LUNG CANCER TREATMENT MODALITIES

There are various treatment modalities for lung cancer. Selection of which treatment or combination of treatments to be used is made by the patient together with the patient’s oncologist, other physicians, and other healthcare professionals.

Surgery

Small cell lung cancer (SCLC) is not generally treated by surgery because the cancer is so rapid and diffuse in its growth.

If a malignant lung tumor is considered operable, several cardiopulmonary evaluations must be done before the surgery can go forward. Pulmonary function studies, arterial blood gases (ABGs), an electrocardiogram (ECG), a complete blood count (CBC) and metabolic panel, and an anesthesia consult must all be performed to assess the cardiopulmonary status of the prospective surgical patient (Harding et al., 2020).

A possible contraindication for the surgical treatment of lung cancer is advanced lung disease such as chronic obstructive pulmonary disease (COPD). A patient with advanced COPD may have insufficient lung capacity to be weaned off the ventilator. Once this patient has demonstrated ventilator dependence, there may not be an opportunity to breathe on their own once they are extubated.

Any lung cancer surgery is a highly invasive procedure for the older adults >70 years of age, with higher rates of morbidity and mortality than for younger patients. With the advent of less invasive surgery, such as video- or robot-assisted thoracoscopy (VAT or RAT), morbidity and mortality rates have improved because of a reduction in cardiopulmonary complications (Zaatar et al., 2020).

(See also “Prehabilitation” below.)

TYPES OF SURGERY

The type of lung resection is determined by the cancer stage at initial presentation and the mass’s size, location, and proximity to adjacent anatomy. Different surgical approaches can be used for lobectomy, segmentectomy, sleeve resection, and mediastinal tumor resection.

Pneumonectomy

A pneumonectomy is the most radical lung surgery and involves excising the entire lung. The first pneumonectomy was documented in the Journal of the American Medical Association (JAMA) in 1933. The extent of this surgery for NSCLC may include the anatomic resection of hemipulmonary tissue and pulmonary artery, vein, and main bronchus, as well as lymph node dissection if there is metastasis to the lymph nodes.

A pneumonectomy may be chosen for treatment of lung cancer given the size and location of the tumor, for example if the tumor is in the center of the chest or an advanced mesothelioma. The 5-year overall survival (OS) rate is 32.3%, and the 30-day mortality rate is 4%.

Lobectomy

Lobectomies are considered the “gold standard” or optimum lung surgeries for treatment of early-stage (stages I–IIA) NSCLC. In this surgery, a single lobe of the left lung or one or two lobes of the right lung are removed. A sleeve lobectomy includes also removing part of the near bronchus. Pulmonary function tests are often performed to determine whether the patient will be able to tolerate a traditional open lobectomy or whether a less-invasive, video-assisted thoracoscopic surgery (VATS) would be the better choice (see below).

Wedge Resection and Segmentectomy

Wedge resection (also called sublobar resection) and segmentectomy (or segmental resection) lung surgeries are two surgical options for high-risk but operable patients with early-stage (stages I or II) lung cancer. Wedge resection or segmentectomy are considered good procedures for borderline surgical candidates with limited pulmonary reserve, such as those with pulmonary comorbidities such as emphysema or interstitial lung disease (ILD) (Kawaguchi et al., 2019).

A wedge resection involves removal of the tumor plus a wedge-shaped section of lung tissue around the tumor to ensure clear surgical margins. A segmentectomy surgery involves removal of only part of a lobe of the lung. Wedge resection or segmentectomy are connected with fewer peri- and postoperative complications, but the incidence of recurrent cancerous lung tumors is higher than among patients who receive a standard lobectomy.

Video-Assisted Thoracic Surgery (VATS)

VATS is a minimally invasive technique for diagnostic and surgical resection of a lung tumor, usually one near the outside of the lung. It is the recommended approach for a stage I NSCLC tumor. Small incisions are placed in the chest wall in order to insert a tiny camera to guide the procedure. Surgical instruments are then inserted through the small incisions to excise the targeted lung tumor.

