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Ann Thorac Surg 2008;85:S733-S736. doi:10.1016/j.athoracsur.2007.11.049
© 2008 The Society of Thoracic Surgeons
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Supplement: The Minimally Invasive Thoracic Surgery Summit

Wedge Resection and Brachytherapy for Lung Cancer in Patients With Poor Pulmonary Function

Robert J. McKenna, Jr, MDa,*, Ali Mahtabifard, MDa, Johnnie Yap, MDa, Robert McKenna, III, BSb, Clark Fuller, MDa, Amin Merhadi, MDa, Behrooz Hakimian, MDa

a Department of Thoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, California
b The University of Pennsylvania, Philadelphia, Pennsylvania

* Address correspondence to Dr McKenna, Cedars-Sinai Medical Center, 8635 W Third, Ste 975W, Los Angeles, CA 90048 (Email: mckennar{at}cshs.org).

Presented at the Minimally Invasive Thoracic Surgery Summit, New York, NY, June 8–9, 2007.


Dr Robert J. McKenna, Jr discloses that he has a financial relationship with Ethicon.

 

   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
Background: Although lobectomy is the standard for lung cancer because a wedge resection has a 3 to 5 times greater incidence of local recurrence, poor pulmonary function may preclude lobectomy. For these patients, low-dose-rate brachytherapy has recently been used to decrease local recurrence after sublobar resection. Current techniques expose operating room personnel and patient contacts to unnecessary radioactivity risks. We present our technique of sublobar resection combined with afterload catheters for high-dose-rate brachytherapy for patient benefit with minimal risk to others.

Methods: Forty-eight patients (25 women, 23 men) underwent wedge resection, node dissection, and brachytherapy. A remote-afterloading high-dose-rate unit for radiation produced a median dose of 2450 cGy (350 cGy per fraction over 7 fractions twice daily for 4 days). The dose was prescribed to 1 cm deep to the stapled line. Biologically, this dose is approximately 5000 cGy and above (180 cGy/d equivalent) at the depth of 5 mm in reference to the resection margin.

Results: Two patients died. The length of mean stay was 5.5 days (median, 5 days). Complications included prolonged air leak in 5 patients, atrial fibrillation in 5, pneumonia in 3, trapped lung in 2, and 1 each with empyema, bleeding, and recurrent laryngeal nerve injury. Three patients required a blood transfusion. Within the follow-up of 1 to 27 months, there were four recurrences.

Conclusions: Wedge resection and brachytherapy appears to be a reasonable treatment for patients with lung cancer and pulmonary function that prohibits a lobectomy.

Some patients with cancer in the lung need an alternative treatment to a lobectomy when pulmonary function is poor. A lobectomy is preferred over a wedge resection for a stage I lung cancer because the latter has a higher local recurrence rate and a lower survival [1–5]. For patients with pulmonary function that precludes a lobectomy, alternative treatment options include radio frequency ablation, external beam radiation, stereotactic radiation, and wedge resection with brachytherapy.

Brachytherapy after wedge resection has been shown to reduce the rate of local recurrence after wedge resection alone [6–8]. One approach for the brachytherapy has been to sew radioactive seeds in a mesh that is then placed on the lung at the resection margin [6, 8]. As an alternative, afterload catheters can be sewn on the resection margin and the radioactive seeds are passed into the catheters for short time intervals for a few days, and then the catheters are removed. This article presents our experience with the latter approach.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
This project was approved by the Institutional Review Board at Cedars-Sinai Medical Center. The series is a review of all patients who underwent video-assisted thoracic surgery (VATS) pulmonary resection and brachytherapy at Cedars-Sinai Medical Center for cancer in the lung. The patients were identified from a prospective database for all operations performed by the service. The charts were reviewed for all patients to collect the demographics and results. This treatment was offered to these patients because their pulmonary function precluded a lobectomy and the location of their tumors was not amenable to a segmentectomy.

Operative Procedure
Under single-lung, general anesthesia, VATS is performed with a 5-mm 30° thoracoscope introduced in the eighth intercostal space the mid-axillary line, a 2-cm incision is made in the sixth intercostal space in the mid-clavicular line, and 2-cm incision is made in the fourth intercostal space in the mid-axillary line. An additional 1-cm incision may be made in the auscultatory line posteriorly for added retraction.

