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Multimodal therapy for mesothelioma combines two or more cancer treatments. It may be the most effective approach for improving mesothelioma survival. Doctors can tailor multimodal treatment for the patient. Multimodal plans commonly include surgery, chemotherapy, radiation and/or immunotherapy.


01. Overview of Multimodal Therapy

What Is Multimodal Therapy for Mesothelioma?

Multimodal treatment for mesothelioma combines multiple therapies in one treatment plan. This approach may be most effective at extending survival. Mesothelioma multimodal therapy often includes chemotherapy, surgery and/or radiation. Newer therapies, such as immunotherapy, may also be used in combination treatment plans.

Other Terms for Multimodal Treatment

  • Combination therapy
  • Multimodality treatment
  • Trimodal therapy
  • Trimodality treatment

This approach arose after single modality treatments failed to sufficiently improve survival. Doctors combined therapies in an effort to address the shortcomings of individual therapies.

Multimodal treatment has extended mesothelioma life expectancy versus singular treatments. Some experts have indicated multimodal treatment constitutes the best chance for a mesothelioma cure.

Multimodal treatment approaches may incorporate additional therapies before or after the primary treatment. Trimodality treatment does both. It may consist of chemotherapy followed by surgery and radiation.

Common Components of Multimodal Treatment

Neoadjuvant Therapy

Neoadjuvant therapy is a treatment given before the primary therapy. It may help shrink the tumor.

Primary Therapy

Primary therapy is the main treatment intended to remove or kill tumor cells.

Adjuvant Therapy

Adjuvant therapy is a treatment given after the primary therapy. It targets the remaining cancer cells.

Multimodal treatment lets patients benefit from the strengths of multiple individual therapies. This approach may allow one treatment to make up for the shortcomings of another. For example, chemotherapy may help kill cancer cells that remain after surgery.

02. How Multimodal Treatment Works

How Does Multimodal Therapy Treat Mesothelioma?

Multimodal therapy treats mesothelioma with a combination of therapies. Together, the treatments use multiple methods to inhibit or kill mesothelioma cells. This strategy may make the overall treatment plan more effective.

One common multimodal mesothelioma treatment approach combines surgery with chemotherapy. During mesothelioma surgery, a doctor attempts to remove as much tumor tissue as possible. However, the surgeon may not be able to see microscopic cells left behind. Chemotherapy administered after surgery may be able to address these remaining cancer cells.

Mesothelioma doctors can incorporate any number of individual treatments in a multimodal plan. This means treatment can be customized to the needs of the individual patient. Doctors consider various things when recommending a treatment plan. These may include mesothelioma type, stage at diagnosis and patient health.

Chemotherapy

How It Works: Chemotherapy drugs damage or kill cells that divide quickly. It affects rapidly growing cells, such as cancer cells, more than normal cells.

Immunotherapy

How It Works: Immunotherapy treatments use the immune system to attack and kill cancer cells. These treatments empower the patient’s body to fight cancer.

Radiation

How It Works: Radiation uses a special form of energy to damage and kill cancer cells. It can also affect healthy cells.

Surgery

How It Works: Surgery focuses on physically removing mesothelioma cells. Its goal is to eliminate all visible cancer.

Experts do not currently agree on an optimal approach to multimodal treatment for mesothelioma. However, research into that topic is ongoing.

Emerging Treatments in Multimodal Therapies

Mesothelioma research covers many different treatment approaches, including multimodal therapy. Some investigators have explored combining experimental treatments with more standard options. Studies have investigated the following methods:

  • Cancer vaccines: Cancer treatment vaccines teach the immune system to recognize and attack cancer cells. They may be considered a form of immunotherapy.
  • Cryotherapy: Cryotherapy uses extremely cold gas or fluid to kill cancer cells.
  • Photodynamic therapy: Photodynamic therapy uses light and a light-responsive drug to kill cancer cells.
  • Tumor treating fields (TTFields): A medical device called the Optune Lua™ administers TTFields. TTFields apply mild electrical currents to disrupt cell division. This may slow or stop cancer growth.

Doctors have investigated these therapies through mesothelioma clinical trials. Such clinical research can expand multimodal treatment options and improve survival.

03. Multimodal Therapy by Type

Multimodal Treatment by Mesothelioma Type

Multimodal mesothelioma treatment varies according to the patient’s type of mesothelioma. This is due to the distinct properties of each form of mesothelioma. Factors affecting multimodal treatment choice include:

  • Overall patient health
  • Treatment center qualifications
  • Tumor location
  • Stage of cancer

Types of Mesothelioma

Mesothelioma cancer most commonly occurs in two main locations:

Mesothelioma rarely occurs in two other locations:

Treatments such as radiation may work differently in pleural versus peritoneal cases. Individual therapies may prove beneficial in one location but lackluster in the other. As a result, oncologists may include some treatments for pleural mesothelioma but not for peritoneal.

