Mesothelioma Multimodal Therapy

How Mesothelioma Multimodal Therapy Works

Mesothelioma is stubborn and is resistant to most single therapies (called “monotherapy”). Tumors often continue growing and spreading despite initial effectiveness from chemotherapy drugs, immunotherapy drugs or radiation beams.

Multimodal therapy attacks mesothelioma tumors in multiple ways. This approach reduces the chances of tumors becoming resistant to a single therapy.

Two treatments working in tandem can make each individual therapy stronger. This is called a synergistic effect:

• Immunotherapy makes the immune system a stronger ally for other therapies fighting mesothelioma
• Chemotherapy weakens tumors, helping the immune system
• Radiation breaks up the DNA of mesothelioma cells, which can inspire a response from the immune system

Components of Multimodal Therapy for Mesothelioma

Multimodal therapy for mesothelioma usually includes a combination of these five:

Specific types of chemotherapy, immunotherapy and tumor treating fields are FDA-approved therapies for malignant pleural mesothelioma. Surgery and radiation are not FDA-approved and still considered experimental, although surgery provides the best survival rates for select patients.

Other multimodal therapy options are tested in clinical trials. They include:

• Gene therapy
• Oncolytic virus therapy
• Photodynamic therapy

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Combining Mesothelioma Surgery With Other Treatments

Surgery is the first option considered for any mesothelioma case. While many patients have metastasis or are not healthy enough for surgery, this option is associated with the best survival times.

Cytoreduction with HIPEC is the best peritoneal mesothelioma surgery. The two surgeries for pleural mesothelioma are:

• Pleurectomy with decortication (P/D)
• Extrapleural pneumonectomy (EPP)

Doctors prefer to build multimodal treatment plans around mesothelioma surgery. The first multimodal therapy approach was combining surgery with chemotherapy and radiation.

Some clinical studies use immunotherapy before or after surgery. While immunotherapy drugs Opdivo and Yervoy are approved for malignant pleural mesothelioma, they’re only allowed for non-surgical cases. Their use as multimodal therapies with surgery is in the experimental phase.

Multimodal Treatment With Mesothelioma Chemotherapy

Systemic chemotherapy works both before and after surgery, especially for pleural mesothelioma. Systemic chemotherapy is delivered intravenously into the bloodstream. The FDA approved intravenous cisplatin and pemetrexed for malignant pleural mesothelioma.

Other studies led to median survival of:

• 32 months for P/D with neoadjuvant and adjuvant chemotherapy
• 32 months for P/D with adjuvant chemotherapy and radiation
• 18 months for EPP with adjuvant chemotherapy and radiation

Multimodal Treatment With Mesothelioma Radiation

Doctors use radiation before or after pleural mesothelioma surgery:

• Radiation is preferable after P/D.
• Radiation is preferable before EPP.

Two trials used P/D followed by radiation therapy:

• Dr. Kenneth Rosenzweig, a mesothelioma specialist, reported in 2017 a median survival of 24 months.
• Dr. Valerie Rusch, another specialist, reported in 2017 a median survival of 20 months.

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One of the best ways to improve your prognosis and the likelihood of beating mesothelioma is through clinical trials.

Clinical trials can provide:

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• One-on-one care from leading mesothelioma specialists
• Alternative options for patients who have exhausted traditional treatments

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Multimodal Treatment With Mesothelioma Intraoperative Therapies

The most well-known intraoperative therapy for mesothelioma is hyperthermic intraoperative chemotherapy (HIOC). There are two forms used for mesothelioma:

• Hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma
• Hyperthermic intrathoracic chemotherapy (HITHOC) for pleural mesothelioma

HIOC sends hot liquid chemotherapy drugs into the abdomen or chest. Specialists deliver the drugs through ports or the surgical incision. This occurs the same day as surgery after the main resection is completed.

HITHOC with P/D or EPP was impressive in multiple studies:

• 42 months median survival in 2019
• 27 months median survival in 2020
• 35.3 months median survival in 2013

Multimodal Treatment With Mesothelioma Immunotherapy

Mesothelioma immunotherapy helps the body fight cancer naturally. Some immunotherapy drugs are approved officially for malignant mesothelioma. Others are still in testing.

