Multimodal therapy is treatment with two or more treatment types.
When treatments are combined, patient survival rates typically improve.
One of the treatments, usually surgery, is considered the primary therapy.
The order that therapies are administered varies by each individual mesothelioma case.
Multimodal therapy, also known as multimodality therapy, is cancer treatment with more than one treatment option. Multiple treatment types are combined to increase the cancer-killing effects and improve patient outcomes. Mesothelioma multimodal treatment plans commonly combine two or more of the standard treatment options: surgery, chemotherapy and radiation therapy. Emerging treatment types, like immunotherapy, may also be added to treatment plans for eligible patients. Multimodal therapy, with standard or experimental treatments, may be used for curative or palliative purposes.
Multimodality Therapy for Mesothelioma Treatment
Multimodality therapy, regardless of the combination of treatments, has been shown to be the most favorable treatment plan for eligible patients. The therapy involves at least two forms of treatment that when used together are more effective than any individual treatment option alone. The main form of therapy, or primary therapy, is augmented with treatments before and/or after it is administered. Any treatment option may be used as the primary therapy, and the order of treatments vary among patients depending on their individual case.
Treatment given prior to the primary therapy, used to increase the efficacy of the primary treatment.
The treatment option deemed most effective for the mesothelioma case, often surgical resection of tumors.
Treatment administered after the primary therapy to help prevent cancer recurrence.
A patient’s team of physicians, including mesothelioma specialists, will determine which treatment options are best used neoadjuvantly, adjuvantly and as the primary therapy. The doctors will consider many factors like a patient’s overall health, mesothelioma cell type and the stage of their cancer when making these treatment recommendations.
Common Treatments Included in Multimodal Therapy
The three most common elements included in mesothelioma multimodal therapy are chemotherapy, surgery and radiation therapy. The conventional treatments are considered the standard of care for mesothelioma.
Chemotherapy is often used neoadjuvantly for mesothelioma. Chemotherapy before surgery has been found to help downstage patients’ tumors, allowing for easier removal. One trial found neoadjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) led to a median overall survival of 23 months.
A mainstay of mesothelioma multimodality treatment is macroscopic complete resection (MCR) of the cancer through either an EPP or pleurectomy/decortication (P/D). Surgery is typically the primary treatment in multimodal therapy when viable for a patient’s case.
Radiation therapy is commonly used after surgical intervention to prevent seeding of cancer cells and reduce rates of cancer recurrence. However, radiation therapy as a neoadjuvant option is still being tested in clinical trials and has found some success.
These three treatment types can be combined in various ways to create personalized treatments and the most favorable outcomes for mesothelioma patients. However, there are certain combinations that have shown more success in various clinical trials.
For malignant pleural mesothelioma patients, the most common course of multimodal treatment involves debulking surgery, through either EPP or P/D, and adjuvant radiation and chemotherapy. Typically the adjuvant treatment is administered between four and six weeks after surgery. The type of surgery will depend on the patient’s case, especially the stage of the cancer and overall health. An EPP is considered more aggressive and is not a viable option for many patients.
Patients that are deemed unfit for EPP will most likely undergo a P/D procedure. This surgical option typically limits possible adjuvant treatments. Pleural mesothelioma patients who’ve had a P/D cannot receive adjuvant radiation therapy, as this treatment combination would damage the lungs. The effects of prior treatment will be thoroughly considered by a patient’s care team when determining which therapies are best combined for multimodal treatment.
Peritoneal mesothelioma patients seeking multimodal treatment will often be treated by the same core therapies. However, the therapies will be utilized in different ways to treat the peritoneal malignancies. Peritoneal mesothelioma patients are commonly treated with surgical resection through cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). The HIPEC, a warm chemotherapy wash circulated through the abdominal cavity, is administered to kill any remaining mesothelioma cancer cells following the surgery.
