Types of Treatment for Small Cell Lung Cancer

The individuals suffering from small cell lung cancer are given therapeutic management by the healthcare team, who have contributed to the diagnosis and drug treatment of the patient to improve their quality of life. The standard type of treatment for small cell lung cancer is the standard of care that represents implementing the best medicine known to date. The consideration of clinical trials is observed as an essential treatment option. The doctors are also integrating to determine the safety of the new treatment and its efficacy showing better outcomes than the standard treatment. The clinical trials use the testing of new drugs involving the combination of traditional therapies or further doses of standard medications or other medicines.

The multidisciplinary healthcare team has contributed to providing appropriate treatment to patients suffering from small cell lung cancer. The interdisciplinary healthcare team involves different health care professionals such as physician assistants, nurse practitioners, oncology nurses, social workers, pharmacists, counsellors, dietitians, and others. The standard treatment for small cell lung cancer have been illustrated below:

1. Chemotherapy: 

It is considered the primary treatment for small cell lung cancer showing the survival rate of the patients. It has effectively improved the survival of patients with small-cell lung cancer with the limited and extensive stage. Still, it shows significantly less efficacy in curing the SCLC in a minority of the patients ​1​. The small cell lung cancer patients have been observed to show distant metastasis that requires localized forms of treatment involving surgical resection or radiation therapy, resulting in long-term survival among the patients. The incorporation of the current chemotherapy regimes within the treatment programs shows prolonged survival while representing an improvement in median survival compared with patients who are given no therapy. It integrates medicines for killing the cancer cells or eliminating their growth. Its mechanism involves the interference with the capabilities of the cancer cells towards division. Most of the cells of the adults are not actively growing due to the adoption of chemotherapy, except bone marrow, hair follicles, and the lining of the gastrointestinal tract (e.g., stomach, intestines). Chemotherapy has major impact on these and other normal tissues give rise to side effects seen during treatment. 

The patients are given a combination of platinum and etoposide, the most commonly used standard chemotherapeutic regimen ​2–4​. Not much consistency towards survival benefits have resulted from platinum versus non-platinum combinations, increased dose intensity or dose density, altered mode of administration of different chemotherapeutic agents while maintaining the chemotherapy ​5​. The small cell lung cancers are highly responsive to chemotherapy, and sometimes improvement may be rapidly evolving certain complexities. In most cases, cancer often returns if treated with a chemotherapy regimen. Some of the other standard chemotherapy regimens for small cell cancer are:

  • Etoposide (available as a generic drug) and cisplatin (known as a generic drug)
  • Etoposide and carboplatin (known as a generic drug)
  • Irinotecan (Camptosar) and cisplatin
  • Irinotecan (Camptosar) and carboplatin

Patients with small-cell lung cancer tend to show metastasis after adhering to previous platinum-based chemotherapy treatment, and the FDA has also approved the chemotherapy drug lurbinectedin (Zepzelca). The chemotherapy’s significant side effects depend on the specific person and the dosage used. At the same time, the most common side-effects include fatigue, risk of infection, nausea and vomiting, loss of appetite, diarrhoea, and hair loss. Nausea and vomiting are avoidable. 

2. Radiation therapy:

It is mainly used in combination with chemotherapy to treat individuals with limited-stage of small cell lung cancer. It mainly uses high-powered x-rays for destroying cancer cells. The radiation therapy is primarily directed at the chest region, also known as thoracic radiotherapy, towards the primary lung tumor and the lymph nodes to which cancer has spread. The SCLC patients treated with chemotherapy and radiation therapy to the chest region tend for receiving preventive radiation therapy to the brain called prophylactic cranial irradiation (PCI). As small cell lung cancer is aggressive cancer that has the capability of spreading to the brain requires the integration of prophylactic cranial irradiation (PCI). PCI can destroy the microscopic cancer cells that may reach the brain and are given to those patients who provide a better response to the initial therapy and prove healthy for undergoing any treatment. Approximately 25% of the patients have been treated with limited-stage small-cell lung cancer with immediate treatment with chemotherapy and radiation therapy.

The small cell lung cancer patients receiving radiation therapy combined with chemotherapy have been recommended to give radiation therapy starting from the chest region with the first or second cycle of chemotherapy. Radiation therapy is given once or twice a day. It is mainly suggested after the surgery for the SCLC patients who are also suffering from some residual disease and whose lymph nodes are affected by cancer. If chemotherapy can shrink the tumor, then the remaining tumors and lymph nodes affected by cancer should receive additional treatment with radiation therapy. 

