Bone

Primary bone neoplasms are rare.1 Most common tumors are: * Osteosarcoma * Ewing’s sarcoma * Chondrosarcoma * Fibrosarcoma * Malignant fibrous histiocytoma of bone * Giant cell tumor * Aneurismal bone cyst * Chordoma || Cancer of the bone is rare, but research has revealed a couple factors that may cause it: 2 Signs and symptoms associated with bone cancer include local swelling and pain in the involved area. It is uncommon to find joint effusion and pathologic fracture at the time of presentation. The signs and symptoms for Chordoma are dependent on the location of the tumor. If a cord compression or nerve root compression exist, pain and an abnormal gait may be present.3 ||
 * **Epidemiolgy:** || Becky
 * **Etiology:** || Adam
 * Patients having previously received external beam therapy or anticancer drugs are more susceptible to osteosarcomas, especially children
 * Heredity
 * Patients with metal bone implants ||
 * **Signs & Symptoms:** || Megan
 * **Diagnostic Procedures:** || Kevin Tsai

There are many different pathologic types of bone tumors, the most common being the following:4 In comparison to metastatic bone malignancies, primary bone tumors are rare and do not spread into the lymphatic’s system very often.1 These primary bone malignancies are usually treated without concern for lymphatic spread unless the tumor arises within the trunk of the body.5 || Bone malignancies especially high-grade tumors tend to metastasize hematologically to sites like the lungs, liver, brain and sometimes even other bones. It is estimated that patients with osteosarcoma have an 80% chance of lung metastases 2 years after being diagnosed. Another way that primary bone tumors can affect individuals is by what is called skip metastases. In this case a secondary lesion may appear in the same bone or on the opposing side of a joint space. Spread by way of the lymph system is usually the case of tumors found in the trunk of the body where there lymph nodes have a greater presence. This is not usually of great concern for physicians because hematological spread is much more common.6 || ¨ Parosteal osteosarcoma ¨ Endosteal osteosarcoma ¨ Secondary chondrosarcoma ¨ Fibrosarcoma, low grade ¨ Atypical malignant fibrous histiocytoma ¨ Giant cell tumor ¨ Adamantinoma While there is no universally accepted staging system for bone cancers, the Enneking system can be used and is as follows: 3
 * General 3
 * History
 * Physical Examination
 * Special Studies
 * Open biopsy, avoiding incision over area not to be irradiated
 * Bone marrow aspiration and biopsy (for Ewing’s)
 * Radiologic Studies
 * Standard
 * Plain radiography of bone and chest
 * CT of affected bone, surrounding soft tissue, and lungs
 * Radionuclide bone scan
 * MR imaging of affected bone and surrounding soft tissue
 * Optional
 * Angiography
 * Laboratory Studies
 * Complete blood cell count on admission
 * Blood chemistry profile
 * Urinalysis
 * Erythrocyte sedimentation rate ||
 * **Histology:** || Erin
 * Osteosarcoma (excluding myeloma)
 * Usually is poorly differentiated (85% of lesions are grade 3 or 4, with varying amounts of cyst formation, hemorrhage, and necrosis - these are important when radiosensitivity is being considered)
 * "Skip" bone mets may be seen
 * Ewing's sarcoma
 * Chondrosarcoma - grade is an extremely important prognostic factor
 * Firosarcoma
 * Malignant fibrous histiocytoma of bone
 * Giant cell tumor - grade is NOT a reliable prognostic factor
 * Aneurysman bone cyst
 * Chordoma ||
 * **Lymph node drainage:** || Spencer
 * **Metastatic spread:** || Pablo
 * **Grading:** || Becky
 * G1, low grade:**
 * G2, high grade:**
 * Classic osteosarcoma
 * Radiation-induced sarcoma
 * Paget’s sarcoma
 * Primary chondrosarcoma
 * Fibrosarcoma, high grade
 * Malignant fibrous histiocyoma
 * Giant cell sarcoma.7 ||
 * **Staging:** || Adam

Grade G1, low grade G2, high grade
 * Parosteal osteosarcoma
 * Endosteal osteosarcoma
 * Secondary chondrosarcoma
 * Fibrosarcoma, low grade
 * Atypical malignant fibrous histiocytoma
 * Giant cell tumor
 * Adamantinoma
 * Classic osteosarcoma
 * Radiation-induced sarcoma
 * Paget's sarcoma
 * Primary chondrosarcoma
 * Fibrosarcoma, high grade
 * Malignant fibrous histiocytoma
 * Giant cell sarcoma

Local Extent T1, intracompartmental T2, extracompartmental
 * Intraosseous
 * Paraosseous
 * Soft tissue extension
 * Extrafascial or deep fascial extension

Metastasis M0 - No distant metastasis M1 - Distant metastasis exists || The side effects associated with bone cancer radiation are many. Interestingly, the exposure to radiation dosages above 60 Gray, like that used during the treatment of retinoblastoma, can lead to the development of bone cancer. The effects of radiation are directly related to the dose and the treatment volume. And they are inversely related to the age of the patient at the time of therapy. Although limited, scoliosis can be a side effect of vertebral irradiation. It can be compensated for by pelvic tilt. Irradiated bone is more apt for infection, fracture, and necrosis because of radiation induced small vessel changes. Side effects of the radiation administered for Ewing's Sarcoma are if the femur is irradiated, 2/3 of the patients will develop shortening of 2 cm or more ad 1/3 develop pathologic fractures. One in 4 patients with a primary tumor in their tibia, require amputation after completing radiation.8 ||
 * **Radiation side effects:** || Megan
 * **Prognosis:** || Kevin Tsai

