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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 1  |  Page : 73-76

Clinical report of intra-arterial interventional chemotherapy for synovial sarcoma on limbs


1 Department of Orthopedics, Affiliated Hospital of Academy of Military Medical Sciences, PLA 307th Hospital, Beijing, China
2 Biomechanics and Medical Information Institute, Beijing University of Technology, Beijing, China

Date of Web Publication13-Apr-2016

Correspondence Address:
Dingfeng Li
PLA 307th Hospital
China
Yanjun Zeng
Beijing University of Technology
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.148662

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 > Abstract 


Objective: The efficiency of implantable intra-arterial interventional chemotherapy before the operation for synovial sarcoma on limbs was evaluated.
Materials and Methods: Drug delivery device (chemotherapy pumps) was implanted percutaneously for 36 patients, and the interventional chemotherapy was conducted for 3-4 cycles. The surgical resection was carried out after obvious improvement was observed by clinical and imaging examination. The evaluation standard for the efficiency of chemotherapy was tumor cell necrosis rate obtained from postoperative pathological test.
Results: The response rate (RR) of pain alleviation was 91% (32/36), and the RR of the changing of lesion imaging was 83% (30/36). Thirty cases received extensive tumor excision, and six cases received amputation because of poor response to tumor chemotherapy and local carcinelcosis. The postoperative pathological test showed 81% moderate and severe chemotherapy response (29/36). The average follow-up time was 39 months. There were three cases presenting with local tumor recurrence, and seven deaths due to pulmonary metastasis.
Conclusion: Intra-arterial interventional chemotherapy before operation for synovial sarcoma can effectively control pain. After chemotherapy, the imaging performance significantly changed, and tumor cells were necrotized extensively. The pathological changes were obvious.

Keywords: Intra-arterial interventional chemotherapy, soft tissue sarcoma, synovial sarcoma


How to cite this article:
Cui Q, Li D, Liu S, Jiang W, Guo J, Liu C, Liu Y, Zhang P, Fan H, Wang L, Zhang B, Zeng Y. Clinical report of intra-arterial interventional chemotherapy for synovial sarcoma on limbs. J Can Res Ther 2016;12:73-6

How to cite this URL:
Cui Q, Li D, Liu S, Jiang W, Guo J, Liu C, Liu Y, Zhang P, Fan H, Wang L, Zhang B, Zeng Y. Clinical report of intra-arterial interventional chemotherapy for synovial sarcoma on limbs. J Can Res Ther [serial online] 2016 [cited 2019 Nov 14];12:73-6. Available from: http://www.cancerjournal.net/text.asp?2016/12/1/73/148662




 > Introduction Top


Synovial sarcoma is a type of malignant soft tissue tumor originating from mesenchyma with high malignant degree, accounting for about 14% of soft tissue tumors.[1],[2] It primarily attacks the limbs of young people, and originates from the joint, synovium and synovial tendon sheath. Some are primarily originated from trunk, thoracic and abdominal wall, head and neck, but rarely from internal organs. The previous research indicated that the treatment of choice for synovial sarcoma is extensive excision of tumor and surrounding tissues in combination with postoperative radiotherapy, but the method has a high recurrence rate.[3],[4],[5],[6],[7] Chemotherapy becomes increasingly important in the comprehensive therapy of synovial sarcoma currently.[8],[9] In our clinical work, preoperative intra-arterial interventional chemotherapy is employed to assist the treatment of synovial sarcoma of limbs. Norcantharidin (NCTD) is administered to accelerate the apoptosis of tumor cells and enhance the chemotherapeutic efficacy. A satisfactory clinical result is usually observed.


