Outcomes and toxicity of radiotherapy for refractory bone and soft tissue sarcomas

Abstract

Abstract. Surgical resection is a well-established treatment option for sarcoma. However, anatomical barriers often hamper radical surgical procedures. The treatment of unresectable sarcoma, including local or distant failures following initial treatment, is challenging. The aim of the present study was to analyze the outcome of radiotherapy (RT) for refractory sarcoma, including unresectable, metastatic and recurrent disease, following radical treatment. We retrospectively reviewed a total of 67 tumors in 28 patients who were treated with RT between 2007 and 2014. Clinical target volume (CTV) was generally not defined in a preventive manner; therefore, in the majority of the cases, CTV equaled the gross tumor volume. The total delivered dose, number of fractions and biological equivalent dose were 52 (range, 40-69), 10 (range, 4-24) and 92.2 (range, 56-119.6) Gy, respectively. Only 1 patient developed local failure, with a median follow-up of 11 months (range, 1-59 months). Therefore, the 12-month progression-free survival rate for 67 sites was 96.8%. The overall survival rates at 12 and 36 months were 75.8 and 30.2%, respectively. A total of 2 patients developed grade >2 toxicities, including grade 3 mucositis and grade 4 pericardial effusion. Our results demonstrated that radical RT using modern techniques is highly feasible, achieves excellent local control, and may be an effective treatment option for refractory sarcoma. IntroductionSurgical removal, requiring wide excision with negative margins, is a standard treatment option for sarcoma (1,2).However, several factors, including anatomical barriers, make radical surgical procedures more challenging.Approximately 50% of patients with sarcoma develop metastases during the course of the disease (3). However, the treatment for metastatic sarcoma is currently insufficient and represents a challenge (1-4).Solid tumor metastases are considered non-curable. In addition, metastatic disease is associated with poor outcome, as few patients achieve durable disease control (4). A number of sarcomas exhibit a unique biological preference for the lungs, which are often the only sites of metastatic disease. Therefore, controlling these specific sites of progression may improve survival (3).In recent years, the use of local treatment for sarcoma has increased. Historically, surgical resection of metastases has been primarily investigated in young patients. There is also evidence supporting the benefit of surgery for the treatment of metastases from soft tissue sarcomas, with surgery improving survival in selected cases (5). This aggressive surgical approach was retrospectively assessed for several sarcoma subtypes, providing an evidential foundation for ablative techniques. Surgery currently has the highest level of evidential support for the ablation of limited metastases, due to reports of patients cured from metastases (6).Radiotherapy (RT) is integral in multimodal treatment and palliative care (1,2). The use of RT is more generally accepted for the treatment of border...

Treatment options in unresectable soft tissue and bone sarcoma of the extremities and pelvis – a systematic literature review

“… 11 Yet, throughout the past years, several studies investigating novel treatment options have been published, with sometimes promising results ( Table 1 ). Besides conventional RTX as the standard of care for local treatment of some histological subtypes such as Ewing’s sarcoma, 12 particle therapy with protons or heavy ions may be used in unresectable or incompletely resected bone sarcoma – including relatively radio-resistant tumours as osteosarcoma – achieving adequate LC rates, especially in small tumours and single-site disease. 13 , 14 Furthermore, chemo-embolization with N-2-btyl-cyanoacrylate (NBCA) has been shown to be effective for symptom palliation in unresectable or recurrent bone sarcomas of the shoulder girdle or pelvis.…”

“… 13 , 14 , 66 Definite RTX in patients with unresectable non-rhabdomyosarcoma STS was shown to result in median disease-free survival rates of 12 months (range 0.1 years to 9.4 years). 12 , 65 Likewise, particle therapy seems to be effective in unresectable STS, although studies identified in the current systematic review either reported on few STS cases only 13 , 14 , or collectively analysed pelvic STS with retroperitoneal, chest wall- and abdominal wall-STS. 65 Of note, carbon ion radiotherapy seems to be more effective regarding LC in liposarcoma and undifferentiated pleomorphic sarcoma (UPS) as compared with malignant peripheral nerve sheath tumour or synovial sarcoma.…”

“…Transarterial chemo-embolization can be used in locally unresectable STS, leading to a reduction in pain scores, promising local response rates and median OS rates of 21 months (range: 11 months to 30 months) 63 to 23.7 months (± 2.1 months). 64 Other therapeutic measurements to achieve LC in unresectable STS include – similar to bone sarcomas – conventional RTX 12 , 65 and particle therapy. 13 , 14 , 66 Definite RTX in patients with unresectable non-rhabdomyosarcoma STS was shown to result in median disease-free survival rates of 12 months (range 0.1 years to 9.4 years).…”

Curative‐intent radiotherapy for pediatric osteosarcoma: The St. Jude experience

“…Overall, although our patient cohort tolerated RT relatively well, requiring little or no medical intervention for treatment complications, the morbidity of RT in this study and others was not insignificant. 7,20,26 With the advances in RT techniques 20 and the incorporation of charged-particle therapy, 8,27 it is hoped that continued progress in enhancing the therapeutic ratio through the reduction in treatment morbidity will improve outcomes for those patients with osteosarcoma who may benefit from RT.…”

Effect of primary tumor location and tumor size on the response to radiotherapy for liver metastases from colorectal cancer

“…The linear-quadratic (LQ) model has been widely used to compare differentially fractionated radiotherapeutic regimens, despite several limitations (35). Our previous studies have described a prescription using IMRT based on the LQ model (23,36,37). Hypofractionated radiotherapy at higher doses per fraction may increase radiation-induced damages due to direct cytotoxicity, and may lead to microvascular disruption (38)(39)(40)(41).…”