Bone

​Epidemiology:
Primary cancer of the bone is rare. The highest incidence occurs in adolescents at the age of 15. The incidence is the same in male and female until the age of 13 then there is a higher incidence in males.2
Etiology:
Skeletal neoplasms arise in areas of rapid growth. The distal femur and proximal tibia are the most active growth plates in adolescents, therefore the most common sites for disease. 2
Signs & Symptoms:
Osteosarcomas usually present with local swelling and pain of the involved area. With chordomas symptoms depend on the tumor location. For example, pain and abnormal gait may be related to cord or nerve root compression, which predominates in paraspinal and sacrococcygeal lesions. Fibrosarcomas and malignant fibrous histiocytomas are usually related to pathological fractures. 1
Diagnostic Procedures:
Diagnostic work-up for bone tumors include the following:
  • History and Physical
  • Open Biopsy (avoiding incision over area not to be radiated)
  • Bone Marrow Aspiration and Biopsy (for Ewing's sarcoma)
  • Standard Radiologic Studies such as x-rays of bone and chest; CT of affected bone, surrounding tissue, and lungs; Nuclear Medicine scans; and MRI of affected bone and surrounding soft tissue
  • Angiography has been used
  • Laboratory Studies include a CBC, complete blood chemistry, urinalysis, and erythrocyte sedimentation rate

Plain films and CT of the lungs is necessary because of the high rate of metastases. CT and MRI images are important in evaluating chordomas because of the soft tissue component. 1
Histology:
Osteogenic:
Osteosarcoma
Conventional osteosarcoma
Telangiectatic osteosarcoma
High-grade surface osteosarcoma
Periosteal osteosarcoma
Parosteal osteosarcoma
Dedifferentiated parosteal osterosarcoma
Small-cell osteosarcoma
Well-differentiated intrameduallary osteosarcoma
Osteosarcoma in Paget's disease
Osteosarcoma in irradiated bones
Osteosarcoma in the jaw
Multicentric osteosarcoma
Chondrogenic:
Chondrosarcoma
Primary central chondrosarcoma
Mesenchymal chondrosarcoma
Clear-cell chondrosarcoma
Dedifferentiated chondrosarcoma
Secondary chondrosarcomas
Histiocytes:
Malignant fibrous histiocytomas
Unknown:
Ewing's sarcoma
Adamantinoma
Notochordal:
Chordoma
Vascular:
Angiosarcoma
Hemangioendothelioma
Hemangiopericytoma
Hematopoietic:
Myeloma
Lymphoma
Lipogenic:
Liposarcoma
Neurogenic:
Neurofibrosarcoma 3

Lymph Node Drainage:
"Lymphatic spread of most bone tumors is not of great concern unless the tumor arises in the trunk of the body. There the lymph vessels and nodes are more prominent and a greater chance exists of the tumor invading the lymph system. If this occurs, the microscopic tumor cells can be carried to other parts of the body through the lymphatic system."4
Metastatic Spread:
The tendancy for most sarcomas is to metastasize hematologically to the lungs (especially the periphery of the lung).
Occasionally, Osteosarcoma, MFH, and chondrosarcoma will metastasize to other sites (bone, liver, and brain). Low grade tumors are locally invasive and do not tend to metastasize readily (easier to control). Local recurrance is common with low grade tumors. Skip metastasis are another pattern of spread with osteosarcomas
. 4
Grading:
G1, low grade
-Parosteal osteosarcoma
-Endosteal osteosarcoma
-Secondary chondrosarcoma
-Fibrosarcoma, low grade
-Atypical malignant fibrous histiocytoma
-Giant cell tumor

G2, high grade
-Classic osteosarcoma
-Radiation-induced sarcoma
-Paget's sarcoma
-Primary chondrosarcoma
-Fibrosarcoma, high grade
-Malignant fibrous histiocytoma
-Giant cell sarcoma
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Staging:
There is no universally accepted staging system for primary bone sarcomas. The Enneking system classifies tumors according to grade, local extent, and presence or absence or distant metastases.

Enneking Staging System for Bone Sarcomas

Grade (G)

G1, low grade
-Parosteal osteosarcoma
-Endosteal osteosarcoma
-Secondary chondrosarcoma
-Fibrosarcoma, low grade
-Atypical malignant fibrous histiocytoma
-Giant cell tumor

G2, high grade
-Classic osteosarcoma
-Radiation-induced sarcoma
-Paget's sarcoma
-Primary chondrosarcoma
-Fibrosarcoma, high grade
-Malignant fibrous histiocytoma
-Giant cell sarcoma

Local Extent (T)

T1, Intracompartmental
-Intraosseous
-Paraosseous

T2, Extracompartmental
-Soft tissue expansion
-Extrafascial or deep fascial extension