 > Materials and Methods Top


Basic data

From January 2005 to June 2013, 36 cases of synovial sarcoma were treated in our hospital, with the ratio of male (22) to female (14) being 1.57:1. The age ranged from 12 years old to 65 years old, with the average of 33. The tumors mainly grew on the large joints of limbs, including hand and wrist joint (8 cases), elbow joint (6 cases), shoulder joint (3 cases), hip joint (4 cases), knee joint (5 cases) and foot-ankle joint (10 cases). All the patients sought treatment due to palpable lumps or postoperative recurrence. Some patients received radiotherapy or chemotherapy, and the disease duration ranged from half a month to two years.

Adjuvant examination

By X-ray, CT and nuclidic bone scan, 36 cases with obvious soft tissue tumor, 12 cases with bone destruction (all showing eccentric pattern beside the soft tissue mass), and 8 cases with calcification in soft tissue masses were found. It was also observed by CT scan that the soft tissue masses and bones had density similar to or lower than that of muscle. Not all boundaries were clear, and the calcification and cystic degeneration in the tumors were also observed. By MRI scan, nonuniform signal of tumor, septa in tumors, nodular strong signal in tumor on T2WI and peritumoral infiltration were found. Pathological characteristics: 24 cases were pathologically diagnosed as synovial sarcoma at other hospitals, and 12 cases received biopsy of tumors at our hospital. According to the histological staging recommended by WHO, there were 19 cases of unipolar type, 12 cases of bipolar type and 5 cases of poorly differentiated type. The diameter of tumor was 4−17 cm, with the average of 10 cm and the median of 7 cm.

Methods

After local anesthesia, the catheter was inserted into the proximal end of nutrient artery of the tumor. On the upper limbs, the catheter was reversely inserted into the subclavian artery through brachial artery. On lower limbs, the catheter was reversely inserted into the external iliac artery through femoral artery. For some cases, the catheter was inserted reversely upward into the common iliac artery at the affected side using guide wire through the femoral artery at the healthy side. Then the catheter was delivered to the external iliac artery or femoral artery at the affected side depending on the specific situation. After that, intra-arterial chemotherapy pump was implanted subcutaneously. Adriamycin (ADR) and cis-platinum were mainly used in chemotherapy in combination with NCTD. The routine dosage of ADR (30 mg) was administered during operation. Before tumor excision, the patients received routine interventional chemotherapy for 3-4 weeks. After operation, 100-120 mg/m 2 cis-platinum and 90 mg/m 2 ADR were injected by arterial chemotherapy pump. After the injection, 500 ml glucose (5%) and NCTD (40 mg/24h) were continuously pumped for 72 h. After arterial chemotherapy, 6 g/m 2 ifosfamide (IFO) was injected intravenously. Adjuvant therapies were given simultaneously such as hydration, diuresis, anti-nausea and hepatic protection.

Observation indicators and evaluation

Pain and discomfort was alleviated or eliminated; the masses on diseased region shrank; the effusion from broken tumor was reduced or the wound was healed; hardness was enhanced; range of motion was improved. The X-ray findings after chemotherapy were as follows: Alleviated soft tissue swelling, distinct boundary of bone destruction, increased bone formation, reduced or limited osteolysis, and increased calcification. CT and MRI findings after chemotherapy included distinct boundary of lesions, alleviated soft tissue swelling, reduced mass, and distinct boundary between tumor and surrounding tissues. Tumor cell necrosis rate (TCNR) was calculated with pathological tumor specimens. According to Huvos classification method [10], there were four grades, Grade I (TCNR ≤ 50%), Grade II (50% < TCNR ≤ 90%), Grade III (90% < TCNR ≤ 99%), and Grade IV (TCNR = 100%). Grade I and II belong to mild response to chemotherapy (TCNR ≤ 90%); Grade III and IV belong to moderate and severe response to chemotherapy (TCNR > 90%).