The use of VATS rather than more traditional and more extensive lung surgery has the benefits of less pain, superior postoperative shoulder range of motion (ROM), and better general function immediately postoperatively. There are fewer postoperative complications, a significantly diminished risk of intensive care readmission, shorter hospital lengths of stay, and diminished necessity for rehabilitation while still in the hospital while recovering from surgery (Al-Ameri et al., 2019).

Robotic-Assisted Thoracic Surgery (RATS)

RATS is being performed more frequently than VATS for diagnosis and lung resections. There are several advantages of using RATS, including a magnified three-dimensional view, a manipulator wrist with better dexterity, and a tremor filtration mechanism. Four to five incisions are necessary for the various arms used in RATS, compared to one incision with VATS. Three-dimensional (3D) video and surgical scopes are then inserted through the incisions. The robotic arms move as flexibly as a human hand and wrist, manipulated by the surgeon from the console in the room.

The use of robotic equipment for a lobectomy increased from <1% in the United States in 2009 to an estimated >20% in 2020. The complexity of lung resections performed by RATS has increased as well (Mazzei & Abbas, 2020). It is primarily used for stage I/II NSCLC.

Robotic segmentectomy is more complex than robotic lobectomy, depending on the ability to access the tumor with the robotic arms. Robotic bronchial sleeve resection is the most difficult of the robotic-assisted lung surgeries. The tumor is excised and then the bronchial tissue is re-anastomosed. The postoperative complication rate is lower than with traditional lung resections (Han et al., 2020).

ADVERSE EFFECTS

The adverse effects of lung surgery are similar to those of any surgery. Hemorrhage intra- and postoperatively is the most dangerous occurrence, possibly due to a slipped ligature. Pre- and postoperative blood counts need to be carefully monitored for this reason.

Depending on the size of the excised lung tissue, the incision can be quite extensive. Posterior-lateral incisions provide the best access but can be very painful. The incision may involve dividing latissimus dorsi, serratus anterior, and trapezius muscles. The resultant pain can cause the patient to hypoventilate, resulting in hypercapnia, atelectasis, or postoperative pneumonia. An air leak intra- or postoperatively can cause pneumothorax, requiring the insertion of a chest tube. A chest tube may also be inserted to measure blood loss or to equalize intrathoracic pressure changes.

Other possible postoperative complications include:

• Pain due to the surgery; treated by opiates immediately postoperatively
• Persistent air leak caused by trauma to the pleura during surgery; treated by fibrin glue, early pleurodesis (adhesion of pleura to the chest wall), a blood patch, or dissection of the visceral pleura
• Atrial fibrillation or other supraventricular dysrhythmias
• Chylothorax (lymph fluid from the digestive system that can migrate to the chest cavity)
  (Nakamura et al., 2021)

PREHABILITATION

Prehabilitation is a relatively new treatment method used preoperatively to assess whether a patient will tolerate surgery and to maximize their physical status prior to surgery. Prehabilitation prepares the patient physiologically and psychologically in order to promote better postoperative outcomes, prevent untoward effects of extensive surgery, improve quality of life, and reduce postoperative morbidity (Lai et al., 2017). Prehabilitation includes interventions in the areas of physical therapy, occupational therapy, and pulmonary rehabilitation.

Before a comprehensive rehabilitation treatment plan can be formulated, it is necessary for the clinician to conduct a comprehensive physical and pulmonary assessment, including vital signs, oxygen saturation, height, weight, and pulmonary function testing (JHM, 2020a).

Functional capacity measures in particular are strong predictors of postoperative complications such as respiratory failure, increased hospital length of stay, and health-related quality of life. These measures are also able to predict postoperative mortality and long-term survival in NSCLC. Testing to determine a prospective surgical patient’s fitness for the operation may include the 6-minute walking distance (6-MWD), peak expiratory flow (PEF), and quality-of-life scores (Lai et al., 2017).

The 6-MWD test is a means to measure a patient’s stamina, endurance, and potential survival. The parameters measured are oxygen saturation, pulse, and a subjective description of the patient’s level of dyspnea. A significant improvement in the 6-MWD measured after a lung resection surgery compared to the prehabilitation measurement proves to be a credible predictor of improvements in morbidity and mortality postoperatively (MDApp, 2020).