Metastases (M)

M0 - No distant metastases
M1 - Distant metastases exists

Staging Grouping
IA G1 T1 M0
IB G1 T2 M0
IIA G2 T1 M0
IIB G2 T2 M0
III G1 or G2 T1 or T2 M1
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Radiation Side Effects:
-The effects of radiation therapy on bone are directly related to the dose and treatment volume and inversely related to age at time of therapy.
-Clinically evident growth abnormalities are evident 6 months and 1 year after treatment in infants and in older children, respectively.
-Scoliosis after vertebral irradiation is limited and is frequently compensated for by pelvic tilt.
-Irradiated bone is more prone to infection, fracture, and necrosis because of radiation-induced small-vessel changes.
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Prognosis:
The most important prognostic factor for primary bone cancer is the size of the tumor at diagnosis. 1 The histologic response and the tumor site are also important. The pelvis and proximal femur sites are associated with a worse prognosis.2
Treatments:
General Radiation Techniques
When treating bone tumors with definitive radiation, it is very important to plan precisely and use effective immobilization. Cerrobend or MLC's should be used to spare a strip of skin, usually 1.5 to 2 cm if possible, on one side of the extremity. The reason for doing this is to limit distal-extremity edema and constrictive fibrosis. Treatment results can be improved by using treatment planning done with CT or MRI imaging. "Use of particle beam irradiation has been suggested because bone tumors are not considered to be very radioresponsive and are frequently located in areas in which a sharp beam collimation is essential to prevent severe side effects (e.g., lesions of the base of the skull). Several retrospective studies showed increased local tumor control when particle beams were used."

Osteosarcoma

"The best treatment for osteosarcoma includes systemic chemotherapy and surgical resection." When comparing surgery approaches, whether radical or limb-sparing, the survival characteristics are the same. The most common problem arising from limb-sparing surgery is soft tissue problems although these have decreased "with the aggressive use of rotational and free flaps at the time of surgery." Also, resection of pulmonary mets may improve survival.
Studies have reported "a response rate of 77% with doxorubicin, vincristine sulfate, high-dose methotrexate, and cyclophosphamide." Another study "showed that a short-term, aggressive, preoperative chemotherapy regimen in operable osteosarcoma gives the same results (in terms of toxicity, percentage of necrosis, and outcome) as longer and more complex multiagent chemotherapy regimens."
Many different methods have been investigated for the use of radiation with osteosarcoma. "A multicenter trial using combined intraarterial chemotherapy and irradiation (up to 45 Gy in 2- to 3-Gy fractions) reported a local tumor-control rate of 98.5% in 66 patients, 60 of whom underwent limb-sparing surgery." Similar positive results "have been achieved with 50 to 60 Gy of intraoperative radiation therapy, with or without preoperative chemotherapy." Aggressive treatment of osteosarcoma with multiple modalities, has been associated with "an impressive morbidity rate."


Malignant Fibrous Histiocytoma of Bone
The main treatment has been aggressive surgery consisting of radical resection, amputation, and disarticulation. "Radiation therapy responses have occurred predominantly with histiocytic rather than fibrocytic histologies." Studies have "reported postoperative tumor control in 75% of patients with malignant fibrous histiocytoma of bone who were treated with a combination of photons and electrons (median dose of 60 Gy in 43 days)." Positive results were also given with intraoperative radiation of 15 to 30 Gy.


Chondrosarcoma
Treatment of choice for chondrosarcoma is surgery. The standard procedure used for surgery is wide total excision with the possibility of amputation. Radiation has been used for inoperable lesions and palliation. For chondrosarcoma, local tumor control rates of 45% to 50% have been reported with 40 to 60 Gy at 2 Gy per fraction using a multiple field technique. If there was medullary involvement, the entire bone would be treated.


Giant Cell Tumor
It has been recommended that surgery should be the primary therapy for this type of disease, using radiation only when in it warranted. It is used for inoperable lesions, incomplete resections, and local recurrences after surgery. Another situation in which radiation is used is when performing surgery would cause significant functional disability. "An 80% local tumor control rate was reported in patients with giant cell tumors who were treated with 45 to 55 Gy."


Aneurysmal Bone Cyst
"Surgery with curretage and bone grafting or cryosurgery, if possible, is the preferred treatement." With postop irradiation, studies have shown a decrease in local recurrence from 32% to 8% with 20 to 30 Gy.


Chordoma
"Radical surgery and radiation therapy often are limited with chordomas because of the proximity of neural structures, expecially at the base of the skull and the spine; this often results in local recurrence." When chordomas are resectable, a combination of surgery and postop irradiation is considered the standard treatment. Because surgical excision is usually incomplete as a result of the tumor location, radiation therapy often plays an important role. "Doses of 50 to 60 Gy have been reported to provide significant tumor control." Chordomas have also been treated with particle beams.


