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Ann Thorac Surg 1998;66:231-233
© 1998 The Society of Thoracic Surgeons

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Original articles: general thoracic

Resection of pulmonary metastases in six patients with disease-free interval greater than 10 years

^a Department of Surgery, National Sanatorium Nishi-Gunma Hospital, Shibukawa, Gunma, Japan

Accepted for publication March 6, 1998.

Address reprint requests to Dr Kamiyoshihara, National Sanatorium Nishi-gunma Hospital, 2854 Kanai, Shibukawa, Gunma 377-0027, Japan
e-mail: (kamiyosi{at}sa2.so-net.ne.jp)

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. The relationship between disease-free interval (DFI) and prognosis has been discussed; however, there is little information on long-term DFI. In this study, we surveyed the cases of pulmonary metastases with DFI greater than 10 years.

Methods. Between January 1980 and December 1995, we saw 6 patients with DFI greater than 10 years. All the patients had a histopathologic diagnosis of pulmonary metastases based on surgical resection, and the patients’ characteristics and clinical course were reviewed.

Results. The median age was 63 years. Primary sites were breast in 2 patients, and one case each of skin, colon, thyroid, and bladder. The numbers of metastases were one in 4 patients and two in 2 patients. The median DFI was 134 months (range, 127 to 235 months). The median tumor-doubling time was 227 days (range, 80 to 815 days). All the patients underwent a lobectomy. Three patients with metastases from the bladder, colon, and breast died of recurrence. One patient with metastasis from the thyroid died of heart failure. Two patients with metastases from breast and skin cancer survived for more than 3 years.

Conclusions. Early death occurred regardless of the long DFI, suggesting that intensive follow-up is mandatory for patients with DFI greater than 10 years.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
The disease-free interval (DFI) is defined as the time elapsing from the diagnosis of primary tumors to the diagnosis of pulmonary metastases. The relationship between the DFI and prognosis has been discussed by many authors [1–4]. We also reported pulmonary metastatic tumors in the lung, from which we concluded that no significant difference was noted in survival for two patient groups with DFI longer or shorter than 5 years [5]. However, there is little information on the clinical course of patients with a very long DFI, especially greater than 10 years. In this study, we surveyed the characteristics and prognosis of pulmonary metastases with a DFI of greater than 10 years.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
Between January 1980 and December 1995, 32 consecutive patients with pulmonary metastases from organs other than the lung underwent surgical treatment. Of the 32 patients, there were 6 patients with a DFI of more than 10 years, ranging from 127 to 235 months (median, 134 months). All the patients had a histopathologic diagnosis of pulmonary metastases based on surgical resection. The resected specimens from metastasectomy were checked against paraffin-embedded specimens from the first operation. At the time of the first operation for the primary site, complete tumor resection was performed in all 6 patients. The clinical features and the disease course of these patients were reviewed.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
Clinical features
Of the 6 patients, 3 were men and 3 were women. The average age was 63.2 years, ranging from 55 to 72 years. Metastatic nodules represented several pathologic cell types. The primary sites were as follows: two in breast (adenocarcinoma and mucinous carcinoma), and one each of skin (leiomyosarcoma), colon (adenocarcinoma), thyroid (papillary carcinoma), and bladder (transitional cell carcinoma). Four of the 6 patients had solitary pulmonary metastasis, and 2 had two metastases. Metastatic nodules were in a single lung in the 2 patients having more than one metastasis. The preoperative diagnosis based on transbronchial or percutaneous lung biopsy indicated primary pulmonary carcinoma in the 6 patients. Computed tomographic scanning of the chest demonstrated no mediastinal lymph node enlargement (1 cm or greater in short-axis diameter). These patients underwent a lobectomy associated with lymph node dissection. One patient with pulmonary metastasis from the breast had positive nodes. All 6 patients had a curative resection. Four patients received adjuvant treatment after pulmonary resection (Table 1).

Prognosis
After surgical treatment of metastatic lesions, recurrence occurred in 3 patients; bone, bilateral lung, and ipsilateral lung (Table 1). Low pulmonary function in these 3 patients precluded surgical treatment. Cancer death occurred in 4 patients: patient 1 died at 16 months, patient 2 at 43 months, patient 4 at 5 months, and patient 5 died of myocardial infarction at 61 months. The remaining 2 patients (numbers 3 and 6) have been alive for 15 and 46 months, respectively (Fig 1).

View larger version (21K): [in this window] [in a new window]   Fig 1. Clinical course of each patient. (P = surgical treatment for primary site; M = surgical treatment for metastasis to lung; rec = recurrence; MI = myocardial infarction.)

Patient 3, who had the shortest TDT, has survived for 15 months. Patients 2, 5, and 6, with TDTs of more than 100 days, survived for more than 3 years (Fig 1).

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
Marincola and Mark [1] reported that Cox covariate analysis showed statistically significant correlation between DFI and survival in pulmonary metastases (p < 0.05). However, no significant difference was noted in patients’ survival rate divided by the median DFI (p = 0.15) or by DFI longer or shorter than 1 year (p = 0.08). The majority of reports [2–4] concluded that there was no relationship. However, previous studies had some potential inaccuracies in the methods of analysis caused by an error in calculating the DFI, and also because patients were divided arbitrarily into two groups based on a DFI of longer or shorter than a few years.