Decades of research have attempted to optimize combinations of mesothelioma treatments. In that time, some approaches have come to the forefront. Doctors often treat the main types of mesothelioma with surgery and chemotherapy. However, many options exist for multimodal mesothelioma treatment.

Multimodal Treatment for Pleural Mesothelioma

Multimodal therapy for pleural mesothelioma commonly combines two or three treatments. The ultimate combination depends on the patient’s eligibility for surgery.

Inoperable Pleural Patients

Mesothelioma patients who do not qualify for surgery commonly receive systemic treatments. These treatments include chemotherapy and immunotherapy.

Operable Pleural Patients

Individuals who qualify for surgery commonly undergo trimodality therapy. This may include chemotherapy, surgery and radiation.

Patients with operable pleural mesothelioma have two common surgical options.

  • Extrapleural pneumonectomy (EPP): EPP is an extensive operation. It removes the pleura and the affected lung. EPP also removes cancerous parts of the diaphragm and heart lining.
  • Pleurectomy/decortication (P/D): P/D is considered a lung-sparing procedure. It removes the pleura and any tumors on the surface of the lung. P/D does not remove the lung on the affected side. Some forms of P/D may also remove tumors on the diaphragm or heart lining.

Both EPP and P/D have been used in effective multimodal treatment plans.

Multimodal Treatment Breakthroughs for Pleural Mesothelioma

The SMART Protocol

The SMART clinical trial combined mesothelioma treatments in a new way. The protocol treated patients first with a high dose of radiation to the affected area. Within one week of radiation, patients underwent radical surgery via EPP.

SMART trial survival reached 24.4 months. Some may consider this lackluster, as more conservative treatments have achieved similar results.

However, the SMART protocol performed differently in patients with the epithelioid cell type. These patients had a median survival of 42.8 months.

Despite this success, experts urge caution in adopting the SMART protocol. It is a technically challenging process. As such, only expert cancer centers with substantial experience should adopt it.

Source: The Lancet

Complex Combination Therapy

Researchers at the University of Maryland explored a more unique combination. Patients in this study received:

  1. Optional neoadjuvant chemotherapy
  2. P/D surgery
  3. Photodynamic therapy
  4. Optional adjuvant chemotherapy

Of study patients, 92% received chemotherapy before or after P/D.

Study patients had a median survival of three years. Patients also lived about 14 months before the mesothelioma came back.

More than 85% of the study patients had stage 3 or stage 4 mesothelioma. Some surgeons might consider such patients ineligible for surgery. This study demonstrates late-stage patients may benefit from combination therapy with surgery.

Source: Annals of Thoracic Surgery

Inoperable pleural mesothelioma patients may receive chemotherapy and immunotherapy. This multimodal approach extended survival in a clinical trial. Patients received standard chemotherapy with or without bevacizumab. Bevacizumab is an immunotherapy drug known by its brand name, Avastin®. It extended survival by almost 20% versus chemotherapy alone.

Multimodal Treatment for Peritoneal Mesothelioma

Multimodal therapy for peritoneal mesothelioma commonly combines surgery and chemotherapy. Doctors refer to this surgical procedure as cytoreductive surgery (CRS). During CRS, doctors remove visible mesothelioma tumors.

After CRS, patients often receive some form of local chemotherapy. This means the chemotherapy only goes into the abdomen, rather than circulating systemically.

One of the most common forms of local chemotherapy is called HIPEC. HIPEC stands for hyperthermic intraperitoneal chemotherapy. It is a heated chemotherapy treatment administered within the abdomen.

Combination therapy with CRS and HIPEC has helped some patients achieve long-term survival. Multimodal approaches using other forms of local chemotherapy have also positively impacted prognosis.

Doctors may use this multimodal treatment therapeutically. The treatment may help the patient recover from mesothelioma. CRS and HIPEC can also provide palliative treatment for mesothelioma patients.

Multimodal Treatment Breakthrough for Peritoneal Mesothelioma

Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy

Researchers have investigated various approaches to CRS and HIPEC treatment. Some have focused on treating patients more than once with CRS and HIPEC. This approach yielded encouraging results.

In one study, patients received one or more rounds of CRS and HIPEC. Patients receiving only one round of treatment had a median survival of 27 months. Those receiving multiple rounds of CRS and HIPEC had a median survival of 80 months.

In another study, patients received only a single round of CRS and HIPEC treatment. These patients had a median survival of about 8 years.

Sources: Annals of Surgical Oncology and Gastroentérologie Clinique et Biologique

04. Multimodal Treatment Prognosis

Mesothelioma Survival and Prognosis After Multimodal Therapy

Several multimodal therapies have extended mesothelioma survival beyond the common range of 18 to 31 months. Mesothelioma prognosis with multimodal therapy depends on several factors, including:

  • Mesothelioma cell type
  • Patient factors
  • Stage at diagnosis
  • The treatment combination

Some multimodal approaches have achieved better survival than others. Survival after multimodal treatment generally ranges from one to three years in pleural mesothelioma. In peritoneal mesothelioma, multimodal therapy has extended survival beyond six years for some patients.

