Mesothelioma Treatment Options

The mesothelioma treatment remained to be, up to this day, one of the biggest challenges in the field of oncology. Having in mind that the first symptoms are the symptoms of a late stage carcinoma, prognosis for malignant mesothelioma is rather poor and the mesothelioma treatment undertaking is also affected afterwards.

New medical approaches brought a glimpse of hope for mesothelioma patients- those who are still in a latency period.

After asbestos exposure (the leading risk factor for malignant mesothelioma), it takes up to approximately fourty years before the disease enters symptomatic phase. Because of this, and the fact that asbestos is still used in developing countries as a building material, being United States the only developed country where it is not prohibited, the increase of malignant mesothelioma incidence is expected in the upcoming decades.

Depending on the patient’s condition different mesothelioma treatment modalities are used. Typically, the mesothelioma treatment consists of surgery, chemotherapy and radiation therapy.

Surgical Mesothelioma Treatment

The surgery is essential not only in the mesothelioma treatment but its staging and diagnosing as well. Just like in case of any other carcinoma, the final staging and diagnosing are done after the surgical mesothelioma treatment, based on the samples collected. Unfortunately, not all patients can undergo surgery- in some cases, the disease spread too much, whereas in others, the overall health condition of a patient is not good enough to carry out the surgery. Therefore, this mesothelioma treatment should be discarded in these cases.

The goal of surgery is complete removal of the tumor. The most widely used techniques are pleurectomy/decortication (P/D) and extrapleural pneumonectomy (EPP).

Pleurectomy / decortication (P/D)

The P/D is not a standardized technique. It varies depending on the surgeon’s assessment or the mesothelioma treatment center approach.

General information about the P/D procedure as a mesothelioma treatment

After the initial assessment by an anesthesiologist, internal medicine specialist and surgeon, the function of the unaffected lung is examined (just in the case that the extrapleural pneumonectomy (EPP) is necessary because cancer spread more than imaging diagnostic revealed). Also, all required diagnostic tests are made (CT, X-ray, laboratory tests, etc.).  The procedure is performed under general anesthesia and can last for several hours (removing the lining around the lungs- visceral pleura, can be time-consuming).

With the help of supportive therapy (chemotherapy, radiation therapy, etc.), for the right patients, P/D is a better solution than EPP. Having in mind the perioperative mortality rates and other “safety” parameters of EPP and P/D, it’s no wonder why P/D is becoming increasingly popular among surgeons as a mesothelioma treatment.

Although the incision used in this procedure is one of the biggest standardized incisions in surgery (thoracotomy), the recovery in hospital lasts 7-10 days. During this time, the patient is closely monitored for complications (most often air leakage into the chest cavity). The complete recovery may take 1-2 months. In some cases, pulmonary rehabilitation is needed to lessen the symptoms.

According to the research studies, long survival times after the P/D correspond with multimodal therapy. It means that using more than one mesothelioma treatment approach (other than surgery, chemotherapy, radiation, and immunotherapy are used as well) leads to a longer survival time. For example, adjuvant therapy can prevent relapse for a significant amount of time and in some cases, several years.

Extrapleural pneumonectomy (EPP)

The EPP has been standardized among surgeons as a mesothelioma treatment. It is a very extensive surgical procedure that includes removal of virtually all organs of the chest on the affected side. During the operation, following structures are removed:

–    Entire lung (notice that the lung is spared in P/D);

–    The membrane that wraps the lung (visceral pleura) and the one that envelops the chest cavity from inside (parietal pleura);

–    Pericardium- the membrane that encloses the heart;

–    A part of the diaphragm- under the affected lung.

General information about the EPP procedure

The first thing doctors want to make sure is that the remaining lung is strong enough to support the body’s respiratory function.

Further assessment by internal medicine specialist and anesthesiologist is made routinely (just like in case of any other general anesthesia major surgery).

Before the surgery, additional diagnostic tests are made, such as CT, X-ray, and laboratory testing (broad spectrum testing) to assess how much cancer has spread.

The procedure is performed under general anesthesia. Through the incision that’s 9 to 10 inches long (about 25 centimeters), the surgeon checks the chest cavity, removes the cancerous lung and other structures (parietal and visceral pleura, pericardium, lymph nodes and part of a diaphragm).

