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ORIGINAL ARTICLE
Year : 2013  |  Volume : 9  |  Issue : 2  |  Page : 219-223

Clinical significance of radiofrequency ablation and metastasectomy in elderly patients with lung metastases from musculoskeletal sarcomas


1 Department of Orthopedic Surgery, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu-city, Mie 514-8507, Japan
2 Department of Interventional Radiology, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu-city, Mie 514-8507, Japan
3 Department of General Thoracic Surgery, Mie University Hospital, 2-174, Edobashi, Tsu-city, Mie 514-8507, Japan

Date of Web Publication13-Jun-2013

Correspondence Address:
Akihiro Sudo
Department of Orthopedic Surgery, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu-city, Mie 514-8507
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.113358

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 > Abstract 

Background: The incidence of sarcoma diagnosed in the elderly population may be rising due to the increasing life expectancy. The purpose of our study was to evaluate the efficacy of lung metastasectomy and radiofrequency (RF) ablation in elderly sarcoma patients (65 years or older) with lung metastases, compared with adult sarcoma patients younger than 65 years (20-64 years).
Materials and Methods: We retrospectively evaluated the clinical efficacy of metastasectomy and lung RF ablation in sarcoma patients with lung metastases.
Results: Between 2001 and 2010, lung metastases were detected in 66 adult patients with musculoskeletal sarcomas. Twenty-five patients with lung metastasis were elderly. Twelve of the 25 patients were treated with lung metastasectomy and/or RF ablation. In contrast, 41 patients were adult patients younger than 65 years. Twenty of these 41 patients were treated with lung metastasectomy and/or RF ablation. The 1 and 3-year survival rates after initial treatment for lung metastases were 81.8% and 38.4% in 12 elderly patients, respectively. Compared with the control group, the survival rate in the elderly patients was not significantly different.
Conclusion: We conclude that elderly sarcoma patients with lung metastases should always be considered for either metastasectomy or RF ablation.

Keywords: Elderly, lung metastasis, metastasectomy, radiofrequency ablation, sarcoma


How to cite this article:
Nakamura T, Matsumine A, Yamakado K, Takao M, Uchida A, Sudo A. Clinical significance of radiofrequency ablation and metastasectomy in elderly patients with lung metastases from musculoskeletal sarcomas. J Can Res Ther 2013;9:219-23

How to cite this URL:
Nakamura T, Matsumine A, Yamakado K, Takao M, Uchida A, Sudo A. Clinical significance of radiofrequency ablation and metastasectomy in elderly patients with lung metastases from musculoskeletal sarcomas. J Can Res Ther [serial online] 2013 [cited 2019 Sep 20];9:219-23. Available from: http://www.cancerjournal.net/text.asp?2013/9/2/219/113358


 > Introduction Top


Musculoskeletal sarcoma is a disease associated with aging. According to the Musculoskeletal Tumor Committee of the Japanese Orthopedic Association, the incidence of bone sarcomas peaks in the second decade and in the sixth and seventh decades of life, whereas the incidence of soft-tissue sarcomas peaks in the eight decades of life. [1],[2] Japan is rapidly aging and approximately 22.5% of the population is older than or equal to 65 years old. [3] Thus, the incidence of sarcoma diagnosed in the elderly population may be rising due to the increasing life expectancy in the Japanese population.

The lung is the most common site of metastatic disease in sarcoma patients. [4],[5] Approximately 30% of sarcoma patients will have isolated lung metastatic disease at some point in the course of their disease. [6] Chemotherapy has not been proven to increase survival after resection of lung metastases, [7],[8] and surgical resection of ling metastases has been considered the only therapeutic option to prolong patient survival. [9],[10],[11]

The 3-year survival rates following metastasectomy have been reported to be 25-54%. [9],[10],[11] However, metastasectomy in elderly sarcoma patients has been performed with considerable hesitation due to a lack of adequate respiratory reserve, cardiac dysfunction, high risk of postoperative complications, or other medial co-morbidities. Recently, lung radiofrequency (RF) ablation has been accepted as a relatively safe and useful therapeutic option for the treatment of unresectable nonsmall cell lung cancer and lung metastases. [12],[13],[14],[15],[16],[17] In our present study, we retrospectively evaluated the clinical efficacy of metastasectomy and lung RF ablation in elderly patients with lung metastases from sarcoma.


 > Materials and Methods Top


Study design

Our retrospective study was approved by our institutional review board, and informed consent was obtained from each patient. The purpose of our study was to evaluate the efficacy of lung metastasectomy and RF ablation in elderly sarcoma patients (65 years or older) with lung metastases, compared with adult sarcoma patients younger than 65 years (20-64 years) with lung metastasis.