If a tissue diagnosis was not obtained preoperatively, a wedge resection of the mass is performed. The intent of all operations is to resect the tumors with a 1- to 2-cm margin. For patients with primary lung cancer, a lymph node dissection is performed.

Three afterload catheters are placed through separate skin incisions and sewn to the lung with 3-0 polydioxanone suture. One catheter is placed on the staple line, and the other 2 catheters are placed 1 cm away from and parallel to the staple line (Fig 1). The catheters have a closed end inside the chest and an open end outside the chestt, which allows a robot to pass the radioactive seeds into position within the patient. During the operation, clips are placed on the staple line to mark the resection margins closest to the tumors for computed tomography (CT) scan planning of the brachytherapy treatments.


Figure 1
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  		Fig 1. Intraoperative photograph shows the staple line from the wedge resection and the afterload catheter sutured to the staple line. Two additional catheters are placed parallel to the first catheter.

 
The procedures are typically performed on a Monday so that the brachytherapy can be performed twice daily Tuesday through Friday. The catheters are removed after the last treatment on Friday, and the intent is to discharge the patients on Friday after the last treatment.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
From March 2004 through April 2007, wedge resection and brachytherapy was performed in 48 patients (25 women and 23 men) with lung cancer. Their age was 74.7 ± 10.03 years (range, 56 to 90 years; Table 1). The final pathalogic staging for the tumors is summarized in Table 2. There were no conversions to thoracotomy. Three patients required blood transfusion.


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  		Table 1 Summary of the Reasons Why a Lobectomy Was Not Performed
 

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  		Table 2 Staging Information for the 48 Patients Who Underwent Wedge Resection and Brachytherapy for Lung Cancer
 
In one additional patient, the intent was to follow the protocol, but the robot could not place the seeds into position. A guidewire was passed through the catheter so it was patent. The seeds have such a high dose of radiation that they could not be passed by the radiation therapist. Therefore, lower-dose seeds placed by the radiologist were left in place for 4 days, and the patient was placed in an isolation room.

Hospital Course
The mean length of stay was 5.5 days (median, 5 days). The chest tubes in 42 patients were removed on postoperative day 5 after the afterload catheters were removed. Five patients were discharged with chest tubes and a Heimlich valve. The patients remained in the hospital for the twice-daily brachytherapy treatments except for 1 patient lived near the hospital and chose to go home and return to the hospital for outpatient brachytherapy treatments.

Mortality
Two deaths occurred death within 30 days of operation or before hospital discharge. An 88-year-old woman and a 90-year-old man had no air leaks at the end of the procedures, but large air leaks developed postoperatively and they died of respiratory failure and pneumonia on postoperative days 10 and 7, respectively.

Morbidity
No complications occurred in 37 patients (71.2%), and those that occurred in the other 15 patients are summarized in Table 3. One patient with a prolonged air leak had pleural symphysis due to a prior thoracotomy and diffuse emphysema that resulted in large intraoperative air leaks that could not be controlled with all conventional measures, so a postoperative Heimlich valve was expected. Another patient with a prolonged air leak had previously undergone a lobectomy on the same side. In both of these patients, the lung would not expand postoperatively to fill the pleural cavity. Two other patients presented with trapped lungs in the lower chest, and reoperation was required to get the lungs to expand to fill the pleural space. An operation for bleeding was required in 1 of 3 patients who needed a blood transfusion.


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  		Table 3 Complications That Occurred in 15 Patients
 
Final Pathology
The final pathology report was adenocarcinoma in 32 patients, squamous cell carcinoma in 7, adenosquamous in 4, bronchioloalveolar carcinoma in 3, carcinosarcoma in 1, and large cell in 2. The final pathologic staging for the primary lung cancers is summarized in Table 1. Preoperatively, all patients were stage I by CT and positron-emission tomography scans, but unsuspected N1 and N2 disease was found in 1 and 4 patients, respectively.

Follow-Up
The mean initial follow-up was 13.5 months (range, 1 to 32 months), with three cases of local recurrence to date. Eight patients have died of recurrent cancer, and 4 additional patients are alive with disease.


