Sarcomatoid Mesothelioma Treatment

Overview of Sarcomatoid Mesothelioma Treatment Options

The top treatment options for mesothelioma are surgery, chemotherapy, immunotherapy and radiation therapy. Other options include tumor treating fields and novel gene therapies, such as CAR T-cell therapy, available through clinical trials.

Doctors prefer some of these treatment options more than others for sarcomatoid mesothelioma due to the specific characteristics of sarcomatoid cells. Many mesothelioma doctors will recommend patients receive chemotherapy or immunotherapy as surgery is often difficult due to the growth pattern and appearance of sarcomatoid mesothelioma cells.

Surgery is often the quickest way to remove any cancer, and most doctors consider it the first possible option for patients. However, mesothelioma spreads quickly – especially sarcomatoid mesothelioma – and surgery might not be a possibility if tumors have already spread to the lungs (for pleural mesothelioma) or deep within the abdominal cavity (for peritoneal mesothelioma).

Surgery can be difficult for sarcomatoid mesothelioma patients. These cells don’t spread as one cluster, and they are more difficult to identify from healthy tissue.

However, some surgeons will operate on patients with sarcomatoid mesothelioma. Dr. Raphael Bueno of Brigham and Women’s Hospital in Boston, Massachusetts, said he has former patients diagnosed with sarcomatoid mesothelioma who are alive more than 5 years after surgery and other treatment.

Sarcomatoid mesothelioma cells are long and narrow, looking like spindles. They have enlarged, elongated nuclei and can have more than one nucleus, which is why they’re hard to distinguish from healthy tissue.

Sarcomatoid cells don’t form or spread in a regular pattern like other mesothelioma cell types. They multiply and spread through soft tissue, making them difficult to find and remove for surgeons.

Sarcomatoid Pleural Mesothelioma Surgical Options

Pleural mesothelioma forms in the lining of the lungs called the pleura. There are two surgical options for pleural mesothelioma:

• Extrapleural pneumonectomy
• Pleurectomy with decortication

Extrapleural pneumonectomy involves removing one of the patient’s lungs – the lung affected by mesothelioma tumors – along with the pleura, all or part of the diaphragm, and any other diseased tissue in or around the thoracic cavity.

Pleurectomy with decortication explicitly spares both of the patient’s lungs but removes the pleura, part of the diaphragm, and any other diseased tissue in or around the thoracic cavity.

Sarcomatoid Peritoneal Mesothelioma Surgical Options

Peritoneal mesothelioma forms in the lining of the abdominal cavity, called the peritoneum. The surgery used to treat peritoneal mesothelioma: cytoreductive surgery with HIPEC (heated intraperitoneal chemotherapy).

Cytoreductive surgery is a “debulking” procedure, which means doctors look for and remove any visible tumors and diseased tissue within the abdominal cavity. During this step, surgeons often remove the:

• Omentum (a layer of fatty tissue that covers the organs in the abdomen)
• Peritoneum
• Spleen

Following the cytoreductive part of surgery, doctors deliver a heated liquid chemotherapy solution through tubing placed into the patient’s abdominal cavity. This is the HIPEC portion of the surgery. The heated chemotherapy drugs wash the tissues of the abdomen in an attempt to kill any remaining mesothelioma cancer cells.

Due to the challenges of treating sarcomatoid mesothelioma with surgery, most doctors prefer to begin with chemotherapy. Traditional chemotherapy is administered to the patient into the bloodstream via an IV drip. The chemotherapy drugs travel to areas of rapid cell growth – which is a sign of cancer – and stop these cells from replicating by poisoning them. Chemotherapy can also attack and damage healthy blood cells, which can cause side effects for patients.

The other type of chemotherapy for sarcomatoid mesothelioma is heated intraoperative chemotherapy, which is performed during surgery and involves delivering the drugs directly to the diseased location instead of traveling through the bloodstream.

Sarcomatoid Pleural Mesothelioma Chemotherapy 

The U.S. Food and Drug Administration (FDA) approved chemotherapy for sarcomatoid pleural mesothelioma in 2004. The FDA approved cisplatin and pemetrexed (Alimta) for the treatment of this cell type of pleural mesothelioma. Cisplatin and pemetrexed are approved for systemic administration through an IV.

Carboplatin is a chemotherapy drug approved as an alternative to cisplatin if patients experience severe side effects or if there is no effective tumor response from cisplatin and pemetrexed. Other chemotherapy drugs – like vinorelbine – are used in studies for sarcomatoid pleural mesothelioma. They are not approved as standalone treatments by the FDA.

The other type of chemotherapy treatment for sarcomatoid pleural mesothelioma is hyperthermic intrathoracic chemotherapy (HITHOC). This is an example of intraoperative chemotherapy where doctors deliver a mixture of heated liquid chemotherapy drugs directly into the thoracic cavity during surgery. The surgeon places tubing into the chest cavity to send the drugs directly into the area where tumors are growing and spreading.

Sarcomatoid Peritoneal Mesothelioma Chemotherapy

Patients with sarcomatoid peritoneal mesothelioma are often treated with systemic chemotherapy. This treatment can be administered before or after surgery or as a standalone therapy for patients not eligible for surgery.

Another form of chemotherapy treatment for sarcomatoid peritoneal mesothelioma is given during cytoreductive surgery. This method of chemotherapy involves delivering heated chemotherapy drugs directly into the abdomen through a catheter placed by the surgeon.

The doctor will allow the chemotherapy drugs to circulate in the abdominal cavity for 1-2 hours. The chemotherapy fluid is then drained from the abdomen and the abdominal cavity is rinsed with a sterile saline solution.