 > Results Top


Clinical therapeutic efficacy

There were 25 cases receiving implantable intra-arterial interventional chemotherapy for three times, and 11 cases for four times. Among these cases, 28 patients showed positive effect after arterial chemotherapy for 12-24 h. The local pain was alleviated, the masses were reduced, the range of motion was increased, and mental status was greatly improved. Before chemotherapy, the proportions of mild and moderate pain (26 cases), and severe pain (10 cases) were 72% and 28%, respectively. After chemotherapy, the proportions of complete response (CR), partial response (PR) and no change (NC) were 42%, 47% and 11% (15, 17 and 4 cases), respectively. The overall response rate (RR) was 89%. The analgesic duration is related to treatment time, size of masses, malignant degree and chemotherapeutic times. After three continuous treatment cycles, the tumor size was reduced by 3-8 cm, with the average of 4 cm.

Imaging performance

After chemotherapy, the images of tumors and surrounding tissues were distinct. The soft tissue masses were reduced, showing a repair trend, and a part of mass was liquidized. Pseudocapsule appeared, and the boundary of tumor region was distinct [Figure 1]. According to the imaging performance, the response degree of lesions was as follows. The proportions of CR (12 cases), PR (18 cases), and NC (6 cases) were 33%, 50% and 17%, respectively. The RR was 83% (30/36).
Figure 1: (a) X-ray and pathological image before chemotherapy; (b) X-ray and pathological image after chemotherapy

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Operation and postoperative pathology

After chemotherapy, extensive excision within 5cm from the boundary of tumor was conducted on 30 patients, and the injury to the important surrounding tissues should be avoided as much as possible. During the operation, the tumors were significantly reduced and pseudocapsule was formed after chemotherapy. The surrounding edema and adhesion were obviously relieved, and the gap between tumor and adjacent tissue was broadened, which made separation easier. Six cases were treated with amputation due to poor response to tumor chemotherapy and local carcinelcosis. The situations of tumor cell necrosis in 36 cases were as follows: 3 cases of Grade I (8%), 6 cases of Grade II (17%), 21 cases of Grade III (58%) and 8 cases of Grade IV (22%). The moderate and severe response to chemotherapy accounted for 81% (29 cases). The tumor tissues showed various extent of degeneration, necrosis, fibrosis and hyaline change. Few classical tumor cells were observed, and necrosis was severe [Figure 1].

Follow-up survey and therapeutic effect

The 36 patients were followed up for 5-78 months, with the average of 39 months. Two-year survival rate was 92% (33 cases), and five-year survival rate was 86% (31 cases). Seven patients died of pulmonary metastasis.


 > Discussion Top


Synovial sarcoma is a type of primary malignant tumor originating from mesenchymal tissue, with high disability rate, which seriously influences the life quality of patients. The patient's life will be threatened if the treatment is not given timely.[1],[2] The tumor treated with local and non-radical resection is easy to relapse, and the recurrence rate reaches 60 − 86.2%. Lymphatic and hematogenous metastasis will occur as well, and repeated recurrence will seriously impact the prognosis. The amputation for the treatment of synovial sarcoma has better local control efficacy, but it will cause disability, lowering the quality of life and living confidence of patients.[3] In a previous study, it was believed that the first choice for the treatment of synovial sarcoma was local radical resection combined with postoperative adjuvant radiotherapy. It was once considered that synovial sarcoma is not sensitive to chemotherapy, and therefore little attention was paid to chemotherapy for soft tissue sarcoma. As a result, many IIB and III patients lost the best opportunity for treatment, and few tumors could be excised extensively. Recently, domestic and foreign clinical researches indicate that radiotherapy and chemotherapy before or after operation is the key for improving curative effect and prognosis.[4],[5],[6],[7] Chemotherapy, especially high-dose chemotherapy, has been widely applied to the treatment of synovial sarcoma, and its importance for the treatment is increased. Systematic chemotherapy can improve the disease-free or the metastasis-free survival of patients [8],[9] 101 patients receiving the operation for synovial sarcoma on limbs were randomly divided into two groups by Eilber et al.[11] One group was treated with chemotherapy (routine scheme, IFO), and the other was not. The four-year survival rates were 88% and 67%, respectively, which means that the postoperative adjuvant chemotherapy can increase the survival rate. ADR is one of the most effective medicines for the treatment of synovial sarcoma. The effective rate is 20 − 30%, and there is a dose dependency.[12] Currently, the commonly used clinical treatment scheme is ADR alone or the combined schemes based on ADR, including ADR + IFO, ADR + DTIC (dacarbazine) and IFO + DTIC + ADR (MAID). MAID is the first choice for the treatment of synovial sarcoma. In 1993, Antman et al.,[13] found that MAID scheme had 32% of effective rate for the initially treated patients at the advanced stage, and the median survival time was 12.5 months. However, the severe hematological and cardiac toxicity restricts the wide application of ADR. Li et al.,[14] employed modified MAID scheme, tetrahydropyran-ADR (THP-ADR), to treat advanced soft tissue sarcoma. The overall effective rate was 42.59%, with mild adverse reaction. Several new medicines such as ET-743,[15] docetaxel and gemcitabine [16] are recently applied in clinical treatment, but they are still in stage II clinical experiment, with uncertain clinical efficiency.