The resectability of the lung metastases was judged by thoracic surgeons (M.T, A.S) after considering the tumor number and location, and the patient's lung function. The indication for metastasectomy was as follows: (a) no extra-pulmonary metastases; (b) primary tumor well controlled; and (c) possible complete resection of metastases.

The indications for lung RF ablation were judged by interventional radiologist (K.Y). The indication for RF ablation were as follows: (a) sarcoma patients with unresectable multiple lung metastases predicted to respiratory, cardiac, or other organ dysfunctions after metastasectomy; and (b) sarcoma patients who refused to undergo metastasectomy.

The pretreatment work-up included brain, lung, abdomen, and pelvic computed tomography (CT) scans with and without contrast medium. Magnetic resonance (MR) images of the primary resected regions with and without contrast enhanced images were acquired.

Patients

Between 2001 and 2010, lung metastases were detected in 66 adult patients (20-86 years) with musculoskeletal sarcomas. Twenty-five patients with lung metastasis were elderly. Twelve of the 25 elderly patients were treated with lung metastasectomy and/or RF ablation (elderly group).

Forty-one of the 66 patients with lung metastases were adult patients younger than 65 years. Twenty of these 41 patients were treated by metastasectomy and/or RF ablation (control group).

In the elderly group, the primary sarcoma originated from the soft tissue in 10 patients and from the bone in the other 2 patients. The 12 patients were histologically classified as follows: 4 leiomyosarcomas, 3 malignant fibrous histiocytomas (MFH), 2 extra-skeletal chondrosarcomas, 1 case each of myxofibrosarcoma, chondrosarcoma, and MFH of the bone. The elderly patients were seven males and five females with a mean age of 73 years (range, 66-86). Two patients had lung metastases at presentation. Eleven patients underwent surgical resection and one patient was treated with radiation for the primary tumor.

In the control group, the primary sarcoma originated from the soft tissue in 16 patients and from the bone in the other 4 patients. The 20 patients were histologically classified as follows: 4 synovial sarcomas, 3 MFH, 3 osteosarcomas, 2 malignant peripheral sheath tumors, 2 leiomyosarcomas, and 6 other tumors. The control group consisted of 12 males and 8 females, with a mean age of 40 years (range, 21-62). Seven patients had lung metastases at presentation. All 20 patients were treated by surgical resection for the primary tumor.

Metastasectomy was done under general anesthesia by thoracic surgeons. The operative approach included open thoracotomy (n=9) and video-assisted thoracic surgery (n=9) for lung metastases. The extent of lung resection was wedge (n=11) and lobectomy (n=7).

The patients were admitted to the hospital for lung RF ablation, which was performed under moderate sedation and local anesthesia. RF ablation was done by interventional radiologists. Real-time CT fluoroscopy (X-Vigor or Aquilion, Toshiba, Tokyo, Japan) was used to place the RF electrode in the tumors. An internally cooled electrode (Cool-Tip RF Ablation System, Valleylab, Boulder, CO) was used for the procedures. After the electrode was connected with each generator (Series CC, Valleylab, Boulder, CO, RF3000), the RF energy was applied for 10-12 minutes at each site of the tumor using an impedance-control algorithm. A maximum of three lung tumors were treated on the same day.

Statistical analysis

The statistical association of the clinicopathological factors was evaluated using the Mann-Whitney U-test for quantitative data, and the Chi-square test or Fisher's exact test for qualitative data. The duration of the overall survival was defined as the interval between the date of initial treatment for lung metastasis and that of death or final follow-up. Survival curves were constructed using the Kaplan-Meier method. The log-rank test was used to compare the survival of the patients. A value of P <0.05 was considered to be significant in all statistical analyses.


 > Results Top


Treatment for lung metastasis

Elderly group

The mean metastatic tumor number (±standard deviation; SD) and maximum diameter (±SD) were 8.6±7.1 (range, 1-20) and 14.2±6.9 mm (range, 7-26 mm) [Table 1].
Table 1: Patient distribution and clinical features

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Four of the 12 patients underwent a metastasectomy for their lung metastases. The mean number of metastasectomies and resected tumors were 1.3 (range, 1-2) and 3 (range, 2-4), respectively. In three patients, the metastatic tumors could be removed by wedge resection, while one patient underwent lobectomy because of the intrapulmonary localization of the metastasis. All 12 patients underwent lung RF ablation. The mean number of RF sessions (±SD) and ablated tumors (±SD) in all 12 patients were 3.7±3.3 (range, 1-13) and 5.4±6.3 (range, 1-23). Five of the 12 patients underwent only RF ablation for the lung metastasis, 4 underwent metastasectomy and RF ablation and 3 underwent RF ablation and chemotherapy.