   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
The standard operation for localized lung cancer has been lobectomy. Warren and Faber [1] and Ginsberg and Rubinstein [2] reported that a lesser resection (wedge or segmentectomy) has a higher incidence of local recurrence and a lower overall survival compared with standard lobectomy. Although a lobectomy is the standard surgical treatment for lung cancer, there may be some patients for whom a lesser resection is appropriate, and an alternative treatment is needed for patients who physiologically cannot tolerate a lobectomy. We do perform segmentectomy for patients who cannot tolerate a lobectomy. The patients in this series had tumors in locations that were not amenable to segmentectomy, so the only surgical option was a we[dge resection.

In our series, two deaths occurred in very elderly patients. The cause of their deaths was severe air leaks and respiratory failure. Perhaps this procedure should not be entertained if the patients have emphysema with severe bullous changes on the CT scan. This bullous disease also contributed to the high use of the Heimlich valve.

Kodama and colleagues [3] reviewed a 10-year experience at the Osaka Medical Center with intentional limited resection, involving extended anatomic segmentectomy, in stage IA non-small cell lung carcinoma (NSCLC) combined with regional node dissection. Survival at 5 years was 93%, no different from a similar group of patients undergoing the standard operation (lobectomy and mediastinal node dissection) during the same time period. In 2002 Yoshikawa and colleagues [4] reported excellent results in a multi-institutional prospective trial of extended segmentectomy for small lung tumors. Emphasis was placed on careful patient selection and the importance of a wide surgical margin to minimize the chance of local recurrence. These procedures using brachytherapy are for patients for whom wide surgical margins are not possible so that something needs to be done to reduce the risk of local recurrence.

In an effort to decrease local recurrence and hopefully increase survival after wedge resection alone, adjuvant external beam radiation therapy has been tried. Unfortunately, that did not reduce local recurrence rates or improve survival [8].

Because local recurrence continues to be a problem for patients who cannot undergo a lobectomy and because external beam radiation has not helped, adjuvant intraoperative brachytherapy has been used [6, 7]. A comparison of 101 patients with clinical stage 1 NSCLC and marginal pulmonary function treated with wedge resection plus brachytherapy was compared with 102 patients treated with wedge resection without brachytherapy [6].The difference in morbidity, mortality, or survival was not significant; however, the brachytherapy group had a lower incidence of local recurrence (2% vs 19%, p = 0.0001). Pulmonary function in the brachytherapy group remained unchanged after the operations, and there were no cases of radiation pneumonitis.

Brachytherapy treatment involved embedding iodine 125 sutures in a Vicryl polyglactin mesh (Ethicon, Somerville, NJ) with appropriate spacing to achieve a prescribed dose of 10,000 to 12,000 cGy to a 0.5-cm depth. These sutures were ordered in advance from the manufacturer (Amersham Health, Princeton, NJ). The 125I implant was then secured over the staple line by the thoracic surgeon with an approximate 2-cm margin. The mesh was secured to the lung with interrupted 3-0 silk sutures [6, 7]. This technique uses low dosimetry radiation (LDR).

Although the use of brachytherapy represents a small risk, it does require special precautions for health care personnel and contacts with patients, as set by the Cancer and Leukemia Group B (CALGB) protocol [6, 7]:

• In the operating room, radiation therapists handle the seeds with special instruments. After the seeds have been secured in place, the radiation dose at 1 m is measured and recorded.
• The operating room is surveyed to ensure that there are no loose or lost radioactive seeds.
• Postoperatively, the patients are in isolation rooms for the duration of their hospitalization.
• No pregnant women are allowed in the area during or after seed implantation.
• Discharge radiation safety instructions are given to patients and families. These instructions include the warning that children may not sit in the patient’s lap for more than 5 minutes per day for 6 months after the procedure.
• There are no restrictions regarding toilet facilities, linen, clothing, dishes, or shaking hands with the patients.

The precautions we have presented here for the current intergroup protocol may be overstated, but they are the current recommendations. If the concerns are proven to be unfounded, then this argument for our protocol will not be an issue.