Ewing's Sarcoma
"Surgery is the treatment of choice for lower-extremity lesions in children with unfused epiphyses, impending pathologic fracture, or bones that are expendable (fibula, clavicle, and certain ribs). Amputation may be saved for after local failures after radiation treatment. "The best results have been achieved with multimodality regimens involving adjuvant irradiation and chemotherapy." "Treatment of metastatic Ewing's sarcoma with VAC-ADR regimen (vincristine sulfate, cyclophophamide, dactinomycin, and doxorubicin) plus 45 Gy of radiation therapy to the primary tumor and smaller total doses of radiation to metastases has resulted in 5-year survival rates of approximately 30%." That study, "required doses of 45 Gy t the whole bone with two boosts of 5 Gy each (including the soft tissue mass) to tumor margins of 5 cm and 1 cm, while sparing the uninvolved epiphysis (if possible) in cases in which the tumor was at or near the end of a long bone." A study done by a pediatric oncology group didn't show any advantage of the whole bone irradiation over that with the "tailored portals with 5-cm margins." Results from a study done at the University of Florida were excellent using hyperfractionation of 1.2 Gy given twice a day with doses totalling at 50.4 Gy to 60 Gy.
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ewingsarcomalocation.JPG
Figure 1. Percentage distribution for primary sites in Ewing's Sarcoma.4

ewingsarcomaportal.JPG
Figure 2. Treatment portal for Ewing's Sarcoma.5

Metastatic Disease
The majority of malignant bone disease are metastatic. "The treatment goal of bone metastases is concentratedon the palliation of pain and the prevention of fractures to weight-bearing bones." Narcotics are often used to help alleviate the pain that these patients are in but these narcotics can lead to things such as constipation and oversedation. For these reasons, radiation is also used to help with bone pain. "The use of radiation therapy is important in the local control of the lesion, relieving pain and preventing the loss of function of the bone or bones involved." Hormone therapy and chemotherapy may be used also depending on the histology of the primary disease site. Surgery is used for patients with bone metastases when there is need for stabilizing a weight-bearing bone or when a mass needs to be debulked to help reduce significant pain. "Radiation therapy is usually introduced after the surgical procedure to help obtain local control." Radiation portals used for treating bone mets need to include all of the involved areas while sparing univolved tissue whenever possible. For those who have had surgery and postop radiation is indicated, the radiation should begin as soon as their wound has healed. "The portal should include the fixation device and any micrometastases that may have been dislodged during the surgical procedure. However, a strip of tissue should be left unirradiated to preserve lymphatic drainage. When there are bone mets involving the pelvis and spine, the treatment must be planned very carefully. The field should encompass the area of tumor involvement while avoiding uninvolved bone to spare the bone marrow and other normal tissue. When treating the spine, the field should include the involved vertebrae with a one-vertebrae margin above and below.

"The intoduction of strontium-89 has provided excellent results in bone-pain relief for patients with prostate and, to a lesser degree, breast cancer that is metastatic to the bone. Strontium-89 is a radiopharmaceutical agent used for the palliation of metastatic bone pain and may be administered in either or both radiation oncology or nuclear medicine facilities. It is a pure beta-emitter that causes minimal irradiation of the normal tissues. This agent localizes to osteoblastic areas or skeletal metastatic lesions from the primary cancer." It has a half-life of 50.5 days so its pain-relieving effect can last for up to 15 months. It may take 1 to 3 weeks before the patient notices any pain relieving effects.
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Figure 3. Metastatic bone portal.4
TD5/5:
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Figure 1. TD 5/5 for areas possibly affected by bone treatment.4
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Figure 2. TD 5/5 for areas possibly affected by bone treatment.4
1. Chao. KS, Perez. CA, Brady. LW. Radiation Oncolgy Management Decisions.2nd edition. Philadelphia, PA; Lippincott Williams & Wilkins. 1999,2002; 606-607. 611, 605-606.
2. Rubin P. Clinical Oncology A Multidisciplinary Approach for Physicians and Students.8th Edition. Philadelphia, PA: W.B. Saunders Company. 2001; 632-643.

3. Lenhard RE, Osteen RT, Gansler T. The American Cancer Society's Clinical Oncology. 1st edition. Atlanta, GA: The American Cancer Society, Inc. 2001: 618.
4.Washington CM, Leaver DT. Principles and Practice of Radiation Therapy Practical Applications. 3rd Edition. St. Louis, Missouri: Mosby.1997:586-588,572-576.
5. Dashers BG, Wiggers NH, Vann AM. Portal Design in Radiation Therapy. Columbia, SC: The R.L. Bryan Company. 1994: 161.