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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2915_Библиотеки_им_академика_М_И_Перельмана.pdf
Bone Metastases
The most common tumors metastasize to bone are breast, prostate, renal,
thyroid, and lung carcinomas.
Improved survival and local control rates in patients with primary and metastatic
carcinomas have resulted in an increased incidence of bone metastases.
The most common bones involved are vertebra (69%) followed by pelvis (41%).
Radiographs of the entire long bone must be obtained for all painful sites; Plain-
film radiography is somewhat limited in evaluating bone destruction because 40
to 50 % of the trabecular bone must be destroyed before it becomes evident on
imaging.
Bone scans, however, can identify lesions as small as 2 mm. Once it has been
determined that the patient has a potentially malignant lesion, a bone scan
should be obtained to identify other sites of involvement.
The goal of orthopedic surgery is to restore the normal structural integrity of the
bone and to achieve tumor control.
Radiotherapy can be considered for patients with a single or limited number of
areas of painful bone metastases.
Chapter 18
Abstract
Introduction
The most common tumors metastasize to bone are breast, prostate, renal, thyroid, and
lung carcinomas.
Improved survival and local control rates in patients with primary and metastatic
carcinomas have resulted in an increased incidence of bone metastases. Pain is the most
common feature and requires thorough imaging studies for evaluation of the risk of
impending fracture.
Patients who are not at risk for impending fracture can be treated with a combination of
radiotherapy and adjuvant drug therapy. In this chapter we will on the management of long
bone metástases.
Gustavo Arruda Viani
262
1. Epidemiology
• Estimated that more than 25 % of patients with newly diagnosed cancer will have
bone metastasis
• The majority of bone metastases (80%) are from five specific carcinomas (breast,
prostate, lung, kidney, and thyroid cancers).
• Among these five histological subtypes breast and prostate cancers are the most
common.
• The median survival of patients with bone metastases from lung cancer is only a few
months, whereas patients with breast cancer or prostate cancer may live for several
years.
References
Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J
Cancer. 1987;55(1):61.
Chow E, Hird A, Velikova G et al. The European Organisation for Research and Treatment of
Cancer Quality of Life Questionnaire for patients with bone metastases: the EORTC
QLQ-BM22. Eur J Cancer. 2009;45:1146–1152
Fidler M. Incidence of fracture through metastases in long bones. Acta Orthop Scand
1981;52:623-627.
2. Anatomy
In the human body there are 126 bones, which serve as a structural support. Bones are
routinely remodeling, with the balance between bone destruction and bone formation
depending on interaction between osteoclasts and osteoblasts, respectively.
Osteolytic metastases result in osteopenia and subsequent mechanical pain (that is, pain
caused by loss of functional integrity). Osteoblastic metastases lead to a loss of structural
integrity and subsequent functional pain.
The most common bones involved are vertebra (69%) pelvis (41%) femur (25%) skull
(14%) and upper extremity (10 -15%.), figure-1. The pain may be local or radiate alone the
course of the nerves.
References
Fidler M. Incidence of fracture through metastases in long bones. Acta Orthop Scand
1981;52:623-627.
263
Figure 1. Bones and sites of metastases.
Bone Metastases
3. Pathology
• Metastases can affect any bone, but they are more common in sites containing red
bone marrow.
• Up to 70% of bone metastases occur in the axial skeleton and 10% in the
appendicular skeleton, usually in the proximal regions.
• Lytic lesions, such as those that are seen in the setting of multiple myeloma,
stimulate the production of factors that promote osteoclast growth and activity.
• Destruction of cortical bone causes weakening and, in the case of vertebral bodies,
resulting at collapse.
• Up to 1% of bone metastases results in pathologic fracture, with annual fracture rates
about 20%.
• Metastasis involves a cascade of linked sequential events that must be completed
before a tumor cell establishes a secondary tumor in bone. The figure-2 shows
multiple steps are involved in the general mechanisms of tumor cell metastasis to
bone.
Reference
Nielsen OS, Munro AJ, Tannock IF. Bone metastases: pathophysiology and management
policy. J Clin Oncol 1991;9:509- 524.
Gustavo Arruda Viani
264
Figure 2. Bone metastases mechanism.
4. Clinical Features
• Bone metastasis may be the presenting manifestation of cancer.
• The differential diagnosis of unexplained musculoskeletal pain in adults should
include primary and metastatic disease.
• Pain in the spine or proximal extremities should raise concern about metastatic
disease.
• Physical examination should focus on differentiating between bone and joint pain.
• If passive motion of the nearby joint is not painful, it should raise suspicion that the
pain is less likely the result of common joint problems. imaging studies Plain-film
radiography is the most specific imaging modality for metastatic disease (Figure-3).
