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  Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 55  |  Issue : 2  |  Page : 176-178
 

Clinical outcomes of limb salvage surgery with postoperative intensity-modulated radiation therapy for soft-tissue sarcoma and metastasis


1 Department of Orthopaedic Surgery, Aichi Medical University, Nagakute, Aichi 480-1195, Japan
2 Department of Orthopaedic Surgery, Kure Medical, Kure, Hiroshima 737-0023, Japan

Date of Web Publication31-Dec-2018

Correspondence Address:
Dr. Katsuhisa Kawanami
Department of Orthopaedic Surgery, Aichi Medical University, Nagakute, Aichi 480-1195
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_618_17

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 » Abstract 


OBJECTIVE: The primary aim of intensity-modulated radiation therapy (IMRT) for treating soft tissue sarcoma of an extremity is the reduction of morbidity and maintenance of local control. METHODS: We evaluated the outcomes and toxicity of adjuvant IMRT following function-preserving surgery to treat patients with soft tissue sarcoma and metastasis of the extremities. We retrospectively reviewed prospective databases at Kure Medical Center and Aichi Medical University between 2013 and 2016 and identified 10 patients with lower extremity soft tissue sarcoma who underwent both limb-sparing surgery and postoperative IMRT at one of our institutions. RESULTS: There were 7 men and 3 women (mean age, 67.2 years; range, 48–87 years) included in the study. Of these, four patients were continuously disease-free, two showed no evidence of disease, and four died due to disease. The average functional score was 82% (range, 53–100%). Among the 10 patients, 2 (22%) had grade 1–2 edema and 1 (11%) had grade 2 joint stiffness. Another patient developed grade 2 acute dermatitis. There were no severe complications such as infection, tissue necrosis, fracture, or nerve palsy. CONCLUSION: Although the number of patients in this study was small, our results show that adjuvant IMRT following function-preserving surgery for soft tissue sarcoma of the extremity can be valuable for treating unmanageable tumors.


Keywords: Intensity-modulated radiation therapy, limb salvage surgery, metastasis, soft-tissue sarcoma


How to cite this article:
Kawanami K, Matsuo T, Yuki S, Shimose S, Takahashi R, Deie M. Clinical outcomes of limb salvage surgery with postoperative intensity-modulated radiation therapy for soft-tissue sarcoma and metastasis. Indian J Cancer 2018;55:176-8

How to cite this URL:
Kawanami K, Matsuo T, Yuki S, Shimose S, Takahashi R, Deie M. Clinical outcomes of limb salvage surgery with postoperative intensity-modulated radiation therapy for soft-tissue sarcoma and metastasis. Indian J Cancer [serial online] 2018 [cited 2019 Jun 18];55:176-8. Available from: http://www.indianjcancer.com/text.asp?2018/55/2/176/249214





 » Introduction Top


Wide local surgical excision is fundamental for the primary management of sarcomas. However, success in the management of soft-tissue sarcomas is often limited by extension of lesions to the neurovascular structures because of difficulty in dissecting the neurovascular bundle from the tumor without compromising function and local recurrence. Patients with soft-tissue sarcoma involving or extending to the neurovascular structures may sometimes be advised to undergo amputation. In an effort to preserve limbs, conservative surgery with various adjuvant therapies such as conventional radiation, brachytherapy, hyperthermia, pasteurization, alcohol soaking, and distilled water soaking for the preservation of the neurovascular bundles has been reported.[1],[2] Evidence from two randomized trials demonstrated that radiation along with limb salvage surgery achieves local control and overall survival rates that are comparable to those of amputation.[3]

Recently, the standard management of soft-tissue sarcoma has changed from conventional radiotherapy to intensity-modulated radiation therapy (IMRT). IMRT allows the operator to better conform the radiation therapy field to the target volume while sparing critical normal tissue.[4] IMRT can conform to the shape of the intended treatment target, which reduces the dose of radiation received by the adjacent organs that are at risk compared to conventional radiation.[5]

We evaluated the outcomes and toxicity of adjuvant IMRT following function-preserving surgery for the treatment of patients with soft-tissue sarcoma and metastasis of the upper and lower extremities.