Prehabilitation interventions such as aerobic exercise and resistance training may improve physical and pulmonary status in patients considered to be poor surgical candidates due to cardiovascular or pulmonary impairment. This may lead such patients to become candidates for surgical resection. Interventions are supervised, outpatient-based, and typically performed five times a week for one to 10 weeks (most commonly, for four weeks).

Exercise training performed preoperatively has been found to improve patient outcomes for patients who undergo surgery for lung cancer. Exercises taught to the patient preoperatively focus on endurance and resistance training. Aerobic training is considered the best way to improve cardiopulmonary fitness, and when part of a pulmonary rehabilitation program, aerobic training has proven to reduce dyspnea, increase functional capacity, and reduce postoperative morbidity. Other prehabilitation interventions may include breathing exercises, incentive spirometry, inspiratory muscle training, stretching, and relaxation.

POSTOPERATIVE MANAGEMENT

Physical therapists play a significant role in postoperative patient care in the form of enhanced recovery after surgery (ERAS), and for longer-term pulmonary rehabilitation. Postoperative physical therapy management includes breathing exercises for pulmonary expansion, inspiratory muscle training (IMT), bronchial hygiene, early mobilization and ambulation, postural correction, and surgical-side shoulder range of motion (ROM) as a recovery and maintenance strategy.

IMT improves inspiratory muscle strength and endurance, functional exercise capacity, dyspnea, and quality of life. Pulmonary muscle weakness is a critical impairment following pulmonary surgery, secondary to muscular injury, central nervous system depression, and pain. Pulmonary muscle weakness causes the inability to cough effectively, reduced lung compliance, and dyspnea related to postoperative immobilization.

In order to avoid atelectasis (lung collapse or closure) and to prevent other postoperative complications, it is imperative to remove secretions from the airways and promote expansion of the lung tissue. Deep-breathing exercises with bronchial clearance, exercising and stretching the surgical-side muscles, and early patient mobilization are essential aspects of the postoperative pulmonary physical therapy program (Kendall et al., 2017).

The respiratory therapist (RT) will manage the patient on a mechanical ventilator immediately after tumor resection surgery or a pneumonectomy and make recommendations for weaning the patient off of the ventilator and extubating the patient. It is the RT who determines the type of oxygen delivery system: nasal cannula, simple mask, Venturimask, tracheostomy collar, or a nonrebreather mask. The RT may draw the arterial blood gases (ABGs) to determine the amount of oxygen needed to be delivered to the patient.

To maintain a clear airway, the RT will give the patient nebulizer treatments and instruct them on how to use medi-halers and discs. It is also the responsibility of the RT to suction the patient’s airway oral pharyngeally, nasal pharyngeally, and tracheally. The RT will also perform chest percussion and provide instruction in handling and removing secretions to promote as much independence during the palliative phase (Harding et al., 2020).

Radiation Therapy

Radiation therapy may be used to treat lung cancer depending on the stage, size, or progression of the tumor and other factors:

• As the main treatment, in conjunction with systemic therapies, if the tumor is inoperable because of a large size or difficult location or if a patient is either a poor candidate for surgery or declines surgery
• Preoperatively, with systemic therapies, to shrink the tumor to facilitate excision
• Postoperatively for thorough eradication of the malignant cells
• To treat metastasis when the lung cancer is the primary site
• To relieve symptoms such as pain, dysphagia, or cough

Side effects of radiation therapy for lung cancer include fatigue; nausea and vomiting; loss of appetite and/or weight loss; skin changes in the area being treated, ranging from redness to blistering and peeling; and hair loss at the site of radiation. Side effects depend on the dose and duration of the treatments. The side effects may be minimal, allowing the patient to continue daily functions, or much more severe. They may go away after treatment. The combination of radiation therapy given with systemic therapies may result in worse side effects (ACS, 2020a).

EXTERNAL BEAM RADIATION THERAPY (EBRT)

In EBRT, high-dose beams of radiation are focused on the tumor utilizing a special machine called a linear accelerator. The machine moves around the body without touching the patient and can deliver high-energy radiation beams to a tumor from any angle and shaped to the contour of the tumor. Targeting a tumor with higher, more precise doses of radiation can reduce damage to healthy tissue and nearby organs. As a result, EBRT may also help reduce the risk of side effects associated with traditional radiation treatment (NCI, 2020c).

