Long-term Survival Following Radiofrequency Ablation of Lung Metastases in an Elderly Patient With Calcaneal Osteosarcoma: a Case Report and Review of the Literature


 Background: Lung metastases are the primary cause of death from osteosarcomas. Complete resection of lung metastases can prolong the survival. However, complete surgical resection in elderly patients is often difficult due to high risk of peri-operative complications. Radiofrequency ablation (RFA) is a minimally invasive technique to destroy tumor nodules using heat. Here, we present an elderly patient with osteosarcoma in calcaneus a scapular osteochondroma, who metachoronusly developed multiple lung metastases. Subsequently, he has been surviving a relatively long period by the use of percutaneous computed tomography (CT)-guided lung RFA against his lung metastases.Case presentation: A 74-year-old male presented with 1-year history of heel pain. Imaging analysis demonstrated a mixture of osteolytic and osteosclerotic lesions in the calcaneus with extraskeletal lesions. The histology of the biopsy specimen showed osteoid matrix with malignant spindle cells, which was diagnosed as a conventional high-grade osteosarcoma. Below-knee amputation was performed. However, 6 lung metastases were found in both lungs 1 year after surgery. During 4.5 years from the initial percutaneous CT-guided lung RFA, 18 lung metastases were treated in 8 procedures. Lung RFA was performed under moderate sedation and local anesthesia. The most frequent complication was pneumothoraxes in 3 procedures followed by pleuritis with pneumothorax in 1 procedure. Chest tube drainage was required in 2 of 8 (25%) lung RF procedures. Mean duration of hospital stay for lung RFA was 5.3 ± 2.1 days (range, 3-10 days). The patient has been alive with disease for 5.5 years after initial surgery. Conclusion: Our experience indicates that lung RFA is effective for elderly patients with lung metastases of osteosarcoma without serious complications.

demonstrated a mixture of osteolytic and osteosclerotic lesions in the calcaneus with extraskeletal lesions. The histology of the biopsy specimen showed osteoid matrix with malignant spindle cells, which was diagnosed as a conventional high-grade osteosarcoma. Below-knee amputation was performed. However, 6 lung metastases were found in both lungs 1 year after surgery. During 4.5 years from the initial percutaneous CT-guided lung RFA, 18 lung metastases were treated in 8 procedures. Lung RFA was performed under moderate sedation and local anesthesia. The most frequent complication was pneumothoraxes in 3 procedures followed by pleuritis with pneumothorax in 1 procedure. Chest tube drainage was required in 2 of 8 (25%) lung RF procedures. Mean duration of hospital stay for lung RFA was 5.3 ± 2.1 days (range, 3-10 days). The patient has been alive with disease for 5.5 years after initial surgery.
Conclusion: Our experience indicates that lung RFA is effective for elderly patients with lung metastases of osteosarcoma without serious complications.

Background
Osteosarcoma is a high-grade malignant bone neoplasm that commonly occurs in the metaphysis of long bones in the second and third decade of life [1]. Despite the advent of combined surgical and chemotherapeutic interventions, the prognosis of patients with lung metastases of osteosarcomas is still poor [2], especially in patients older than 65 years [3,4]. Complete resection of lung metastases can improve life prognosis [5]. However, metastasectomy in elderly patients is often performed with considerable hesitation due to lack of adequate respiratory reserve, high risk of perioperative complications, or other medial co-morbidities [6].
Radiofrequency ablation (RFA) is a technique to destroy tumor nodules using heat. The major advantage of RFA is a minimally invasive and relatively safe technique. Recently, a few papers reported the usefulness of this technique against lung metastases of osteosarcomas [7][8][9]. However, the feasibility of this technique has not been reported for elderly patients.
Here, we describe an elderly patient with osteosarcoma in calcaneus, who metachoronusly developed multiple lung metastases. Subsequently, he has been surviving a relatively long period (5.5 years) by the use of percutaneous CT-guided lung RFA against his lung metastases.

