Limited Lung Resection and Brachytherapy May Benefit Cancer Patients Whose Lung Function is Compromised

Abstract & Commentary

Synopsis: The standard of care for early lung cancer is surgery. However, in aged or frail patients, or in those whose pulmonary or cardiac status is compromised, radical surgery may be contraindicated. Alternatives are observation, external beam radiotherapy, and limited resection in conjunction with brachytherapy. The latter has the advantage of selectively irradiating the regions at highest risk for local recurrence, while sparing the adjacent normal lung. Investigators from Tufts University reported results in a series of 33 patients who were followed for a minimum of 20 months and concluded that brachytherapy might improve the outcome following limited resection for early lung cancer.

Source: Lee W, et al. Ann Thorac Surg. 2003;75:237-243.

Between 1993 and 2000, Lee and colleagues at the Tufts New England Medical Center performed implants of I-125 seeds arranged in suture strands after limited resection of early stage non-small-cell lung cancers in 33 medically compromised patients. These patients were not lobectomy candidates because of poor pulmonary function (n = 21), poor cardiac status (n = 6), or age older than 75 years with refusal to undergo lobectomy (n = 6). All patients had an FEV1 of < 1.0 liters or were intolerant of < 1 flight of stairs. Median patient age was 69 years (age range, 46-86). There were 35 resections, including 32 wedge resections and 2 segmental resections. All patients were staged preoperatively with CT scans, and intraoperatively, 19 underwent mediastinal nodal sampling/dissection while 3 had mediastinoscopy. There were 19 patients with T1N0 disease (58%), 10 with T2N0 disease (30%), and 1 each with T2N1, T1N2, T3N0, and unspecified disease. Lee et al performed a retrospective analysis in order to determine whether I-125 brachytherapy was effective at reducing lung cancer recurrences at the surgical margin.

Each limb of the wedge resection was approximately 6 cm in length. Gross surgical margins were > 1 cm. One to 3 I-125 strands with 10 seeds apiece were implanted at or near both sides of the resection margin. The prescribed dose was 125-140 Gy at 1-cm depth. The I-125 strands were secured in place with 3-0 silk sutures. The average strength per seed was 0.7 mCi.

Minimum follow-up in all patients was 20 months. There were no complications related to brachytherapy. There was 1 operative death related to ARDS. Implant quality was assessed via orthogonal x-rays or CT-based 3D reconstruction. Patients were assessed clinically with a chest x-ray during the follow-up period. Local recurrence was defined as failure at the resection margin, and regional recurrence was a failure at either the mediastinum, chest wall, or ipsilateral lung. The overall recurrence rate for the entire group was 30%, including 5 locoregional recurrences (15%), 2 distant recurrences (6%), and 3 with both (9%). Among T1N0 patients, 36% developed locoregional recurrences, including 2 with local recurrences (10.5%) and 5 (26%) with regional failures. There were 4 other regional recurrences (12%). Median overall survival for the entire group was 45 months. The projected 5-year disease-free survival (DSF) for T1N0 patients was 77%, and it was 53% for the T2N0 patients. For the whole group, the projected 5-year DFS rate was 61%.

Lee et al concluded that their results were comparable to those in the literature and that limited resection accompanied by brachytherapy is a reasonable compromise in patients who are not suitable for lobectomy. Compared to nonoperative management (ie, external beam radiotherapy) there is more lung sparing. Longer follow-up is needed to validate whether brachytherapy indeed reduces the incidence of local recurrence following wedge resection for early lung cancer.

Comment by Edward J. Kaplan, MD

Wedge lung resections are known to be plagued by local recurrences, as reported by the Lung Cancer Study Group in their published randomized trial results1 cited by Lee et al in the above study. In general, survival following lobectomy was cited by Lee et al as being in the 40-75% range and 13-21% following definitive radiotherapy. The latter range seems somewhat low for modern RT series. For example, data from M.D. Anderson Cancer Center included 3-year local control rates of 89% and 61% for medically inoperable T1 and T2 patients, respectively, and DFS rates of 49% and 47% with doses > 60 Gy.2 Sibley and associates from Duke University published an overview of 10 studies where primary RT was used to treat medically inoperable stage I NSCLC patients and reported that 30% of patients die of distant metastases, while another 30% die due to local failure. Trials of dose escalation were suggested.3

Interestingly, the Japanese have conducted retrospective analyses of 2 different forms of dose escalation. Uematsu et al treated 50 patients from 1994-1999 with CT-guided frameless stereotactic radiotherapy delivering 50-60 Gy in 5-10 fractions with or without supplemental conventional RT and reported a 3-year DFS of 88%.4 Fukumoto et al used small-volume hypofractionated image-guided RT to deliver 48 or 60 Gy in 8 fractions to patients with stage I tumors. They reported a 67% 2-year DFS rate at 24 months follow-up.5 Based on such studies, dose escalation to limited lung volumes does appear to offer a benefit. Therefore, although using radioactive seeds in sutures is not a new idea,6-7 it may offer a timely, convenient, and effective way of sterilizing the surgical margin in the setting of minimally invasive surgery, as in wedge resections that might be done thoracoscopically.

Dr. Kaplan is Acting Chairman, Department of Radiation Oncology, Cleveland Clinic Florida, Ft. Lauderdale, FL and Medical Director, Boca Raton Radiation Therapy Regional Center, Deerfield Beach, FL.

References

1. Lung Cancer Study Group. Ann Thorac Surg. 1995;60:615-623.

2. Kupelian PA, et al. Int J Radiat Oncol Biol Phys. 1996; 36:607-613.

3. Sibley GS, et al. Cancer. 1998;82:433-438.

4. Uematsu M, et al. Int J Radiat Oncol Biol Phys. 2001; 51:666-670.

5. Fukumoto S, et al. Cancer. 2002;95:1546-1553.

6. Scott WP. Am J Roentgenol Radium Ther Nucl Med. 1975;124:560-564.

7. Palos B, et al. Int J Radiat Oncol Biol Phys. 1980;6: 381-385.