An Overview of Small Cell Lung Cancer

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Small cell lung cancer accounts for 15 percent of lung cancers. Unlike the more common non-small cell lung cancers, small cell lung cancer grows rapidly but often responds well to chemotherapy initially. Unfortunately, it tends to recur after initial treatment and become more resistant to subsequent chemotherapy treatment.

Small cell lung cancers usually begin in the large airways (bronchi) of the lungs, but spread early, often to the brain. They are broken down into only two stages, limited and extensive stage small cell lung cancer. 60 to 70 percent of people already have extensive stage disease at the time of diagnosis.

Small cell lung cancer is strongly linked to smoking, although other factors such as exposure to radon and asbestos are also linked to small cell lung cancer. This type of lung cancer is more common in men than in women, and is the most common type of lung cancer to have symptoms referred to as paraneoplastic syndrome—that is, symptoms due to hormones secreted by a tumor or by the body’s immune response to a tumor. Unlike the recent increase in non-small cell lung cancer in people who have never smoked, the incidence of small cell lung cancer is declining.

Symptoms

Symptoms of small cell lung cancer can include:

Symptoms due to the spread of lung cancer to other regions of the body. The most common areas to which small cell lung cancer spreads include:

  • The brain: Brain metastases from lung cancer may occur early, and may be the first symptom of these cancers. These include headaches, vision changes, weakness, or seizures.
  • Bones: Bone metastases can cause pain in the back, hips, chest, shoulder, or ribs.
  • The liver: Liver metastases may cause abdominal pain, bloating, and a yellowish discoloration of the skin called jaundice.
  • The adrenal glands: Adrenal metastases are usually found on a CT scan rather than by symptoms, but may cause abdominal pain.

Small cell lung cancer can also result in a broad variety of symptoms due to paraneoplastic syndromes. Some of these include:

  • Muscle weakness in the upper limbs, vision changes, and difficulty swallowing (Lambert-Eaton myasthenic syndrome)
  • Weakness, fatigue, and a low sodium level in the blood (syndrome of inappropriate antidiuretic hormone secretion [SIADH])
  • Loss of coordination and difficulty speaking (paraneoplastic cerebellar degeneration)
  • Clubbing (rounding) of the fingernails

Stages

There are two stages of small cell lung cancer:

  • Limited Stage Lung Cancer - Limited stage small cell lung cancer is defined as a small cell cancer that is present in only one lung and may have spread to nearby (supraclavicular) lymph nodes or to the space between the lungs (mediastinum), but has not spread (metastasized) to other regions of the body.
  • Extensive Stage Lung Cancer - In extensive-stage small cell lung cancer, the cancer has spread (metastasized) to another region of the body, such as another lobe of the lungs or the brain.

Treatments

The treatment for small cell lung cancer varies depending on the stage of the cancer as well as other factors.

Surgery

Surgery is rarely performed for small cell lung cancer (it is usually considered inoperable,) but surgery is occasionally considered if a small nodule is found incidentally on a chest X-ray or CT scan (for very early limited stage cancers). Adjuvant chemotherapy (chemotherapy after surgery) is usually recommended if surgery is done for small cell lung cancer.

Chemotherapy

The treatment of limited and extensive stage disease usually consists of chemotherapy and with or without radiation therapy, though immunotherapy in combination with chemotherapy has now been approved first line for extensive stage disease. Small cell lung cancer often responds very well to chemotherapy initially, but resistance develops. It's been found that treating even extensive stage small cell lung cancer with chemotherapy raises median survival by a factor of 4 or 5 relative to no treatment. Common chemotherapy agents used include a combination of Platinol (cisplatin) or Paraplatin (carboplatin) with VePesid (etoposide) or Camptosar (irinotecan).

Recently, the drug lurbinectedin was granted orphan status approval by the FDA for the treatment of extensive stage small cell lung cancer. In a clinical trial with 61 patients, the overall response rate was 39.3% with clnical benefit in 50.8%. The median overall survival in those treated was 11.8 months.

Radiation Therapy

For both limited and extensive stage cancers, radiation therapy is often used along with chemotherapy.

Immunotherapy

The immunotherapy drug (checkpoint inhibitor) Tecentriq (atezolizumab) is now approved first line for the treatment of extensive stage small cell lung cancer along with Paraplatin and VePesid. For those who progress, the checkpoint inhibitors Keytruda (pembrolizumab) or Opdivo (nivolumab) may also be used.

Prophylactic Cranial Irradiation (PCI)

 In people who respond well to treatment and achieve a complete response, prophylactic cranial irradiation (PCI)—preventative radiation therapy to the brain is sometimes recommended in order to lower the risk of brain metastasis, a very common site of cancer recurrence. Side effects can include cognitive changes (such as decreased memory and concentration) though treatment with a drug previously used for dementia appears to reduce symptoms.

Clinical trials

Several clinical trials are in place looking for better treatments for small cell lung cancer. The National Cancer Institute recommends that people with lung cancer consider participating in clinical trials. Together, several of the lung cancer organizations have set up a free clinical trial matching service for lung cancer patients, in which a navigator can assist you in finding out whether any clinical trials in progress could match your particular tumor and wishes.

Palliative Therapy

In addition to treating the cancer, methods such as radiation therapy are often used to help control the symptoms of small cell lung cancer. Radiation may be helpful in managing symptoms such as bone pain due to bone metastases, headaches and weakness caused by brain metastases, bleeding from the lungs, and shortness of breath caused by obstruction of the airways.

Prognosis

The overall survival rate for small cell lung cancer is very different depending on the stage. Currently, the average 5-year survival rate for small cell lung cancer overall (all stages) is 5% to 10%.

Factors that are associated with improved survival include female gender, and better performance status—that is better health in general at the time of diagnosis. Continued smoking may lower survival. Since small cell lung cancer grows rapidly, and since we have come a long way with other fast-growing cancers such as leukemia, it is hoped that better treatments will be found in the future.

It's important to note that current survival statistics are based on people who were treated with chemotherapy and radiation. With the recent approval of immunotherapy drugs, as well as other options (such as targeted therapies) being studied in clinical trials, the current statistics may not represent what you may expect at this time.

Coping

Studies suggest that learning what you can about your lung cancer can improve your quality of life, and possibly even your outcome. Ask questions. Learn about clinical trials that might be appropriate for you., and how to be your own advocate in your cancer care.

Many people find it helpful to become involved in a support group or support community. Ask for and allow your loved ones to help. And hang on to hope. The treatment of lung cancer—and survival rates—are improving after many years of what seemed like little change. There is a lot of hope.

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Article Sources

  1. Perez, J., Leary, A., Besse, B. et al. Efficacy and Safety of Lurbinectedin (PM1183) in Small Cell Lung Cancer (SCLC): Results From a Phase 2 Study. Journal of Clinical Oncology. 2018.

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