Primary bone tumors in children and teens

Author(s): Katarzyna Ibanez, MD

Originally published:09/15/2015

Last updated:09/15/2015

1. DISEASE/DISORDER

Definition

Primary bone tumors are defined as tumors originating in a bone. They can be benign or malignant. Bone tumors can be classified based on histological features (i.e. chondrogenic, osteogenic, fibrogenic, etc.).1 Benign tumors are subdivided into nonaggressive (i.e. nonossifying fibroma) or aggressive (i.e. aneurysmal bone cyst). Most bone tumors are benign. Most common malignant bone tumors in children are osteosarcoma and Ewing sarcoma.

Etiology

Etiology is largely unknown. Some inherited syndromes, such as Li-Fraumeni syndrome, hereditary multiple exostoses, Ollier’s disease, Maffucci syndrome, familial retinoblastoma syndrome, Werner syndrome or Rothmund-Thomson syndrome increase the risk of bone malignancy. Benign bone lesions may rarely transform into malignant lesions (osteochondroma into chondrosarcoma; bone infarct dedifferentiation into osteogenic sarcoma, fibrosarcoma or malignant fibrous histiocytoma). Osteosarcoma and malignant fibrous histiocytoma have been associated with radiation exposure, chronic osteomyelitis and Paget disease. There is an association between trauma and development of aneurysmal bone cyst.

Epidemiology including risk factors and primary prevention

Annual incidence of malignant bone tumors in the United States in children under the age of 20 is 8.7 per million. About 700 children are diagnosed with malignant bone tumors in the United States each year. Malignant bone tumors account for 6% of all childhood malignancies, 56% of which are osteosarcomas and 34% are Ewing sarcomas. Osteosarcomas are slightly more common in African American than Caucasian populations. Ewing sarcoma affects predominantly Caucasian populations, and 80% of patients are under the age of 20 at the time of diagnosis. Bone tumor incidence peaks at the age of 15 (time of adolescent growth spurt).

Patho-anatomy/physiology

In osteosarcoma the malignant cell produces osteoid. Osteosarcoma preferentially arises in the metaphyseal areas of the most rapidly growing long bones (distal femur, proximal tibia, and proximal humerus). Over 50% of osteosarcomas occur around the knee. Ewing sarcoma is a small round blue cell tumor. The most common translocation is between chromosomes 11 and 22 (85% of cases). Other translocations are t(21;22) and t(7;22). Ewing sarcoma arises in the lower extremity in 46% of cases, followed by the pelvic bone (20%).

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time):

Natural history of untreated osteosarcoma and Ewing sarcoma is disease progression ultimately resulting in death. The most common site of metastases are the lungs. Tumor may also metastasize to bone elsewhere, including the spine. Prognosis for non-metastatic disease has improved significantly over the past few decades.

Patients with newly diagnosed malignant bone tumors typically undergo extensive work up and imaging. Treatment regimens typically consist of chemotherapy (systemic control) and surgery (local control – tumor resection, limb salvage procedure or amputation) and/or radiation therapy. Ewing sarcoma is radiation sensitive, while osteosarcoma is considered radiation resistant. Patients with resectable lung metastases have better prognosis than those with unresectable disease. Patients commonly undergo thoracotomies and/or lung radiation if there is a concern for or evidence of lung metastases.

Specific secondary or associated conditions and complications

Multi-regimen chemotherapy used for systemic control of disease may have negative physical, psychosocial and socioeconomic sequelae. Physical complications include weakness, pain, neuropathy, impaired balance and cardiac dysfunction. Surgery used for local control may result in impaired wound healing, infection, pain, etc. Depending on the type of limb salvage surgery performed, patients might have weight bearing and activity restrictions. Radiation therapy may result in impaired skin integrity and fatigue.

2. ESSENTIALS OF ASSESSMENT

History

The majority of patients with malignant bone tumors typically present with several months of localized pain. About half of them will also report swelling and limited range of motion. Minority (10-15%) present with pathological fracture. History of trauma is not uncommon. While systemic symptoms are uncommon in osteosarcoma (unless disease is advanced), fever is present in 20% of Ewing sarcoma patients at presentation. Comprehensive history should be obtained. Red flags include worsening/persistent pain, night and morning pain, pain with activity/weight bearing, pain lasting longer or more severe than expected in those with a proceeding trauma, etc. Osteoid osteoma presents with progressively worsening night pain and is relieved by aspirin or nonsteroidal antiinflammmatory drugs.