 » Patients and Methods Top


We retrospectively reviewed prospective databases at Kure Medical Center and Aichi Medical University from 2013 to 2016 and identified ten patients with lower extremity soft-tissue sarcoma who underwent both limb-sparing surgery and postoperative IMRT at one of our institutions.

The surgical techniques used in limb-sparing surgery for soft-tissue sarcoma of the upper and lower extremities have been described extensively.[6] Briefly, all visible or palpable tumors were resected in an en bloc fashion. Patients with soft-tissue sarcoma involving or extending to the main neurovascular structures underwent resection in an effort to prevent vascular and nerve damage. Surgical margins were determined to be positive microscopically in all cases.

The dose of postoperative IMRT varied depending on tumor grade and margin status. The IMRT techniques were as previously described, but, briefly, all patients were immobilized with vacuum cushions and underwent computed tomography (CT) simulation.[5],[7] CT was performed with a 2.5 mm thickness from the pelvis to below the knee for thigh lesions, from the mid-thigh to the foot for leg lesions, and from the shoulder to the hand for upper extremity lesions.

The treated limb was immobilized in as close to the neutral anatomical position as possible to minimize patient movement. For patients treated with IMRT postoperatively, the initial clinical target volume consisted of the reconstructed surgical bed, and surgical clipping was performed at the time of resection. The radiation range of IMRT is determined in the hypodense region that was seen on CT simulation slices in the superior and inferior direction by 3 cm.

Orthopedic oncologists monitored all patients who underwent treatment. Imaging of the primary site and chest was performed four times per year, and the longest follow-up period was 19 months. All patients underwent clinical follow-up at Kure Medical Center or Aichi Medical University. Functional mobility of the limb was expressed according to the International Symposium on Limb Salvage Scale, which is based on Enneking's criteria, for all patients. Grading of toxicity was based on the Common Terminology Criteria for Adverse Events, version 3.0, and the highest grade of any observed toxicity was reported for each patient at the time of follow-up.


 » Results Top


There were seven males and three females, with a mean age of 67.2 years (range: 48–87 years). Of these, four patients presented with myxofibrosarcoma, two with liposarcoma, and one each with synovial sarcoma, epithelioid sarcoma, leiomyosarcoma, and renal metastasis. The tumors were located in the thigh (six patients), upper arm (two patients), forearm (one patient), and hand (one patient). The tumor size was evaluated by measuring the largest diameter on magnetic resonance images. The average tumor size was 11.9 cm (range: 5–20 cm). The clinical data are shown in [Table 1]. All patients underwent marginal or intralesional resection. [Figure 1] are magnetic resonance imaging of patient 6. [Figure 2] are magnetic resonance imaging of patient 8.
Table 1: Clinical characteristics

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Figure 1: (a) Magnetic resonance imaging coronal figure of Patient 6 before surgery. (b) Magnetic resonance imaging axial figure before surgery. (c) Delineation of the target volume for the postoperative treatment of sarcoma with extension to the inguinal lesion (Patient 6)

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Figure 2: (a) Magnetic resonance imaging coronal figure of Patient 8 before surgery. (b) Magnetic resonance imaging axial figure before surgery. (c) Delineation of the target volume for the postoperative treatment of sarcoma with extension to the sciatic nerve (Patient 8)

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The oncological prognosis was as follows: four patients were continuously disease free, two showed no evidence of disease, and four died due to disease. There was no local recurrence in any patient after surgery. The average functional scores were 82% (range: 53–100). Among the 10 patients, 2 (22%) had grades 1–2 edema and 1 (11%) had grade 2 joint stiffness. Another patient developed grade 2 acute dermatitis. There were no severe complications such as infection, tissue necrosis, fracture, or nerve palsy.