Recovering takes time. In the first few days, the patient breathes with the help of respirator and drainage tubes are used to evacuate all the fluid that may collect inside the chest cavity. The hospital recovery phase lasts for at least two weeks. The full recovery lasts up to two months, and quite often a lot longer. It takes up to six months for the remaining lung to take over the respiratory function entirely. Some patients have a low tolerance for physical effort and report shortness of breath even after six months after surgery.

The decision about the surgical technique is based on how much the mesothelioma has spread. Available diagnostic tools cannot reveal with satisfactory precision the extent of tumor spread. That is why the surgeon and his patient enter the operating room not knowing for sure what technique will be used as a mesothelioma treatment. The definitive decision is made during surgery.

The perioperative mortality rate favors P/D over EPP

The perioperative mortality is death, regardless the reason, during and 30 days after the surgery. It is very important parameter that health professionals use when assessing the risk to benefit ratio of a particular surgical procedure as a mesothelioma treatment.

It includes intraoperative causes of death (complications that occur during the procedure, such as bleeding) and complications following the surgery (sepsis, pulmonary embolism, shock, neurological complications, renal, liver, heart failure, etc.).

Compared to the EPP, P/D technique has a lower perioperative mortality rate.

The study published in July 2018 revealed an interesting insight on this matter1.

–    EPP mortality rate within 30 days after the surgery was three times higher than after P/D (10.5% compared to 3.1%).

–    The complication rate of P/D was 3.8% compared to 24.2% of EPP.

–    Unexpected reoperation rate in EPP group was 9.5% compared to 1.5% in P/D group.

–    Respiratory distress syndrome rate was significantly higher after EPP (8.4%) compared to 0.8% after P/D (those rates are the result of a lung removal in EPP and sparing the lung in P/D technique).

–    Sepsis rate was significantly higher in the EPP group as well.

Chemotherapy as a mesothelioma treatment

It is used as an additional or only therapy in the management of all cancers and some other conditions such as rheumatoid arthritis. This includes of course utilizing chemotherapy as a mesothelioma treatment.  Chemotherapy drugs suppress cell division throughout the body. Unfortunately, they are not entirely selective, so all tissues in the body that divide frequently are affected by chemotherapy. Therefore, the well known harsh adverse effects of chemotherapy occur. The new research in the field of chemotherapy is focused on finding a selective chemotherapy drug, or at least more selective than the ones used today. Although patients with malignant mesothelioma can take part in clinical trials of such medications, up to this day a drug with “perfect selectiveness“ has not been discovered yet.

Regarding mesothelioma treatment, chemotherapy shrinks the tumor mass, relieves the symptoms, improves the quality of life and increases the survival time. The study published in 2018 shows that chemotherapy significantly extends survival time after the surgery2. Additionally, the survival time of patients who got two-line chemotherapy was doubled compared to those who used one-line. The most common first-line chemo combination was cisplatin or carboplatin combined with pemetrexed followed by the same protocol or gemcitabine as a second line. In some cases the second line is just an extension of the first (same drugs, same doses), while in others doctors decide to change the combination of drugs used in the mesothelioma treatment. With different medication profiles to choose from, doctors can optimise chemotherapy protocol to each patient.

Although health condition of some patient does not allow them to use a combination of chemo drugs, studies show that two-drug combinations have supremacy over mono-component therapy. Would a three-drug combination in the mesothelioma treatment improve survival rate even more? No, it seems. It has been tried and studies did not reveal any supremacy of the three-drug combination.

In numbers, one-year survival rates between the patients (depending on whether or not they got chemo) look like this:

  • The group of patients who did not receive any chemotherapy: 17%
  • The group of patients who got one line therapy: 35%
  • The group of patients who got two line therapy: 64%

Chemotherapy is divided into cycles. Each cycle lasts for a few weeks and consists of medication and recovery period. How many of them, how often and which medications will be used is a decision of a mesothelioma specialist (depending on the type of the tumor cells, how much it has spread, how aggressive is it, overall patient health condition, etc.)

The chemotherapy plans are roughly divided into three modalities:

Multimodal therapy

This kind of mesothelioma treatment is reserved for patients who are strong enough to withstand an aggressive treatment protocol. Usually, the patient goes through the neoadjuvant therapy (this treatment shrinks the tumor before the surgery) and after the surgery adjuvant therapy protocol is prescribed (it reduces the chance of a tumor recurrence).

Chemotherapy

It is used for the patients who cannot go to surgery for some reason (overall health condition, tumor spread, etc.) Most often, two-line therapy is administered (if the patient’s health condition allows). Two-line therapy protocols showed supremacy over one line modalities.