Physical examination

Comprehensive physical examination should be performed. Vital signs should be obtained. Heart, lung and abdominal exam should be included. Lymphadenopathy should be assessed. Musculoskeletal, vascular, neurological and functional evaluation should be performed. Pain on palpation, visible deformity, restrictions or asymmetry in range of motion, focal weakness, limp or focal neurological finding warrant further investigation. Leg length discrepancy and scoliosis should not be missed. Pain with weight bearing raises a concern for a pending pathological fracture and requires immediate work up.

Clinical functional assessment: mobility, self care cognition/behavior/affective state

Prior functional status should be ascertained. Inquire about patient’s functional goals and environmental barriers. Impairments in mobility and self-care as well as need for assistive devices and bracing should be assessed. Home environment and availability of caregiver support should be taken into consideration. Emotional state and coping of the patient and the family should be assessed and appropriate referrals initiated. Depression and anxiety are common in this population.

Laboratory studies

Labs in a patient with suspected bone cancer should include inflammatory markers (ESR, CRP), blood count, chemistry including alkaline phosphatase and LDH. Patients undergoing treatment typically require frequent lab monitoring. Rehabilitation professionals should always review the most recent laboratory studies and imaging to prescribe appropriate rehabilitation interventions and guide/modify exercise program.

Imaging

Plain radiography is the initial modality used to evaluate suspected bony lesion. Computed tomography (CT) or magnetic resonance imaging (MRI) are used for cross-sectional evaluation of suspected malignant bony lesion. Nuclear bone scan is used to assess for bony metastases. Positron emission tomography is also frequently used for evaluation of disease burden and response to treatment.

Supplemental assessment tools

Urodynamic studies might be considered in patients with spine or pelvic tumors affecting the spinal cord or nerves. When etiology of pain or weakness is unclear electrodiagostic study might be of benefit, although rarely performed in children given the unpleasant nature of this test.

Early prediction of outcomes

Poor prognostic indicators include metastatic disease, poor response to systemic chemotherapy and location of disease in the spine or pelvis given its poor resectability.

Environmental

Home environment might affect rehabilitation goals and home modifications to enhance patients’ independence might be recommended. Ramp to enter the house might be needed for children in a wheelchair. Sometimes a stair lift is recommended. Bathroom accommodations like elevated toilet seat and grab bars might be needed.

Social role and social support system

Maintaining “normalcy” as much as possible during treatment might help alleviate the patient’s and family’s anxiety and a sense of “lack of control”. Children typically receive home instructions and some enjoy interaction with their classmates by attending classes virtually. Chronic overprotection by caregivers might be limiting the patient’s independence and a sense of control. Some children need neuropsychological and rehabilitation evaluations to assess appropriateness of individualized education plan (IEP) or 504 plan.

Professional issues

Discussion of prognosis should be deferred to the patient’s oncologist. Informing the child about his or her condition should be done at a developmentally appropriate level by a trained professional and with parental permission. Quality of life and symptom management are of paramount importance. Safety of rehabilitation interventions is always considered.

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

Treatments vary based on multiple factors, including type, grade, stage and location of bone tumor. For instance, localized resectable high grade osteosarcoma is treated with neoadjuvant chemotherapy for about 10 weeks, followed by surgery to remove the tumor (sometimes radiation therapy might also be given to the area), followed by additional chemotherapy (up to one year). Chemotherapy drugs (usually 2 or more are given together) commonly used to treat osteosarcoma include methotrexate, doxorubicin, cisplatin or carboplatin, cyclophosphamide, etoposide and ifosfamide.

At different disease stages

Patients benefit from rehabilitation interventions during the continuum of treatment. Symptomatic control (i.e. pain) and quality of life should always be among top considerations. Goals of rehabilitation interventions are to restore function, minimize disability/handicap and decrease the caregiver burden.

Children undergoing oncological treatment may suffer from physical and psychosocial ailments. Side effects of treatment may include wound infections/dehiscence, hardware failure in those with limb salvage surgery, edema/lymphedema, cardiac dysfunction, neuropathy, weakness, impaired balance and limited activity tolerance, as well as depression and anxiety. Patients following limb salvage surgery or amputation require rehabilitation interventions to assist with early mobility, teaching the use of assistive devices, weight bearing precautions, gait training and strengthening. Patients with metastatic or recurrent disease commonly undergo additional chemotherapy and surgical/radiation treatments (including thoracotomies, orthopedic surgeries, radiation therapy) and will continue to benefit from rehabilitation interventions focusing on managing pain, energy conservation, optimizing independence in self-care and mobility and caregiver education and training.