 » Discussion Top


IMRT has been used in sites such as the prostate, head, neck, and breast, as well as for gynecological malignancies.[8],[9],[10],[11] The use of IMRT to treat sarcoma in the soft tissues of the upper and lower extremities is limited, but it appears to be increasing.[12] The feasibility of IMRT for large-field irradiation, which plays an important role in the treatment of sarcoma of the extremities, has been investigated.[13],[14] IMRT was associated with significantly reduced local recurrence compared with both conventional external beam radiation therapy and adjuvant brachytherapy for primary soft-tissue sarcoma of the extremities.[15]

One large study from the Memorial Sloan-Kettering Cancer Center reported that the treatment outcomes following preoperative and postoperative IMRT in patients with soft-tissue sarcoma in the extremities were excellent for local control and overall survival.[15] The main advantage of IMRT is its ability to conform the shape of the intended treatment target and minimizing the dose of radiation received by the surrounding normal structures.[4] Dose conformation is especially important for large tumors such as sarcomas so that adequate coverage of the periphery can be provided, and homogeneous coverage ensures that all tumor cells within the clinical volume receive an adequate dose.[15] In addition, the toxicities that were observed in the current study highlight some of the potential added benefits of IMRT in the soft tissues. In the previously mentioned study, postoperative IMRT resulted in significantly lower rates of complications than in earlier studies.[15]

Large areas of irradiated normal soft tissue increase the patient's risk of developing severe late morbidity such as fibrosis, atrophy, decreased range of movement, increased risk of fracture, peripheral nerve injury, and dependent edema.[16] The risk of late toxicity following radiation therapy for sarcoma of the extremities has been shown to increase as the radiotherapy field size increases.[17],[18] Although the number of patients in this study was small, our findings suggest that IMRT may not adversely affect peripheral nerve function and circulation when used in the treatment of tumors with neurovascular involvement. Latency also must be considered in the evaluation of radiation neuropathy due to IMRT. A long-term follow-up study of radiation therapy reported that the incidence of complications involving the nerves increased with time after radiation.[16],[17] Therefore, more clinical data on patients who are treated with IMRT including longer follow-up periods are required to identify further long-term morbidity.

The primary aim of IMRT for treating soft-tissue sarcoma of an extremity is a reduction of morbidity and maintenance of local limb control. Excellent local control and good limb function were observed in our study, despite almost all patients having large-sized and high-grade tumors. Furthermore, our study demonstrated that tumors with positive margins did not exhibit local recurrence. This finding may indicate that IMRT can control local recurrence and result in good functional outcomes.

This study is limited by its retrospective nature. Prospective assessment of functional outcomes was not possible, which might have biased our results. Due to the small number of patients and short follow-up period, the long-term complications of IMRT for treating malignancies of the extremities need further evaluation. In this study, IMRT in malignant tumors of the extremities provided excellent local control and preserved good limb function. To date, neurotoxicity and severe complications following IMRT have not been documented in previous studies. Our results show that adjuvant IMRT following function-preserving surgery for soft-tissue sarcoma of the extremity can be valuable for treating unmanageable tumors. Wide resection is best for treating soft-tissue sarcoma of extremities, but if not feasible, radiation is a good option.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Alektiar KM, Brennan MF, Singer S. Local control comparison of adjuvant brachytherapy to intensity-modulated radiotherapy in primary high-grade sarcoma of the extremity. Cancer 2011;117:3229-34.  Back to cited text no. 1
    
2.
Alektiar KM, Velasco J, Zelefsky MJ, Woodruff JM, Lewis JJ, Brennan MF, et al. Adjuvant radiotherapy for margin-positive high-grade soft tissue sarcoma of the extremity. Int J Radiat Oncol Biol Phys 2000;48:1051-8.  Back to cited text no. 2
    