Palliative chemotherapy

This mesothelioma treatment is reserved for the patients in late stages of a disease and bad overall health. The mild chemotherapy protocol is prescribed to relieve the symptoms, improving the quality of patient’s life.

Systemic chemotherapy mesothelioma treatment protocol: how does it looks like?

The drugs are administered through the I.V. line, they circulate throughout the system affecting every single cell in the body.

Chemotherapy is harsh. Different patients react differently to it, but there are some anticipatable side effects. In the preparation process each patient is introduced with benefits, side and adverse effects of chemotherapy. Here the  specialist takes all necessary diagnostic tests and picks the mesothelioma treatment modality depending on the patient’s decision and medical findings. Of course, the process takes multiple visits.

Before inducing a chemotherapy protocol, the patient receives drugs for reducing its side effects. Medications are administered through the I.V. line, and each session usually lasts for 2-3 hours. During that time, the patient is supervised by a nurse, and blood samples are collected for further analysis. Typically, sessions are repeated every three weeks. After the entire mesothelioma treatment protocol is completed, follow-up visits are scheduled during which the decision about further treatment is made.

Side effects of chemotherapy

Unlike the regional chemo and radiation therapy which affect only specific areas of the body, systemic chemo runs through the entire circulatory system, affecting all cells on its way. The most sensitive are the cells that often divide (blood, liver, skin and epithelium cells).

–    Fatigue

Since the chemo affects blood cells, and indirectly food absorption, the patients almost always report mild to severe fatigue after the chemotherapy cycle. To ease it, for some it is enough to rest and sleep more than usual, while others need help in everyday tasks. In case of fatigue that significantly lowers the quality of life, correction of the chemotherapy in the mesothelioma treatment is needed.

–    Diarrhea or constipation

Digestive system problems are a common side effect of chemotherapy. In some patients with malignant mesothelioma, diarrhea and constipation may be caused by the spread of the tumor, while in others the irritation of the gut lining is the cause. Taking care of the diet, water intake and drug support if necessary, the symptom can be resolved. Typically, in days after the chemotherapy session all intestinal symptoms intensify, and then everything goes back to normal within a week.

–    Nausea/ vomiting

This symptom is a direct consequence of chemotherapy effects to the gut epithelium (the most “active“ tissue in the body, when it comes to the speed of division, besides blood is epithelium- it completely changes every three days!). Up to 80% of patients of this mesothelioma treatment complain of nausea and vomiting. Depending on the primary mechanism that triggered the symptom, it may last anywhere between few hours and one week. Typically, nausea and vomiting become more prominent towards the end of the treatment regimen. With many effective nausea drugs available, in most of the cases, nausea and vomiting are quickly resolved.

–    Mouth ulcers

Just like it damages the gut epithelium, chemotherapy affects the mouth epithelium as well. Mouth ulcers may be very unpleasant, making the food intake nearly impossible.

–    Hair loss

Hair follicle is a rapidly dividing structure. Shortly after the first chemo session, hair starts to fall off. Once the regimen is over, within a few weeks, it starts to regrow again. In the meantime, patients often wear wigs. Since all hairs on the body just fall off within a few days, it is advisable to take a short haircut before starting chemotherapy, to avoid seeing long hair strands on the pillow, what is an experience that is particularly frightening and unpleasant for patients on chemotherapy.

–    Blood count

The white blood cells and platelets count drop are always seen in the days after the chemo session in this mesothelioma treatment. As a result thereof, patients are prone to infections and have difficulties stopping the bleeding. Avoiding crowded and closed public spaces is highly advisable (public transportation, theater, malls, etc.) since on these places a patient could easily get infected by other people.

 

Regional chemotherapy mesothelioma treatment protocol: how does it looks like?

While the chemotherapy drug circulates throughout the entire body in the systemic protocol, in case of regional chemo, the medications are injected into the area of carcinoma growth.

This approach is combined with surgical treatment. During the operation, heated to 42°-43°C (centigrades are used as a scale of measurement), chemotherapy solution is pumped into the abdomen for up to 90 minutes (. After 60-90 minutes, surgeon drains and rinses the abdominal cavity. Compared to systemic chemo, regional treatment has significantly fewer side effects. Not all patients are indicated for this kind of treatment (only those with the diagnosis of peritoneal mesothelioma, a condition in which cancer has spread to the lining layers of the abdomen). Before this mesothelioma treatment technique was used, life expectancy in patients with peritoneal mesothelioma was not more than twelve months, and today (thanks to HIPEC- hyperthermic intraperitoneal chemotherapy) it is more than five years.

