Radiotherapy controversies in the radical treatment of soft-tissue sarcomas of the limb _ touch oncology _ independent insight for medical specialists

Soft-tissue sarcomas (STSs) should be managed by multidisciplinary teams, including specialist surgeons, radiation oncologists, medical oncologists, pathologists and radiologists. Is sarcoma cancer curable The aim of radical treatment for any STS should be to achieve the best possible local control rates with as little treatment-related morbidity and adverse effect on quality of life, as possible. Sarcoma botryoides Combination surgery and radiotherapy is currently regarded as standard treatment for STS of the extremity. Stromal sarcoma of breast 1

This article examines the treatment of non-metastatic STS, particularly the use of radiotherapy as an adjunct to limb-preserving surgery.

Myxoid sarcoma prognosis The arguments for and against neoadjuvant, intraoperative, adjuvant or no radiotherapy will be discussed.

In the 1960s it was shown that radiotherapy alone could produce complete histological response in STS, dispelling the long-held belief that all sarcomas were radioresistant. Ewing sarcoma arises from 2 STSs have variable degrees of radiosensitivity. Synovial sarcoma prognosis Some subtypes such as myxoid liposarcoma are very radiosensitive while others, such as malignant peripheral nerve sheath tumours (MPNST), are less so. Ovarian sarcoma The predicted radiosensitivity of any sarcoma should be considered when deciding on the most appropriate treatment regimen for an individual patient.

In most centres in Europe and North America, radiotherapy is given as external beam techniques (external beam radiotherapy [EBRT]). Uterine sarcoma risk factors Brachytherapy is another technique of administering radiotherapy usually in the intraoperative setting.

The major therapeutic goals when treating extremity STS are patient survival, local tumour control, maximising limb function and minimising morbidity from treatment. Treatment of sarcoma Treatment-related morbidity can cause considerable physical and psychological disability resulting in reduced quality of life. Ewing sarcoma cancer stage 4 New treatment paradigms for sarcoma should concentrate not only on local control and survival but also on the consequences of the treatment itself.

Historically neoadjuvant radiotherapy has been used in extremity STSs where upfront limb-conserving surgery is considered difficult. Kaposi sarcoma icd 10 If shrinkage of the sarcoma could facilitate conservative surgery then radiotherapy may be tried. Epithelioid sarcoma proximal type This approach requires extensive collaboration between radiologists, surgeons and radiotherapists. Sarcoma in children It is generally accepted if a sarcoma is truly unresectable without an amputation then neoadjuvant treatment, either radiotherapy or chemotherapy, is unlikely to render the tumour operable. Bone sarcoma cancer Over the last 15 years, neoadjuvant radiotherapy has become the standard of care in several countries, particularly Canada. Cancer sarcoma survival rates Trials have shown equivalent local control and survival rates to adjuvant radiotherapy. Metastatic ewing sarcoma 3 The toxicity profiles are different, with increased acute wound complications with neoadjuvant radiotherapy and increased late toxicities with adjuvant radiotherapy (see section below).

Traditional Response Evaluation Criteria In Solid Tumors (RECIST) criteria for neoadjuvant radiotherapy in STSs are not reliable predictors of pathological response. Aggressive sarcoma Myxoid liposarcomas are extremely radiosensitive tumours that frequently show 100 % necrosis after neoadjuvant radiotherapy. Sarcoma and carcinoma difference 4 Traditional RECIST radiological reporting in these cases usually report stable disease or no response to treatment. Symptoms of sarcoma in upper leg This is clearly not the case, and radiologists who are experienced in sarcoma radiology and the radiological changes in response to treatment are crucial in the discussion of these patients’ management. Malignant sarcoma tumor 5

Surgery is usually planned for four to six weeks postneoadjuvant radio therapy to allow for any cytoreduction to occur, but before late toxicities such as fibrosis and oedema that could make surgery more difficult.

Potter et al. Is sarcoma cancer treatable 6 first reported that limb-preserving surgery with radiotherapy had equivalent local control results to amputation in extremity STS patients without affecting overall survival. Sarcoma clinical trials Adjuvant radiotherapy then became standard of care after the results of several non-randomised studies and one randomised controlled study suggested limb-preserving surgery combined with radiotherapy appeared to give similar disease control but with significantly improved patient function. Sarcoma bone cancer prognosis 7 In the only randomised controlled trial (RCT), 91 high-grade extremity STSs were randomised between adjuvant chemotherapy alone or adjuvant chemotherapy plus adjuvant radiotherapy. Sarcoma tumor photos In the radiotherapy arm, no local recurrences were seen while in the surgery and chemotherapy alone arm the local recurrence rate at 10 years was 22 %. Soft tissue sarcoma staging There was no difference in overall survival and indeed no trial to date has reported any survival advantage with adjuvant radiotherapy. Ewing sarcoma symptoms in adults Radiotherapy at doses between 50–66 Gy can eradicate microscopic disease beyond the gross lesion. Sarcoma meaning With combined modality treatment, most centres report local control rates between 85–90 % for high-grade extremity STS.

Indications for adjuvant radiotherapy follow European Consensus Guidelines and have recently been supported by UK guidelines on the management of STSs. Osteogenic sarcoma bone cancer 8 Nearly all intermediate or high-grade STSs require postoperative radiotherapy. Hemangio sarcoma Low-grade tumours are unlikely to need radiotherapy unless they are large, deep and have been incompletely resected, with further surgery likely to compromise function.

The theoretical radiobiological arguments in favour of neoadjuvant or adjuvant radiotherapy can be seen in Table 1. Ewing sarcoma pathology outlines The only phase III RCT comparing neoadjuvant and adjuvant radiotherapy was performed in Canada by O’Sullivan et al. Bone sarcoma staging 3 One hundred and ninety patients with extremity STS were randomised to either neoadjuvant or adjuvant radiotherapy. Single cell sarcoma The neoadjuvant group received 50 Gy presurgery with a postoperative boost of 16–20 Gy if the surgical margins were involved. Uterine cancer sarcoma survival rates The adjuvant group received 66 Gy. Sarcoma surgery recovery time Primary and secondary endpoints included acute and long- term complications, the impact of morbidity on patient function, local recurrence rates and overall survival. Sarcoma symptoms and signs The study was terminated early when at interim analysis, with a mean follow up of 3.3 years, acute wound complications were significantly higher in the neoadjuvant radiotherapy arm compared with the adjuvant radiotherapy arm (35 versus 17 %; p=0.01). Prognosis of sarcoma The latest update at nearly seven years has shown no difference in local control rates between the two arms. Endometrial sarcoma Similar results for progression-free and overall survival are reported. Sarcoma clinic However, late grade 2–4 toxicity was significantly higher in patients receiving postoperative radiotherapy (86 versus 68 %). Metastatic sarcoma lung cancer This is predominantly due to an increase in subcutaneous tissue fibrosis causing either severe induration and loss of subcutaneous tissue or contracture >10 % (grade 3) or tissue necrosis (grade 4). Metastatic ewing sarcoma prognosis With neoadjuvant radiotherapy, the incidence of grade 3–4 fibrosis was 23 % versus 36 % with adjuvant radiotherapy. Sarcoma breast cancer survival rates Late limb oedema and joint stiffness were also more common in patients having adjuvant radiotherapy, but this did not reach statistical significance. Low grade sarcoma in dogs 9,10

Patients in the study who developed grade 2 or higher fibrosis, joint stiffness or oedema had significantly lower functional scores as measured by the Musculoskeletal Tumour Rating Scale (MSTS) and the Toronto Extremity Salvage Score (TESS).