxicity for interstitial planar seed implantation after thoracic surgical resection. The high local control results suggest that an incomplete oncologic surgery plus a brachytherapy implant for treating advanced thoracic malignancy merit further investigation. Ó 2010 Elsevier Inc. Thoracic tumors, Mediastinal tumors, Thoracic surgery, Brachytherapy seed implant, Lung brachytherapy.

survival. When planar 125I implants were placed following resection of metastatic and locally invasive paraspinal tumors, excellent local control rates with minimal toxicity were seen, despite high localized doses to the spinal cord. In an effort to improve local control in cases of marginally resectable thoracic malignancy, patients with close or positive resection margins can have a customized planar radioactive implant placed at the time of surgery. Presented here is the Brigham and Women’s Hospital and Dana-Farber Cancer Institute experience with permanent 125I seed implantation as an adjunct to optimal surgical resection in locally advanced thoracic malignancy.

INTRODUCTION Surgery is the primary treatment for certain thoracic malignancies, both primary and metastatic. In cases of locally advanced disease, neoadjuvant chemotherapy and/or radiotherapy may be used to downsize the tumor to make surgical resection more attainable. However, an oncologic surgical margin (tumor plus a rim of normal tissue) may still not be achievable due to the anatomical location of the tumor. As in most disease sites, incomplete surgical resection is associated with a higher incidence of local recurrence (1). Published studies describe the use of intraoperative, permanent implantation of iodine-125 (125I) seeds for the treatment of thoracic malignancies (2). In early-stage non-small-cell lung cancer (NSCLC), the addition of intraoperative brachytherapy to sublobar resection improved predicted rates of local control and overall survival compared to sublobar resection alone. In more advanced disease with residual tumor or positive lymph nodes at surgery, the addition of thoracic brachytherapy resulted in favorable rates of local control and

METHODS AND MATERIALS This retrospective review was approved by the local institutional review board. Patients who had received permanent very-low-doserate 125I brachytherapy seed implants in their thorax between September 1999 and December 2006 were included. Fifty-nine patients were identified from their written brachytherapy directives as having Subhakar Mutyala and Alexandra Stewart are joint first authors. Conflict of interest: none. Received Aug 20, 2008, and in revised form Feb 25, 2009. Accepted for publication Feb 27, 2009.

Reprint requests to: Subhakar Mutyala, M.D., Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, 1625 Poplar St., Bronx, New York, 10461. Tel: (718) 405-8550; Fax: (718) 405-8561; E-mail: smutyala@ montefiore.org 1114

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undergone this procedure. The medical records were reviewed, and data for patient demographics, tumor details, operative details, histopathology, and posttreatment morbidity and mortality were recorded. The radiotherapy notes were reviewed, and data for brachytherapy were recorded, and external beam radiotherapy (EBRT) details were obtained where appropriate. Prior to surgery, all patient cases were reviewed by the brachytherapy team because the patients were identified by the surgeon as having a high risk for close or microscopically positive resection margins. Consent was obtained for a brachytherapy implant to be placed intraoperatively should complete resection not be attainable. At the time of surgery, the surgeon and the radiation oncologist reviewed the preoperative images, the operative findings, and the frozen section examination findings to determine the size and geometry of the area at risk for recurrence. The size of the region at risk for tumor recurrence was determined, and margins of at least 1 cm were then added, dependent on the size of the affected area and the anatomy of the implant area. As a general rule, these margins were increased as the size of the treatment field increased. The target plus associated margins formed the active area. A 125I brachytherapy planar implant was customized according to these dimensions. The prescription dose varied according to the location of the implant, the curvature of the implant site, and the presence or absence of previous radiation. A rectangular grid was drawn on polyglactin (Vicryl; Ethicon Inc., Somerville, NJ) mesh with line spacing dependent on the seed activity and prescribed implant dose. The spacing was determined from in-house nomograms comparing the activity, number of seeds, and dose at 0.5 cm. The mesh was punctured at equal intervals to allow the seeds to pass easily through the mesh. Stranded 125I seeds in a polyglactin suture carrier (Oncura Inc., Plymouth Meeting, PA) were sutured into the polyglactin mesh along the grid lines to provide a uniform dose at 0.5 cm. The ends of the suture were tethered using surgical clips and were then trimmed. The implant was cut out with 1-cm margins to allow the implant to be sutured in place (Fig. 1). The mesh was placed flat against the target and sutured to tissue or bone, using long-handled tools. The prescribed dose was determined intraoperatively according to factors such as the surrounding healthy tissues and patient anatomy and whether the patient had previously undergone irradiation to the surgical site (3). Postoperative dosimetry was routinely obtained for all patients following surgery, prior to the patient’s discharge from hospital, using CT-based treatment evaluation The implant dosimetry was determined using three-dimensional seed identification and CT imaging. The very-low-dose rate was defined at 0.5 cm from the best plane of the implant, usually taken in the center of the region of positive or suspected margin. The patient and the room were surveyed for the presence of radiation after wound closure. In the rare situation that radioactivity was registered at the patient’s skin surface, appropriate radiation protection advice was given. Survival and local control were calculated using Kaplan-Meier analysis (4). Survival and follow-up times were calculated from the date of brachytherapy implantation. Local control was compared for positive versus negative surgical margins and metastatic versus primary disease, using Fisher’s exact test. Toxicity levels were retrospectively graded according to the CTCAE version 3.0 toxicity grading system (5).