Stereotactic Body Radiotherapy (SBRT)

Stereotactic body radiotherapy, also referred to as stereotactic ablative radiotherapy (SABR), is a form of EBRT. It involves several high-dose beams of radiation focused on the tumor from different angles to target the tumor precisely in order to minimize damage to surrounding tissue and extends for one to five treatments. SBRT is used for early-stage lung cancer that may be inoperable due to age, health problems, or location of tumor; when the patient rejects surgery; or in cases with limited metastasis to other organs (ACS, 2020a).

The precisely focused high-dose radiation beams use 3D imaging as a noninvasive means to treat a tumor and prevent harm to the surrounding tissue. This can be performed by using a linear accelerator or proton beam therapy, which requires only one to five treatment sessions, depending on the size of the tumor. Early side effects are usually temporary and may include fatigue, swelling, and nausea and vomiting. Late side effects are rare and may occur months after the treatment(s). These may include weakened or broken bones, bowel changes, changes in the lungs, changes in the spine, a secondary cancer, or lymphedema (Mayo Clinic, 2022).

Three-Dimensional Conformal Radiation Therapy (3D CRT)

Three-dimensional conformal radiation therapy is a form of EBRT that uses a computer to precisely determine the location of the tumor. Radiation beams are shaped and delivered in multiple angles to focus on the tumor and preserve the surrounding lung tissue, protecting it from the radiation.

Intensity-Modulated Radiation Therapy (IMRT)

Intensity-modulated radiation therapy is a type of 3D radiation therapy that also uses a computer to shape the beams of radiation and direct them at the lung tumor from various angles. In this type of radiation therapy, the intensity of the beams can be adjusted to help preserve the surrounding lung tissue. Volumetric modulated arc therapy (VMAT) is another variation in which a device rotates quickly around the body and aims a precise dose at the tumor in just a few minutes.

PROPHYLACTIC CRANIAL RADIATION

Prophylactic cranial radiation is used for SCLC with early metastasis to the central nervous system (CNS). It decreases the instances of cerebral metastases and improves the survival rate in limited SCLC. Since most chemotherapies are unable to penetrate to the blood-brain barrier, prophylactic cranial radiation is given to treat metastasis to the brain from a primary site. The purpose is to improve the patient’s overall survival rate (Harding et al., 2020).

BRACHYTHERAPY

Brachytherapy treats cancer by implanting radioactive seeds, ribbons, rods, wires, or capsules into the interstitium of the tumor tissue to destroy the abnormal cancer cells directly and with minimal destruction of the surrounding tissue. The radioactive material is injected into the tumor via a catheter or applicator tube.

• A low-dose radiation treatment remains implanted for one to seven days.
• A high-dose radiation treatment is left in place for 10 to 20 minutes at a time and then removed. The treatment may also be given twice a day for two to five days, or once a week for two to five weeks.
• Permanent implants remain in place for the life of the patient, and the radiation gradually weakens.

A patient receiving brachytherapy is placed in a private room to prevent exposure from the radiation to others. Clinicians provide care in short intervals to minimize exposure to themselves. The following are the considerations for visitors to the patient during this time period:

• Not being allowed to visit when the radiation is first put in
• Needing to check with the hospital staff before visiting
• Standing by the doorway rather than going into the patient’s room
• Keeping visits short (30 minutes or less each day), depending on the type of radiation being used and the part of the body being treated
• Not having visits from pregnant women and children younger than 1 year
  (NCI, 2020b)

The side effects of brachytherapy are diarrhea, nausea, skin irritation, fatigue, and dysuria.

RESPIRATORY-GATED RADIATION THERAPY

Respiratory-gated radiation therapy is a very new treatment that uses the period of time when the lungs are relatively immobile between respirations to administer the radiation therapy. This method allows the radiation to be administered more precisely to the tumor, preserving more of the surrounding healthy lung tissue (Dartmouth, 2020).

Chemotherapy

Chemotherapy is used in most cases of SCLC, as these patients are not considered candidates for surgical intervention. Some patients with NSCLC may also require chemotherapy depending on the stage of their cancer. Chemotherapy is also utilized as an adjuvant to other therapies (ACS, 2020b).