The patients suffering from stage I and II SCLC have not shown metastasis to the lymph nodes and cannot be treated with surgery recommended for radiation therapy. The integration of stereotactic body radiation therapy (SBRT) is an option for small cell lung cancer patients as a sizeable precise radiation therapy dose is delivered to a small tumor area. 

The extensive-stage SCLC patients often undergo radiation therapy for treating the remaining disease in the chest region if the chemotherapy has shown efficacy in reducing the size of tumour cells in the other areas of the body. Radiation therapy is only recommended after the completion of the chemotherapy. 

The highly radiosensitive and thoracic radiation therapy has shown efficacy in the survival rate of the patients with tumors in the limited and extensive stage of small cell lung cancer ​6​. PCI prevents central nervous system recurrence and may improve the long-term survival of patients with good performance status who have responded to chemoradiation therapy ​7​

Also, small cell lung cancer patients often receive radiation therapy showing side effects such as fatigue and loss of appetite. The patients receiving radiation therapy in the regions of the neck or centre of the chest, side effects of sore throat and difficulty in swallowing are observed. The appearance of skin irritation, similar to sunburn, is regarded within the area where radiation is directed. The patients also develop cough, fever, or shortness of breath months and sometimes years after the radiation therapy ends if the radiation irritates the lungs. Approximately 15% of the patient goes through radiation pneumonitis.

3. Immunotherapy: 

It is known as the biological therapy that helps in boosting the natural defense system (immune system) within the body to fight against cancer. It utilizes the materials made either by the body or in a laboratory to improve, target, and restore the immune system’s function. The PD-1 pathway has shown efficacy in controlling cancer growth within the immune system. PD-1 and PD-L1 antibodies block the path, stopping and slowing the development of small cell lung cancer among the patients. The most type of immunotherapy used for small cell lung cancer are:

  • Atezolizumab (Tecentriq)
  • Durvalumab (Imfinzi)
  • Nivolumab (Opdivo)

Different types of immunotherapy have tended to cause several side effects, including skin reactions, flu-like symptoms, diarrhoea, and weight changes—some of the patients show infusion reactions when given the drugs for immunotherapy. The infusion reaction is an allergic reaction and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. Autoimmune reactions have also been reported in patients when immunotherapy-based drugs tend to remove safeguards on the body’s immune system. Other body parts are also affected as it causes severe or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, or other organs.

Surgery:

Surgery is rarely used to treat small-cell lung cancer as cancer has already spread to the body till its diagnosis. Small cell lung cancer is found only in single lung tumors, with no spread to lymph nodes or other organs in very few patients, estimating only 1 out of 20 patients. Hence, surgery is considered an option only when the small cell lung cancer is diagnosed in the very early stage, followed by some additional chemotherapy treatment. Some major tests are performed for surgery among the small cell lung cancer patients:

  • Pulmonary function tests are used to check for any healthy cells after the surgery.
  • The tests are performed to check the functioning of the heart and other organs to ensure the patient’s good health after surgery.
  • The determination of cancer metastasis to the lymph nodes between the lungs is mainly carried out by mediastinoscopy or other techniques before the surgery.   

Also, some of the surgeries have been proven effective in treating small cell lung cancer as the nearby lymph nodes are removed for determining the possible spread of the tumor. General anesthesia is provided to the patients at the time of surgery. It is usually done through a large surgical incision between the ribs in the side of the chest or the back, known as thoracotomy. Others are mentioned below:

  • Pneumonectomy: It removes the entire lung and is required if the tumor is close to the centre of the chest region.
  • Lobectomy: The lungs consist of 5 lobes (3 in the right lung and 2 in the left). The entire lobe containing the tumors is removed in this surgical approach. It is often the preferred type of operation for small cell lung cancer.
  • Segmentectomy or wedge resection: It often involves the removal of only part of the lobes with the tumor and is only done if the patient does not have normal lung function for withstanding the removal of the entire lobe.
  • Sleeve resection: It is used for treating the cancers of large airways within the lungs. The sleeve resection cut across the airways above and below the tumor and then sewed the cuff back onto the shortened airways. 