HIPEC approach has been tried in the chest cavity, but the researchers haven’t been able to offer a conclusive answer about this mesothelioma effectiveness up to the date this article about mesothelioma treatment was written, what is 2018.

Radiation therapy as a mesothelioma treatment

The radiation therapy is used for malignant mesothelioma treatment in all of its stages, most often in combination with other treatment modalities (surgery and chemotherapy). Its goal is to prevent or limit and improve life expectancy.

Unlike chemotherapy which affects the entire body and all of its cells, well-targeted radiation therapy affects only  the desired area reducing chances for the development of side effects.

According to the research studies radiation therapy as a mesothelioma treatment significantly increases survival rates- depending on the tumor stage it increases the life expectancy for three to five years.

Also, it reduces the risk of mesothelioma local recurrence. By reducing the size of a tumor, radiation therapy alleviates the pain and reduces the tumor pressure to the heart and lungs. More than 60% of patients report pain relief after this mesothelioma treatment. As a palliative therapy, it does not increase the life expectancy, but temporarily improves the quality of life3.

During the surgery, cancer cells can seed to other areas of the body. The seeding phenomena cannot be controlled, but radiation along the incision lines and drain tubes reduce the risk of it. In simple words, seeding causes metastatic disease.

External beam radiation therapy (EBRT)

Just like its name says, radiation beam directly targets the tumor tissue. Mesothelioma specialist assesses which areas will benefit the most from the therapy and decides where the beam will be directed. It is a noninvasive method. The process of beam guides and radiation dose applied is almost entirely automated- this way the risk of adverse effects are lessened to a minimum.

The most effective type of radiation therapy as a mesothelioma treatment is IMRT (Intensity-modulated radiation therapy)- a 3D beam that can change the strength in certain areas, precisely targeting the tumor tissue and reducing the radiation effects on healthy cells. Compared to conventional radiation technology, IMRT reduces the recurrence risk by almost 60%.

EBRT session lasts a few minutes. Placing the patient in the right position may take longer, though. Typically, five sessions a week are applied, and entire treatment regimen lasts for a few weeks.

The most common side effects are fatigue and radiation skin burn. Radiation skin burns are very similar to sunburns (actually, sunburns are radiation burns- UV). Radiodermatitis- the skin injury caused by radiation therapy presents as redness, tenderness, swelling, peeling, and darkening of the skin (it is the most apparent in the area of the skin where the beam was focused).

Brachytherapy

Brachytherapy is not that commonly used in the treatment of this type of cancer since the EBRT is more efficient. Nevertheless, it has its place in mesothelioma treatment.

The radiation source (implant) is placed close to, or inside the area requiring the treatment. Compared to EBRT, it reduces the risk of adverse effects even more. The implant is set during the operation or inserted afterward (often under general anesthesia). Most often, implants are used to reduce the risk of seeding (inside the incision or biopsy scar- temporarily).

Other Mesothelioma Treatment Options

Complementary medicine methods can improve the quality of life in mesothelioma patients. Oncology nutrition offers solutions for balanced diet in all stages of the mesothelioma treatment- before, during and after the chemo- and radiotherapy. Herbal medicine tinctures, teas and creams proved to be an effective strategy to fight against nausea and pain.

Staying on the course of classical medicine, while practicing the principles of complementary medicine methods is probably the best way to fight against the disease. Before starting any of the alternative methods, it is highly advisable to consult a health care professional about their safety.

References utilized

1. Malignant pleural mesothelioma treatment and the Society of Thoracic Surgeons Database: An analysis of surgical morbidity and mortality. Burt, Bryan M. et al. The Journal of Thoracic and Cardiovascular Surgery , Volume 148 , Issue 1 , 30 – 35

2. Mesothelioma Treatment in the United States: a Surveillance, Epidemiology, and End Results (SEER)–Medicare investigation of treatment patterns and overall survival; Beebe-Dimmer JL, Fryzek JP, Yee CL, Dalvi TB, Garabrant DH, Schwartz AG, Gadgeel S; 26 October 2016 Volume 2016:8 Pages 743—750

 

  1. Bissett D, Macbeth FR, Cram I. The role of palliative radiotherapy in malignant mesothelioma treatment. Clin Oncol (R Coll Radiol). 1991 Nov;3(6):315–317.