Palliative Radiotherapy for Bone Metastases: Single Versus Multiple Fractions.

Phase III Study of Palliative Radiotherapy for Bone Metastases Comparing Single to Multiple Fractions.

The aim of the investigators study was to determine whether 8 Gy in a single fraction provides equivalent pain and narcotic relief compared to 30 Gy in 10 fractions for patients with painful bone metastases.

The secondary objectives were to evaluate the frequency, duration of pain relief, narcotic relief, toxicity and the effect on quality of life measures for each of the two treatment arms.

Study Overview

• Status: Completed
• Conditions: Pain; Bone Metastases
• Intervention / Treatment: Radiation: single fraction; Radiation: multiple fractions

Detailed Description

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 1months.

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.

RADIATION THERAPY

Treatment Plan

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.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • Marilia, Sao Paulo, Brazil, 17501570
      • Radiation Oncology Department at Marilia Medicine school

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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 1 month.
• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 8 Gy arm; 8.0 Gy in 1 fraction to 8.0 Gy total dose.	Radiation: single fraction; 8 Gy x 1 fraction to 8 Gy total dose in single dose.
Active Comparator: 30 Gy arm; 3.0 Gy x 10 fractions to 30.0 Gy total dose in two weeks.	Radiation: multiple fractions; 3.0 Gy x 10 fractions to 30.0 Gy total dose in two weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Pain relief

Secondary Outcome Measures

Outcome Measure
duration of pain relief, narcotic relief, toxicity and the effect on quality of life measures for each of the two treatment arms.

Collaborators and Investigators

• Sponsor: Marilia Medicine School

Study record dates

Study Registration Dates

• First Submitted: March 6, 2009
• First Submitted That Met QC Criteria: March 9, 2009
• First Posted (Estimate): March 10, 2009

Study Record Updates

• Last Update Posted (Estimate): March 10, 2009
• Last Update Submitted That Met QC Criteria: March 9, 2009
• Last Verified: March 1, 2009

More Information

Terms related to this study

• Keywords: bone metastases from any histological subtype.
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Site; Hematologic Diseases; Musculoskeletal Diseases; Neoplastic Processes; Bone Diseases; Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases
• Other Study ID Numbers: FAMEMA - BONE METASTASES