The mean treatment number (±SD) and treated tumors (±SD) treated by metastasectomy and/or RF ablation in all 12 patients were 4.1±3.8 (range, 1-15) and 6.4±7.3 (range, 1-27) [Table 2].
Table 2: Treatment for lung metastases in each group

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The mean and median follow-up durations in elderly group after the initial treatment for lung metastases were 22 and 15 months, respectively.

Control group

The mean metastatic tumor number (±SD) and maximum diameter (±SD) were 2.3±1.9 (range, 1-9) and 8.8±5.0 mm (range, 3-21 mm) [Table 1].

Fourteen of 20 patients underwent metastasectomy for their lung metastasis. The mean number of metastasectomies and resected tumors were 1.4 (±0.8) (range, 1-3) and 2.7 (±2.4) (range, 1-10), respectively. In 14 patients, the metastatic tumor could be removed by wedge resection in 8 patients, while in 6 patients lobectomy was performed because of the intrapulmonary localization of the tumors or multiple lung metastases.

Fourteen patients underwent lung RF ablation. The mean number of RF sessions (±SD) and ablated tumors (±SD) were 3.8±4.1 (range, 1-10) and 4.5±6.8 (range, 1-22) [Table 2], respectively.

Four of the 20 patients underwent metastasectomy and chemotherapy for the lung metastasis, 4 underwent metastasectomy, 3 underwent metastasectomy, RF ablation and chemotherapy, 3 received lung RF ablation and chemotherapy, 3 underwent metastasectomy and RF ablation, and 3 received RF ablation alone. The mean treatment number (±SD) and treated tumor (±SD) by metastasectomy and/or RF ablation in all 20 patients were 3.6±3.9 (range, 1-18) and 5.3±5.8 (range, 1-24) [Table 2].

The mean and median follow-up durations in control group after the initial treatment for lung metastasis were 39 and 31 months, respectively.

The number and size of initial lung metastases in elderly patients were significantly larger than that in control group ( P <0.05) [Table 1].

Survival after initial treatment for lung metastasis


In the elderly group, 7 of 12 patients died of disease progression. Six of these seven patients died of lung metastasis and the remaining patient died of liver metastasis. The 1-, 2-, and 3-year survival rates after initial treatment for lung metastases were 81.8%, 51.1%, and 38.4% in all of the elderly patients, respectively. The median survival was 19 months.

In the control group, 13 of the 20 patients died of disease progression. Eleven of these 13 patients died of lung metastasis, 1 patient died of brain involvement, and the other patient died of adrenal metastasis. There were no deaths related to the metastasectomy and lung RF ablation procedures. The 1-, 2-, and 3-year survival rates were 94.7%, 63.2%, and 47.4% in all control patients, respectively. Their median survival was 29 months.

There were no prognostically significant differences between the elderly patients and control patients ( P =0.36) [Figure 1].
Figure 1: The Kaplan– Meier curve shows the survival after initial treatment for lung metastases. (A; Adult sarcoma patients B; Elderly sarcoma patients)

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Complication

Elderly group

There were no deaths related to the metastasectomy and lung RF ablation procedures. There were no major complications in all four patients with metastasectomy.

A total 65 tumors were treated in 44 RF sessions. Pneumothorax developed from 40 of the 65 sessions in 10 patients. A chest tube was placed during 15 sessions in eight patients. In the other 25 sessions, a chest tube was not needed because the pneumothorax was very small and asymptomatic. A high grade fever and pleural effusion each occurred in one patient.

Control group

There were no deaths related to the metastasectomy and lung RF ablation procedures.

There were no major complications in all four patients with metastasectomy.

A total 82 tumors were treated in 57 RF sessions. A pneumothorax developed in 32 of 57 sessions in 13 patients. A chest tube was placed during 19 sessions in 7 patients. In the other 38 sessions, chest tube placement was not necessary because the pneumothorax was very small and asymptomatic. Diaphragmatic injury and pleural effusion each occurred in one patient.

