الفهرس 
EPIDEMIOLOGY, PREDICTIVE AND PROGNOSTIC FACTORS OF BONE METASTASISOnly 14 pages are availabe for public view
 |  | from | 267 |  |  |
| | | from | 267 | | |
Abstract
After the liver and lung, bone is the third most common site
of metastases. Eighty percent of all bone metastases are secondary
to breast, prostate, and lung carcinomas.
Cancer cells metastasize to bone almost exclusively via
hematogenous spread, although this may also result via direct
extension of tumor. Bone metastases are generally classified into
two types. Osteoblastic metastases are characterized by the
deposition of new bone via increased osteoblastic activity,
whereas osteolytic metastases are characterized by the destruction
of normal bone via increased osteoclastic activity. Metastatic
lesions can contain both components
Bone metastases are a significant cause of morbidity and
can lead to bone pain, immobility, hypercalcemia, pathological
fractures, nerve root damage, and spinal cord compression.
When bone metastases are suspected, imaging is needed to
confirm the suspicion and determine the location and extent of
involvement. Typically, the first test is a bone scan, which is a
good whole-body screening test, followed by plain films to further
characterize any lesions found on the bone scan. CT scan and MRI
can be helpful in areas that remain in question or in cases where
metastases were not detected, but suspicion is high.
The goals of therapy are to relieve pain, improve function,
and maintain skeletal integrity. Treatment should be
individualized, and consideration should be given to the overall
Summary
193
prognosis of a patient because long-term survivors are more at risk
for late toxicities and require longer lasting relief.
Current management of skeletal metastasis includes pain
management/analgesia, systemic therapy (bone modifying agents,
chemotherapy, hormone therapy), radiation therapy (externalbeam
radiation therapy, radiopharmaceuticals), and surgery.
Optimal treatment of skeletal metastasis is complex, and a
multidisciplinary approach is often needed.
Analgesic medication is the first-line therapy for pain
management and is often administered with a stepwise approach.
Surgery may be indicated when there is a fracture (or high
risk of fracture) of the long bones or hips, as well as spinal cord or
nerve compression. Post surgical radiation is also indicated to
prevent further tumor growth. New, less invasive, surgical
techniques are being investigated, including kyphoplasty and
vertebroplasty. Both techniques involve injection of a bone
cement into the collapsed vertebral bodies. In kyphoplasty, a
balloon is inflated prior to adding the cement to recreate the
normal height of the vertebrae. Both are outpatient procedures
with few complications that are effective in providing pain relief.
Radiation therapy is indicated for the treatment of spinal
cord compression, treatment of bones at risk for pathologic
fracture and palliation of pain caused by bone lesions. The
American Society for Radiation Oncology Guidelines for
palliative radiotherapy in bone metastases state that a single dose
of radiation (8Gy) is as effective in providing pain relief as
fractionated courses. Fractionated courses have lower retreatment
Summary
194
rates (8% versus 20%), however, the single treatment is more
convenient for the patient and retreatment is usually feasible when
needed. Treatment of spinal cord compression typically requires a
longer course of 10 fractions.
Radioisotopes are a viable treatment option for multifocal
bone metastases, and are typically used in prostate and breast
cancer cases with osteoblastic lesions. Strontium-89 and
samarium-153 are the isotopes currently used. These are effective
in providing pain relief in 80% of patients, with 10% becoming
pain free, with relief lasting 3-6 months. Both isotopes are
myelosuppressive and are contraindicated in patients with
leukocyte counts below 2400/mm3 and/or platelet counts below
60,000/mm3. Chemotherapy must be held typically for 6 weeks
after treatment.
Bisphosphonates decrease bone loss by inhibiting osteoclast
activity. Pamidronate and zoledronic acid, are more potent
osteoclast inhibitors than their first generation counterparts. These
agents are effective in reducing the frequency of skeletal-related
events in patients with bone metastases and in decreasing pain
related to bone lesions in both multiple myeloma and solid
tumors. Studies have shown zoledronic acid to be a more potent
inhibitor and it may be given in a shorter infusion than
pamidronate.
Denosumab is a monoclonal antibody that inhibits RANKL,
which in turn inhibits osteoclast activity. In clinical trials,
denosumab significantly prolonged the time to a skeletal event in
patients with bone metastases from breast and prostate cancer,
Summary
195
when compared to zoledronic acid. In another study, early results
show the median time to a skeletal event was significantly longer
with denosumab in other malignancies, including myeloma, renal
cell and lung cancers.
The goals of chemotherapy and hormone therapy in patients
with bone metastases are to control the tumor’s growth, thus
potentially reducing the risk of associated bony complications.
Even though the pain response is the most important end
point for patients with metastatic bone disease receiving palliative
care, the use of radiological or nuclear medicine imaging response
criteria may allow an objective evaluation of the therapeutic
outcome. Monitoring markers of bone turnover may be useful in
assessing the extent of bone disease in patients with solid tumors
metastatic to bone