Coordination of care

Patients benefit from interdisciplinary rehabilitation team consisting of physicians, nursing staff, physical therapists, occupational therapists, speech-language therapists, neurophysiologists, psychologists, case managers, child-life and social workers. Rehabilitation physicians should communicate closely with the therapists regarding rehabilitation goals and precautions based on clinical developments and lab and imaging findings.

Patient & family education

Family education should include recommended home exercise program, weight bearing or activity restrictions and appropriate use of assistive devices. Fall and safety precautions should be reviewed. Rationale for continued rehabilitation interventions should be shared with the family. American Cancer Society website contains helpful patient and family education information.

Measurement of Treatment Outcomes including those that are impairment-based, activity participation-based and environmentally-based

Functional Mobility Assessment is a validated objective measure for patients with lower extremity sarcomas.2 Musculoskeletal Tumor Society Scale (MSTS) is a clinician administered tool used for assessment of disability. Toronto Extremity Salvage Scale (TESS) is a patient questionnaire. Short Form-36 version 2 (SF-36v.2) is a commonly used measure of a health related quality of life.3

Translation into Practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Weight bearing and activity/range of motion precautions should always be explicitly communicated by the orthopedic surgeon to the rehabilitation team. Lower extremity osteosarcoma patients might need to use crutches following biopsy until definitive surgery is performed as they are at increased risk for pathological fracture. Any pain with weight bearing should prompt evaluation and possibly imaging to rule out impending pathological fracture. Exercise program should be adjusted based on laboratory values (i.e. hemoglobin, platelets). Neutropenic patients should be treated in protective isolation. Patients who had anthracycline exposure should be educated on weight lifting and exercise restrictions.4 A substantial percentage of survivors of osteosarcoma and Ewing sarcoma have self-reported physical performance limitations (40.8% and 30.9%, respectively).5

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Gene expression profiling might help predict response of each tumor to chemotherapy. Compressed chemotherapy regimens are being studied. New drugs and immunotherapy treatments are being developed. Improved surgical techniques and imaging allows for removal of cancer while preserving normal tissue. Newer types of internal prostheses used for limb salvage surgeries can be expanded without the need for additional surgeries. Intensity modulated radiation therapy (IMRT) limits the dose to normal tissues but delivers high doses to the tumor and is more effective in controlling the tumor growth. Proton radiation allows delivery of higher doses of radiation to the tumor with little damage to normal tissues.

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Children Oncology Group is a clinical trials group supported by a National Cancer Institute and their research has led to significant improvement in treatment outcomes of pediatric tumors. It has nearly 100 clinical trials open at any time. There are still multiple unanswered questions. What are the etiologies of bone tumors? What are the optimal treatment regimens? Why is there such variable response to treatment? Who is at increased risk for relapse and developing metastatic disease? Who can be treated with lower doses/less toxic chemotherapy regimen?

REFERENCES

  1. Kleihues P, Sobin LH. World Health Organization classification of tumors. Cancer. 2000 Jun 15;88(12):2887.
  2. Marchese VG, Rai SN, Carlson CA, et al. Assessing functional mobility in survivors of lower-extremity sarcoma: reliability and validity of a new assessment tool. Pediatric blood & cancer. 2007 Aug;49(2):183-9.
  3. Ginsberg JP, Rai SN, Carlson CA, et al. A comparative analysis of functional outcomes in adolescents and young adults with lower-extremity bone sarcoma. Pediatric blood & cancer. 2007 Dec;49(7):964-9.
  4. Okada M, Meeske KA, Menteer J, Freyer DR. Exercise recommendations for childhood cancer survivors exposed to cardiotoxic therapies: an institutional clinical practice initiative. Journal Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses. 2012 Sep-Oct;29(5):246-52.
  5. Ness KK, Hudson MM, Ginsberg JP, et al. Physical performance limitations in the Childhood Cancer Survivor Study cohort. Journal Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses. 2009 May 10;27(14):2382-9.

Author Disclosure

Katarzyna Ibanez, MD
Nothing to Disclose

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