COMPLICATIONS OF LUNG CANCER

There are several complications secondary to lung cancer. One of the most feared complications is a recurrence of the original disease. This may be in the same site, in nearby lymph nodes, or in a different body system due to metastasis. Pneumonia is another common complication, usually caused by neutropenia from systemic therapies or smoking, that greatly increases mortality rates in the patient with lung cancer.

Lung cancer may also cause the abnormal secretion of hormones, enzymes, or cytokines, resulting in neoplastic syndromes. Endocrine syndromes include abnormal secretion of antidiuretic hormone or vasopressin, polycythemia, and Cushing’s syndrome. Rare neurological disorders caused by lung cancer include Eaton-Lambert reverse myasthenic syndrome, subacute cerebellar degeneration, and limbic encephalopathy. Hypercalcemia can be caused by the secretion of an excess of a parathyroid hormone-like substance from a malignant tumor.

Recurrence

Lung cancer recurrence can be defined by where it occurs:

• Local recurrence is when cancer returns in the lung near the site of the original tumor.
• Regional recurrence is when cancer recurs in the lymph nodes near the site of the original tumor.
• Distant recurrence is when lung cancer recurs far away from the original tumor, such as in the bones, brain, adrenal glands, or liver.

A patient with lung cancer must have a period of remission of greater than 3 months in order for recurrence to be considered more than disease progression. The most common form of the disease, NSCLC, has a recurrence rate of 30%–55%. Recurrence depends primarily on the stage of the lung cancer at the time of diagnosis. Stage I has a recurrence rate of approximately 30% within 5 years, while stage IV recurs in up to 70% patients within 2 years.

With SCLC, which is not as treatable as NSCLC, the recurrence rate can be up to 70% within 1–2 years of treatment. The rate of recurrence after 5 years is rare.

The most common cause of lung cancer recurrence is the spread of the original cancer. Prevention of recurrence is largely based on the success of changing modifiable risk factors such as smoking (Verywell Health, 2021).

Metastasis

Lung cancer most commonly spreads to the lymph nodes either in the lung tissue or in the airways. When there is no further spread beyond the lungs, it is not considered metastatic. If there is further metastasis, it usually results in hard lumps in the neck or the axillae where there are lymph nodes.

However, metastasis is a condition frequently related to lung cancer. Since lung cancer is slow growing, it is not unusual for a metastatic tumor to be diagnosed at the same time the lung cancer itself is diagnosed. The presence of metastasis causes a poorer prognosis, with a shorter life expectancy regardless of the kind(s) of treatment given.

Some metastatic tumors are slow growing, such as lung cancer with metastasis to the breast, pancreas, and thyroid. It is not unusual for the lungs and thyroid glands to be concurrent primary sites, resulting in a poor life expectancy.

BRAIN METASTASIS

Lung cancer is the most common primary cancer site for brain metastasis. Up to 40% of all lung cancers result in metastasis to the brain. This is exacerbated by the presence of nicotine, including in the form of a nicotine patch or gum. The nicotine skews the polarity of M2 microglia, macrophages that remove infections and damaged neurons from the central nervous system (Wu et al., 2020).

Often, lung cancer metastasis to the brain occurs so quickly that the brain metastasis is diagnosed well before the primary lung cancer is recognized. This can often be prevented by treatment with prophylactic cranial irradiation (PCI).

Diagnosis is made by a computerized tomography (CT) scan of the brain. Treatment may be corticosteroids to treat or prevent swelling and symptomatic medications such as analgesics, anti-emetics, and anticonvulsants. Radiation therapy focused on the brain tumor may be given to reduce symptoms from the tumor. When the brain metastases are few, they are referred to as oligometastasis and may be treated with either surgery or stereotactic body radiotherapy (SBRT), cyber knife, or gamma knife.

BONE METASTASIS

Lung cancer frequently metastasizes to the bones. As many as 30%–40% of patients with lung cancer experience metastasis to the bones. The most common site of this metastasis is the spine and vertebrae. The pelvis is also an area of metastasis that is hard to treat and has a 40% rate of recurrence. Lung cancer may metastasize to the femur, humerus, hands, and feet as well (Eldridge, 2020).