4. Palliative care:

Palliative care in treating small cell lung cancer helps manage physical symptoms and side effects and emotional, social, and financial effects. It majorly focuses on improving the patient’s feeling during the treatment by managing symptoms and supporting patients and their families with other non-medical needs. Psychosocial support is needed for the family of the patients, which is considered a fundamental approach in improving the quality of life of the patients. Different organizations have provided adequate support and information on lung cancer. The individuals who are suffering from small cell lung cancer and still have the habit of smoking have been motivated to quit smoking. Regardless of age, type, and stage, any patients are intended to receive such kind of cancer care. And it shows efficacy if it works with the cancer diagnosis. The individuals receiving palliative care and their treatment tend to show less severe symptoms while improving the quality of life and reporting their satisfaction level towards their treatment. 

The palliative treatments involve medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies as per the patient’s medical history. Also, the palliative treatments are given to the patients showing similarities with those to get rid of cancer involving chemotherapy, surgery, or radiation therapy. Following medicines are given to the patients for helping them to get relieved from the symptoms of small cell lung cancer:

  • Photodynamic therapy: It is most often used for helping the patients to open up the airways blocked by tumors for providing better breathing ability among the patients. Light-activated drug known asporfimer sodium (Photofrin) is injected into the patients’ veins that initiates the collection of medicine in the cancer cells rather than in normal cells. After a few days, the bronchoscope targets the tumor that activates the drug and kills the cells. Later, the dead cells are then removed during bronchoscopy. Some of the side effects of PDT involve the swelling within the airway leading to shortness of breath and coughing up blood or thick mucus. 
  • Laser therapy: It is effective in opening the airways blocked by the tumors for helping the patients in breathing effectively. The laser is on the end of a bronchoscope passed down the throat and next to the tumor. The expert then aims the laser beam at the tumor to burn it away. This treatment can usually be repeated if required.
  • Stent placement: In case the lung tumor grows into the airways while causing some significant issues, the bronchoscope is used to put a rugged silicone or metal tube called a stent within the airway for keeping it open. It is often done after other treatments such as PDT or laser therapy. 
  • Thoracentesis: It is a method for the removal of fluid. The experts are supposed to numb the area within the lower back and later place a hollow needle into the space between the ribs to drain the fluid around the lung. The use of ultrasound helps in guiding the needle into the liquid.
  • Pleurodesis: It is the process for fluid removal and keeps it from coming back. Its primary classification is:
    • Chemical pleurodesis: It is carried out by making a small cut within the skin of the chest wall and a hollow tube placed into the chest to remove the fluid. A substance is put into the chest region through the tube that causes the linings of the lung called visceral pleura and chest wall known as parietal pleura to stick together, sealing the space and limiting further fluid buildup. The substances such as talc, the antibiotic doxycycline, or a chemotherapy drug like bleomycin are used for chemical pleurodesis.
    • Surgical pleurodesis: Talc is blown into the space around the lungs during an operation. It is done through a small incision using thoracoscopy.
  • Catheter placement: One of the ends of the catheter is the thin, flexible tube placed in the chest region through a small cut within the skin, and the other end is left outside the body. Once it reaches a specific place, the catheter is attached to the unique bottle to allow the fluid to drain out regularly.
  • Pericardiocentesis: It is the process of draining out the fluid with a needle placed into the space around the heart. It is usually done using an echocardiogram, an ultrasound of the heart to guide the needle.
  • Creating a pericardial window: In this, the pericardium, the sac around the heart, is removed to allow fluid to drain into the chest or belly. This opening is referred to as a pericardial window that helps in keeping the fluid from building up again. 

Other palliative care includes:

  • Medications have been used for treating cancer pain. Most hospitals and cancer centres possess pain control specialists who provide pain relief, even for severe cancer pain. Several drugs have been used to treat cancer pain, mainly the morphine that gives comfort from shortness of breath caused due to cancer.
  • The medications have shown effectiveness in suppressing coughs, opening closed airways, or the reduction of bronchial secretions.
  • Prednisone or methylprednisolone have been effective in reducing the inflammation caused by radiation therapy in cancer and improving the breathing rate of the individuals.
  • Extra oxygens are provided from the small, portable tanks that help combat the lungs’ reduced ability to pull oxygen from the air.
  • The medications have been effective in strengthening the bones, reducing bone pain, and helping prevent future bone metastasis.
  • The appetite and weight loss are required to minimize among the small cell lung cancer patients by giving them appetite stimulants and nutritional supplements.