RESULTS Patient characteristics Fifty-nine patients received 64 implants. The median follow-up was 17 months (mean, 25 months; range, 0–88

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Fig. 1. 125I seeds are shown in a carrier suture woven into a polyglactin mesh to form an implant with an active area of 6  10 cm.

months). The median follow-up for survivors was 17 months (mean, 26 months; range, 0–88). The median patient age was 53 years (range, 15–80 years), with a male-to-female ratio of 3:2. The areas implanted and percentage were the mediastinum, 39.0% (23 patients); chest wall, 28.8% (17 patients); superior sulcus, 13.6% (8 patients); vertebral body, 10.2% (6 patients); chest wall at apex, 5.1% (3 patients); diaphragmatic crus, 1.7% (1 patient); and lung parenchyma, 1.7% (1 patient). The percent distribution of histology was NSCLC, 40.7% (24 patients); sarcoma, 32.2% (19 patients); mesothelioma, 10.2% (6 patients); carcinoid tumor, 5.1% (3 patients); thymic carcinoma, 5.1% (3 patients); metastatic adenocarcinoma, 3.4% (2 patients); thymoma, 1.7% (1); and nonseminomatous germ cell tumor, 1.7% (1 patient). Patients with NSCLC were the only subjects amenable to formal staging: 2 patients had a local recurrence of previously resected NSCLC; 1 patient with stage T1 disease underwent subtotal lobectomy due to poor pulmonary reserve; 2 patients had stage T2 disease; and all of the other NSCLC patients were staged at T3 or T4 disease. Sarcoma patients had the following histology findings: 8 patients had synovial cell sarcoma, 3 had liposarcoma, 2 had leiomyosarcoma, 2 had myofibroblastic sarcoma, and 1 patient each had rhabdomyosarcoma, malignant fibrous tumor, giant cell tumor, and alveolar sarcoma. Thirty patients underwent extensive mediastinal dissection, 7 patients underwent mediastinal lymph node sampling, and the remaining patients did not undergo significant mediastinal dissection. Mediastinal dissection was performed for a variety of histology tests, including sarcoma (11 patients), NSCLC (9 patients), carcinoid (3 patients), thymic cancer (3 patients), mesothelioma (2 patients), metastatic adenocarcinoma (1 patient), and NSGCT (1 patient). Final histopathology findings showed negative resection margins (>0.3 cm from the nearest margin) for 20 patients; NSCLC (13 patients), sarcoma (5 patients), metastatic adenocarcinoma (1 patient), and thymic cancer (1 patient). This does not take into account frozen section results which were later reversed on full histology

Patient

Previous radiation

26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41

No Yes No No

Yes Yes No Yes No Yes Yes No Yes Yes No Yes Yes Yes Yes Yes No

No No No Yes No No Yes Yes No No

NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC NSCLC Synovial sarcoma

Vertebral body Apex Superior sulcus Superior sulcus Chest wall Vertebral body Vertebral body Mediastinum Lung parenchyma Mediastinum Mediastinum Chest wall Chest wall Mediastinum Vertebral body Chest wall Mediastinum Mediastinum Vertebral body Superior sulcus Mediastinum Superior sulcus Superior sulcus Apex Right Lung apex

