Newly Diagnosed With Mesothelioma: First Steps

A history of asbestos exposure is reported in about 70% to 80% of mesothelioma cases.

Write yours down early. List every job, every employer, every year, and every product. The VA names the work areas that matter most. They are mining, milling, shipyards, construction, carpentry, and demolition. It also names products. Those are flooring, roofing, cement sheet, pipes, insulation, and friction products such as clutch facings and brake linings.

If you served in the military, VA disability compensation may apply. Two things must both be true: you have a health condition caused by asbestos exposure, and you had contact with asbestos while serving.

The evidence VA asks for is specific. Medical records stating your condition. Service records listing your job or specialty. And a doctor's statement connecting your service exposure to the condition. Ask for that third item explicitly, because it is the one that will not appear on its own.

This is where mesothelioma differs from almost every other diagnosis.

Trying to diagnose it from cytology, meaning cells in fluid, often fails. So does a needle biopsy of the pleura. Telling mesothelioma from adenocarcinoma in a small sample is especially hard.

Thoracoscopy is a camera procedure inside the chest. It can get enough tissue for a real answer. Special stains, and sometimes electron microscopy, do the rest. Pancytokeratin stains are positive in nearly all mesotheliomas.

If your diagnosis rests on fluid cytology alone, ask whether a larger tissue sample is needed before treatment is chosen.

Under the microscope, mesothelioma is made of epithelial cells, spindle cells, or both.

Epithelioid tumors account for roughly 60% of diagnoses. Sarcomatoid tumors are the spindle cell form. Biphasic tumors contain both. Desmoplastic mesothelioma is a subtype of sarcomatoid disease. It shows bland tumor cells between dense bands of connective tissue.

Cell type drives outcome. Among patients treated with aggressive surgery, three factors track with better long-term survival. They are epithelioid cell type, negative lymph nodes, and negative surgical margins. In the EORTC prognostic index, nonepithelioid cell type counts against you.

So the first question is not the stage. It is which cell type the pathologist found.

The AJCC TNM system covers diffuse malignant pleural mesothelioma. It does not cover localized pleural mesothelioma or other primary tumors of the pleura.

T1 means tumor limited to the parietal pleura on one side. The visceral, mediastinal, or diaphragmatic pleura may or may not be involved. T2 means all the pleural surfaces on that side are involved. It also needs either the diaphragm muscle or spread into the lung tissue below. T3 describes locally advanced but still removable disease. It reaches the chest wall lining, the fat in the middle of the chest, a single removable spot in chest wall tissue, or part of the sac around the heart.

Stage IA is T1 with no nodes and no distant spread. Stage IB is T2 or T3, still node-negative.

If you are offered a clinical trial, you may see a CALGB or EORTC prognostic index. They are stratification tools, not verdicts.

The CALGB index came from 337 patients and defines six groups. Median survival ran from 13.9 months in the best group to 1.4 months in the worst. A later check in 105 patients found 29.9 months in the best group and 1.8 months in the worst. The middle groups overlapped.

The EORTC index came from 181 patients. Five things predicted poorer survival. They are a white blood cell count above 8.3 x 10^9/L, an ECOG performance status of 1 or worse, unconfirmed histology on central review, nonepithelioid cell type, and male sex. Low-risk patients had a 1-year survival of 40%. High-risk patients had 12%, with a relative risk of death of 2.9.

Two radical operations exist. Extrapleural pneumonectomy removes the lung along with the pleura. Radical pleurectomy with decortication strips the pleura and leaves the lung.

Combining radical surgery with chemotherapy, radiation, or both has been linked to fairly long survival. But that comes from observational series, not randomized trials. The NCI flags the selection differences between series as a reason for caution.

Ask which operation is proposed, why that one, and how many the surgeon does a year.

Nivolumab plus ipilimumab. The CheckMate 743 trial enrolled 605 patients with advanced, untreated pleural mesothelioma. They got either this combination or chemotherapy. Median overall survival was 18.1 months with the immune pair. It was 14.1 months with chemotherapy. The hazard ratio was 0.74. Progression-free survival and response rates were not significantly different. Grade 3 to 4 treatment-related events occurred in 30% versus 32%. Three treatment-related deaths occurred in the immunotherapy arm and one in the chemotherapy arm.

Cisplatin plus pemetrexed. One trial established this pair. Pemetrexed with cisplatin, both by vein on day 1 of a 21-day cycle, beat cisplatin alone. Median survival was 12.1 months versus 9.3 months, hazard ratio 0.77. Time to progression was 5.7 months versus 3.9 months.

That regimen comes with a vitamin protocol that is not optional. Folic acid runs 350 to 1,000 micrograms by mouth daily, starting 1 to 3 weeks before the first chemotherapy and carrying on until 1 to 3 weeks after treatment ends. Vitamin B12 is 1,000 micrograms by injection, 1 to 3 weeks before the first dose, then roughly every 9 weeks. Dexamethasone 4 mg by mouth twice daily prevents the rash; it is taken the day before, the day of, and the day after each pemetrexed dose. Use the schedule your own clinic writes out for you rather than these figures — they are the trial's protocol, printed so you can see why the tablets around each cycle are not optional. Missing the steroid or the vitamins is what causes trouble here, so tell the team if you have skipped any before you go in. Among the patients who did get the vitamins, median survival was 13.3 months on the combination against 10.0 months on cisplatin alone. The vitamins cut most grade 3 to 4 side effects, with no loss of benefit.

Adding bevacizumab. One trial enrolled 448 patients whose disease could not be removed. Adding bevacizumab lifted median survival from 16.1 to 18.8 months, hazard ratio 0.77. The cost was more toxicity. Grade 3 or higher high blood pressure hit 23%, against none in the other arm. Clotting events hit 6% versus 1%.

Durvalumab with platinum and pemetrexed. A single-arm trial enrolled 55 untreated patients. Median overall survival was 20.4 months, against a historical control of 12.1 months. The response rate was 56.4%. Single-arm results carry less weight than randomized ones.

Effusions, meaning fluid collecting in the chest or abdomen, are a major symptomatic problem for at least 66% of patients.

Options include drainage, chest tube pleurodesis, and thoracoscopic pleurodesis. Pleurodesis seals the space so fluid cannot return.

• Call 911 or go to an emergency department if you cannot catch your breath at rest, your lips or fingertips look blue or grey, or chest pain arrives suddenly alongside breathlessness. Swelling and pain in one calf with new breathlessness fits the same category, because a clot can travel to the lungs.
• Call your care team the same day if breathlessness is creeping up, or lying flat has become difficult. Also call for a temperature of 100.4°F (38°C) or higher, or for redness, leaking or pain around a drain or catheter site.
• Call your care team within a day or two if chest pain is sharper than it was or wakes you at night, or your abdomen is swelling and your weight is climbing quickly.

• The exact cell type: epithelioid, sarcomatoid, or biphasic
• Whether the diagnosis came from fluid or from tissue
• Whether the disease is pleural or peritoneal, and the stage if pleural
• Whether surgery is being considered, and which operation
• Whether your case has been reviewed at a center that treats mesothelioma regularly
• Whether a VA claim or other exposure claim applies, and who will write the linkage statement

https://www.cancer.gov/types/mesothelioma/hp/mesothelioma-treatment-pdq https://www.va.gov/disability/eligibility/hazardous-materials-exposure/asbestos/ https://www.cancer.gov/about-cancer/treatment/side-effects/infection