Patients in poor health may not be candidates for intense doses of chemotherapy or a combination of drugs due to tolerance, but older age itself is not a contraindication for chemotherapy.

• Chemotherapy may be utilized along with radiation therapy as the main treatment for locally advanced NSCLC cancers that have grown into nearby structures such that surgery is not an option or for people who are not healthy enough for surgery.
• Chemotherapy may be given for metastatic (stage IV) NSCLC that has spread to areas outside of the lungs, including bones, liver, or adrenal gland.
• Neoadjuvant (before surgery) chemotherapy may be used (sometimes with radiation therapy) to shrink a tumor in order to remove it with less-extensive surgery.
• Adjuvant (after surgery) chemotherapy may be used (sometimes with radiation therapy) to kill any cancer cells that might have been left behind or have spread but cannot be seen on imaging tests.
  (ACS, 2020b)

CHEMOTHERAPY ADMINISTRATION

Chemotherapy drugs for lung cancer are usually given intravenously (IV), either as a slow IV push or as a “piggyback” infusion intermittently over a longer period of time. They can also be administered orally if nausea and malabsorption are not issues for the patient.

Administration can be performed in a physician’s office, chemotherapy clinic, or the hospital. Long-term chemotherapy may require the placement of a device left in place in a large vein, such as a peripherally inserted central catheter (PICC) or a vascular access device (VAD). Patients in poor health may not be able to tolerate higher doses of chemotherapy or a combination of drugs.

Chemotherapy is given in cycles, with each period of treatment followed by a rest period to allow recovery from the side effects of the drug(s). Cycles are usually three or four weeks in length. The schedule depends on the type of chemotherapy being given. With some drugs, the chemotherapy is given just on the first day of the cycle. Other chemotherapy is given for a few days in a row or weekly. Then the cycle repeats.

Adjuvant and neoadjuvant chemotherapy are given for three to four months, depending on the drugs that are ordered. The length of treatment for advanced lung cancer is based on the effectiveness of the treatment regimen and side effects.

For late-stage or extensive lung cancers, the initial chemotherapy combination is usually given for four to six treatment cycles. Often it is recommended to give the chemotherapy treatment for longer with a single chemotherapy or targeted drug.

Patients who have a good response to their initial chemotherapy or no worsening of their cancer may receive maintenance chemotherapy for a more prolonged period of time. Maintenance therapy can prevent or delay the return of the cancer if the patient is in remission, thus extending life expectancy (ACS, 2020b).

Combinations of two or more chemotherapy drugs are often used to treat early-stage lung cancer. Late-stage lung cancer may be treated at first by a combination of different chemotherapy drugs, such as gemcitabine with vinorelbine or paclitaxel, but the treatment regimen may be switched to a single drug such as docetaxel or pemtrexed to focus on the tumor(s). This may be done for patients who find combination chemotherapy intolerable, such as those in poor general health or of advanced age. For some people with late-stage lung cancer, a targeted therapy drug or an immunotherapy drug may be given along with chemotherapy (NCCN, 2021).

TYPES OF CHEMOTHERAPY

Platinum-based chemotherapy is considered the “gold standard” for the treatment of NSCLC because of its effectiveness in reducing the size of the tumor. It may be given prior to surgery.

Cisplatin is a platinum-based chemotherapy that acts as the primary treatment for advanced NSCLC, including squamous cell carcinoma, adenocarcinomas, adenosquamous carcinoma, large cell carcinoma, and sarcomatoid carcinoma. This may be combined with vinorelbine, gemcitabine, docetaxel, or pemetrexed to increase the efficacy of the drug.

Carboplatin is a platinum-based chemotherapy that can be used for chemotherapy treatment in patients with complicating comorbidities or in patients who are unable to tolerate cisplatin for a variety of reasons.