28.3 2.6 15.6 30.8 0.7 82.5 7.3 88.2 36.3 86.8 28.8 46.0 17.0 35.0 73.7 7.3 2.4 23.9 57.4 9.6 11.4 27.7 37.7 28.5 53.3

Dissected No No No Dissected No No Dissected Dissected Sampled Sampled Dissected No Dissected Sampled Sampled No Dissected Dissected No No No

Synovial sarcoma Synovial sarcoma Synovial sarcoma Synovial sarcoma Synovial sarcoma Synovial sarcoma Synovial sarcoma Liposarcoma Liposarcoma Liposarcoma Giant cell tumor Carcinoid Carcinoid Carcinoid Leiomyosarcoma Leiomyosarcoma

Mediastinum Mediastinum Chest wall Superior sulcus Mediastinum Mediastinum Mediastinum Mediastinum Mediastinum Vertebral body Chest wall Mediastinum Mediastinum Mediastinum Superior sulcus Post-chest wall

3.5 0.5 8.2 2.8 85.5 20.5 2.0 4.4 0 31.6 80.9 18.9 10.7 25.0 0.2 33.8

Dissected Dissected No Dissected Dissected Dissected Dissected Dissected Dissected No No Dissected Dissected Dissected No Dissected

Sampled Dissected

Final margin status

Local control

Metastatic at surgery

Later metastatic disease*

Negative Positive Negative Positive Negative Negative Positive Positive Negative Negative Positive Positive Negative Positive Positive Negative Negative Positive Positive Negative Positive Negative Negative Negative Positive

Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No Yes

No No No No No No No No No No No No No No Yes No No No No No No No No Yes No

Positive

Yes Yes No Yes Yes Yes Yes No Yes No Yes Yes No Yes Yes Yes

Yes Yes No Yes Yes Yes No Yes Yes Yes No No No Yes Yes Yes

Positive Positive Positive Positive Positive Positive Positive Negative Positive Positive Positive Positive Positive Negative

Death

Toxicity

Yes Yes Yes Yes No No No No Yes No No No Yes No No Yes No No No Yes No No No Yes No

Yes Yes

No No Yes Yes Yes Yes No No Yes Yes No No No Yes No Yes

Yes

Late pneumonitis Bronchopleural fistula None None None None None None None None None None None None None None None None None None None None None None Hemopneumothorax, sympathetic chain damage Possible aortic rupture None None None None None None None None None None Esophageal fistula Esophagus perforation None None None (Continued )

Yes Yes

No No No Yes No

No

Yes

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Yes Yes Yes Yes Yes No Yes

Histology

Follow-up (months)

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Mediastinal lymph node surgery

Disease location

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Table 1. Patient characteristics, histology, treatment, and outcomes

Table 1. Patient characteristics, histology, treatment, and outcomes (Continued )

Patient

Previous radiation

Histology Myofibroblastic sarcoma Myofibroblastic tumor Malignant fibrous tumor Alveolar sarcoma

43 44

No No

45

No

46

Yes

47 48 49 50 51 52 53 54 55 56 57 58

No No No Yes Yes No No Yes Yes Yes Yes Yes

Rhabdomyosarcoma from NSCGT NSGCT Mesothelioma Mesothelioma Mesothelioma Mesothelioma Mesothelioma Mesothelioma Thymic Ca Thymic Ca Thymic Ca Thymoma Adenocarcinoma

59

Yes

Adenocarcinoma

Mediastinal lymph node surgery

Final margin status

Local control

Metastatic at surgery

Later metastatic disease*

Death

Toxicity

Chest wall

10.6

No

Positive

No

Yes

Yes

No

None

Chest wall Superior sulcus

4.2 17.4

Yes No

Negative Positive

Yes Yes

No Yes

No No

No

None None

Chest wall

0.7

No

Negative

Yes

Yes

Yes

Chest wall

3.5

Dissected

Positive

Yes

Yes

Yes

Yes

Persistent pneumothorax None

15.7 9.7 1.8 16.0 5.8 6.6

Positive Positive Positive Positive Positive Positive Positive Positive Positive Negative Positive Negative

