SUPR-3D: A Randomized Phase III Trial Comparing Simple Unplanned Palliative Radiotherapy Versus 3D Conformal Radiotherapy for Patients With Bone Metastases
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 160
- 试验地点
- 8
- 主要终点
- Patient Reported Quality of life related to Radiation Induced Nausea and Vomiting (RINV)
研究概览
简要总结
The primary objective is to patient-reported Quality of Life related to complete control of Radiation Induced Nausea and Vomiting (RINV) between standard palliative radiotherapy and VMAT. Secondarily, we will assess rate of complete control of RINV. However, the investigators hypothesize that there will be no difference in pain response between the two arms, because they are receiving the same dose.
详细描述
For this study, SUPR (simple unplanned palliative radiotherapy) refers to the delivery of radiation to the treatment area with a simple technique, either two opposed fields (parallel opposed pair), or a single direct field. The entire portal is exposed to the specified dose and therefore does not spare normal tissue. This technique requires minimal calculation, and typically the dose distribution is not reviewed by the radiation oncologist or medical physics.
In general, the adverse event profile of RT is associated with irradiation of normal tissue within the treatment field. With the dose prescribed in this study, the probability of serious adverse effects is exceedingly low. However, fatigue, soreness, pain flare, and skin-redness in the irradiated area are relatively common adverse events. In addition, site-specific toxicity could occur, including esophagitis, nausea, or diarrhea when there is dose delivered to the GI tract. Avoiding this toxicity is a motivating factor for the study.
In order to deliver 3D Conformal Radiotherapy, a computerized tomography (CT) simulation is used to develop the treatment plan. The goal is to deliver a conformal radiation dose to the target volume with maximal sparing of the normal tissue. VMAT (Volumetric Modulated Arc Therapy) is a type of 3D conformal RT, and delivers the radiation dose more conformally than SUPR, possibly reducing acute and late toxicity. The disadvantages of VMAT include more complex planning and quality assurance processes compared with SUPR. The complex planning required can be time-consuming, which can have a significant impact on departmental resources, and the wait time for the patient.
Bone metastases are the most common site of distant metastases and can cause severe and disabling effects, including pain, spinal cord compression and pathologic fracture. These complications can greatly affect a patient's quality of life and cause immense suffering.
Radiotherapy (RT) is an effective treatment for palliative patients with painful bone metastases. It is also efficacious in preserving function and maintaining skeletal integrity, while minimizing the occurrence of adverse skeletal related events. There is a significant amount of evidence showing that a single fraction (SF) of RT provides equivalent pain relief as multiple fractions (MF), which are associated with more acute toxicity, are less convenient for patients and costlier for the health care system. Therefore, single fraction radiation therapy (SFRT) is encouraged, but 20 Gy in 5 fractions is also allowed in this study, though should be chosen only in patients with a complicated bone metastases by fracture, neurological deficit (e.g. spinal cord compression), or a large soft tissue component. In patients with advanced disease, management strategies focus on improving quality of life (QOL), rather than conventional endpoints such as survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 or older
- •Able to provide informed consent
- •Clinical diagnosis of cancer with bone metastases (biopsy not required)
- •Currently being managed with palliative intent RT to 1-3 RT fields for bone metastases, at least one RT field (PTV) must (at least) partly lie within T11-L5 or pelvis.
- •ECOG Performance Status 0-3
- •Patient has been determined to potentially benefit from 8 Gy or 20 Gy
- •Radiation Oncologist is comfortable prescribing 8 Gy in 1 fraction or 20 Gy in 5 fractions RT for bone metastases
- •Negative pregnancy test result for women of child-bearing potential
- •The baseline assessment must be completed within required timelines, prior to randomization.
- •Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
- •For simplicity of planning, expected GTV should be less than 20 cm based on radiological or clinical evidence
- •Patient must be prescribed a 5-HT3 receptor antagonist (e.g. Ondansetron) as antiemetic prophylaxis prior to RT start.
- •Patient is able and willing to complete the quality of life questionnaires, and other assessments that are a part of this study, via paper or using PatientPortals.ca or REDCap if they provide their email address on the informed consent
排除标准
- •Serious medical co-morbidities precluding radiotherapy
- •Clinical evidence of spinal cord compression
- •Spinal cord in treatment field has already received at least >30 Gy EQD2
- •Whole brain radiotherapy (WBRT) within 4 weeks of RT start or planned WBRT in the first 4 weeks after last RT
- •Solitary plasmacytoma
- •Pregnant or lactating women
- •Target volume cannot be encompassed by a single VMAT isocentre
- •Custom mould room requirements (shells and other immobilization that is standard-of-care is acceptable)
- •Greater than two organs-at-risk requiring optimization.
- •Patients requiring treatments outside standard clinical hours
- •Implanted electronic device within 10 cm of the RT fields
- •Prostheses in the axial plane of the target, or within 1 cm of the PTV out-of-plane
- •Previous RT that requires an analysis of cumulative dose (i.e. sum plans or EQD2 calculations)
- •Oral or IV contrast if the local standard-of-care requires compensation for this in planning.
研究组 & 干预措施
SUPR (Arm 1)
Planning according to local protocols. No more than 2 fields; no beam modifying devices, other than multileaf collimators (MLCs). Alternate weighting of beams allowed (ie. 1:2 AP:PA). Review of dosimetry not required, if performed as per institutional standard.
Minimum of kV image matching on unit daily.
干预措施: SUPR (Radiation)
VMAT rapid (Arm 2)
Contouring: GTV based on available imaging (CT sim scan alone-no special imaging), expect to be between 1.5cm and 20cm clinically or from imaging. CTV-optional in all scenarios. If using CTV=GTV +0.5 to 0.7cm adjust to anatomy as follows:
- If only bone involved: recommend not to expand past bone; but a 0.5-0.7cm CTV expansion outside of bone into muscle or soft tissue is allowed at RO discretion
- If bone and soft tissue involved: 0.5 to 0.7cm CTV expansion is optional, allowed at RO discretion
- If spinal metastases: CTV is optional. If used can include whole vertebral body at RO discretion PTV=CTV or GTV+(1 to 1.5)cm at RO discretion. PTV_eval=PTV cropped 0.5cm below skin. OARs: max 2 OARs permitted for VMAT arm. OAR constraints are at RO discretion. If lung/kidneys are within 5cm of PTV, absence of constraints for contours should be noted in treatment plans or dose constraint sheet prior to planning. PTV can be compromised for OAR at RO's discretion. Kidneys considered 1 organ
干预措施: VMAT (Radiation)
结局指标
主要结局
Patient Reported Quality of life related to Radiation Induced Nausea and Vomiting (RINV)
时间窗: day 1-5
RINV as measured by the Functional Living Index - Emesis (FLIE) at day 5 post RT start
次要结局
- Economic Analysis(baseline, 2 weeks, and 4 weeks post treatment)
- Control of RINV Radiation Induced Nausea and Vomiting (RINV)(day 1-5)
- Patient Reported Pain Response(baseline, 2 weeks, and 4 weeks post treatment)
- Patient Reported Use of Medications(baseline, 2 weeks, and 4 weeks post treatment)
- Patient Reported Fatigue, Nausea, Vomiting(baseline, 2 weeks, and 4 weeks post treatment)
- Patient Reported Quality of Life(baseline, 2 weeks, and 4 weeks post treatment)
研究者
Robert Olson
Radiation Oncologist & Department Head Radiation Oncology & Developmental Radiotherapeutics
British Columbia Cancer Agency