3.
Yang JC, Chang AE, Baker AR, Sindelar WF, Danforth DN, Topalian SL, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 1998;16:197-203.  Back to cited text no. 3
    
4.
Stewart AJ, Lee YK, Saran FH. Comparison of conventional radiotherapy and intensity-modulated radiotherapy for post-operative radiotherapy for primary extremity soft tissue sarcoma. Radiother Oncol 2009;93:125-30.  Back to cited text no. 4
    
5.
Hong L, Alektiar KM, Hunt M, Venkatraman E, Leibel SA. Intensity-modulated radiotherapy for soft tissue sarcoma of the thigh. Int J Radiat Oncol Biol Phys 2004;59:752-9.  Back to cited text no. 5
    
6.
Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF, et al. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 1996;14:859-68.  Back to cited text no. 6
    
7.
Alektiar KM, Hong L, Brennan MF, Della-Biancia C, Singer S. Intensity modulated radiation therapy for primary soft tissue sarcoma of the extremity: Preliminary results. Int J Radiat Oncol Biol Phys 2007;68:458-64.  Back to cited text no. 7
    
8.
Hunt MA, Zelefsky MJ, Wolden S, Chui CS, LoSasso T, Rosenzweig K, et al. Treatment planning and delivery of intensity-modulated radiation therapy for primary nasopharynx cancer. Int J Radiat Oncol Biol Phys 2001;49:623-32.  Back to cited text no. 8
    
9.
Ling CC, Burman C, Chui CS, Kutcher GJ, Leibel SA, LoSasso T, et al. Conformal radiation treatment of prostate cancer using inversely-planned intensity-modulated photon beams produced with dynamic multileaf collimation. Int J Radiat Oncol Biol Phys 1996;35:721-30.  Back to cited text no. 9
    
10.
Chui CS, Hong L, Hunt M, McCormick B. A simplified intensity modulated radiation therapy technique for the breast. Med Phys 2002;29:522-9.  Back to cited text no. 10
    
11.
Mundt AJ, Lujan AE, Rotmensch J, Waggoner SE, Yamada SD, Fleming G, et al. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys 2002;52:1330-7.  Back to cited text no. 11
    
12.
Mell LK, Roeske JC, Mundt AJ. A survey of intensity-modulated radiation therapy use in the United States. Cancer 2003;98:204-11.  Back to cited text no. 12
    
13.
Wu Q, Arnfield M, Tong S, Wu Y, Mohan R. Dynamic splitting of large intensity-modulated fields. Phys Med Biol 2000;45:1731-40.  Back to cited text no. 13
    
14.
Chan MF, Chui CS, Schupak K, Amols H, Burman C, Ling CC, et al. The treatment of large extraskeletal chondrosarcoma of the leg: Comparison of IMRT and conformal radiotherapy techniques. J Appl Clin Med Phys 2001;2:3-8.  Back to cited text no. 14
    
15.
Folkert MR, Singer S, Brennan MF, Kuk D, Qin LX, Kobayashi WK, et al. Comparison of local recurrence with conventional and intensity-modulated radiation therapy for primary soft-tissue sarcomas of the extremity. J Clin Oncol 2014;32:3236-41.  Back to cited text no. 15
    
16.
Paulino AC. Late effects of radiotherapy for pediatric extremity sarcomas. Int J Radiat Oncol Biol Phys 2004;60:265-74.  Back to cited text no. 16
    
17.
Davis AM, O'Sullivan B, Turcotte R, Bell R, Catton C, Chabot P, et al. Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiother Oncol 2005;75:48-53.  Back to cited text no. 17
    
18.
Stinson SF, DeLaney TF, Greenberg J, Yang JC, Lampert MH, Hicks JE, et al. Acute and long-term effects on limb function of combined modality limb sparing therapy for extremity soft tissue sarcoma. Int J Radiat Oncol Biol Phys 1991;21:1493-9.  Back to cited text no. 18
    


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