5. Treatment options by stage:

The specific therapeutic procedures and related interventions show variations as per the different factors such as disease stage, tumor size, the metastasis of cancer and its effect on other organs of the body, presence or absence of the system, age and health of the patient. The decisions regarding the use of specific drug regimen and other treatment need to be taken by the experts or other members of the healthcare team in careful consultation with the patient by specifying the patient condition thorough discussion of the potential benefits and risks, including possible side effects and long-term effects, patient preference, and other appropriate factors. 

Small cell lung cancer is staged as a limited or extensive stage. In most cases, small cell lung cancer has already spread until it is diagnosed. The treatment options for small cell lung cancer has been represented below:

  • Treatment of limited-stage small-cell lung cancer: 
    • Stage I cancer: If only one small tumor is diagnosed in the lungs, no evidence of cancer in lymph nodes or elsewhere is observed. Hence, the doctors recommend surgery for removing the tumor and nearby lymph nodes. Very few patients suffering from small cell lung cancer have been treated similarly. Mediastinoscopy or other tests check the lymph nodes within the chest region before surgery. Surgery is usually followed by chemotherapy. Radiation therapy is recommended if cancer diagnosed in the lymph node is removed. The radiation is given during the chemotherapy, which increases the side effects of the treatment. Hence, one after the other treatment is recommended for the small cell lung cancer patients at stage I. Prophylactic cranial irradiation (PCI) is recommended for small cell lung cancer patients mainly prone to metastasis towards the brain. 

For most patients with limited-stage small-cell lung cancer, surgery is not an option due to the large size of the tumors, which cannot be removed easily and may have the chances of getting spread to nearby lymph nodes or other lobes in the same lungs. If the patient is in good health, chemo and radiation together in the chest region are given to the patients, known as concurrent chemoradiation. The combination of etoposide with either cisplatin or carboplatin is given to the patients as chemo drugs.

Concurrent chemoradiation has helped the patients of small cell lung cancer with limited-stage to live longer and provide them with a better chance for cure. The individuals with small cell lung cancer with limited-stage have their tumor treated with chemo while with or without the use of radiations that will reduce the tumor size. 

  • Treatment of extensive-stage small-cell lung cancer: The extensive stage of small cell lung cancer has shown a broader extent of metastasis to be treated with surgery or radiation. Therefore, the initial treatment involves integrating chemotherapy with immunotherapy drugs, which shrinks the tumor cell, treats the symptoms and helps to live longer—the combination of chemo drugs etoposide with either cisplatin or carboplatin. The use of immunotherapy drugs atezolizumab (Tecentriq) or durvalumab (Imfinzi) with etoposide and a platinum drug (cisplatin or carboplatin) have been influential in the initial treatment and are continued alone as maintenance therapy. It reduces the tumor size and, in some cases, cannot be seen on imaging tests. Combining PD-L1 immunotherapy with chemotherapy is recommended for more extended living to small cell lung cancer patients. 

In the extensive stage of small cell lung cancer, radiation in the chest region is recommended as the initial form of treatment. The metastasis to the brain within an extensive stage is controlled by giving prophylactic cranial irradiation or PCI to prevent cancer progression in the brain. Radiation therapy and laser therapy effectively relieve symptoms among the patients who have shown metastasis in the bones, brain and spinal cord. If the patients cannot withstand chemotherapy, then palliative care support is provided to the patients with lower doses of chemo that helps treat the symptoms of pain, breathing issues and other symptoms.

Clinical trials have also been recommended to the patients to administer new chemo drugs and combinations and integrate new treatments.

6. Remission and chance of recurrence:

There is a chance of getting back with the cancer disease even after the treatment. Any further treatment will entirely depend upon the location and extent of cancer and the prior treatment that the patient had during the initial phase of cancer. If the patient has been regularly checked for cancer and it is found that the tumor continues to grow during the initial chemotherapy treatment or if a tumor starts to grow after chemo has been stopped for less than six months, another type of chemotherapy involving topotecan is recommended, although it may not be effective. The selection of chemo drugs during the recurrence of cancer after the initial treatment depends on the duration of the remission.

The recovery from small cell lung cancer is not always possible. If the cancer is not cured, it is often known as advanced or terminal cancer. Patients diagnosed with such cancer have been expected to live less than six months and may look forward to hospice care. Hospice care is given to provide the best life quality to patients near the end of their lives. The family members are motivated by communicating with the healthcare team. The nursing homes and special equipment helps in making the stay at home a workable option for many families. Advanced care planning is also provided to the patients and their families. 

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