Because, in general, brachytherapy after wedge resection appears to have advantages—but there are also disadvantages to leaving the radioactive seeds in patients—an alternative approach for the technique of brachytherapy may be advantageous. Afterload catheters were placed intraoperatively in the patients in this series. No radioactive seeds were in the operating room, so there was no radiation exposure to the operating room personnel. Postoperatively, no special postoperative precautions are required for health care personnel and patient visitors. This technique uses high dosimetry radiation (HDR) for a short time.

The experience with both approaches is relatively new. There is no randomized comparison and not enough long-term data for either approach to prove if one method is superior to the other. The American College of Surgeons Oncology Group (ACOSOG) 4032 is a current intergroup, randomized prospective trial to determine if placing radioactive seeds in a mesh reduces local recurrence or affects survival. Perhaps a future trial can compare the efficacy of these two methods for brachytherapy.

Not enough data are currently available to determine the relative efficacy of LDR vs HDR. The total radiation dose delivered by LDR is larger than our dose for HDR; however, the overall dose of radiation for LDR is administered over several half-lives of radioactive sources. One should question whether the last couple of half-lives contribute any significant tumoricidal doses to the suture line. Also, the stability of impregnated mesh with LDR placed at time of surgery is not something that has been answered. Do we know that the LDR seeds or mesh do not migrate over time? We know that the initial experience with prostate brachytherapy raised some concern about seed migration. This is not an issue with HDR because the CT scan confirms the location of the catheters and seeds. The biologic activity of HDR fractionation is different, and extrapolation from gynecologic malignancies can best determine equality of the two measures.

The technical procedures of brachytherapy with radioactive seed placement in mesh or by afterload catheters appear to be comparable. The same wedge resection and node dissections are performed. Both procedures require suturing of the catheters or mesh to the lung. Both can be performed with an open or VATS procedure.

The long-term results of the two techniques are currently not available. Santos and colleagues [6] reported that brachytherapy with seeds reduced the incidence of local recurrence after wedge resection from 19% to 2%. The short-term results from brachytherapy with afterload catheters look encouraging, but longer follow-up is needed.

In conclusion, the short-term results indicate that wedge resection and brachytherapy with afterload catheters appears to be a safe treatment for lung cancer in patients where a lobectomy is not advisable because of poor pulmonary function. Long-term follow up is needed to determine the cure rate for wedge resection and brachytherapy and which method is preferable.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Warren W, Faber P. Segmentectomy versus lobectomy in patients with stage I pulmonary carcinoma J Thorac Cardiovasc Surg 1994;107:1087-1094.[Abstract/Free Full Text]
  2. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1N0 non-small cell lung cancer Ann Thorac Surg 1995;60:615-621.[Abstract/Free Full Text]
  3. Kodama K, Doi O, Higashiyama M, Yokouchi H. Intentional limited resection for selected patients with T1N0M0 non-small-cell lung cancer: a single-institution study J Thorac Cardiovasc Surg 1997;114:347-353.[Abstract/Free Full Text]
  4. Yoshikawa K, Tsubota N, Kodama K, Ayabe H, Taki T, Mori T. Prospective study of extended segmentectomy for small lung tumors: the final report Ann Thorac Surg 2002;73:1055-1059.[Abstract/Free Full Text]
  5. Okada M, Yoshikawa K, Hatta T, et al. Is segmentectomy with lymph node assessment an alternative to lobectomy for non-small lung cancer of 2 cm or smaller Ann Thorac Surg 2001;7:956-960.
  6. Santos R, Colonias A, Parda D, et al. Comparison between sublobar resection and 125 I brachytherapy following sublobar resection in high-risk patients with stage 1 Non-small cell lung cancer Surgery 2003;134:691-697.[Medline]
  7. Lee W, Daly BD, DiPetrillo TA, et al. Limited resection for non-small cell lung cancer: observed local recurrence with implantation of I-125 brachytherapy seeds Ann Thorac Surg 2003;75:237-242.[Abstract/Free Full Text]
  8. Shennib H, Bogart JA, Herndon J, et al. Thoracoscopic wedge resection and radiotherapy for T1N0 non-small lung cancer: preliminary analysis of a Cancer and Leukemia Group B and Eastern Oncology Group phase II trial Int Radiat Oncol Bio Phys 2000;48(3 suppl)abstract 240.




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