Multimodal therapy is a combination of cancer treatments including: chemotherapy, radiation and surgery. Clinical studies have shown that multimodal therapy can improve a mesothelioma patient's survival by combining those treatments, instead of just using one treatment option.
Multimodal therapy is a treatment approach for mesothelioma and other cancers that includes two or more treatment types. Traditionally, this involves some combination of the most popular modalities (types of treatment) for cancer: surgery, chemotherapy and radiation therapy.
Multimodal therapy aims to improve survival and quality of life. Doctors can accomplish these goals by offering multiple treatments that remove or shrink tumors and control symptoms. Although each individual treatment option can have a positive impact on patients, clinical studies have proven the best results can only be achieved with a multimodal approach.
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Doctors still are experimenting to find the most effective combination and timing of therapies for mesothelioma treatment. Most specialists recommend trimodal therapy, a three-pronged approach that combines surgery, chemotherapy and radiation therapy.
In recent years, mesothelioma specialists have started combining traditional therapies with new and experimental treatments like immunotherapy, gene therapy and photodynamic therapy (PDT). For now, most of these treatments are only available to patients participating in a clinical trial.
A man with stage I mesothelioma underwent multimodal therapy. Two years after surgery, the patient is alive and has no evidence of mesothelioma.
The practice of combining treatments became a standard of care after researchers noticed that patients treated with only one therapy typically did not experience increased survival. To find out which treatments have the strongest effect on survival, experts started comparing various combinations.
They also performed studies to learn the best order to give the treatments. Peritoneal mesothelioma specialists, for example, learned that delivering heated chemotherapy drugs directly to the abdomen after extensive surgery can add years to the lives of some patients. This technique is called HIPEC, a form of heated chemotherapy.
A 1988 review of 180 mesothelioma patients treated at Dana-Farber Cancer Institute and Brigham and Women's Hospital from 1965 to 1985 shows a combination of extrapleural pneumonectomy (EPP) and chemotherapy was associated with significantly better survival than any other treatment plan.
The authors mentioned several studies that described improved survival after surgery combined with other treatments. Compared to studies involving chemotherapy or radiation therapy without surgery, patients treated with a multimodal approach including surgery experienced longer survival. There were several cases of disease-free survivors.
Following the success of these early studies, doctors started to recognize the potential of combining treatment strategies. To this day, mesothelioma specialists are ambitiously testing new strategies and improving on old ones to extend survival and work toward uncovering the best way to manage the disease.
When developing a multimodal treatment strategy, a team of doctors will evaluate your case individually. They decide on a plan that is most appropriate for you, carefully weighing the risks and benefits of each potential treatment.
Depending on your unique situation, your doctors will choose from several treatments that together offer the most hopeful outlook. If you respond poorly (or especially well) to any one treatment, they can adjust the treatment plan moving forward. They may add a more promising treatment option, replace an ineffective one or select a new dose for chemotherapy.
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Mesothelioma specialists need to consider several important factors when designing a treatment plan, including:
The patient's age and over health
The potential risks of surgery and the toxicity of chemotherapy drugs and radiation therapy
The location, stage and cell type of the cancer
How to approach cases where the cancer has spread to the lymph nodes and other organs
In addition to selecting the most promising treatments, doctors must also decide on the best order to give them. Any treatment option can be the primary therapy, an adjuvant or a neoadjuvant therapy.
Given before primary therapy to improve results.
The most hopeful and effective treatment option, most commonly surgery.
Given after primary therapy to help symptoms and prevent cancer from returning.
Most experts recommend trimodal therapy with surgery, chemotherapy and radiation therapy, but not all patients are healthy enough for all three treatments. The advanced size and spread of tumors in stage IV mesothelioma patients often means they won't qualify for aggressive surgery. In these cases, doctors may offer chemotherapy as a primary therapy, or recommend a clinical trial that explores a new type of treatment.
Surgery is associated with the best chance of survival, so most doctors will choose it as the primary therapy whenever possible. For eligible patients, they select a surgery like extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) that attempts to remove as much tumor growth as possible.
Fast Fact: With surgery alone, it is nearly impossible for doctors to remove all tumors and prevent them from returning later on. To boost results, they may provide chemotherapy or radiation therapy before or after surgery. David J. Sugarbaker, M.D. pioneered trimodal therapy using extrapleural pneumonectomy (EPP), chemotherapy and radiation therapy while at Brigham & Women's Hospital.
In certain cases, doctors perform chemotherapy before surgery, an example of neoadjuvant chemotherapy. This can improve survival by reducing the size of tumors and increasing the chances of complete removal after surgery. In one study, patients who received neoadjuvant chemotherapy with the drugs cisplatin and gemcitabine before EPP and radiation therapy experienced a median survival time of 23 months.