Other chemotherapy drugs used include:

• Paclitaxel (Taxol)
• Albumin-bound paclitaxel (nab-paclitaxel, Abraxane)
• Docetaxel (Taxotere)
• Gemcitabine (Gemzar)
• Vinorelbine (Navelbine)
• Etoposide (VP-16)
• Pemetrexed (Alimta)

CHEMOTHERAPY SIDE EFFECTS

Chemotherapy can cause many and severe side effects or adverse reactions. (The same side effects can also be caused by physiologic placement of the mass or lymphadenopathy compressing the esophagus or the diaphragm.) Some common side effects include:

• Nausea and vomiting
• Dysphagia
• Hair loss
• Mouth sores
• Loss of appetite or weight changes
• Diarrhea or constipation

Nausea and vomiting may happen within one hour of chemotherapy (or a few hours after radiation to the chest or abdomen). The duration of vomiting may persist for up to 24 hours after treatment.

Fatigue can either be caused by the cancer itself or as a side effect of chemotherapy. After treatment, accumulation of toxic substances may remain in the body, thereby causing fatigue.

Chemotherapy can also affect the blood-forming cells of the bone marrow, which can lead to:

• Increased chance of infections (from low white blood cell counts)
• Easy bruising or bleeding (from low blood platelet counts)
• Fatigue (from anemia secondary to low red blood cell counts)

Some drugs, such as cisplatin, vinorelbine, docetaxel, or paclitaxel, can cause peripheral neuropathy (ACS, 2020b).

Weight loss in patients with cancer may be due to pain causing a loss of appetite (anorexia), fatigue precluding the patient from preparing meals or taking the time to eat (cachexia), and dysphagia. At diagnosis, approximately 60% of patients with lung cancer have already experienced substantial weight loss (Chandrasekar et al., 2016).

Anorexia (loss of appetite) may result from the cancer itself or the treatment(s). Anorexia peaks at approximately four weeks into chemotherapy or radiation treatments and then resolves. Precautions must be taken to prevent weight loss and dehydration. It may become necessary to replace eating with enteral or parenteral nutrition.

Difficulty chewing or swallowing may result from an inflamed mouth or esophagus caused by chemo- or radiation therapy. As with nausea and vomiting, and anorexia, this symptom can interfere with the patient’s ability to ingest adequate nutrition. In this instance, the patient may indicate a lump as they swallow or that food gets stuck when they are eating (Harding et al., 2020).

Targeted Therapy

Targeted therapy uses drugs to inhibit the growth of the malignant molecules rather than kill cancer cells. It may be less toxic than chemotherapy or may be given in conjunction with chemotherapy or other lung cancer treatments.

The most common side effects seen with targeted therapies are diarrhea and liver problems, such as hepatitis and elevated liver enzymes. Other side effects seen with targeted therapies include:

• Skin problems (acneiform rash, dry skin, nail changes, hair depigmentation)
• Problems with blood clotting and wound healing
• High blood pressure
• Gastrointestinal perforation (a rare side effect of some targeted therapies)
  (NCI, 2021)

Indications for the use of targeted therapy include:

• Epidermal growth factor receptor (EGFR) gene mutations
• Anaplastic lymphoma kinase (ALK) rearrangements
• ROS1 rearrangements
• Mesenchymal epithelial transition factor (MET) amplifications
• V-Raf murine sarcoma viral oncogene homolog B1(BRAF) mutations

TYROSINE KINASE INHIBITORS

Tyrosine kinase inhibitors block signals for growth in the cancer cells. Tyrosine kinase is an enzyme that speeds up molecular growth. Blocking its usual function slows the malignant cell growth. They can be used in patients with EGFR mutations.

Examples include:

• Cetuximab (Erbitux)
• Erlotinib (Tarceva)
• Afatinib (Gilotrif)
• Gefitinib (Iressa)
• Osimertinib (Tagrisso)
• Necitumumab (Portrazza)
  (Harding et al., 2020)

KINASE INHIBITORS / ALK INHIBITORS

Another variety of kinase inhibitor is given to patients with NSCLC with an abnormal anaplastic lymphoma kinase (ALK) gene. These drugs inhibit the kinase protein manufactured by the ALK gene that causes cancer cell growth and development. Examples include:

• Crizotinib (Xalkori)
• Ceritinib (Zykadia)
  (Harding et al., 2020)

ANGIOGENESIS INHIBITORS

Angiogenesis inhibitors slow the growth of new blood vessels by targeting the vascular endothelial growth factor. This inhibits the growth of a tumor by denying it an adequate blood supply. Examples include:

