Phase III Study of Palliative Radiotherapy for Bone Metastases Comparing Single to Multiple Fractions.
This prospective, phase III, randomized study was conducted by department of radiation
oncology at Marilia Medicine School, São Paulo, Brazil.
Eligibility requirements included:
Age of 18 years or older, histologically proven primary malignancy of any histological type,
radiographic evidence of bone metastasis, pain corresponding to the area of bone metastasis,
a Karnofsky performance status of at least 40, and an estimated life expectancy of at least
Histologic diagnosis was established from needle biopsy, bone marrow biopsy, cytology, or a
surgical biopsy or resection.
Radiographic evidence of bone metastasis was required and performed within 8 weeks prior to
randomization. Acceptable studies included plain radiographs, radionuclide bone scans,
computed tomography scans and magnetic resonance imaging. Other studies were acceptable with
the approval of the principal investigator.
Eligible treatment sites were: pelvis, femur, sacrum and/or sacroiliac joints, tibia,
cervical, thoracic or lumbar vertebral bodies, humerus, fibula, radius ± ulna, clavicle,
sternum, scapula and púbis.
Patients had a "Worst Pain Score" of > 5 on a scale of 10 (as scored on the Brief Pain
Inventory [BP]: 0 = no pain; 10 = worst possible pain) or if BPI is < 5, had be taking
narcotic medications with a daily morphine equivalent dose ≥ 60 mg p.o. Patients receiving
systemic therapy were eligible for this study as long as there has been no introduction of
any systemic therapy within the 30 days prior to entry into this study.
The patient was ineligible if the systemic agent commences within the 30 days prior to
registration. This includes hormonal therapy, chemotherapy, and immunotherapy. Patients were
ineligible if the painful area had received prior radiation therapy or palliative surgery,
if there was pathologic fracture or impending fracture of the treatment site, or if there
was planned surgical fi xation of the bone. Patients with clinical or radiographic evidence
of spinal cord or cauda equina compression and/or effacement were not eligible.
Required information before randomization included history and physical examination,
Karnofsky performance status, radiographically documented bone metastases within 8 weeks
before randomization, and completed Brief Pain Inventory.
Arm A: 3.0 Gy x 10 fractions to 30.0 Gy total dose in two weeks. Arm B: 8.0 Gy in 1 fraction
to 8.0 Gy total dose.
Simulation of treatment fields was required prior to the first treatment. Prior to the first
treatment, an acceptable simulator and portal film documenting that the treatment site was
adequately covered and verified by the treating radiation oncologist.
Treatment was given using megavoltage equipment with Cobalt-60 or 6-Mev photons. The minimum
Source-Axis Distance (SAD) was 80 cm. All fields were treated each day. Treatment volume was
including the radiographic abnormality with at least a 2 cm margin. Treatment of the entire
bone is not required. Anterior and posterior parallel opposed fields were used for lumbar
spine, sacrum, pelvis, and extremity sites. Equal weighting was recommended, although
unequal weighting was used for the lumbar or sacral spine with a ratio of doses of 1:2
AP:PA. Dose was prescribed at mid thickness at the central axis, or at the center of target
volume if unequal weighting is used. The cervical spine was treated with either parallel
opposed lateral fields or with a single posterior field. When lateral fields were used, the
isocenter should be at mid-thickness, with the dose prescribed to the mid-vertebral body.
For a single posterior field, the dose was prescribed at a depth of 5 cm or other depth as
determined from a lateral simulator film. When more than one osseous site was included into
one treatment field, the treating radiation oncologist used differing field arrangements at
her/his discretion, with the fields arranged to provide relatively uniform treatment of the
target sites with a minimum of uninvolved normal tissues.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Brazil: National Committee of Ethics in Research
FAMEMA - BONE METASTASES