Compared with the control group, the rate of chest tube placement in the elderly patients was not significantly different ( P =0.49) [Table 3].
Table 3: Pneumothorax related to RF ablation procedure

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 > Discussion Top


Our study shows that metastasectomy and lung RF ablation are relatively safe and useful therapeutic options in selected elderly patients with lung metastases from sarcoma. The 3-year survival rates after initial treatment for lung metastasis were 38.4% in elderly patients. The median survival time was 19 months. The 3-year survival achieved in our study is almost same as the survival following surgical metastasectomy, which have been reported to be 25-54%. [9],[10],[11]

There is little in the literature concerning musculoskeletal sarcoma in elderly patients. [18],[19],[20] Longhi reported that the median survival and 5-year overall survival were 19 months and 22%, respectively, in 43 elderly patients with osteosarcoma. Torigoe reported that the 5-year survival was 35% in their 20 patients with musculoskeletal sarcoma who were older than 70 years.

In our previous study, we found that 83% of the patients with metastatic musculoskeletal sarcoma succumbed to lung metastasis. [4] Although there is evidence that surgical resection can be effective for the treatment for lung metastases, the efficacy of surgical resection of the lung metastases in elderly patients on its prognosis has been controversial. Multiple surgical series have also suggested greater perioperative mortality in the elderly. [21],[22] In our study, a metastasectomy was received by only 4 (16%) of the 25 patients with lung metastases.

RF ablation has been accepted as a relatively safe and useful therapeutic option for the treatment of unresectable nonsmall cell lung cancer and lung metastases. [12],[13],[14],[15],[16],[17] Some studies have shown the clinical utility of lung RF ablation in controlling lung metastases from sarcoma. [15],[16] One of the major advantages of RF ablation is that it allows ablation of tumors without major damage to the surrounding normal parenchyma. It has been demonstrated that RF ablation did not change lung function parameters and is possible even in patients with severe respiratory dysfunction. [23] In addition, this technique can be performed percutaneously, avoiding the need for a lobectomy in patients with severe co-morbidities or those who refuse open resection.

The main adverse event of this procedure is a pneumothorax requiring chest tube drainage, which occurs in 10-38% of the procedures. [12],[13],[14],[15],[16],[17] In our series, the most important complication was also pneumothorax, although it did not cause any serious clinical deterioration or disease progression in any of our patients. Chest tube placement was necessary in 15 sessions (23%) in 8 of the 12 elderly patients. This rate of chest tube insertion was not significantly different from that in the control patients. By paying particular attention to progression of a pneumothorax, RF ablation of lung tumors can be considered to be a safe and minimally invasive procedure. Although RF ablation may be as effective as surgery, further prospective randomized controlled studies are needed to clarify the impact of RF ablation on sarcoma patients by comparing with metastasectomy.

There were some limitations to our study. First, there were a relatively small number of patients examined in this study. A lack of histological proof of lung metastases in the patients treated with only RF ablation was also a limitation. The study was also retrospective in nature.


 > Conclusion Top


We conclude that elderly sarcoma patients with lung metastases should always be considered for either metastasectomy or RF ablation. RF ablation can be considered a safe and minimally invasive procedure for patients with severe co-morbidities, those with multiple metastases or those who refuse a surgical resection.

 
 > References Top

1.Japanese Orthopaedic Association Musculoskeletal Tumor Committee. Bone tumor registry in Japan. Tokyo: Japanese Musculoskeletal Oncology Group; 2008.  Back to cited text no. 1
    
2.Japanese Orthopaedic Association Musculoskeletal Tumor Committee. Malignant soft tissue tumor registry in Japan. Tokyo: Japanese Musculoskeletal Oncology Group; 2008.  Back to cited text no. 2
    
3.A National Institute of Population and Society Security Research. Available from : http://www.ipss.go.jp/index-e.asp. [Last Accessed on 2012 Apr 28].  Back to cited text no. 3
    
4.Nakamura T, Matsumine A, Matsubara T, Asanuma K, Niimi R, Uchida A, et al. Retrospective analysis of metastatic sarcoma patients. Oncol Lett 2011;2:315-8.  Back to cited text no. 4
    
5.Vezeridis MP, Moore R, Karakousis CP. Metastatic patterns in soft-tissue sarcomas. Arch Surg 1983;118:915-8.  Back to cited text no. 5
    
6.Antunes M, Bernardo J, Salete M, Prieto D, Eugénio L, Tavares P. Excision of pulmonary metastases of osteogenic sarcoma of the limbs. Eur J Cardiothorac Surg 1999;15:592-6.  Back to cited text no. 6
    
7.Lanza LA, Putnam JB Jr, Benjamin RS, Roth JA. Response to chemotherapy does not predict survival after resection of sarcomatous pulmonary metastases. Ann Thorac Surg 1991;51:219-24.  Back to cited text no. 7
    
