Written By: Karen Selby, RN,
Last modified: March 25, 2021

Unlocking the Mystery of Mesothelioma

Because mesothelioma is so rare, the cancer was misdiagnosed for decades. It wasn’t until the 1960s that doctors started to research mesothelioma and its connection to asbestos in depth.

Researchers still have plenty to learn about mesothelioma, which accounts for less than 0.3% of all cancer diagnoses in the United States. While the cause of mesothelioma is undeniable — exposure to asbestos — other aspects of the cancer remain a challenge for the medical community.

Mesothelioma carries a long latency period. It can take anywhere from 15 to 70 years for the cancer to develop after a person’s first exposure to asbestos. Researchers have yet to perfect early diagnosis techniques, so mesothelioma is typically diagnosed in the later stages when it is more difficult to treat.

The cancer is still considered incurable, although advances in treatment allow patients to live longer, better-quality lives. However, only about 15% to 20% of people with pleural mesothelioma — the most common type — qualify for surgery.

Doctors, researchers and advocacy groups continue to raise awareness about mesothelioma in hope to one day find a cure.

When Was Mesothelioma First Discovered?

The earliest mention of a tumor in the pleura (lining of the lungs) was made in 1767 by Joseph Lieutaud, the founder of pathologic anatomy in France. In a publication detailing the study of approximately 3,000 autopsies he performed, Lieutaud mentioned two cases of “pleural tumors,” possibly the first recorded cases of pleural mesothelioma.

In 1819, René-Théophile-Hyacinthe Laennec, the French physician who invented the stethoscope, suggested malignancy could arise from the pleura, based upon his understanding of the nature of pleural cells.

However, in 1843, Karl Freiherr von Rokitansky, professor of pathological anatomy at Vienna University, challenged that notion. He stated pleural cancer was always secondary to a primary cancer elsewhere in the body.

Regardless of the lack of compelling evidence, this became the accepted theory of the medical establishment for many years. Ironically, von Rokitansky later described primary tumors of the peritoneum, likely the first recorded cases of peritoneal mesothelioma.

By the early 1900s, the medical community began to finally accept that cancers could originate in the pleura without having spread from a primary cancer elsewhere in the body.

Historical Studies of Mesothelioma and Asbestos Exposure

After many years of research, conjecture and controversy, most of the world’s medical establishment unequivocally accepted two important facts about mesothelioma:

  1. The disease was a distinct diagnostic entity.
  2. The association between mesothelioma and asbestos exposure had been proven conclusively.

Groundbreaking German Study

In 1943, H.W. Wedler was the first to report a connection between asbestosis and cancer of the pleura among German asbestos workers. Approximately 20% of the workers developed cancer, with lung cancer more common than mesothelioma.

Wedler’s study was well received in Germany, but the political climate at the time caused the rest of the world to ignore research coming from Nazi Germany.

South African Study

Perhaps the most important study that documented the unmistakable connection between asbestos exposure and cancer was presented by medical researcher J.C. Wagner and physician Chris Sleggs.

In their paper published by the British Journal of Medicine in 1960, Sleggs and Wagner detailed 33 cases of mesothelioma they discovered in residents of South Africa’s northwest Cape Province where crocidolite asbestos was mined.

In eight cases, the asbestos exposure history was occupational. The rest of the patients had lived near the mines for most of their lives.

American Study

American physician Dr. Irving J. Selikoff presented his findings at the 1964 Biological Effects of Asbestos conference, sponsored by the New York Academy of Science.

For more than a year, Selikoff had examined more than 1,000 workers from the Union Asbestos & Rubber Company plant in Patterson, New Jersey.

Selikoff found the mortality rate among these employees was 25% higher than would be expected statistically. The deceased workers had died from a variety of diseases, including asbestosis, asbestos-related lung cancer and other types of lung, stomach and colorectal cancers.

British Study

Another study by British physician Molly Newhouse found mesothelioma cases among people who lived near, but were not employed by, a London asbestos factory.

By 1968, the British Medical Journal claimed asbestos was the direct cause of most mesothelioma cases. Controversy still raged as to what types of asbestos were the most carcinogenic — a contentious argument that still echoes to this day.

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History of Mesothelioma Treatment

Despite decades of research, there still is no definitive cure for the four types of mesothelioma. However, more precise surgical procedures, improved chemotherapy regimens and emerging treatments such as immunotherapy are helping patients survive longer than ever before.

Cutting-edge clinical trials are currently testing these treatments and others in search of a cure.

Surgery

Surgical treatment of mesothelioma began in the 1940s with the use of pneumonectomy and pleurectomy.

In the 1960s, the pleurectomy and decortication procedure was introduced, a surgery that is still widely used today. It was originally used on patients with trapped lung caused by tuberculous empyema.

In the 1970s, doctors experimented with another surgery called an extrapleural pneumonectomy, which was also originally used to treat tuberculous empyema. The mortality rate for the surgery back then was as high as 31%. Today it’s around 4% in leading cancer centers.

Chemotherapy

A number of chemotherapy drugs were used to treat mesothelioma from the 1970s through the 1990s, such as doxorubicin and cisplatin, with response rates between 20% and 40%.

In 2003, the phase III trial of cisplatin and pemetrexed for mesothelioma reported the best response rate to date of 41.3%.

After that study, the U.S. Food and Drug Administration added cisplatin and pemetrexed to the standard-of-care treatment for mesothelioma. The drug combination remains the most common mesothelioma treatment.

Radiation Therapy

Doctors began experimenting with radiation therapy for mesothelioma in the 1950s using intrapleural instillation of radioactive colloidal gold. For decades, it was believed radiation therapy was too difficult to deliver to the pleura without harming other vital organs such as the heart.

A 2001 phase II clinical trial changed that perspective when it reported a low 13 percent local recurrence rate when radiation therapy was applied after EPP surgery. Advanced techniques are used today to reduce radiation exposure to vital organs, such as intensity modulate radiation therapy.

Emerging Treatments

Researchers continually search for the next breakthrough in mesothelioma treatment.

Immunotherapy drugs such as pembrolizumab (Keytruda) and nivolumab (Opdivo) have shown promise in mesothelioma clinical trials and compassionate use programs. However, no immunotherapy drug is approved by the FDA for the treatment of mesothelioma, and the drugs only work for a small percentage of patients.

Clinical trials also are testing experimental treatments such as photodynamic therapy and gene therapy on mesothelioma.

Future of Mesothelioma Research

The first and only standalone research facility developed to focus on mesothelioma opened in Sydney, Australia, in 2009. The Asbestos Diseases Research Institute conducts research primarily on mesothelioma treatment, including looking for new ways to treat the cancer.

The center also studies the diagnosis of mesothelioma and the psychological impact the cancer has on patients and families.

Certain cancer centers in the U.S. feature programs that focus on the treatment of mesothelioma and participate in clinical trials, such as the International Mesothelioma Program at Brigham and Women’s Hospital in Boston.


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