Warren Zevon, 'The Wind,' and Understanding Mesothelioma

The symptom that sent him to a doctor

Warren Zevon wrote "Werewolves of London" and "Keep Me in Your Heart." Rolling Stone reported that he learned he had mesothelioma in late August 2002, after going to a cardiologist because he was short of breath. He talked about it in public, in his own dry register. Asked about the prognosis, he imagined saying to a stranger in a checkout line, "Excuse me, I have terminal cancer. Can you help her with her coupons?"

NPR reported that Zevon kept writing and producing after the diagnosis and finished a last album, The Wind. He died in September 2003 at age 56. NPR described the disease at the time as a rare and inoperable form of lung cancer.

That is all that is publicly known and worth repeating. What follows is the medicine.

A cancer with one dominant cause

Mesothelioma starts in the mesothelium. That is the thin lining of tissue wrapped around the lungs, the chest wall, the abdomen, and the heart. Its job is to make a slick fluid so those surfaces glide instead of scraping.

The National Cancer Institute (NCI) reports that asbestos exposure is identified in about 70% to 80% of mesothelioma cases. Asbestos is a group of six minerals that occur naturally as bundles of fibers. They are prized for resisting heat, fire, and chemicals. Inhaled fibers can lodge in the lining and stay there for decades.

The lag is the cruel part. NCI's asbestos fact sheet states that it can take 10 to 40 years or more for symptoms of an asbestos-related condition to appear. Someone exposed at 25 may not get sick until 65.

Who breathed it

NCI names shipbuilding, asbestos mining and milling, textile manufacturing, construction and insulation work, demolition, drywall removal, firefighting, and auto repair as exposure settings. Household members are not safe by default, either. NCI notes that living with a person who works near asbestos is itself a risk factor. Fibers ride home on clothes and hair.

Two more facts from that fact sheet are worth knowing. NCI states there is no safe level of asbestos exposure. And smoking does not raise the mesothelioma risk from asbestos, though smokers exposed to asbestos face a lung cancer risk greater than the two risks added together.

What it does inside the chest

The dominant problem is fluid. NCI's clinical summary states that effusions, meaning fluid collecting in the chest or the abdomen, are a major symptomatic problem for at least 66% of patients. Fluid in the chest presses the lung and makes breathing hard, which is why breathlessness so often starts the story.

NCI lists these symptoms: trouble breathing, cough, pain under the rib cage, pain or swelling in the abdomen, lumps in the abdomen, constipation, problems with blood clots, weight loss for no known reason, and fatigue.

Get checked, and say the word "asbestos"

Book an appointment if any of the following has been going on for more than two or three weeks:

• Shortness of breath that is new, or that keeps getting worse week over week
• Pain under the rib cage or along the lower chest wall
• A dry cough that will not settle
• Belly swelling, belly pain, or new lumps you can feel
• Weight loss you did not intend, especially more than 10 pounds

Go to an emergency department for breathlessness that comes on suddenly and severely, or chest pain with lightheadedness. A large effusion can be drained the same day.

Tell the clinician outright about any asbestos exposure, including a parent's job decades ago. That single sentence changes which tests get ordered.

Why the diagnosis takes work

Getting the answer requires real tissue. NCI states that needle biopsies are often unsuccessful. So is cytology, meaning the study of cells floating in drained fluid. Thoracoscopy, a camera procedure through a small chest incision, is what usually yields an adequate sample.

The pathologist then runs immunohistochemistry, a set of stains that tag specific proteins. NCI notes that pancytokeratin stains are positive in nearly all mesotheliomas. Cytokeratin 5 and 6, calretinin, WT-1, and D2-40 are also useful. These separate mesothelioma from lung cancer and from sarcoma. Those look similar under a microscope but are treated very differently.

Staging uses the AJCC TNM system, which grades tumor extent, lymph node spread, and distant spread from stage IA to stage IV.

Cell type shapes the outlook

Mesothelioma comes in three patterns. Epithelioid accounts for about 60% of cases. Sarcomatoid is made of spindle-shaped cells. Biphasic mixes both. NCI states that epithelioid histology carries a more favorable prognosis than sarcomatoid or biphasic disease. Stage, age, performance status, and cell type together drive the prognosis.

What treatment involves

For localized stage I disease, NCI lists surgical options including pleurectomy with decortication, which strips the lining off the lung, and extrapleural pneumonectomy, which removes the lung along with the lining. The risk difference is stark. NCI reports operative mortality below 2% for pleurectomy with decortication, against 6% to 30% for extrapleural pneumonectomy.

For advanced disease, drug therapy is the mainstay. CheckMate 743 enrolled 605 patients. Nivolumab plus ipilimumab, two immunotherapy drugs, produced median overall survival of 18.1 months. Chemotherapy gave 14.1 months. Cisplatin plus pemetrexed, the older standard, gave 12.1 months versus 9.3 months for cisplatin alone. Toxicity is not trivial: serious treatment-related side effects hit 30% of patients on the immunotherapy pair.

Mesothelioma in the abdomen is a separate situation. Selected patients get cytoreductive surgery plus heated chemotherapy delivered into the abdomen. NCI reports median survival of 53 months in that group, with 47% alive at five years.

These are trial averages across groups of people. They describe what happened in a study population, not what will happen to one person.

Sources

• https://www.cancer.gov/types/mesothelioma/hp/mesothelioma-treatment-pdq
• https://www.cancer.gov/types/mesothelioma/causes-risk-factors
• https://www.cancer.gov/types/mesothelioma/symptoms
• https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/asbestos/asbestos-fact-sheet
• https://www.rollingstone.com/music/music-news/warren-zevon-and-the-art-of-dying-38326/
• https://www.npr.org/2003/09/08/1423402/singer-songwriter-warren-zevon-dies-at-56