Radiation therapy has been a controversial topic in the treatment of bone lesions. Many trials and approaches have been experimented with using radiation therapy.
 * The most important factor in osteosarcoma is metastasis at presentation. Radiation-induced osteosarcoma has a worse prognosis1
 * Prognostic factors in chondrosarcoma include histologic grade, size, cell type, location, stage at presentation, patient age, degree of local aggressiveness, and presence or absence of pain at presentation. Metastases developed in 0% of patients with grade 1 chondrosarcoma, 10% with grade 2, 73% with grade 3.
 * The most important prognostic indicators for chordoma are site of origin and local extension of tumor.9 ||
 * **Treatments:** || Erin

Osteosarcoma:10
 * Treatment choice: systemic chemotherapy and surgical resection
 * A Multi-Institutional Osteosarcoma Study has shown significant benefit to postoperative adjuvant chemotherapy
 * Memorial Sloan-Kettering has recommended combined radiation therapy and chemotherapy for extrapulmonary mets and small primary lesions in patients with metastatic disease
 * Resection of pulmonary mets may improve survival
 * Numerous radiation therapy trials/approaches have been used
 * Combined chemo and RT (up to 46Gy in 2-3 fractions)
 * 50-60Gy intraoperative RT with or without preoperative chemotherapy
 * Pulmonary irradiation, with or without chemotherapy

Chondrosarcoma:
 * Treatment of choice: surgery
 * Standard surgical procedure is wide total excision with possible amputation
 * Radiation therapy has been used for inoperable lesions and for palliation
 * 40-60Gy at 2Gy/fraction using multiple fields (MD Anderson reported local control rates of 45-50%)
 * Entire bone can be treated if medullary involvement is present
 * Comined photon-neutron therapy (has been done at MD Anderson)

Malignant Fibrous Histiocytoma of Bone:
 * Treatment of choice: aggresive surgery (involving radical resection, amputation or disarticulation)
 * Radiation therapy responses have occurred predominately wit hhistiocytic rather than fibrocytic histologies
 * Combined photons and electrons (median dose of 60Gy in 43 days) - has reported 75% postoperative local control rate
 * Intraoperative radiation therapy of 15-30Gy

Giant Cell Tumor:
 * Treatment of choice: surgery
 * Radiation therapy is used for inoperable lesions, incomplete resections, and local recurrences after surgery
 * 45-55Gy (shows an 80% local tumor control rate)

Aneurysmal Bone Cyst:
 * Treatment of choice: surgery with curettage and bone grafting or cryosurgery
 * 20-30Gy postoperative radiation therapy (shows a decrease in local recurrence from 32% to 8%)

Chordoma:
 * Treatment of choice: combined surgery and postoperative irradiation
 * Radical surgery and radiation therapy are often limited becaues of the proximity of neural structures (this often results in local recurrence)

Ewing's Sarcoma: Depending on where the primary bone lesion is located, there are a variety of different organs that could be at risk.11
 * Treatment of choice: surgery (for lower-extremity lesions in children)
 * Amputation - for local failures after radiation therapy
 * Best results have been achieved with multimodality regimens involving adjuvant irradiation and chemotherapy
 * VAC-ADR regiment (vincristine sulfate, cyclophosphamide, dactinomycin, and doxorubicin) + 45Gy RT to the primary tumor and smaller doses of radiation to mets (has resulted in 5 yr survival rates of ~30%)
 * 45Gy to the whole bone with two boost of 5Gy each (including the soft tissue mass) to tumor margins of 5cm and 1cm are given
 * The Pediatric Oncology Group study 8346 showed no advantage of whole-bone irradiation versus more conformal fields with 5cm margin. ||
 * **TD 5/5:** || Spencer
 * Articular Cartilage: >500 Gy – No Injury
 * Bladder: 60 Gy – Contracture
 * Esophagus: 60 Gy – Ulceration and Stricture
 * Heart: 45 Gy – Pericarditis
 * Bone Marrow: 2.5 Gy – Aplasia
 * Intestine: 45 Gy – Ulcer, Perforation, and Hemorrhage
 * Kidney: Whole – 15 Gy/ Partial – 20Gy – Acute and Chronic Nephrosclerosis
 * Spinal Cord: 45 Gy – Infarction and Necrosis ||
 * **References:** || 1. Chao KSC, Perez CA, Brady LW. Bone and Ewing’s sarcoma. In: Chao KSC, Perez CA, Brady LW, eds. Radiation Oncology Management Decisions. Philadelphia, PA: Lippincott, Williams and Wilkins; 2011: 691-702.

2. Bone Cancer. National Cancer Institute Web Site. http://www.cancer.gov/cancertopics/factsheet/Sites-Types/bone. Accessed July 12, 2013.

3. Chao C, Perez C, Brady L. Radiation Oncology Management Decisions. 3rd ed. PA: Lippincott Williams and Wilkins; 2011:691-702.

4. Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002:605-612.

5. Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 3rd edition. Philadelphia, PA: Lippincott Williams & Wilkins. 691-702.

6. Washington, CM & Leaver, DT. Principles and Practice of Radiation Therapy. 3rd ed. St. Louis, MO; 2010. P585-589 . 7. Chao KSC, Perez CA, Brady LW. Bone and Ewing’s sarcoma. In: Chao KSC, Perez CA, Brady LW, eds. //Radiation Oncology Management Decisions//. Philadelphia, PA: Lippincott, Williams and Wilkins; 2011: 691-702.

8. Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002:610.

9. Chao C, Perez C, Brady L. Radiation Oncology Management Decisions. 3rd ed. PA: Lippincott Williams and Wilkins; 2011:691-702.

10. Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002:605-612 . 11. Washington CM, Leaver D. Principles and Practice of Radiation Therapy. 3rd ed. St. Louis, MO: Mosby Inc; 2010:82. || Back to Week 7