Bone metastasis causes the development of bone pain, fractures, hypercalcemia, and nerve compression. With bone cancer, osteoblasts secrete cytokines that cause bone reabsorption, leading to symptoms suggesting the need for diagnostic testing to rule out the cause. Patients whose cancer metastasizes to the bone have an extremely poor prognosis (Teng et al., 2020).

LIVER METASTASIS

Liver cancer is one of the most common metastases secondary to lung cancer. This is usually an asymptomatic cancer, but in the later stages the following symptoms may appear:

• Loss of appetite
• Weight loss
• Fatigue
• Bloating and leg swelling (edema)
• Itching
• Jaundice, yellowing of the skin or whites of the eyes
  (Eldridge, 2020)

When lung cancer metastasizes to the liver, there are usually several other organ sites of metastasis and the prognosis is usually poor, with a short life expectancy. Multiple metastatic sites will preclude the possibility of corrective surgery due to this poor prognosis. When the liver is the only site of metastasis, surgery is more likely to be performed. It is not uncommon for the liver cancer to exhibit symptoms after the lung has already been resected surgically; hepatic surgery may be successful in extending life expectancy in this case (Hokada et al., 2019).

Liver metastasis is diagnosed with an abdominal ultrasound, a CT scan, or a positive emission tomography (PET) scan. Systemic therapies are usually employed to treat the liver and the primary lung tumor (Eldridge, 2020).

STOMACH METASTASIS

Small cell lung cancer is frequently accompanied by a distant metastasis, such as to the stomach. The symptoms of stomach cancer in the presence of other cancers are not definitive, and the diagnosis of metastasis to the stomach is often made upon an autopsy examination. SCLC has a rapid progression and a poor prognosis. Systemic therapies used to treat SCLC can also be beneficial in treating metastatic stomach cancer (Peng et al., 2019).

ADRENAL GLANDS METASTASIS

Lung cancer may metastasize to the adrenal glands. Adrenal metastasis is usually asymptomatic and discovered when a scan is done to stage the primary tumor. Excision of the tumor is usually successful.

PANCREAS METASTASIS

Cancer of the pancreas rarely occurs as a form of metastasis secondary to lung cancer. The identifying symptoms are pancreatitis, obstructive jaundice, and lumbar back pain, found in 43% of cases. The other 57% of cases are asymptomatic for pancreatic symptoms. The average life expectancy for pancreatic cancer due to metastasis from lung cancer is 8.8 months. Patients with pancreatic symptoms have a shorter life expectancy than those who are asymptomatic. Systemic therapies significantly prolong life in the case of pancreatic cancer. Radiation therapy to the pancreas helps to relieve symptoms but does not extend life (Zhang, 2020).

Paraneoplastic Syndromes

The tumor cells of a person with lung cancer or the antibodies produced by the tumor cause the secretion of hormones, enzymes, and cytokines that destroy healthy cells. These substances can cause one or more paraneoplastic syndromes. Paraneoplastic syndromes are rare disorders that may be caused by a compromised immune system responding to a tumor or production of a hormone, enzyme, or cytokine.

Symptoms may include fever, night sweats, weight loss, and decreased appetite and can affect many organ systems (neuro, skin, endocrine, hematologic systems). The ectopic secretion of these substances can cause a metabolic emergency that may be evident before the symptoms of the lung cancer are evident. These syndromes may show improvement when the underlying tumor is treated and either reduced in size or removed (Harding et al., 2020; Tan, 2019).

ENDOCRINE SYNDROMES

Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

A cancerous tumor in the lung can cause the abnormal secretion of antidiuretic hormone or vasopressin. The results are a concentrated urine and diluted plasma. The symptoms of SIADH and hyponatremia are the same. They mostly include central nervous system problems and are exhibited when the plasma osmolality falls to <240 mOsm/kg. Symptoms include changes in mental status, altered personality, lethargy, and confusion. As the serum sodium falls to <115 mEq/L, symptoms progress to stupor, neuromuscular hyperexcitability, hyperreflexia, seizures, coma, and eventually death if the condition goes untreated. Treatment is with water restriction, sometimes with oral salt pills or intravenous 3% sodium chloride (Harding et al., 2020).