For early stage patients, doctors can administer neoadjuvant chemotherapy intrapleurally — meaning directly to the cancer-ridden pleural space. With traditional chemotherapy, on the other hand, drugs travel throughout the entire body. Intrapleural chemotherapy minimizes the toxicity of the drugs and may allow patients to better tolerate surgery.
It is also increasingly common for doctors to offer chemotherapy immediately after surgery, an example of adjuvant chemotherapy. There is a high probability that mesothelioma will return later, even after extensive surgery that removes all visible tumors. Adjuvant chemotherapy aims to kill any microscopic cancer cells left behind after surgery, which researchers blame for the cancer's high rate of recurrence.
One new and promising adjuvant therapy is called intensity modulated radiation therapy (IMRT). This technique allows doctors to deliver precise blasts of radiation to the pleura, with the ability to adjust the dose as necessary. IMRT can prevent the cancer from returning locally while reducing the amount of harmful radiation absorbed by healthy tissues. In one recent study involving 136 pleural mesothelioma patients, 55 percent of patients who received IMRT after EPP surgery survived one year after the procedure. After two years, 32 percent survived.
The type of surgery a patient receives often affects their adjuvant therapies. For instance, if a patient only has part of his or her lung removed, such as by P/D or pleurectomy surgery, doctors can only offer low levels of adjuvant radiation therapy. Higher doses may be more effective, but at the cost of potential damage to the healthy lung tissue that remains.
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For decades, radiation therapy has played a crucial role in trimodal therapy. Despite plenty of evidence of this treatment’s benefits, some mesothelioma researchers argue that it is most effective for palliative therapy and not a valuable part of potentially curative multimodal therapy.
In one review of numerous studies on radiation therapy for mesothelioma, the author states, “radiotherapy is widely used in treating mesothelioma with little supporting evidence.” He claims that more randomized studies are needed to justify the treatment’s current widespread use.
Mesothelioma most commonly appears as diffuse growths, meaning there are many small tumor nodules instead of a single mass. This growth pattern makes it difficult for doctors to deliver radiation safely to every tumor. Some studies show that patients treated with surgery and chemotherapy survive longer than patients treated with surgery, chemotherapy and radiation therapy.
Fast Fact: Doctors rarely use radiation therapy to treat peritoneal mesothelioma.
Throughout the years, researchers have explored a wide range of treatment combinations for multimodal therapy, including plans that do not follow the standard trimodal approach.
A four-modality approach that combines surgery, chemotherapy, radiation therapy and immunotherapy has been growing in popularity. Immunotherapy, which allows a patient to fight cancer with his or her own immune system, has shown promise as both a neoadjuvant and adjuvant therapy.
In one study investigating four-modality therapy, 41 patients received neoadjuvant immunotherapy with interleukin-2. Doctors delivered immunotherapy directly to the pleural space and followed up with P/D surgery. After surgery, adjuvant therapies included intrapleural chemotherapy, systemic chemotherapy, radiation therapy and a long-term interleukin-2 regimen. After 59 months, 13 patients were still alive. The median survival of all patients was 26 months.
As technology and medical knowledge improves, doctors will likely adopt new treatments for the multimodal therapy model. One exciting new treatment uses extremely small particles called nanoparticles to deliver chemotherapy drugs directly to mesothelioma tumors.
In an early animal study testing this technique, researchers delivered paclitaxel-loaded nanoparticles to mice infected with mesothelioma after they removed tumors with surgery. The study concluded that mice treated with nanoparticle chemotherapy had improved survival over those treated with surgery alone.
Dr. Robert Cameron is one of the nation’s foremost experts in mesothelioma treatment. He has been conducting research on several new treatment modalities that can be combined with surgery. Initial studies of interferon, a medication that prevents tumor cells or viruses from growing in the body, have shown that patients live up to three times longer after receiving the treatment. He is planning a larger clinical trial once he obtains funding.
Dr. Cameron is also investigating cryotherapy as an alternative to adjuvant radiation therapy. Cryotherapy involves freezing a tumor by injecting it with a needle. A cryotherapeutic agent like liquid nitrogen can completely freeze a tumor nodule and destroy its cancerous cells. Dr. Cameron used this technique while treating patients at the UCLA Jonsson Comprehensive Cancer Center to destroy tumors without using toxic radiation therapy.
Researchers are now performing clinical trials to test the safety and effectiveness of these and other emerging treatments for mesothelioma. In time, they may discover new approaches that replace the standard treatments of today.
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