Lung cancer is the most common and most deadly cancer in China. Bone metastases occur in 30% to 40% of lung cancer patients, and the 1-year survival rate is about 40%. A retrospective analysis of lung cancer patients in China showed that bone metastases most often occurred in the spine (50%), femur (25%), sternum, and ribs (12%).
Which lung cancer patients are prone to bone metastases?
Previous studies have found:
- Adenocarcinoma is more likely to develop bone metastases than squamous carcinoma;
- Patients with foci larger than 7 cm in size, tumors in multiple unilateral lung lobes, and metastases in supraclavicular lymph nodes also had a significantly increased risk of bone metastases;
- Patients with blood tests suggesting low blood calcium and those with elevated bone salivary acid protein and carcinoembryonic antigen also appear to be more likely to develop bone metastases.
What conditions occur that should lead to suspicion of bone metastases?
The vast majority of bone metastases from lung cancer are osteolytic bone metastases. This is because when lung cancer cells metastasize to bone, they release some cytokines that form bone-dissolving mediators, causing bone to dissolve and resorb, and vacuoles to appear. To use an analogy, this process is like throwing glass into hydrofluoric acid, and a smooth, hard piece of glass quickly becomes riddled with holes.
Osteolysis occurs, triggering discomfort. Doctors usually suspect bone metastases when a lung cancer patient has
Bone pain
Bone pain occurs in more than half of patients with bone metastases. The pain may be so severe that it prevents the patient from sleeping and seriously interferes with life. Patients may also have to stay in a particular position because of the pain.
Pathologic fractures
Some patients with pathologic fractures have no obvious symptoms and may feel only mild pain, numbness, or weakness at the fracture site, with ecchymosis and swelling of the surrounding skin. However, in some cases, pathologic fractures can damage nearby internal organs and may also lead to fatal bleeding and fat embolism.
Symptoms of spinal cord or nerve compression
The spine is the most common site of bone metastases from lung cancer, and as the metastatic cancer grows, it can compress the spinal cord and nerves and cause a range of symptoms. This includes a tightening sensation in the chest, as well as back pain, limb weakness, incontinence, and even paralysis in severe cases. In addition, these symptoms usually appear suddenly.
Hypercalcemia
That is, an increase in the amount of calcium in the blood. Common symptoms include nausea, vomiting, loss of appetite, abdominal pain, frequent thirst, decreased urination, weakness, constipation, and irregular heartbeat. Hypercalcemia is very dangerous and is the leading cause of death in patients with bone metastases from lung cancer and can be diagnosed definitively with a simple blood test.
What should I do if I suspect bone metastases?
Patients should visit an oncologist or orthopedic surgeon when they develop the symptoms described above. Usually, to clarify the diagnosis, the doctor will have the patient undergo the following tests:
- ECT (radionuclide bone scan) or PET-CT: These tests can detect early bone metastases, but they are more expensive.
- Patients with a positive ECT test may also need an X-ray, CT, or MRI to help your doctor better understand the extent of bone destruction and compression of surrounding tissue.
- Bone biopsy: This is the gold standard for diagnosing bone metastases. The test can be performed if the hospital allows. For lung cancer patients who have their own genetic mutations, bone biopsy tissue can also be tested for genetic testing to better guide clinical use.
- Blood sampling: In bone metastases, patients usually have elevated blood calcium. In addition, blood tests can be done to see if the patient is anemic, and for liver and kidney function to better guide medication use.
How are bone metastases treated?
Metastatic cancer often has the same characteristics as the primary cancer. For example, EGFR-mutated lung cancer that metastasizes to bone and brain is also positive for the EGFR mutation in the vast majority of cases, despite the location, and is effectively treated with EGFR-targeted drugs.
So, for patients with bone metastases from lung cancer, the first step is to do systemic therapy (chemotherapy, targeted therapy, or immunotherapy, etc.) for the lung cancer. On top of that, the following treatment options are available for bone metastases:
Biphosphonates
Including hydroxyethylphosphonic acid, clodronate, pamidronate, ibandronate sodium, and zoledronic acid, which inhibit bone destruction by cancer cells and impede osteolysis. These drugs can relieve symptoms such as bone pain and hypercalcemia, and may also prolong the patient’s survival time.
For this reason, the CSCO guidelines recommend that patients with lung cancer should receive bisphosphonates as soon as bone metastases are diagnosed. The duration of dosing can exceed 2 years.
Targeted drug therapy
Denosumab inhibits osteolysis and is effective in patients with rapidly developing bone metastases in the short term, making it suitable for short-term dosing.
Extracorporeal radiation therapy
Extracorporeal radiation therapy improves bone pain and also prolongs the survival time of patients.
Radionuclide therapy
Strontium 89 (89Sr) and strontium 153 (153Sr) are commonly used to treat bone metastases from lung cancer. However, it is important to note that radionuclide therapy can lead to bone marrow suppression and slow recovery, which may interfere with the use of systemic therapies such as chemotherapy, and therefore is generally not preferred.
Surgery
Surgical resection is indicated for single bone metastases in patients with PS 0 to 1, non-N2 pulmonary lesions that are completely resectable; joint replacement when bone metastases involve a joint; and surgical correction and fixation is also usually required for pathologic fractures resulting from bone metastases.
Analgesia
The treatment of pain in cancer patients follows the WHO three-step cancer pain management principle: for mild pain, nonsteroidal analgesics, such as celecoxib and ibuprofen, are preferred; for moderate pain or more, opioids, such as morphine, oxycodone, and fentanyl, are required; depending on the patient’s symptoms, adjuvant medications such as glucocorticoids and lidocaine patches can also be added.
Psychological support therapy
Surveys have found that the incidence of psychological problems in patients with bone metastases from lung cancer is very high, with more than 40% of patients experiencing depression and more than 25% of patients experiencing anxiety. Therefore, the application of antidepressant or anxiolytic drugs, as well as behavioral interventions, is helpful for such patients.