Case Presentation
A 74-year-old male presented with a right heel pain for 1 year. A tumor was found by radiography taken at a regional hospital when he noted increased heel pain. At presentation of our department, physical examination showed tenderness at the medial and lateral aspects of the calcaneal body. Radiography revealed an ill-de ned osteolytic and osteoblastic lesion in the calcaneus with extension into soft tissues on the plantar aspect (Fig. 1A A needle biopsy was performed. The histology of the specimen showed osteoid matrix with malignant spindle cells, which was diagnosed as a conventional high-grade osteosarcoma (Fig. 5). Neoadjuvant chemotherapy was not applicable since adverse effects were expected due co-morbidities of hypertension, diabetes mellitus, and renal dysfunction in addition to high age. A right below-knee amputation was performed to achieve a wide margin. Two months postoperatively, the patient regained the ability to walk with lower limb prosthesis.
However, 6 lung metastases with a mean diameter of 6.3 ± 2.5 mm (range, 4-11 mm) were found in both lungs at 1 year after surgery. Surgical intervention for lung metastases was abandoned because of tumor multiplicity and high-risk surgery. Therefore, lung RFA was chosen to treat lung metastases. Lung RFA was performed under moderate sedation and local anesthesia. Real-time CT uoroscopy (SOMATOM, Siemens, Forchheim, Germany) was used to place the RF electrode in the tumors. An internally cooled electrode (Cool-Tip RF Ablation System, Covidien, Boulder, CO, USA) was used for the procedures. After the electrode was connected with the generator (Series CC, Covidien, Boulder, CO, USA), the RF energy was applied for 10-12 minutes at each site of the tumors using an impedance-control algorithm. The 6 lung metastases were treated by 2 RFA procedures, 3 in each procedure (Fig. 6).
Six months after initial lung RFA, new lung metastases developed. Therefore, additional lung RFA was performed. In 4.5 years from the initial lung RFA, a total of 18 lung metastases with a mean diameter of 10.7 ± 6.8 mm (range, 4-25 mm) were treated in 8 lung RF procedures. The most frequent complication was pneumothoraxes in 3 procedures followed by pleuritis with pneumothorax in 1 procedure. Chest tube drainage was required in 2 of 8 (25%) lung RF procedures. Mean duration of hospital stay for lung RFA was 5.3 ± 2.1 days (range, 3-10 days). Due to the large tumor embolism of right inferior pulmonary vein, removal of the vein and the right lower lobectomy were also required. The patient has been alive with disease for 5.5 years after the initial surgery.

Discussion
Recently, the number of osteosarcomas has been increasing in elderly patients due to human longevity. In a nationwide Japanese database from 2006 to 2013, 183 out of 1497 patients (22%) with osteosarcomas were found in the age of more than 65 years old [4]. The need for studies on elderly patients with osteosarcomas is therefore increasing. Several papers have reported on poor prognosis of the elderly patients with osteosarcomas [3,4,10]. Longhi et al. reported that the median survival and 5year overall survival were 19 months and 22%, respectively, in 43 patients who had high-grade osteosarcoma and were older than 65 years.
Lung metastases are the primary cause of death from osteosarcomas. Complete surgical resections of all pulmonary lesions contribute to prolonged survival [5]. However, surgical resection in elderly patients with osteosarcomas is not always applicable. In fact, multiple surgical series have reported greater perioperative mortality in the elderly [11,12].
Percutaneous CT guided RFA has been reported to provide a safe and effective minimally invasive treatment for lung metastases [13]. Lung RFA was introduced in 2000 [14], and applied to patients with osteosarcoma in 2009 [9]. Thereafter, several authors have reported the feasibility of this technique in patients with lung metastases from osteosarcomas (Table 1). However, no paper has reported any patient older than 65 years with high-grade osteosarcoma and with lung metastases treated by percutaneous CTguided lung RFA. In addition, the importance of the present case is the longest follow-up among patients with osteosarcomas treated by this technique (Table 1).
In our institute, RFA is applied to tumor size of 3 cm or less. Basically, the electrode is placed in the center of the tumor when the tumor size is 2 cm or less. When the tumor size is larger than 2 cm, the electrode is placed sequentially at 2-4 different sites in the tumor based on size and shape [13]. A maximum of 3 lung tumors, developing in one lung, can be treated on the same day.
The advantage of RFA is that it allows ablation of tumors without major damage to the surrounding normal parenchyma. It has been demonstrated that RFA does not change lung function parameters and is possible even in patients with severe respiratory dysfunction [15]. In addition, this technique can be performed percutaneously under moderate sedation and local anesthesia. It can be applied several times in patients with severe co-morbidities or/and elderly patients. In the present case 8 lung RF procedures could be performed.
The risk of failure of RFA is in patients with large pulmonary lesions. In such a case, surgical resection should be considered. The advantages and disadvantages of RFA and surgical resection for the patient with sarcoma lung metastases are summarized in Table 2. The usefulness of combination therapy of RFA and surgical resection has been shown against lung metastases for improvement of curability [7,16].
The most frequent complication is pneumothorax requiring chest tube drainage, which occurs in approximately in 10-23% of the procedures [6][7][8]. Nakamura et al. reported the feasibly of RFA in elderly patients more than 65 years old with soft tissue and bone sarcomas. In their series, chest tube drainage was required in 15 out of 65 procedures (23%) in 12 patients, which was not statistically different from the results of sarcoma patients younger than 65 years. In the present osteosarcoma case, pneumothorax occurred in 4 of 8 (50%) and chest tube drainage was needed in 2 of 8 (25%) lung RF procedures.
However, no serious clinical deterioration was found.
In conclusion, percutaneous CT-guided lung RFA is a less invasive and safe technique for the elderly patient of more than 65 years, with lung metastases of osteosarcoma. The present patient has been alive with disease for 5.5 years after initial surgery.

Consent for publication
Written consent was obtained from the patient and his family for publication of this study.

Availability of data and materials
All data generated or analyzed during this study are included in this published article.