Survival of Mesothelioma Patients Treated With Multimodal Therapy

Pleural Mesothelioma

  • Treatment: Chemotherapy followed by surgery, then radiation therapy
  • Median Survival: 39.4 months

Peritoneal Mesothelioma

  • Treatment: Two rounds of CRS and HIPEC
  • Median Survival: More than 8 years

Multimodal Treatment and Long-Term Survival in Mesothelioma

Medical literature indicates some multimodal approaches have achieved long-term survival. One study treated pleural mesothelioma patients with chemotherapy and P/D. Nearly one third of study patients lived five years or longer.

Heather Von St. James knows the power of multimodal mesothelioma treatment. She underwent EPP followed by local chemotherapy more than ten years ago. She says she sacrificed her lung to live a full life. As part of that, Heather celebrates the anniversary of her treatment yearly on Lung Leavin’ Day.

A small peritoneal mesothelioma study treated patients with CRS and HIPEC. Patients also received at least three cycles of intra-abdominal chemotherapy. All study patients survived at least eight years. One patient survived 19 years or more.

Mesothelioma patients should discuss treatment options with an oncologist. The cancer specialist can help determine the best approach for the patient’s individual needs.

05. Multimodal Treatment Side Effects

Side Effects of Multimodal Treatment for Mesothelioma Patients

Multimodal mesothelioma treatment can cause a range of side effects. This trait is shared among most cancer treatments. Side effects for mesothelioma will vary based upon the individual treatments in a given plan.

Side Effects of Multimodal Treatment for Mesothelioma by Individual Treatment Type

Chemotherapy

  • Abnormal immune cell levels
  • Nausea
  • Vomiting

Immunotherapy

  • Fatigue
  • Muscle or joint pain
  • Skin rash

Radiation

  • Fatigue
  • Hair loss
  • Skin irritation or rashes

Surgery

  • Blood loss
  • Pneumonia
  • Respiratory failure

The cancer care team can effectively manage many side effects. Patients may help in this effort by sharing any adverse reactions with their doctors. Patients may also benefit from palliative care. Palliation can help patients manage side effects and quality of life at all stages of the cancer journey.

06. Multimodal Treatment Process

The Mesothelioma Multimodal Treatment Process and Experience

Each patient may have a unique multimodal treatment experience. The details of the process can vary based upon individual patient factors and treatments. However, multimodal treatment plans share some general steps, including:

  1. Diagnosis and staging of mesothelioma
  2. Careful consideration of patient factors to determine the best treatment approach
  3. Treatment with neoadjuvant, primary and adjuvant treatments where applicable
  4. Side effect or symptom management
  5. Monitoring for cancer progression or return

Researchers have made progress in second-line treatment of mesothelioma. This means patients still have options even if the cancer returns after multimodal treatment.

For example, one recent study successfully added immunotherapy as a second-line treatment. Study patients had received up to six therapies before enrolling. In the study, patients received a combination immunotherapy treatment. It consisted of CAR T cells and a checkpoint inhibitor called Keytruda® (pembrolizumab).

Patients had a median survival of about two years. This marks an improvement of more than one year versus prior second-line treatments. This study also demonstrates the flexibility of multimodal treatment approaches.

07. Eligibility for Multimodal Treatment

Who Is Eligible for Multimodal Mesothelioma Treatment?

Eligibility for multimodal mesothelioma therapy depends on several factors, including:

  • Mesothelioma stage
  • Patient health
  • Tumor location

For instance, mesothelioma doctors recommend multimodal treatment for pleural mesothelioma patients in stages 1 – 3 and in good overall health. Patients with a poor performance or functional status may not be candidates for multimodal therapy.

Any mesothelioma patient interested in multimodal treatment should discuss it with their oncologist. A mesothelioma specialist can provide an informed evaluation of eligibility criteria.

08. Common Questions

Common Questions About Multimodal Therapy for Mesothelioma

What are the benefits of multimodal therapy for mesothelioma?

  • Experts say multimodal treatment offers “the best chance for a cure” for mesothelioma.
  • Multimodal approaches are flexible. This means doctors can tailor them to the needs of each individual patient.
  • Single treatments have failed to meaningfully improve survival in the past. Multimodal approaches have proven more effective.

What is the difference between single modality and multimodal treatment for mesothelioma?

Single modality mesothelioma treatment consists of only one therapy. A patient receiving only systemic chemotherapy is undergoing single-modality treatment. Multimodal treatment combines more than one single modality treatment. A common multimodal treatment for mesothelioma consists of surgery and chemotherapy.

Who is eligible for multimodal mesothelioma treatment?

Patient eligibility depends on the patient’s specific case. Multimodal treatments involving surgery are generally available to patients with operable mesothelioma. Patients with inoperable mesothelioma often qualify for chemotherapy and immunotherapy treatment.