• Bevacizumab (Avastin)
• Ramucirumab (Cyramza)

Immunotherapy

Immunotherapy therapy boosts the immune response caused by the body to fight cancer cells. It targets the PD-1/PD-L1 protein on T cells that keeps them from attacking other cells. Immunotherapy drugs can shrink some tumors to prepare for excision or alleviate symptoms or slow their growth. The drugs also effectively treat metastatic NSCLC that continues to grow after other treatments have been tried. Tumors that actively express PD-1/PD-L1 are also treated by these targeted drugs. Examples include:

• Nivolumab (Opdivo)
• Pembrolizumab (Keytruda)
• Atezolizumab (TelCentris)
• Durvalumab (Imfinzi)
  (Harding et al., 2020; Niu et al., 2021)

Similar to PD-1/PD-L1 inhibitors, CTLA-4 inhibitors boost the immune response to fight cancer and have a similar mechanism of action to PD-1/PD-L1 inhibitors. An example is:

• Ipilimumab (Yervoy)
  (ACS, 2021c)

Immunotherapy for lung cancer may cause side effects, usually related to inflammation, such as:

• Pneumonitis
• Fatigue
• Cough
• Shortness of breath
• Nausea
• Anorexia
• Diarrhea
• Muscle and bone pain
  (ALA, 2020c)

Photodynamic Therapy (PDT)

Photodynamic therapy is a two-stage treatment that combines light energy with a photosynthesizer drug. It can be used in early-stage cancers that have not metastasized in order to destroy cancerous cells that are easy to reach. The photosynthesizer drug is given intravenously and concentrates around the tumors in the esophagus and outer airway. After 48 hours a bronchoscopy is performed to apply a laser to the targeted areas, which activates the drug, causing cell death. Another bronchoscopy is performed a few days later to remove necrotic tissue. PDT can cause the cancerous tissue to “starve” and the immune system to fight the cancer cells. The most commonly used photosynthsizer drug is porfimer (Photofrin) (Harding et al., 2020).

The most common side effect of PDT is sensitivity in the patient to bright lights and sunlight. Reactions caused by PDT light can show up on the skin where the drug is applied. They usually involve redness and a tingling or burning sensation. Interventions include:

• Staying out of strong, direct light
• Staying indoors as much as possible
• Wearing protective clothing and wide-brimmed hats to avoid sunlight when outdoors
• Avoiding beaches, snow, light-colored concrete, or other surfaces where strong light may be reflected

Sunscreens will not protect the skin from photosensitivity reactions (ACS, 2020a).

Radiofrequency Ablation

Radiofrequency ablation treats small NSCLC near the outer edge of the lungs. It is used as an alternative treatment method when surgery is either not possible or not desired. A needle is passed into the tumor through the skin under CT visualization. High-energy radio waves create an electric current that passes through the needle, heating and destroying the cancerous cells. Side effects are mild and may include numbness, weakness, soreness, or itching (Harding et al., 2020).

Lung Cancer Symptom Treatments

Symptoms of lung cancer are related to the type, size, location, and extensiveness of the disease. Managing a patient’s symptoms can lead to better patient outcomes. For patients with primary lung cancers confined within the lung(s), symptoms are usually related to issues with the respiratory tract (see “Clinical Manifestations” earlier in the course).

Patients who have lung cancer that has spread to other parts of the body may have a variety of symptoms. For example, patients with metastatic disease in the brain (a common site of metastasis) may have headaches, vision impairment, personality changes, or other neurological deficits. Additionally, patients with metastatic disease to the bone often have significant pain and are at higher risk of bone fractures (also called pathological fractures). (Considerations for patients with different metastatic disease sites are also discussed later in this course.)

BRONCHODILATORS

Bronchodilators are given to patients with lung cancer to increase the volume in the airway that may be obstructed due to swelling, excessive secretions, or a tracheal or bronchial tumor. Several types of bronchodilators can serve this purpose by reducing the obstruction. Use of bronchodilators in patients with lung cancer has been measured to significantly increase the forced exhaled volume (FEV) (Ueda et al., 2018).

