Hypofractionated 5x5 Gy Radiotherapy With Sequential Doxorubicin and Ifosfamide-based Chemotherapy in Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall
试验速览
- 阶段
- 2 期
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- The ratio of en limb-sparing/conservative R0 resections.
研究概览
简要总结
After a screening, which consists of biopsy, physical examination, initial diffusion-weighted magnetic resonance imaging (DWI-MRI), body computed tomography (CT) scan, blood tests and case analysis on Multidisciplinary Team (MDT) meeting, a patient will receive the first course of chemotherapy - doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm (AI regimen) with prophylactic mesna. Then a patient will be irradiated 5x5 Gy and after radiotherapy he or she will receive two courses of AI within 4-6 weeks, depending on the tolerance. Then the response analysis in DWI-MRI and toxicity assessment and will be performed. On the second MDT meeting, a final decision about resectability of the tumor will be made. In case of resectability, a patient will be referred to surgery.
详细描述
There is lack of standard treatment of marginally resectable sarcomas. Results of commonly used approaches are unsatisfactory. The addition of neoadjuvant/induction chemotherapy before the irradiation and in the prolonged gap between the end of hypofractionated 5x5 Gy radiotherapy and surgery may allow to obtain the R0 resection rate, high pathological response rate and/or a higher rate of limb-sparing/conservative surgery as well as to increase patients' survival.
Hypofractionation represents a variation of radiotherapy fractionation in which the total dose is divided into fewer fractions with an increased fraction dose. Such treatment may lead to additional biological effects when compared to conventionally fractionated radiotherapy (eg. vascular damage, increased immunogenicity, and antigenicity). The main advantages of hypofractionation are those related to the decreased overall treatment time what is more convenient for both patients and physicians, increased compliance and makes the treatment more cost-effective. Intriguing, such an approach may provide an additional benefit when treating non-radiosensitive tumors with a low alpha/beta ratio (eg. sarcomas).
The basis of the study was a trial conducted by Kosela et al. in our center, which showed that preoperative short 5x5 Gy radiotherapy with immediate surgery is an effective and well-tolerated treatment of resectable sarcomas of extremities or trunk wall.
The rationale of chemotherapy comes from the interim analysis of a multicenter, international EORTC study comparing neoadjuvant systemic approaches in high-risk sarcomas. It was proven that AI regimen, which consists of ifosfamide and anthracyclines allowed to obtain 20% benefit in relapse-free survival and overall survival as compared to pathologically-tailored chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to provide informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
- •Age ≥18 years old
- •Histologic diagnosis of soft tissue sarcoma
- •Primary or recurrent tumor localized on extremities or trunk
- •Grade 2 or grade 3 tumor
- •Marginally resectable tumor as assessed by a multidisciplinary team
- •Adequate renal function (serum creatinine ≤ 1.5 ULN)
- •Adequate liver function (total bilirubin, AST, ALT 3x < ULN)
排除标准
- •Radiation-induced sarcoma
- •Second active malignancy, not including localized basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with a history of other malignancies are eligible if they have been continuously disease-free for > 10 years prior to the time of registration.
- •History of radiation to the affected volume
- •Histologic diagnosis of rhabdomyosarcoma (except pleomorphic subtype), angiosarcoma, epithelioid sarcoma, clear cell sarcoma, extraskeletal chondrosarcoma, alveolar soft part sarcoma, osteogenic sarcoma, Ewing's sarcoma/PPNET, aggressive fibromatosis, dermatofibrosarcoma protuberans
- •Contraindications to radiotherapy, chemotherapy or surgery
- •Metastatic disease except primary resectable isolated lung metastases
研究组 & 干预措施
Sequential chemoradiotherapy
1xAI (doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm) + 5x5 Gy radiotherapy + 2xAI + surgery
干预措施: Sequential chemotherapy - 3 courses of AI (Drug)
Sequential chemoradiotherapy
1xAI (doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm) + 5x5 Gy radiotherapy + 2xAI + surgery
干预措施: Hypofractionated radiotherapy (Radiation)
结局指标
主要结局
The ratio of en limb-sparing/conservative R0 resections.
时间窗: 24 months
次要结局
- 2-years overall survival(24 months after treatment completion)
- 2-years local control rate(24 months after treatment completion)
- Pathological response in resected tumors according to EORTC Soft Tissue and Bone Sarcoma Group criteria(24 months)
- Radiological response in diffusion-weighted MRI(24 months)
- Toxicity of planned schedule of therapy according to CTCAE v.4.0.(24 months after treatment completion)