No No Yes No Yes No Yes Yes Yes Yes Yes No

Yes No No No No No No No No No No Yes

Yes No No Yes Yes Yes No Yes No No Yes Yes

Yes

Positive

No

Yes

Yes

Mediastinum Chest wall Chest wall Chest wall Diaphragmatic crus Chest wall Chest wall Mediastinum Mediastinum Mediastinum Chest wall Mediastinum

49.7 1.8 1.3 23.6 59.8

Yes Yes Sampled No No Dissected No Dissected Dissected Dissected No Sampled

Mediastinum

28.2

Dissected

Abbreviation: NSCGT = non-seminoma germ cell tumor. * For patients who underwent surgery for a metastatic lesion this represents metastases at other distant sites.

Yes Yes Yes No No No

None None None None None None None None None None None Radiation pneumonitiscough None

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No

Follow-up (months)

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42

Disease location

1117

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findings or extremely close margins at surgery that could not be defined histopathologically. All other patients had positive margins (defined as macroscopic margins or those less than 0.3 cm from the nearest excision margin). Radiotherapy details Thirty-one patients had a history of preoperative EBRT; the dose data were available for 25 patients. The majority of the patients undergoing preoperative EBRT had NSCLC (18); other histological findings were thymic carcinoma (3 patients), sarcoma (3 patients), metastatic adenocarcinoma (2 patients), carcinoid (2 patients), mesothelioma (2 patients), and thymoma (1 patient). The median dose to the affected area was 50 Gy (range, 44–68.4 Gy). Thirty-eight patients underwent chemotherapy prior to surgery; 27 of these patients also had EBRT prior to surgery. Of the 21 patients who did not have chemotherapy before surgery, 4 underwent neoadjuvant radiotherapy only. The dose prescribed varied depending on previous radiation exposure and location of the implant. The dose prescribed for de novo radiation was 100 to 150 Gy at 0.5 cm from the plane, with the higher dose used for the chest wall or parenchymal lesions and the lower dose used when implants were placed directly on vessels or nerves. The dose was decreased for patients who had undergone previous radiation to that site, ranging from 50 to 70 Gy. The median active area was 40 cm2 (range, 9–225 cm2). The median number of seeds per implant was 40 (range, 10–150), with a median activity per seed of 0.31 mCi (range, 0.14–0.55 mCi). The median implant activity was 16.0 mCi (range, 1.98–50.83 mCi), leading to a median activity/cm2 of 0.42 mCi/cm2 (range, 0.17–1.03 mCi/cm2). Survival and disease control Twenty patients (33.9%) underwent surgery for resection of a metastatic lesion, and the remaining 39 patients had primary lesions resected. Fourteen (35.9%) patients with primary lesions developed distant metastases at a later date. The median time to develop distant metastasis was 11 months (range, 1–30 months). There were 15.8% (6/39) of patients who had local failure in the group with nonmetastatic disease at presentation and 35% (7/20 patients) of patients who had local failure in the group that had metastatic disease at presentation (p = 0.11). The median time to develop local recurrence was 11 months (range, 1–39 months). Local control with negative margins was observed in 85% (17/20) of patients, and local control with close or positive margins was observed in 74% (29/39) of patients (p = 0.51). The histology findings, treatment, and outcomes for all patients are listed in Table 1. The outcome was assessed clinically and radiographically where appropriate. The 1-year and 2-year local control rates were 80.1% and 67.4%, respectively (Fig. 2). The 1-year and 2-year Kaplan-Meier estimated overall survival rates were 94.1% and 82.0%, respectively (Fig. 3). No perioperative mortality was observed. One grade-2 toxicity incident was identified as a cough due to radiation pneu-