Polycythemia

Polycythemia vera is a condition in which the overproduction of red blood cells causes the blood to become hyperviscous and hypervolemic. A malignant tumor in the lungs can artificially induce hypoxia, causing the kidneys to hypersecrete erythropoietin to stimulate the bone marrow to produce new red blood cells. The symptoms of polycythemia are secondary to the hypertension caused by the hypervolemia and the hyperviscosity of the blood. They include headache, vertigo, dizziness, tinnitus, visual disturbances, pruritus, and paresthesias. Worsened symptoms may exhibit as angina, heart failure, intermittent claudication, and thrombophlebitis (Harding et al., 2020).

Cushing Syndrome

Cushing syndrome is a disease in which the body is saturated with corticosteroids in the form of glucocorticoids. Ectopic adrenocorticotropic hormone (ACTH) production can be caused by several types of tumors, including lung cancer. Clinical manifestations of Cushing syndrome are multisystem and a result of the body’s response to excessive corticosteroid production. Weight gain, redistribution of adipose tissue, hyperglycemia, muscle wasting, osteoporosis, loss of collagen, and reddish striae on the torso are the most common symptoms (Harding et al., 2020).

NEUROLOGIC SYNDROMES

Eaton-Lambert Reverse Myasthenic Syndrome

Eaton-Lambert reverse myasthenic syndrome is a rare neurologic condition that interferes with the messages normally sent from the nerves to the muscles, impacting the muscle’s ability to contract. Middle-aged or older adults with lung cancer comprise approximately 50% of all Eaton-Lambert reverse myasthenic syndrome cases. The symptoms appear gradually over weeks to months, including weakness in the legs, arms, neck, and face, and difficulty with controlling automatic body functions such as blood pressure. Other symptoms that occur fairly commonly are muscle pain, difficulty walking, difficulty with stairclimbing, inability to lift or raise the arms, drooping eyelids, dry eyes and mouth, visual blurriness, dysphagia, orthostatic dizziness, constipation, and erectile dysfunction (NHS, 2019).

Paraneoplastic Cerebellar Degeneration

A paraneoplastic cerebellar degeneration (PCD) is a rare complication of a tumor. PCD causes the production of antibodies that attempt to work against the tumor-produced antigens (which are a type of protein). The cancer-fighting antibodies may inadvertently attack these normal protein cells in the cerebellum. Clinical manifestations may include mild dizziness, nausea, vertigo, and nystagmus that may suggest a peripheral vestibular problem. These symptoms precede ataxia of the limbs, oscillopsia, dysarthria, tremor, and sometimes dysphagia and blurred vision (Tan, 2019).

Subacute Sensory Neuropathy

Subacute sensory neuropathy is an inflammatory disorder of the central nervous system. Although various malignancies can cause subacute sensory neuropathy, 80% of cases are caused by small cell lung carcinoma in the bronchi. There is no effective treatment for this disorder, but the use of immunosuppressants may help to improve the symptoms (Tan, 2019).

Limbic Encephalopathy

SCLC can attack the proteins that are necessary for the development, maturation, and maintenance of the vertebrate peripheral nervous system. The symptoms of limbic encephalopathy may include memory loss, personality changes, anxiety, depression, neuropsychiatric disturbances, partial or generalized seizures, status epilepticus, sensory hallucinations of smell and taste, and sleep disturbances.

HYPERCALCEMIA

Hypercalcemia can be caused by an excess of a parathyroid hormone-like substance secreted by malignant tumors such as lung cancer. Natural parathyroid hormone (parathormone) works to produce a therapeutic amount of calcium in normal circumstances. A calcium level greater than 12 mg/dl will most likely cause adverse symptoms. The most common symptoms are apathy, depression, fatigue, muscle weakness, ECG changes, polyuria, nocturia, anorexia, and nausea and vomiting (Harding et al., 2020).

COVID-19

Research studies have shown that patients with lung cancer are at a significantly increased risk of contracting the COVID-19 virus. Radiation and systemic therapies for cancer affect the immune system, contributing to the higher risk (Passaro et al., 2021).

A prospective observational study of 800 patients from 55 hospitals showed the mortality rate of COVID-19–positive patients with cancer was not different from COVID-19 patients without cancer. The risk factors for higher mortality rates in both groups proved to be age >60 years, male sex, hypertension, cardiovascular disease, COPD, and diabetes. The results of the study highlighted these factors as a more important consideration than COVID-19 positivity when deciding about systemic cancer treatments (Haider et al., 2021).