Assessment, Treatment, and Rehabilitation of Bone and Spinal Metastasis in Lung Cancer

Bone Metastases

Approximately 30%–70% of bone metastases are associated with lung cancer, with nonsmall cell lung cancer (NSCLC) being the third most common cause of bone metastases. Osseous metastases are found in 20%–40% of lung cancer patients at the time of diagnosis and are a frequent extrapulmonary site of recurrence, particularly for patients with NSCLC. ^{, ,} It is more common for patients to be diagnosed with multiple bony metastatic lesions than oligometastases. ^, The most common site of osseous metastases in lung cancer is the spine, followed by the ribs and pelvis. Spinal metastases are evenly distributed along the length of the spinal column; however, some lung cancer series have shown a disproportional propensity for the thoracic spine.

Spinal Epidural Metastasis

Spinal epidural metastasis refers to tumor growth into the epidural space, anywhere along the spinal column. These metastases can cause epidural spinal cord compression (ESCC) through mechanical injury to axons and myelin and spinal cord ischemia/infarction via compression of spinal arteries and the epidural venous plexus. While spinal epidural metastasis occurs in 5%–10% of cancer patients overall, 30% of lung cancer patients have one or more noncontiguous epidural lesions at the time of presentation ^, which may or may not be symptomatic. Lung carcinoma is the cancer type most often identified in patients for whom spinal epidural metastases is the presenting feature of a previously undiagnosed neoplasm. Most epidural involvement occurs in the thoracic and lumbosacral regions and generally extends over 1–2 spinal segments. The prognosis for patients with spinal epidural disease ranges from months to years depending on cancer type.

Intramedullary Spinal Cord Metastasis

Intramedullary spinal cord metastasis represents <5% of total spinal cord lesions and typically occurs in the setting of extensive metastatic disease. ^, Lung cancer is the most common source of intramedullary spinal cord metastases, accounting for more than 50% of cases. ^, This type of metastatic disease is more prevalent in small cell lung cancer (SCLC) than NSCLC. Intramedullary metastases are theorized to arise from hematogenous spread and can occur as a solitary lesion in the spinal cord. The cervical spine, a vascular-rich area, tends to be the most common site. Prognosis is typically poor, with mortality common within 3 months.

Intradural Extramedullary Spinal Metastasis (Leptomeningeal Disease)

Leptomeningeal disease (LMD) is more common in SCLC than NSCLC. Patients with SCLC with LMD typically have widely disseminated disease, and approximately half of this population also has brain metastases. Similar to epidural metastases, LMD is thought to occur through hematogenous spread or direct extension. LMD typically occurs at the base of the brain or along the cauda equina and can result in cord compression and vascular compromise. Vascular compromise in this setting can result not only in cord ischemia but subarachnoid hemorrhage, particularly in those on anticoagulation. Like intramedullary metastases, the prognosis for LMD is poor, often limited to months.

Pain

Bone pain is one of the most common types of pain cancer patients experience. Most patients initially experience intermittent and dull aches, becoming more severe and constant as the disease progresses. Bone pain intensifies during movement, can be accompanied by fever, and increases in severity at night.

Pain from bone metastasis can be attributed to tumor cells causing osteolysis, leading to the release of pain mediators such as endothelin. Periosteal irritation and nerve damage are secondary effects of bony destruction which can also cause pain. Treatment of pain from osseous metastases requires a multimodal approach with tumor-targeted treatments, such as local surgery, radiation therapy, systemic therapies, analgesics, bone-targeted therapies, and adjuvant agents such as steroids.

This pain is referred to as “tumor-related pain” or “biologic pain” in the spine. Biologic pain typically occurs at night and is thought to be related to nocturnally reduced endogenous steroid secretion. Biologic pain typically responds well to anti-inflammatory medications, which may help distinguish this pain from other types of back pain. Radiation therapy is often incorporated to treat biologic pain with good results.

Hypercalcemia

Hypercalcemia in malignancy can result from bony destruction, with osteolytic metastases present in 80% of cases. A common sequela of squamous cell lung cancer, hypercalcemia, can lead to fatigue, anorexia, constipation, impaired renal function, and altered mental status. Hypercalcemia in malignancy is associated with a poor prognosis, with approximately 50% of patients dying within 30 days of this diagnosis. Stewart describes mild hypercalcemia to be a serum calcium level of 10.5–11.9 mg per deciliter (2.6–2.9 mmol per liter), moderate hypercalcemia a level of 12.0–13.9 mg per deciliter (3.0–3.4 mmol per liter), and severe hypercalcemia a level of 14.0 mg per deciliter (3.5 mmol per liter) or greater . Treatment includes aggressive hydration, calciuresis with diuretics, and initiation of intravenous bisphosphonates, which inhibit bone resorption.