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monitis at 5 months after implant. Grade-3 to -4 toxicity at all sites was 10.2% to 11.9% at 12 months (due to the uncertainty of one complication). No grade-1 to -4 toxicity was observed after 1 year. The specific toxicities were esophageal/bronchial fistulas (3 patients), radiation pneumonitis (1 patient), hydropneumothorax (1 patient), persistent pneumothorax (1 patients), and possible aortic rupture (1 patient). Of these patients, 4 patients underwent extensive mediastinal dissection (3 had fistulas and 1 had possible aortic rupture), 2 patients underwent mediastinal nodal sampling (both for pneumonitis), and 2 patients did not have a mediastinal intervention (both were pneumonothoraces). Five patients had positive excision margins (3 patients had fistulas, 1 had hydropneumothorax, and 1 had possible aortic rupture), and the margins of the remaining patients were negative. One patient who developed a bronchopleural fistula had had a radiotherapy implant placed directly over the bronchial resection margin at the time of tumor resection, and the bronchial margin had not been reinforced with muscle or similar tissue substitute, as was the case with other patients within this series. This fistula occurred 80 days after surgery, with extensive mediastinal dissection in a patient who had undergone chemoradiation preoperatively. There was no evidence of disease recurrence at the time of fistula formation; unfortunately the patient’s condition deteriorated, and the patient died before repair was possible. The remaining two fistulas were in patients with mediastinal carcinoid, who had received neoadjuvant chemoradiation. At the time of surgical resection, each tumor was grossly adherent to the esophagus. The esophageal wall was partially resected at the area of adherent tumor in an attempt to produce negative margins. The subcarinal space in both patients was extensively dissected. Both of the fistulas were repaired, but unfortunately, both of the patients subsequently died. Neither patient had evidence of local disease progression at the time of death. DISCUSSION This review shows generally low toxicity for interstitial planar 125I seed implantation after incomplete or close resection of thoracic tumors in a variety of tumor histologies in highly selected patients. Generally, permanent implantation of 125I seeds can be safely used in areas where the total dose of radiation received is usually limited by significant late toxicity, such as directly on pulmonary tissue or in close proximity to the spinal cord. Two patients developed fistulas following brachytherapy implantation on a partially resected esophagus with extensive subcarinal space dissection. Fusion dosimetry for these patients revealed high doses to small volumes of esophagus and close proximity of the implant to previously irradiated critical normal tissue (6). Another patient, in whom a small volume of previously irradiated bronchial resection margin received a highly localized dose of radiation, developed a fistula in the setting of extensive mediastinal dissection. Complete surgical resection is the gold standard for the curative treatment of localized lung cancer; however, it is not always feasible. Since 1957, brachytherapy implants have

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Fig. 2. Kaplan-Meier estimate data show local control for all patients following brachytherapy implantation.

Fig. 3. Kaplan-Meier estimate data show overall survival for all patients following brachytherapy implantation.

been used in thoracic surgical procedures where oncologic margins are not achievable (7). The isotopes, surgical techniques, and brachytherapy dosimetry have been refined since then, but the basic concept of combining a localized radiotherapy boost in a highly conformal manner with incomplete surgical resection to improve local disease control remains the same. Retrospective series have shown improved local control with minimal toxicity in comparisons of incomplete surgical resection combined with thoracic brachytherapy versus surgery without brachytherapy. Other retrospective series have shown high local control in the setting of incomplete resection and brachytherapy implantation (2). The findings of our review are compatible with those studies showing high local control and overall survival in this heterogeneous group of patients who would traditionally have a poor prognosis due to their advanced disease. The use of brachytherapy seeds in cases of early-stage thoracic malignancy has increased recently with a multiinstitutional Phase III trial (American College of Surgeons Oncology Group [www.acosog.org] Z4032). This study examines patients undergoing sublobar resection for early-stage lung cancer, randomized to receive 125I brachytherapy implantation or not to receive brachytherapy. The single-institution Phase II studies leading up to this protocol have shown safety and good local control by adding brachytherapy seed implants after a sublobar or wedge resection. In this type of procedure, the seeds are implanted directly in lung tissue and might not deliver any dose to any other structure, thus decreasing toxicity. Although found to be safe and with minimal side effects, the efficacy and toxicity profiles for 125I brachytherapy implantation for early-stage lung cancer may be different than 125I brachytherapy implantation for locally advanced lung cancer, as in this current series. Generally, permanent implantation of 125I seeds can be safely used in areas where the total dose of radiation received is usually limited by significant late toxicity, such as directly