In the situation involving the calculation error, there was a difference in time between the occurrence of pulmonary metastases and the detection of metastatic lesions. However, as it is impossible to correspond with this interval, this difference may be acceptable, provided that the tumor size of pulmonary metastases is not large. In the current series, patient 1 had a large-sized tumor when the pulmonary metastasis was detected. Therefore, it may not be completely accurate to regard this patient as having a DFI of more than 10 years.

In the second situation, in many studies [1–4] survival rates were calculated according to the actuarial curve or the Kaplan-Meier table for patients with a DFI period of longer or shorter than a few years. The difference in survival was analyzed by a statistical test for equality of the survival curve. For some primary sites, the prognosis after surgical treatment for pulmonary metastasis was good at 1 year but worse at more than 3 years [1, 2]. The question arises as to whether it is scientifically adequate to divide a series of patients by only a few years. The DFI is one of the clinical factors used to directly evaluate the biologic behavior of tumors. Could a long DFI become one of the important prognostic factors?

In many reports [1–4], a good prognosis was obtained in patients with a solitary and unilateral pulmonary metastasis. In our series, 4 patients had a solitary metastasis and 2 patients had two metastases. The metastatic lesion was localized with no diffuse metastasis [1–4, 6]. This series was biased because of selection of resected cases. There was no report, however, in which patients with a DFI of more than 10 years had numerous or diffuse metastases.

Collins and coworkers [7] reported that the growth rate in pulmonary metastases ranged from 11 days to 164 days (median, 41.5 days) in a doubling time, and was classified by the duration of the TDT; "slow-growing tumor" of more than 75 days of TDT and "rapid-growing tumor" of less than 25 days of TDT. The measurable TDT in our study was more than 75 days, which is classified as slow-growing tumor.

Some authors [8, 9] reported that breast cancer had a long TDT and DFI, but sarcoma did not. In our series, 2 patients with breast cancer had a long TDT (323 days and 815 days, respectively) and DFI (128 days and 236 days, respectively), suggesting that after surgical treatment for breast cancer, patients should be monitored for a longer time.

We assumed that patients with a DFI of greater than 10 years have a good prognosis after adequate surgical intervention. Recurrence did occur however in several patients within a short period after pulmonary resection. Some authors [7, 8, 10, 11] reported that the TDT was affected by environment or properties of tumors. Sakai and associates [3] reported that the growth rate increased rapidly after resection of metastatic lesions in spite of a long DFI (144 months and 162 months). There is a possibility that latent metastasis may be activated by operative stress [12] and that surgical procedure causes dissemination of tumor cells to surrounding organs.

Despite the DFI greater than 10 years in our series, the prognosis is not necessarily good. This suggests that continuous and intensive follow-up is mandatory after operation, in spite of the length of DFI; however, the current study includes too few patients to conclude this definitively. In future studies, we will be accumulating larger numbers of patients to demonstrate significant differences in characteristics or survival.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

1. Marincola F.M., Mark J.B.D. Selection factors resulting in improved survival after surgical resection of tumors metastatic to the lungs. Arch Surg 1990;125:1387-1393.[Abstract/Free Full Text]
2. Wilkins E.W., Head J.M., Burhe J.F. Pulmonary resection for metastatic neoplasms in the lung. Am J Surg 1978;135:480-483.[Medline]
3. Sakai T., Ikeda T., Nishimura Y. Results of resection of pulmonary metastases and analysis of long term survivors. Nippon Kokyuki Geka Gakkai Zasshi 1988;2:263-269.
4. Girard P., Baldeyrou P., Le Chevalier T., Le Cesne A., Brigandi A., Grunenwald D. Surgery for pulmonary metastases. Who are the 10-year survivors?. Cancer 1994;74:2791-2797.[Medline]
5. Kamiyoshihara M., Hirai T., Kawashima O., Ishikawa S., Morishita Y. The surgical treatment of metastatic tumors in the lung: is lobectomy with mediastinal lymph node dissection suitable treatment?. Oncol Rep 1998;5:453-457.[Medline]
6. Salsali M. Solitary pulmonary metastasis: an enigma. J Surg Oncol 1987;34:230-234.[Medline]
7. Collins V.P., Loeffler R.K., Tivey H. Observation on growth rates of human tumors. Am J Roentgenol 1956;76:988-1000.
8. Ishihara T., Kikuchi K., Ikeda T., Yamazaki S. Metastatic pulmonary disease: biological factors and mode treatment. Chest 1973;63:227-232.[Abstract/Free Full Text]
9. McDonald M.L., Deschamps C., Ilstrup D.M., Allen M.S., Trastek V.F., Pairolero P.C. Pulmonary resection for metastatic breast cancer. Ann Thorac Surg 1994;58:1599-1602.[Abstract]
10. Geddes D.M. The natural history of lung cancer: a review based on rates of tumour growth. Br J Dis Chest 1979;73:1-17.[Medline]
11. Usuda K., Saito Y., Sagawa M., et al. Tumor doubling time and prognostic assessment of patients with primary lung cancer. Cancer 1994;74:2239-2244.[Medline]
12. Sakata K., Kida T., Saji T., Tanemura H. Operative stress and cancer metastasis—an experimental study. Geka Chiryo 1987;57:466-467.

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