Implantable intra-arterial interventional chemotherapy was employed in our research. The interval between two treatment cycles was shortened by utilizing the distinct feature of this method, i.e. higher local concentration, no drug degradation and inactivation in liver, and lower toxic and adverse effect compared with the intravenous administration at the same dosage. Moreover, NCTD was simultaneously administered for arterial chemotherapy. Many researches indicated [17],[18] that orcantharidin can inhibit the DNA synthesis in several tumor cells, interfere with cell division, destroy the skeleton and ultrastructure of tumor cells, improve the respiratory control rate of tumor cells, increase the lysosomal enzyme activity in cells, and change the expression of some tumor cell genes and physiological activity of enzymes. Orcantharidin inhibits the proliferation of tumor cells and therefore has anti-tumor effect.

The diseased locations of patients in our research were mainly distributed on the joints with more tendons, such as hand, wrist, foot and ankle. For some recurring patients, the local skin scar contracture occurred, and the tumors grew in broken joint and bone, showing infiltrative growth. These tumors closely adhered to nerves and vessels, so the risks of surgical resection and the possibility of recurrence were larger. It is difficult to conduct extensive resection and limb salvage operation without the control of tumor boundary by effective preoperative adjuvant therapy. Therefore, adjuvant therapy was employed to determine the constraints on operation. Effective intra-arterial chemotherapy can limit the boundary of tumor, and form capsular reaction region, which provides favorable conditions for surgical resection. In this research, after the chemotherapy for 36 patients, it can be seen clinically that the pain on diseased region was obviously alleviated or eliminated. Local skin temperature declined; the masses were reduced and hardened, with distinct boundary; the range of movement between subcutaneous tissue and mass was increased (RR32/36). By imaging examination, it can be seen that the soft tissue mass was reduced, and the boundary was distinct (RR30/36). Postoperative pathological test showed obvious necrosis of tumor cells, and more cases presented with moderate and severe chemotherapy response (27/36). The blood supply to tumor tissues and distinct boundary caused by chemotherapy provided better condition for extensive tumor excision. The significance of intra-arterial chemotherapy was manifested in the comprehensive treatment process of synovial sarcoma. After intra-arterial chemotherapy, the tumor excision surgery was conducted. The chemotherapeutic response of tissue specimens after surgery had different extent of guiding effect for the whole process of treatment. The cases with moderate and severe chemotherapeutic response can be treated with original scheme to consolidate the treatment after surgery, so as to avoid recurrence and improve the survival rate.

To sum up, a comprehensive treatment should be applied to synovial sarcoma so as to solve the problem of high recurrence rate, reduce metastasis and prolong the survival. In the implantable intra-arterial interventional chemotherapy, not only the high-concentration medicine around the tumor, but also the concentration in the whole body was ensured. The infiltration range of tumor was effectively controlled; the tumor boundary was reduced; local recurrence rate after operation declined; and the survival rate was increased.

 
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