on pulmonary tissue or in close proximity to the spinal cord (8) or aorta (9). The higher tolerance of healthy tissues to brachytherapy than to EBRT may be due to the rapid falloff of the brachytherapy dose and the small volumes irradiated. However, in two of the patients who developed severe late healthy tissue toxicity in this series, the brachytherapy implant was placed directly on a partially resected esophageal wall in the setting of extensive subcarinal space dissection. Disruption of the natural spacers caused a high localized dose to be delivered to previously irradiated tissue. It may be that mucosa previously exposed to chemoradiation responds differently to subsequent injury secondary to brachytherapy than other radiosensitive tissues such as that of the spinal cord. All of the fistulas occurred in patients who had received neoadjuvant chemoradiation. Esophageal fistulas are a recognized complication of mediastinal EBRT with or without intraluminal brachytherapy, occurring in 0 to 50% of cases (10–13). Retrospective series of patients with lung cancer, including patients with mediastinal brachytherapy implants, have reported rates of fistula formation up to 10% (7, 14). The patients in the present series who underwent radiotherapy all had preoperative radiotherapy, either as a radical treatment with subsequent surgery for local failure or as part of a planned down-staging strategy. In a phase II study of 75 patients with stage II NSCLC, including some T4 patients, undergoing preoperative chemoradiation followed by thoracotomy without a brachytherapy boost, the rate of grade-3 or -4 complication was 11% (8/75 patients), of which the majority (6 patients) were believed to be postsurgical complications (15). Fistula formation was not reported in this group of patients at a median follow-up of 68 months. A previous pilot trial (3) added a 125I or palladium-103 planar implant for locally advanced lung cancer with a local control of 78%. Although that study had a small number of patients (12), the pilot trial suggested that the addition of planar brachytherapy implantation improves local control. The

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current study shows that the addition of 125I planar implantation to therapy for thoracic malignancy has excellent local control, high overall survival, and low toxicity. Further prospective study is warranted. If these outcomes continue to hold, patients who would not be considered eligible for surgery due to its proximity to critical structures may be considered for surgical resection plus an 125I planar brachytherapy implant. CONCLUSIONS The low toxicity and high local control results suggest that brachytherapy implantation may be safe and provide

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improved outcomes in the setting of incomplete surgical resection of thoracic tumors, although a longer followup is necessary in this heterogeneous group of patients. The extremely good 1- and 2-year survival rates may also reflect careful surgical selection for this extensive surgery. Care should be taken in unusual situations where natural tissue planes have been disturbed and may decrease the normal tissue spacing required to decrease the dose intensity of a brachytherapy implant. The effect of neoadjuvant treatment on the sensitization of healthy tissues must be carefully considered before placing a brachytherapy implant.

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brachytherapy in cancer of the lung. Brachytherapy 2008;7: 50–54. Hama Y, Uematsu M, Shioda A, et al. Severe complications after hypofractionated high dose rate intracavitary brachytherapy following external beam irradiation for oesophageal carcinoma. Br J Radiol 2002;75:238–242. Fukuhara K, Osugi H, Tokuhara T, et al. Surgical repair of esophagobronchial fistula caused by radiation injury. Hepatogastroenterology 2004;51:754–756. Kuliszkiewicz-Janus M, Mazur G, Gabrys K, et al. Tracheoand broncho-esophageal fistulas in Hodgkin’s disease. Acta Haematol 1993;24:71–75. Okawa T, Dokiya T, Nishio M, et al. Multi-institutional randomized trial of radiotherapy with and without intraluminal brachytherapy for esophageal cancer in Japan. Int J Radiat Oncol Biol Phys 1999;45:623–628. Hilaris BS, Dattatreyudu N, Beattie EJ Jr., et al. Value of perioperative brachytherapy in the management of non-oat cell carcinoma of the lung. Int J Radiat Oncol Biol Phys 1983;9: 1161–1166. Kunitoh H, Kato H, Tsuboi M, et al. Phase II trial of preoperative chemoradiotherapy followed by surgical resection in patients with superior sulcus non-small-cell lung cancers: Report of Japan Clinical Oncology Group trial 9806. J Clin Oncol 2008;26:644–649.