Conservative talk show host Rush Limbaugh announced that he has been diagnosed with advanced lung cancer. The 69-year-old told listeners that he began to experience shortness of breath earlier this month. This ultimately led to his diagnosis, which was confirmed by two medical institutions on January 20.
"I have to tell you something today that I wish I didn't have to tell you," Limbaugh . "But it is what it is. And you know me, I'm the mayor of Realville." Although I will have to miss some of my shows to undergo tests and treatment, "my intention is to come here every day I can. And to do this program as normally and competently ... as I do each and every day."
Limbaugh is a longtime cigar smoker and smoking advocate. In , he told a caller that Americans should thank smokers because of the money they add to the economy. He also denied that second-hand smoke caused illness, and that it took 50 years for first-hand smoke to cause cancer.
President Trump paid tribute to Limbaugh on , writing: "Many people do not know what a great guy & fantastic political talent the great Rush Limbaugh is. There is nobody like him. Looking for a speedy recovery for our friend!" The next night, during the 2020 State of the Union address, Trump .
Lung Cancer in General
Lung cancer includes two main types: non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). NSCLC is any type of epithelial lung cancer other than small cell lung cancer and is the cause of approximately 85% of lung cancers. The most common types of NSCLC are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma, but there are several other types that occur less frequently, and all types can occur in unusual histologic variants. Although NSCLCs are associated with cigarette smoke, adenocarcinomas may be found in patients who have never smoked. As a class, NSCLCs are relatively insensitive to chemotherapy and radiation therapy compared with SCLC.
The single most important risk factor for the development of lung cancer is smoking. For smokers, the risk for lung cancer is on average tenfold higher than in lifetime nonsmokers (defined as a person who has smoked <100 cigarettes in his or her lifetime). The risk increases with the quantity of cigarettes, duration of smoking, and starting age.
The estimates that there will be 228,820 new cases and 135,720 deaths from lung cancer (NSCLC and SCLC combined) in the U.S. in 2020.
Lung cancer is the leading cause of cancer-related mortality in the U.S. According to NCI data, approximately 6.3% of men and women will be diagnosed with lung and bronchus cancer at some point during their lifetime (based on 2014-2016 data).
The overall 5-year survival rate for lung and bronchial cancer is 19.4%, however the cancer stage at diagnosis is an important factor in survival rates.
The 5-year relative survival rate for patients with lung cancer with local-stage is 57%, regional-stage 30.8%, and distant-stage disease 5.2%. At the time of diagnosis, 16% of patients have localized disease, 22% regional (spread to regional lymph nodes), and 57% have distant/metastasized disease.
Advanced Lung Cancer
Advanced lung cancer usually implies that a patient has either stage IIIB or stage IV lung cancer. Stage IIIB tumors are of any size and have spread to lymph nodes on the other side of the chest, near the collarbone, or have invaded other structures in the chest such as the heart or esophagus. Stage IV tumors have spread to the space between the layers lining the lungs (known as malignant pleural effusion) or to another region of the body. Lung cancer most commonly spreads to the bones, the liver, the brain, or the adrenal glands.
Clinical Features
Lung cancer may present with symptoms or be found incidentally on chest imaging. Symptoms and signs may result from the location of the primary local invasion or compression of adjacent thoracic structures, distant metastases, or paraneoplastic phenomena. The most common symptoms at presentation are worsening cough or chest pain. Other presenting symptoms include the following:
- Hemoptysis
- Malaise
- Weight loss
- Dyspnea
- Hoarseness
Symptoms may result from local invasion or compression of adjacent thoracic structures such as compression involving the esophagus causing dysphagia, compression involving the laryngeal nerves causing hoarseness, or compression involving the superior vena cava causing facial edema and distension of the superficial veins of the head and neck. Symptoms from distant metastases may also be present and include neurological defect or personality change from brain metastases or pain from bone metastases. Infrequently, patients may present with symptoms and signs of paraneoplastic diseases such as hypertrophic osteoarthropathy with digital clubbing or hypercalcemia from parathyroid hormone-related protein. Physical examination may identify enlarged supraclavicular lymphadenopathy, pleural effusion or lobar collapse, unresolved pneumonia, or signs of associated disease such as chronic obstructive pulmonary disease or pulmonary fibrosis.
Molecular Features
The identification of mutations in lung cancer has led to the development of molecularly targeted therapy to improve the survival of subsets of patients with metastatic disease. In particular, subsets of adenocarcinoma now can be defined by specific mutations in genes encoding components of the epidermal growth factor receptor (EGFR) and downstream mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinases (PI3K) signaling pathways. These mutations may define mechanisms of drug sensitivity and primary or acquired resistance to kinase inhibitors.
Other genetic abnormalities of potential relevance to treatment decisions include translocations involving the anaplastic lymphoma kinase (ALK)-tyrosine kinase receptor, which are sensitive to ALK inhibitors, and amplification of MET (mesenchymal epithelial transition factor), which encodes the hepatocyte growth factor receptor. MET amplification has been associated with secondary resistance to EGFR tyrosine kinase inhibitors.
Treatment of Advanced Lung Cancer
for patients with newly diagnosed stage IV, relapsed, or recurrent disease can include:
- Cytotoxic combination chemotherapy with platinum (cisplatin or carboplatin) and paclitaxel, gemcitabine, docetaxel, vinorelbine, irinotecan, protein-bound paclitaxel, or pemetrexed
- Combination chemotherapy with monoclonal antibodies with bevacizumab, cetuximab, or necitumumab. Bevacizumab is an antibody targeting vascular endothelial growth factor. Cetuximab and necitumumab are epidermal growth factor receptor (EGFR) inhibitors
- Maintenance therapy after first-line chemotherapy (for patients with stable or responding disease after four cycles of platinum-based combination chemotherapy) can be pemetrexed or erlotinib. Pemetrexed is in a class of medications called antifolate antineoplastic agents
- For patients with EGFR mutations, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) such as osimertinib, gefitinib, erlotinib, or afatinib may be used
- Patients with ALK translocations may be given anaplastic lymphoma kinase (ALK) inhibitors. These include alectinib, crizotinib, ceritinib, brigatinib, and lorlatinib
- For patients with other select mutations, "nib" drugs (small-molecule inhibitor of kinase enzymes) may be available. These include ROS1 inhibitors (crizotinib); BRAF V600E and MEK inhibitors (dabrafenib and trametinib); and neurotrophic tyrosine kinase (NTRK) inhibitors (larotrectinib)
- Immune checkpoint inhibitors with or without chemotherapy. Pembrolizumab is a humanized monoclonal antibody that inhibits the interaction between the PD-1 coinhibitory immune checkpoint expressed on tumor cells and infiltrating immune cells and its ligands, PD-L1 and programmed cell death-ligand 2 (PD-L2)
Clinical trials for patients with advanced lung cancer can be found at: .
Michele R. Berman, MD, and Mark S. Boguski, MD, PhD, are a wife and husband team of physicians who have trained and taught at some of the top medical schools in the country, including Harvard, Johns Hopkins, and Washington University in St. Louis. Their mission is both a journalistic and educational one: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.