Official Title
SUPR-3D: A Randomized Phase III Trial Comparing Simple Unplanned Palliative Radiation Therapy Versus 3D Conformal Radiation Therapy for Patients With Bone Metastases
Summary:
The primary objective is to patient-reported Quality of Life related to complete control of
Radiation Induced Nausea and Vomiting (RINV) between standard palliative radiation therapy 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.
Trial Description
Primary Outcome:
- Patient Reported Quality of life related to Radiation Induced Nausea and Vomiting (RINV)
Secondary Outcome:
- Control of RINV Radiation Induced Nausea and Vomiting (RINV)
- Patient Reported Pain Response
- Patient Reported Use of Medications
- Patient Reported Fatigue, Nausea, Vomiting
- Patient Reported Quality of Life
- Economic Analysis
For this study, SUPR (simple unplanned palliative radiation therapy) 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 Radiation Therapy, 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.
Radiation Therapy (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.
Currently, the standard of care in British Columbia for palliative patients with bone
metastases is SUPR. In other jurisdictions, however, factors such as physician remuneration
make other complex planning techniques more popular.
BC Cancer is publicly funded with no direct costs to patients. All RT in the province is
provided by 6 centres where radiation oncologists receive an annual salary, which are
independent of RT treatment technique and duration. Due to the lack of financial incentive
associated with a more complex RT plan, BC Cancer is a unique clinical setting to assess the
use of VMAT versus SUPR.
As facilities providing RT have gained more experience with VMAT and improvements to VMAT
planning software have been made, the planning time required has been reduced. Previously,
approximately 2 weeks was required for a team at the BC Cancer to create a VMAT plan for a
palliative patient with bone metastases; however, we hypothesize this can now be reduced to
three days in settings with low dose prescription.
This study will allow the investigators to determine if there is reduced toxicity associated
with VMAT compared to SUPR with only a modest impact on resources. The investigators
hypothesis is that VMAT will have reduced toxicity compared with SUPR for palliative patients
with bone metastases. The investigators also hypothesize that there will be no difference
between the two arms in terms of pain response, due to the fact that the doses are equal.
This hypothesis is driven by the radiobiologic rationale, which defines effective RT as the
ability of radiation to induce tumour cell death while sparing normal cells.
The importance in determining if there is any benefit in terms of toxicity with VMAT compared
with SUPR for palliative patients with bone metastases is obvious when consequences related
to its adoption are considered. As previously discussed, although the planning time has been
drastically reduced, there is still an expected modest increase in resources required to
carry out a VMAT plan. For patients, the pre-treatment process of VMAT is more burdensome,
i.e. patients have to wait longer before receiving VMAT as compared to SUPR, due to the
increased plan complexity. Therefore, it is important to consider the patient experience in
relation to the RT administration.
In summary, evidence that either supports or refutes the hypothesis that VMAT will have
reduced toxicity compared with SUPR for patients with bone metastases will be helpful in
guiding future practices. We are not aware of any other randomized control trials (completed
or ongoing) that have addressed this issue, though a London Ontario study is randomizing
patients receiving palliative lung RT to SUPR vs VMAT. Due to the implications of VMAT on
departmental resources and patient experience, better evidence from a randomized control
trial is required before the widespread use of this technique can be justified.
View this trial on ClinicalTrials.gov