Side Effects of Sarcomatoid Mesothelioma Chemotherapy 

There are many potential side effects of chemotherapy for patients with sarcomatoid mesothelioma. These side effects vary from manageable (such as nausea) to severe (liver damage).

Some of the most common side effects of chemotherapy for sarcomatoid mesothelioma are: 

Some of the severe side effects of chemotherapy for sarcomatoid mesothelioma are: 

Immunotherapy is a treatment option growing in support for sarcomatoid mesothelioma. Numerous studies show how patients with this mesothelioma cell type benefit more than patients with other cell types from receiving immunotherapy.

The two main FDA-approved immunotherapy treatments for mesothelioma are Opdivo (nivolumab) and Yervoy (ipilimumab). These two drugs are a combination therapy approved for the treatment of unresectable pleural mesothelioma. Another immunotherapy called Keytruda (pembrolizumab) is approved by the FDA for a small subset of patients with unresectable pleural mesothelioma.

These three immunotherapies are called immune checkpoint inhibitors. They block proteins in cancer cells from suppressing the immune system.

In one study, Opdivo and Yervoy had a tremendous impact on the survival of patients with sarcomatoid mesothelioma. Sarcomatoid patients survived for 17 months after receiving Opdivo and Yervoy, which is far better than chemotherapy (9 months).

In another study for pleural mesothelioma, six patients with sarcomatoid cell type had an average survival of 28 months.

“I think it’s wonderful we have this new instrument that works with these other therapies, particularly in sarcomatoid and biphasic mesothelioma cases,” said Dr. Hassan Khalil of Brigham and Women’s Hospital.

Side Effects of Sarcomatoid Mesothelioma Immunotherapy 

A major benefit of receiving immunotherapy rather than chemotherapy is the smaller number of extreme side effects. Despite this advantage, some patients will experience uncomfortable side effects from mesothelioma immunotherapy drugs, such as:

Radiation therapy is another treatment option for sarcomatoid mesothelioma. While radiation is not used to treat peritoneal mesothelioma, it is a common option for pleural mesothelioma. Doctors do not use radiation therapy for peritoneal mesothelioma due to the number of vital organs in the abdominal cavity that can be affected by the radiation beams.

Radiation therapy delivers high-energy radiation beams through the skin and into the diseased area with the goal of damaging tumors. The experience is painless for patients and similar to receiving an X-ray.

Mesothelioma specialists use a linear accelerator to send the beams into the body. The beams do not kill cancer cells immediately but rather cause irreparable damage to the cells, which can die without replicating.

There are different types of radiation therapy for sarcomatoid mesothelioma:

• Photon radiation (traditional method)
• Intensity-modulated radiation therapy
• Proton radiation
• Intraoperative radiation therapy

Side Effects of Sarcomatoid Mesothelioma Radiation Therapy

The side effects of radiation therapy for sarcomatoid mesothelioma include damage to lung tissue. When radiation beams cause lung tissue scarring, this leads to a medical condition called pulmonary fibrosis.

Other side effects of sarcomatoid mesothelioma radiation may include: 

• Nausea
• Fatigue
• Shortness of breath 
• Coughing
• Skin irritation (burning, itchiness, dryness or peeling)

Multimodal therapy is the medical term used to describe using multiple types of cancer treatments. Multimodal therapy for sarcomatoid mesothelioma involves patients receiving a combination of:

• Surgery
• Chemotherapy
• Immunotherapy
• Radiation therapy
• Other types of cancer therapy

Many doctors believe multimodal therapy is the best course of action for treating mesothelioma. The cancer is difficult to eliminate with just one treatment option, and using multiple methods provides patients with the best odds of beating this disease.

The FDA approved Optune Lua (NovoTTG-100F System) in 2019 for the treatment of unresectable malignant pleural mesothelioma. This therapy is an option for patients with sarcomatoid pleural mesothelioma, but it is not FDA-approved yet for peritoneal mesothelioma.

Optune Lua is a wearable device that creates tumor treating fields, or electrical fields, to interrupt cancer cell division. The device must be worn for the large majority of the day and provides low-intensity electrical fields to disrupt cancer cell growth in the chest cavity.

In the phase 2 STELLAR clinical trial, patients with sarcomatoid mesothelioma who received Optune Lua had an average survival of 12 months. This is a slight improvement in patients who receive only chemotherapy.

Palliative care for mesothelioma is a treatment approach aimed at improving the patient’s quality of life. The goal of palliative care is to decrease the cancer symptoms, minimize pain from disease symptoms or treatment, manage treatment side effects, and provide emotional and spiritual support. In many cases, palliative care involves “maintenance” chemotherapy, which uses lower doses of the drugs to prevent the cancer from spreading while also minimizing side effects.

Other examples of palliative care for mesothelioma include:

• Draining fluid buildup from the pleural or peritoneal cavity
• Reducing chest or abdominal pressure
• Supporting the patient’s psychosocial needs

Clinical trials for mesothelioma are available to patients wishing to receive treatment options other than FDA-approved chemotherapy or immunotherapy drugs. Clinical trials for mesothelioma can feature surgery, immunotherapies, radiation, multimodal therapy combinations and more novel therapies such as oncolytic virus and gene therapies.

There are many open clinical trials that accept patients with sarcomatoid mesothelioma. A lot of clinical trials for mesothelioma welcome patients with all cell types. Others may limit enrollment to just one specific cell type, such as epithelioid mesothelioma or biphasic mesothelioma.