Figure 3. Plain film radiography showing a osteolitic lesion.
Bone Metastases
265
References
Janjan N, Lutz S, Bedwinek J et al. Therapeutic guidelines for the treatment of bone
metastasis: A report from the American College of Radiology Appropriateness Criteria
Expert Panel on Radiation Oncology. 2009; J Palliat Med 12:417–423.
Peteet J, Tay V, Cohen G, MacIntyre J. Pain characteristics and treatment in an outpatient
cancer population. Cancer 1985;57:1259-1265.
5. Diagnosis and Evaluation
• The clinical evaluation should focus on any previous cancer diagnosis and treatment,
diagnostic evaluations for cancer, occupational and exposure history, and signs and
symptoms specific to organs from which common osteophilic primary cancers may
arise.
• Radiographs of the entire long bone must be obtained for all painful sites; these
should be carefully inspected for the type and extent of disease, the presence of
multiple lesions within the same bone, and the involvement of adjacent joints.
• Multiple lesions are a characteristic feature of metastatic disease. Lung, thyroid, and
kidney carcinomas typically are lytic and prostate cancer is blastic, whereas breast,
cervical, testicular, and ovarian cancers are mixed.
• Plain-film radiography is somewhat limited in evaluating bone destruction because
40 to 50 % of the trabecular bone must be destroyed before it becomes evident on
imaging.
• Bone scans, however, can identify lesions as small as 2 mm. Once it has been
determined that the patient has a potentially malignant lesion, a bone scan should be
obtained to identify other sites of involvement (figure-4). Similarly, a patient with a
known primary cancer and unexplained pain should undergo a bone scan even if
radiography is normal, because this study is more sensitive than plain-film
radiography and can detect lesions two to 18 months earlier.
• Computed tomography (CT) is the preferred method for evaluating cortical
destruction and juxta-articular metastatic disease. CT also is an important tool in
detecting a primary tumor. Thus, a CT scan of the chest, abdomen, and pelvis with
oral and intravenous contrast media is helpful in the evaluation of suspected bone
metastasis. Magnetic resonance imaging can help determine the degree of marrow
infiltration and extraosseous tumor extension, and it is useful in patients with
vertebral and epidural lesions (figure-4).
Reference
Algra PR, Bloem JL, Tissing H, et al. Detection of vertebral metastases: comparison between
MR imaging and bone scintigraphy. Radiographics 1991;11:219-232.
Gustavo Arruda Viani
266
Figure 4. Bone scan and MRI showing bone metastases.
6. Prognostic Factors
Several prognostic factors have been associated with survival and/or risks of developing
complications of bone metastases. Among these factors we can highlight:
• Tumor histology (median survival is higher for breast and prostate cancers (years)
than for lung cancer ( months).
• The number of sites and location of bone metastases
• The extent and volume of bone metastases
• Presence or absence of visceral metastases (lung, liver, and brain),
• Cachexia and performance status
References
Dawson R, Currow D, Stevens G, et al. Radiotherapy for bone metastases: a critical appraisal
of outcome measures. J Pain Symptom Manage 1999;17:208-218.
Chandler SS, Sarin R. Single fraction radiotherapy for bone metastases: are all questions
answered? Radiother Oncol 1999;52:191-193.
Treatment
• Any treatment plan for bone metastases must take into account the prognostic factors
associated with survival.
Bone Metastases
267
• Prognostic factors predicting survival duration of <6 months include low
performance status, visceral organ involvement, the extent and time for developing
bone metastases.
• In general there are two phases in the management of bone metastases: Phase I, when
the metastatic burden is low, anti-neoplastic therapy may be given in an aggressive
manner with the intent of increasing patient’s survival. Phase II when bone
metastases are treated with the intent to relieve distressing symptoms or to prevent
complications such as spinal cord compression or fracture of weight-bearing long
bones.
• Bone metastases alter two basic elements of bone: the material properties of bone
tissues and the structural properties of the entire bone.
• It can be assisted by the use of bisphosphonates. Thus, it is indicated to begin
bisphosphonates when there are lytic or mixed lytic/blastic bone metastases, or when
painful sites correspond to areas of bone destruction on bone imaging studies.
• On the other hand, a surgical fixation can be necessary. The goal of orthopedic
surgery is to restore the normal structural integrity of the bone and to achieve tumor
control.
• A scoring system for prediction of pathologic fractures based on a score of 1–3 and
four variables have been proposed. This score has also been used to guide orthopedic
surgery, as described in figure-5. Using this score patients with score higher than 7
should be submitted to surgical fixation (figure-6).