Pathologic Fractures

When metastatic lesions invade bone, the load-bearing ability can become impaired, resulting in painful microfractures. Pathologic fractures most commonly occur in ribs and vertebrae.

Mirels' criteria ( Table 4.1 ) is a scoring system used to determine if surgical intervention is needed to stabilize long bone structures affected by metastatic disease. It includes imaging assessment of the lesion site, nature of the lesion, size of the lesion, and presence of pain. Lesion sites include the upper extremity, lower extremity, and peritrochanteric area of the femur. Lesion types include blastic, mixed, or lytic. Lesion size is expressed as a fraction of cortical thickness, classified by lesion/cortex ratios of <1/3, 1/3 to 2/3, and >2/3. Each characteristic is scored from 1–3 based on the severity.

Mirels recommends prophylactic surgical fixation for a lesion with an overall score of ≥9. Radiotherapy and observation are recommended for a lesion scoring ≤7.

In 2010, the Spine Oncology Study Group (SOSG) created the Spinal Instability Neoplastic Score (SINS) to serve as a prognostic tool for surgical evaluation and decision-making for patients with spinal metastases and concerns of instability. It scores six variables: location of the lesion, characterization of pain, type of bony lesion, radiographic spinal alignment, degree of vertebral body destruction, and involvement of posterolateral spinal elements ( Table 4.2 ). Scores range from a minimum of 0 to a maximum of 18. Scores 7–12 are associated with potential instability, while 13–18 denote instability. SOSG recommends surgical consultation for all patients with SINS >7.

Spinal Cord Compression

Metastatic spinal cord compression is one of the most feared SREs in lung cancer. Symptoms associated with cord compression depend on the spinal segments and spinal tracts involved. Patients may experience weakness, sensory impairments, and bowel and bladder dysfunction. Anterior cord, posterior cord, Brown–Sequard, central cord, conus medullaris, and cauda equina patterns have been described.

Radiation-Induced Bony Injury

Radiation therapy intended to treat metastasis to bone can lead to adverse reactions, including radiation osteitis, osteoradionecrosis, and insufficiency fractures. ^, The pathophysiology of these sequelae is only partly understood and thought to be related to a decline in bone marrow cells in the treated tissue and impaired bone remodeling. Multiple factors play a role in the risk and likelihood of developing radiation-induced bony injuries, including radiation dose and fractionation and target tissue exposure. Irradiated bone can appear osteopenic about 1 year after treatment. Radiation osteitis, a radiologic finding of a mottled appearance of bone with coarse trabeculation, occurs 2–3 years after radiation therapy. Osteoradionecrosis is often associated with facial bones but can occur in any bone subject to radiation. It is considered a nonhealing bone that persists at least 3 months after radiation and can lead to pain and impaired mobility. Radiation-induced insufficiency fractures are stress fractures that occur under everyday physiologic loads applied to bone weakened by radiation. Sacral fractures from pelvic radiation are the most frequent insufficiency fractures reported in the literature.

Imaging Studies

X-ray (Plain Films, Radiograph)

Radiographs can be helpful in the assessment of pathologic fractures. They can also help determine whether metastatic lesions are osteolytic, osteoblastic, or mixed. Unfortunately, X-rays have limitations. For a destructive lesion in the trabecular bone to be recognized, it must be > 1 cm in diameter with a loss of ∼50% of the bone mineral content. Plain films are also insensitive when assessing for paraspinal masses and epidural disease, as they are difficult to visualize. Pedicle erosion can be seen on radiographs, which is a red flag for epidural disease ( Figs. 4.1 and 4.2 ).

Computed Tomography

Computed tomography (CT) scan is a convenient tool for the initial evaluation of fracture risk in a long bone given its accessibility and low cost. CT scans are particularly useful in localizing lesions for biopsy, allowing for tissue diagnosis in the setting of metastatic disease. They are, however, limited in use when evaluating for treatment response in the bone due to difficulty in differentiating between metabolically active versus inactive bony lesions ( Figs. 4.3 and 4.4 ).