8.Casper ES, Gaynor JJ, Harrison LB, Panicek DM, Hajdu SI, Brennan MF. Preoperative and postoperative adjuvant combination chemotherapy for adults with high grade soft tissue sarcoma. Cancer 1994;73:1644-51.   Back to cited text no. 8
    
9.van Geel AN, Pastorino U, Jauch KW, Judson IR, van Coevorden F, Buesa JM, et al. Surgical treatment of lung metastases: The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients. Cancer 1996;77:675-82.  Back to cited text no. 9
    
10.Smith R, Pak Y, Kraybill W, Kane JM 3rd. Factors associated with actual long-term survival following soft tissue sarcoma pulmonary metastasectomy. Eur J Surg Oncol 2009;35:356-61.  Back to cited text no. 10
    
11.Billingsley KG, Burt ME, Jara E, Ginsberg RJ, Woodruff JM, Leung DH, et al. Pulmonary metastases from soft tissue sarcoma: Analysis of patterns of diseases and postmetastasis survival. Ann Surg 1999;229:602-10; discussion 610-2.  Back to cited text no. 11
    
12.Dupuy DE, Zagoria RJ, Akerley W, Mayo-Smith WW, Kavanagh PV, Safran H. Percutaneous radiofrequency ablation of malignancies in the lung. AJR Am J Roentgenol 2000;174:57-9.  Back to cited text no. 12
    
13.Suh RD, Wallace AB, Sheehan RE, Heinze SB, Goldin JG. Unresectable pulmonary malignancies: CT-guided percutaneous radiofrequency ablation-preliminary results. Radiology 2003;229:821-9.  Back to cited text no. 13
    
14.Akeboshi M, Yamakado K, Nakatsuka A, Hataji O, Taguchi O, Takao M, et al. Percutaneous radiofrequency ablation of lung neoplasms: Initial therapeutic response. J Vasc Interv Radiol 2004;15:463-70.  Back to cited text no. 14
    
15.Nakamura T, Matsumine A, Yamakado K, Matsubara T, Takaki H, Nakatsuka A, et al. Lung radiofrequency ablation in patients with pulmonary metastases from musculoskeletal sarcomas [corrected]. Cancer 2009;115:3774-81.  Back to cited text no. 15
    
16.Ding JH, Chua TC, Glenn D, Morris DL. Feasibility of ablation as an alternative to surgical metastasectomy in patients with unresectable sarcoma pulmonary metastases. Interact Cardiovasc Thorac Surg 2009;9:1051-3.  Back to cited text no. 16
    
17.von Meyenfeldt EM, Prevoo W, Peyrot D, Lai A Fat N, Burgers SJ, Wouters MW, et al. Local progression after radiofrequency ablation for pulmonary metastases. Cancer 2011;117:3781-7.  Back to cited text no. 17
    
18.Longhi A, Errani C, Gonzales-Arabio D, Ferrari C, Mercuri M. Osteosarcoma in patients older than 65 years. J Clin Oncol 2008;26:5368-73.  Back to cited text no. 18
    
19.Osaka S, Sugita H, Osaka E, Yoshida Y, Ryu J. Surgical management of malignant soft tissue tumours in patients aged 65 years or older. J Orthop Surg (Hong Kong) 2003;11:28-33.  Back to cited text no. 19
    
20.Torigoe T, Terakado A, Suehara Y, Kurosawa H, Yazawa Y, Takagi T. Bone versus soft-tissue sarcomas in the elderly. J Orthop Surg (Hong Kong) 2010;18:58-62.  Back to cited text no. 20
    
21.Ginsberg RJ, Hill LD, Eagan RT, Thomas P, Mountain CF, Deslauriers J, et al. Modern thirty-day operative mortality for surgical resections in lung cancer. J Thorac Cardiovasc Surg 1983;86:654-8.  Back to cited text no. 21
    
22.Deslauriers J, Ginsberg RJ, Piantadosi S, Fournier B. Prospective assessment of 30-day operative morbidity for surgical resections in lung cancer. Chest 1994;106:329S-330S.  Back to cited text no. 22
    
23.de Baère T, Palussière J, Aupérin A, Hakime A, Abdel-Rehim M, Kind M, et al. Midterm local efficacy and survival after radiofrequency ablation of lung tumors with minimum follow-up of 1 year: Prospective evaluation. Radiology 2006;240:587-96.  Back to cited text no. 23
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]


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