The FDA approved Opdivo and Yervoy for unresectable malignant pleural mesothelioma in October 2020. These two drugs are immune checkpoint inhibitors. They “take the breaks off” the immune system, as specialist Dr. Daniel Sterman explained, and help the body’s T-cells fight mesothelioma effectively.

The FDA’s approval was due to impressive results from a study:

• Immunotherapy with chemotherapy led to median survival of 18 months.
• This outperformed chemotherapy on its own.

Another study paired ramucirumab with chemotherapy. The median survival was 14 months, and more than half reached the one-year mark.

A study at Johns Hopkins Hospital in Baltimore, Maryland, gives patients Opdivo and Yervoy six weeks before surgery. This study is a groundbreaking example of pairing immunotherapy with aggressive pleural mesothelioma surgery.

Multimodal Treatment With Other Emerging Mesothelioma Therapies

Other mesothelioma therapies include:

• Tumor treating fields
• Gene therapy
• Oncolytic virus therapy
• Photodynamic therapy

These therapies are often paired with some of the main options — surgery, chemotherapy, radiation or immunotherapy — in clinical studies. In some trials, these emerging options are paired together.

Multimodal Treatment With Mesothelioma Tumor Treating Fields

A tumor treating fields device is FDA-approved to treat malignant pleural mesothelioma. It’s approved for unresectable cases and must be used with chemotherapy. The device, Optune Lua, sends electric waves through the patient’s body.

Multimodal Treatment With Gene Therapy

Gene therapy is still in the infant stages of investigation for mesothelioma. The theory is to alter the genetics of cancerous cells, causing them to die, or repair the cells to health status.

Some trials use gene therapy with oncolytic virus therapy or chemotherapy.

Multimodal Treatment With Mesothelioma Oncolytic Virus Therapy

Oncolytic virus therapy delivers a programmed virus to attack mesothelioma cells or induce an immune response — or both.

An example is ONCOS-102, a multimodal therapy despite being just one drug. It applies elements of oncolytic virus therapy and immunotherapy. ONCOS-102 is an oncolytic adenovirus that breaks up mesothelioma cells and signals for the immune system’s help.

Multimodal Treatment With Mesothelioma Photodynamic Therapy

Photodynamic therapy (PDT) sends a special drug, called a photosensitizer, into the patient. The drug attaches to mesothelioma cells.

These drugs are sensitive to light, and doctors aim a laser light at the location of the cancer. This causes the drug to react and kill the cancer cells.

Dr. Joseph Freidberg at the University of Maryland Medical Center paired PDT with P/D surgery. The median survival was 31.7 months.

PDT is still an experimental treatment. It can be used with surgery and chemotherapy.

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How to Get Multimodal Treatment for Your Mesothelioma

The top Mesothelioma Centers of Excellence offer some form of multimodal treatment. Each cancer center may have a unique tweak to some of the combinations.

For instance, Michigan Medicine is the first U.S. cancer center to implement the SMART approach of radiotherapy before surgery. Wake Forest Baptist Cancer Center in North Carolina is one of the premier institutions for cytoreduction and HIPEC to treat peritoneal mesothelioma.

Other cancer centers offer clinical trials testing new multimodal approaches. A few other top mesothelioma hospitals are:

• Brigham and Women’s Hospital (Boston, Massachusetts)
• The National Cancer Institute (Bethesda, Maryland)
• Baylor St. Luke’s Medical Center (Houston, Texas)
• Mount Sinai Medical Center (New York City)
• Moffitt Cancer Center (Tampa, Florida)

Many community hospitals don’t offer multimodal therapy for a rare cancer like mesothelioma. They’ll likely offer just one therapy, such as chemotherapy or radiation, but don’t have experienced surgeons for aggressive operations. Going to a community hospital may hinder your potential for long-term survival.

We can help you find multimodal treatment for mesothelioma. Our patient advocates will connect you with a top cancer center within a reasonable travel distance from your location.

If you need to travel a considerable distance, we can help you get financial assistance to pay for it. You shouldn’t face barriers to getting life-saving multimodal treatment, and our staff can help you overcome any obstacles.

Frequently Asked Questions About Multimodal Therapy for Mesothelioma

What does mesothelioma multimodal therapy mean?

Multimodal therapy is a combination of mesothelioma treatment options. Mesothelioma multimodal therapy involves a combination of:

• Surgery
• Chemotherapy
• Radiation
• Immunotherapy
• Tumor treating fields

What is the best multimodal therapy for mesothelioma?