Success from this multimodal peritoneal mesothelioma treatment is evident according to recent reports. One retrospective study, analyzing results from more than 400 patients treated in this way, recorded a median overall survival of 53 months. Some other studies noted in the report found even higher median survival times of 92 and 94 months after complete cytoreduction. This is more than double the median survival outcomes for peritoneal mesothelioma patients treated with chemotherapy alone. Typically patients undergoing chemotherapy treatment survive 12 – 27 months. This course of treatment is typically used for curative purposes, but may be used palliatively for patients whose mesothelioma is advanced.
Treatment Success with Mesothelioma Multimodal Therapy
The different combinations of treatments possible through multimodal therapy create countless opportunities for patient success. The standard trimodality therapy using chemotherapy, surgery and radiation creates more promising survival times for mesothelioma patients than when the therapies are used alone. When surgical resection through EPP is accompanied by adjuvant chemotherapy and radiation, researchers report median overall survival between 13 – 23.9 months. When the chemotherapy treatment is applied neoadjuvantly, the median overall survival range increases to 29.1 months.
An important aspect of mesothelioma cancer research is improving the typically poor prognosis. By further improving the efficacy of multimodal treatment options for patients, including the standard trimodal therapy and experiential therapies, researchers hope to mitigate side effects and increase long-term survival. Emerging treatments that have shown early success when used in multimodal treatment plans include photodynamic therapy (PDT), gene therapy and immunotherapy.
When PDT is used adjuvantly after surgical resection with P/D or EPP, researchers have found pleural mesothelioma patients achieve improved survival times. Studies have reported that this treatment plan, P/D or EPP followed by PDT delivered intraoperatively creates patient survival of up to 31 months. Greater still, median survival for participants with epithelioid mesothelioma who underwent P/D was 58 months.
Multimodal plans utilizing a combination of immunogene therapy and chemotherapy have also been shown to increase patient survival time. A study from 2016 found that malignant pleural mesothelioma patients treated with the regime as a second-line treatment achieved a median overall survival of 21.5 months. Among all patients receiving the treatment, either as first-or second-line therapy, disease control rate was 88%. Overall, further study is expected after the trial’s success in inhibiting metastasis, or spreading of disease, without high levels of toxicity. The researchers are advocating for further multicenter clinical trials to further investigate the efficacy of the treatment regime.
Patient Eligibility for Treatment
Multimodal treatment plans are aggressive and not viable for all mesothelioma patients. Those interested in multimodal therapy as a treatment option should discuss their case with their physicians. Generally, the combination therapy is best tolerated by patients with early-stage disease, epithelial mesothelioma cell type, no lymph node involvement and no metastasis. However, the cancer care team will evaluate each individual case to create a unique treatment plan, so even patients ineligible for surgery could undergo a different combination of treatments for better survival and quality of life.
Patients undergoing multimodal therapy must be strong enough to withstand potential side effects from each treatment modality used for their case. Side effects from treatment may include any and all side effects associated with each therapy used. Patients should discuss potential side effects with their physicians before adding any therapies to their treatment plan.
Common Side Effects by Treatment Type
- Hair loss
- Loss of appetite
- Low white blood cell count
- Mouth sores
- Nausea and vomiting
- Arrhythmia (change in heart rhythm)
- Blood clots
- Pain at incision
- Peritoneal effusion
- Pleural effusion
- Wound infections
- Hair loss
- Inflammation of the esophagus
- Inflammation of the lungs
- Sunburn-esque skin irritation
If participating in clinical trials to incorporate emerging treatment modalities into their multimodal treatment plan, patients should ensure the physicians conducting the trial and their general oncologist are aware of any possible interaction between prior treatments and the therapy being studied.
Incorporating a multimodal approach into one’s care plan has been shown to be the most effective mesothelioma treatment option, increasing overall survival for some malignant mesothelioma patients. Patients should be sure to discuss all treatment options, as well as potential benefits and risks, with their doctors before starting any treatment plan.