The two most common classifications of bronchodilators used for lung cancer include:

• Beta-2 agonists (salbutamol, salmeterol, and formoterol)
• Anticholinergics (ipratropium, tiotropium, and glycopyrronium)

The route of administration is inhaled via nebulizer or a powder disc. Common side effects are shakiness, tachycardia, palpitations, dyspepsia, insomnia, and muscle cramps.

MUCOLYTIC AGENTS

Mucolytic agents are used to reduce the viscosity of unusually thick respiratory secretions in order to promote improved expectoration of the sputum. Patients with lung cancer frequently produce secretions that are excessively thick or purulent. Effective use of mucolytics reduces the amount of a patient’s disability, reduces the hospitalization length of stay, causes respirations to ease, and improves quality of life.

Examples of mucolytic agents include:

• N-acetylcysteine
• Carbocysteine
• Erdosteine
• Ambroxol

The route of administration is oral (tablets and liquid) or nebulization. Side effects may include nausea, sore throat, nasal drainage, white patches on the lips and mouth, and diarrhea (Poole et al., 2019).

Cancer Pain Management

Pain is one of the most common adverse effects of cancer and one of the biggest negative effects on a patient’s quality of life. Multiple studies and clinical practice have shown that premedicating before known painful procedures, medicating prophylactically for anticipated pain, and medicating for pain before it becomes too severe are proven to be the most successful means of managing pain. There are many pharmacologic and nonpharmacologic means of preventing and alleviating lung cancer pain.

Various subclassifications of analgesics can be used to prevent or treat the pain from lung cancer, including acetaminophen (Tylenol), aspirin, and ibuprophen (Advil or Motrin). (Aspirin and ibuprofen are also classified as non-narcotic anti-inflammatory drugs [NSAIDs].) Antidepressants such as duloxetine (Cymbalta) or anticonvulsants such as gabapentin (Gralise or Neurontin) are also used effectively against cancer pain in some situations.

Routes of administration are primarily oral, but acetaminophen can also be given rectally or by intravenous drip. Acetaminophen has no significant side effects, but long-term usage can cause hepatic disease. It is recommended that the daily dosage of acetaminophen not exceed 3,000 mg. NSAIDs may have side effects of dyspepsia. Gabapentin side effects are dizziness, staggered gait, nystagmus, drowsiness, and xerostomia (dry mouth).

Opioids are the strongest medications available to treat pain. There are a variety of medications that may be ordered for the extreme pain that results from cancer, such as morphine, oxycodone, fentanyl, and methadone. The routes of administration are oral, topical, intramuscular, and intravenously.

Opioids carry with them the possible stigma of addiction or a loss of control due to dependency on the drugs for pain relief. Older adults in particular may be fearful that the use of opioids will cause them to become addicted. This may cause patients who are in extreme pain to forego taking sufficient prescribed medications. It is essential that patients take sufficient opioids to preserve a successful quality of life. The patient and family must also be educated that the stress caused by chronic pain may interfere with the patient’s ability to heal.

The most common side effects of opioids are meiosis, constipation, itching, respiratory depression, hypotension, and euphoria. The side effects are more common with the injectable routes.

Cannabinoids (medical marijuana) are a more recent and remarkably effective classification of drugs used to treat all forms of cancer. Cannabinoids contain THC, which is the active ingredient found in marijuana. The majority of U.S. states have legalized medicinal marijuana for treating chronic pain and the nausea and vomiting that often accompanies cancer treatments.

Several research studies involving individuals undergoing cancer treatment have shown that medical marijuana can work similarly to opioids when treating patients living with chronic pain. They also have anti-inflammatory effects that can effectively treat cancer-related pain. Cannabinoids can be given in conjunction with opioids for better effect. The routes of administration for cannabinoids are smoking, vaporizing, oral, and subcutaneous spray. Common side effects of cannabinoids are lethargy, dizziness, dry mouth, increased appetite, and paranoid ideation.

Other modalities that have proved effective in treating all forms of pain, including cancer pain, include physical therapy, acupuncture, acupressure, yoga, diversion, guided imagery, and massage. Radiation treatment used to shrink the size of a lung tumor can also reduce pain (LungCancer.org, 2020).