Top mesothelioma cancer centers use surgery, chemotherapy and radiation as the multimodal approach. More specialists are adjusting the order of these three therapies, sometimes using surgery first and other times using radiation first.

How does multimodal treatment work for mesothelioma?

Mesothelioma tumors are stubborn and able to resist single therapies. Using multiple treatments attacks the diseased cells in multiple ways, which reduces the chances of resistance. This stalls the cancer’s spread for a longer time, which helps the patient’s survival.

Sources & Author

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2. A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the “SMART” approach for resectable malignant pleural mesothelioma. Journal of Thoracic Oncology. Retrieved from:
   https://www.ncbi.nlm.nih.gov/pubmed/24445595. Accessed: 04/28/2020.
3. A pilot trial of high-dose-rate intraoperative radiation therapy for malignant pleural mesothelioma. American Brachytherapy Society. Retrieved from: https://www.brachyjournal.com/article/S1538-4721(04)00213-2/abstract. Accessed: 01/22/2021.
4. Extrapleural pneumonectomy (EPP) vs. pleurectomy decortication (P/D). Annals of Translational Medicine. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497106/. Accessed: 12/07/2020.
5. Pleurectomy/decortication and hyperthermic intrathoracic chemoperfusion using cisplatin and doxorubicin for malignant pleural mesothelioma. Journal of Thoracic Disease. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588772/. Accessed: 01/22/2021.
6. Pleurectomy/decortication and hyperthermic intrathoracic chemoperfusion using cisplatin and doxorubicin for malignant pleural mesothelioma. Journal of Thoracic Disease. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/31285889. Accessed: 07/18/19.
7. Radical pleurectomy/decortication and intraoperative radiotherapy followed by conformal radiation with or without chemotherapy for malignant pleural mesothelioma. The Journal of Thoracic and Cardiovascular Surgery. Retrieved from: https://www.sciencedirect.com/science/article/pii/S0022522302003240. Accessed: 01/22/2021.
8. Pleurectomy Decortication in the Treatment of Malignant Pleural Mesothelioma. Annals of Surgery. Retrieved from: https://journals.lww.com/annalsofsurgery/Abstract/9000/Pleurectomy_Decortication_in_the_Treatment_of.93886.aspx. Accessed: 12/07/2020.
9. Malignant pleural mesothelioma: adjuvant therapy with radiation therapy. US National Library of Medicine National Institutes of Health. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497112/. Accessed: 11/13/18.
10. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancy: Experience with 1,000 Patients. US National Library of Medicine National Institutes of Health. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965636/. Accessed: 11/13/18.
11. Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma. Journal of Thoracic Oncology. Retrieved from: https://www.jto.org/article/S1556-0864(17)30213-7/fulltext. Accessed: 11/13/18.
12. Continued survival benefit in Targovax’s ONCOS-102 trial in mesothelioma at the 21-month follow-up. PRNewswire. Retrieved from: https://www.prnewswire.com/news-releases/continued-survival-benefit-in-targovaxs-oncos-102-trial-in-mesothelioma-at-the-21-month-follow-up-301233073.html. Accessed: 02/23/2021.
13. FDA Approves Drug Combination for Treating Mesothelioma. U.S. Food and Drug Administration. Retrieved from: https://www.fda.gov/news-events/press-announcements/fda-approves-drug-combination-treating-mesothelioma. Accessed: 10/04/2020.
14. Nivolumab Plus Ipilimumab Improves OS in Malignant Pleural Mesothelioma. Cancer Network. Retrieved from: https://www.cancernetwork.com/view/nivolumab-plus-ipilimumab-improves-os-in-malignant-pleural-mesothelioma. Accessed: 08/11/2020.
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About the Writer, Karen Ritter, RN BSN

Karen Ritter, a registered nurse, is the lead patient advocate for Mesothelioma Guide. She has a deep passion for patient care, which includes helping patients and their families search for treatment options at the top mesothelioma cancer centers. She finds the balance between encouraging patients to receive the best treatment possible while enjoying their time with loved ones and friends. Karen is a valuable asset for patients due to her knowledge of mesothelioma, compassion for the victims of this disease and dedication to guiding patients through their treatment journey.