• Radiotherapy can be considered for patients with a single or limited number of areas
of painful bone metastases. In the literature there are several schedules of
fractionation, typically the treatment schedules are separeted in multiple fractions or
single fraction.
• A single fraction of 8 Gy to the involved area is recommeded due to provides similar
palliation with improved patient convenience and cost effectiveness when compared
with fractionated schedules.
• Multiple fractionation should be reserved for patients with a relatively long life
expectancy. Generally the preferred fractionated regimens are 30 Gy in ten fractions
or 20 Gy in five fractions depending on clinical scenario.
• Reirradiation is indicated if severe pain recurs (table-1).
Figure 5. Prognostic system for prediction of pathological fractures.
Gustavo Arruda Viani
268
Study
Description
Metaanalysis
(Chow et al.
2007)
Metanalysis 16 randomized trials comparing single fraction vs. multiple
fraction palliative RT regimens.
No difference in response rates. Trend for increased risk of pathological
fractures and spinal cord compression with single fraction RT. A 2.5×
increased retreatment rate with single fraction RT.
Bone Pain Trial
Working Party
(1999):
761 patients with painful bone mets were randomized to 8 Gy in single
fraction vs. 20 Gy in 5 fractions or 30 Gy in 10 fractions.
No difference in time to pain relief, proportion achieving relief, duration of
relief, or toxicity.
Retreatment given more frequently after 8 Gy (23% vs. 10%).
RTOG 9714
(Howell et al.
2009):
898 patients with breast or prostate cancer and KPS >40 were randomized to 8
Gy in 1 fxn vs. 30 Gy in 10 fractions.
Higher acute toxicity with 30 Gy (17% vs. 10%).
Pain CR/PR rates at 3 months were equivalent, 15%/50% for 8 Gy and
18%/48% for 30 Gy, but higher retreatment at 3 years for 8 Gy (18% vs. 9%).
Figure 6. Plain x ray of femur showing big osteolytic lesion of lesser trochanter and sub-trochanteric
area of shaft.
Table 1. Clinical evidence for multiple or single fractionation
radiotherapy for bone mets
References
Chow E, Harris K, et al. Palliative Radiotherapy Trials for Bone Metastases: a Systematic
Review. J Clin Oncol 2007;25:1423-1436.
Bone Pain Trial Working Party. 8 Gy Single Fraction Radiotherapy for the treatment of
Metastatic Skeletal Pain: Randomised Comparison with a Multifraction Schedule over 12
Months of Patient Follow-Up. Radiother Oncol 1999;52:111-121.
Bone Metastases
269
Howell DD, James JL, Hartsell WF, et al. Randomized Trial of Short-Course Versus Long-
Course Radiotherapy for Palliation of Painful Vertebral Bone Metastases: A
Retrospective Analysis of RTOG 97-14. J Clin Oncol 2009;27:7s. ASCO 2009, abstract.
7. Radiotherapy Techniques
The local to be treated is planned using a virtual CT or conventional simulation with
reference to diagnostic X-rays, bone scans, CT, MRI and sites of symptoms (figure-7).
Immobilisation is made individually for each patient and the site of the bone metastases to be
treated. Most sites can be treated with the patient supine, except vertebral lesions which are
ideally treated with the patient prone. This is especially relevant for cancers with a long
natural history, for which there is a possibility of re-treatment. Ankle stocks and head rests
can be used to aid immobilisation. Lesions in the upper cervical spine are best treated with the
patient supine, immobilised in a thermoplastic shell so that opposing lateral beams can be
used to avoid irradiating the oral cavity and pharynx. Patients who are to be treated with
electron or orthovoltage applicators can be immobilised supine, prone or on their side.
Figure 7. CT simulator for radiotherapy treatment.
The foci of the pain must be ascertained to ensure the correct site is treated. For example
knee pain may radiate from the hip, femur or spine, and rib pain may radiate from the
vertebral body. The volume chosen must balance symptom relief with sparing of normal
tissues to minimise side effects (e.g. small bowel with pelvic treatments). When possible, the
whole structure should be treated. It is usual to include one or two vertebrae above and below
the site of involvement. In the postoperative setting, the entire prosthesis or intramedullary
nail should be covered with a margin of normal bone. Because the risk of residual tumor at
surgical bed. In patients with multiple painful bone metastases, wide field volumes can be
treated (figure-8).
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270
Figure 8. Treatment fields of lombar and sacral bone metastases using IMRT.
Treatment portals are marked on the patient with reference tattoos as a permanent record.
DRRs or simulator films should be taken as a record and for reference for future treatment
planning. Actually, there are several fractionation schedules used to treat painful bone
metastases, such as: