Before we go into details of various treatment options available for those who have mesothelioma, it is essential to understand that it is one of the rarer forms of cancer. It is known to affect around 2500 individuals in the US each year. It is one of the difficult to treat malignancies with the poor response rate to the therapy.
It is cancer that arises due to a mutation in the thin layer covering the internal organs; this thin cellular layer is called mesothelium. As this form of cancer is rare, it received less attention from the researchers, and that explains why it is still challenging to treat mesothelioma.
Though mesothelioma may occur in any internal organ including testicles, but the most commonly found type is that of lungs, that is mesothelioma due to a mutation in the outer covering of lungs. Perhaps the reasons for it is that lungs are often exposed to toxins, with asbestos being one such toxin with demonstrated relation to this type of cancer of lungs.
Further, it is also important to understand that even the same kind of cancer may be caused due to the little different type of mutations. It means that even the same sort of therapy is not equally effective in all people. As we are all different from each other genetically, it means that development of resistance to drugs also occurs by various dissimilar mechanisms in individuals.
Three kinds of treatments form the backbone of any cancer treatment; they are surgical treatment, radiotherapy, and chemotherapy. Apart from these three approaches, there are an array of experimental drugs, some working to change immunity, while others specially made to work against the specific type of cancer. Finally, there is alternative medicine, which may benefit in some cases.
How the doctor or cancer specialist chooses the treatment approach?
It is something that depends on the combination of factors, with most important being the stage of disease followed by the age of the patient. Based on these two criteria doctor has to decide whether treatment should be focused on curing the patient, or prolonging the life, or just helping to improve the quality of life (in last stages of the disease).
So let us look at examples to understand the treatment approach. If the patient is young and disease has been diagnosed in early stage, and there is no metastasis to surrounding organs and lymph nodes, in that case, the efforts would be in providing the complete cure to the patients. In such case, the doctor would generally start with the urgent surgical removal of cancer, further followed by radiation therapy to kill the remaining cells, and at the same time providing the chemotherapy for final clearance of all the cancer cells from the body.
But quite often such an ideal treatment would not be possible, as cancer is something that mostly remains symptomless in early stages, and mesothelioma is no exception. Thus in real life condition, it is entirely possible that a person would be diagnosed at a later stage, or more often in advanced age. Let us say a patient at the age of 68 and is diagnosed with fourth stage mesothelioma. In such case, both due to advanced cancer and age of the patient surgery would be utterly futile, and even radiotherapy may do little good. In such case, the doctor may either consider drug therapy for extending the life, or even a treatment aimed at relieving the symptoms only.
Now let us look for more details regarding the various treatment modalities. Though there would be a minor difference in the treatment approach according to its location, but in most cases, overall strategy or methods would remain the same.
Surgical treatment of mesothelioma
Be it mesothelioma or any other cancer; a surgical procedure is the treatment of choice when the target is to cure the patient altogether. It is a decision which would be taken after taking into consideration several factors like age of the patient, location of the cancer, stage of disease, and so on.
The logic here is to simply remove the cancerous tissues with the help of a scalpel if that is realistic. Surgical treatment of mesothelioma is not done by a single surgeon. It would depend on the location of the cancer. Hence if the mesothelioma is in the stomach, surgery may be performed by a surgeon specializing in gastroenterological surgery, while the operation of lung mesothelioma would be done by the thoracic surgeon.
Surgical treatment of mesothelioma of pleura
It is cancer or mesothelioma of the outer lining of the lungs and is the most common type of mesothelioma. In this case there are two surgical options, first is less traumatic and involves mainly removing the pleura (outer covering of lung). This type of surgical operation is called Pleurectomy/Decortication (P/D). It would usually be used in stage 1 of mesothelioma of pleura. It has the benefit of being least traumatic as other surrounding structures including lungs are mostly unscarred.
However, if the mesothelioma is more widespread surgeon may make a decision to remove the surrounding tissues that include the part of the lungs, diaphragm and so on. Such type of surgical procedure is called Extra-Pleural Pneumonectomy (EPP). EPP is more traumatic as compared to P/D, but at the same time a better option if the specialist doubts that mesothelioma has metastasis.
Choice of surgical procedure is generally best done by the specialist after taking into consideration all the factors.
Surgical treatment of mesothelioma of abdominal organs or peritoneum
If the mesothelioma has been diagnosed in the abdominal cavity, that is of the outer covering of organs like stomach, intestines, rectum, ovaries or other organs than the most common option would be surgery called Cytoreduction with HIPEC. As the name of the procedure says, it is a combination of two components; the first element is Cytoreduction or surgical removal of all the visible cancer cells and surrounding tissues, while HIPEC is a short form of heated intraperitoneal chemoperfusion, an entirely different kind of procedure.
HIPEC is performed immediately after the surgery of abdomen. It involves washing of abdominal cavity with anticancer drugs. It is a kind of sterilization of peritoneum or abdominal cavity with the help of powerful cytotoxic medications. It mostly involves circulating the anti-cancer medicines heated at temperature 41 degrees Celsius or above for about 90 minutes. Anticancer drugs used in this way are at much higher concentration than given by mouth or intravenous route. Studies have shown that anticancer medications are thrice better at killing the mesothelioma cells when given at higher temperature. Because the therapy is local, it means that procedure is quite safe.
Above discussed are perhaps two of the most common types of surgical maneuvers used in patients suffering from mesothelioma, but surely in some cases, doctors may choose some other option.
Survival rate after the surgeries mentioned above have improved a lot, but still, on average, there is 5-7% risk of death after the surgery. In case of successful operation, life may be prolonged by several years. If mesothelioma is of lungs, a person may on average survive for a couple of years. However, the outlook is much better in mesothelioma of abdominal organs. In case of the abdomen, after the multimodal treatment, life may be prolonged for several years.
In cases when full-scale removal of the cancer is not possible, doctors may go for procedures that can prolong a life a bit and ease up the suffering of the patients. These methods involve removing the fluid built up in thoracic cavity or abdomen (thoracentesis or paracentesis).
Radiation therapy in mesothelioma
It is the treatment that works almost at any stage of mesothelioma. Radiotherapy involves giving the high dose of focused radiation to the person in order to kill the cancer cells. It is a procedure that does not include making any cuts in the body. Single radiation therapy procedure would not last more than half an hour in the majority of cases. Kind of equipment used in radiotherapy would vary from one clinic to another
Radiation therapy is not just about killing the cancer cells via radiation, but it may also be used to reduce the cancer pain. This pain relief may be provided either by killing most of the cancer cells or even targeting the nerves.
Radiation therapy can also be used in those who cannot undergo surgery for various reasons like age or advanced form of mesothelioma, as radiation therapy may help to reduce the cancerous tissues and thus prolong the overall survival of the patient.
In most cases, radiation therapy would be done after the surgery. Although recently a new SMART technique has evolved, which included giving the radiation therapy before the surgical treatment. SMART is a short form of Surgery for Mesothelioma After Radiation Therapy. It is something that has demonstrated the effectiveness. It is thought that SMART treatment helps to better eliminate the cancer cells in mesothelioma.
Improving effectiveness of radiation therapy
Several techniques are used to enhance both the safety and efficacy of the radiation therapy. Thus a doctor may prescribe certain drugs before the surgery that may improve the absorption of radiation waves by the cancer cells; these drugs are called radiosensitizers. On another hand, the doctor may also prescribe medicines that help to protect the healthy tissues, and help them to recover quickly after the radiation therapy. These class of drugs is called radioprotectors. Further, the doctor may also give medicines to decrease the side effects like nausea, vomiting, hair-loss and so on.
Another technique to protect the healthy tissues from unnecessary radiation exposure is to use the protective shields. For example, shield to protect the facial tissues when providing radiation therapy for mesothelioma of lungs.
At present in early stages of cancer especially 1st and 2nd stage mesothelioma, aggressive surgical treatment followed by the high dose radiation therapy is the most effective treatment available. Clinical studies have shown that this combination treatment can significantly improve the survival rates in mesothelioma.
Chemotherapy in mesothelioma
Chemotherapy is name for cancer treatment with drugs. Anticancer drugs are also called cytotoxic medications as they are used to kill the cells. Chemotherapy is one of the fastest evolving branches of cancer treatment with lots of promises. At present chemotherapy works best when used in combination with surgery and radiation therapy to kill the cancer cells that are not possible to suppress with radiation or surgery alone.
Chemotherapy clearly has some benefits over the surgery, as it is a non-invasive method. The ideal chemotherapeutic drug would eliminate the cancer cells completely, without harming the healthy cells of the body. Regretfully, the Ideal anticancer drug remains a distant dream in case of mesothelioma. At present chemotherapy can only prolong the life of the patient.
Chemotherapy has other benefits of better predictability of results. For example, in surgery risks are always higher, and benefits are not still predictable. At present several drugs have been approved for chemotherapy in mesothelioma.
Combination of pemetrexed with cisplatin is the most commonly used treatment. It would be the first-line treatment in most cases. This combination has been demonstrated to be most effective and has been well studied in numerous of clinical trials.
Vinorelbine, doxorubicin, irinotecan, gemcitabine, and raltitrexed are other drugs that are used in combination with cisplatin in mesothelioma.
In some cases, cisplatin may be replaced by another drug called carboplatin.
Histological and genetic study of mutation may one of the way to decide which drug to use in a particular patient.
Folic acid supplementation is one of the ways to reduce the toxic effect of these drugs, but it should be taken strictly as per the recommendation of the specialist, else it may decrease the effectiveness of therapy.
At present the results of chemotherapy are only modest, they may typically increase the life by few months in most cases, and by years only when used in combination with surgery and radiation therapy.
Chemotherapy side effects
As we already mentioned that search for ideal chemotherapy drug still remains a dream. Some of the side effects of chemotherapy are well known to people, mostly due to media coverage. Common side effects are hair loss, nausea and vomiting, change in bowel motility, fatigue, fall in immunity, higher risk of infections, sore mouth and throat, peripheral neuropathy, hearing loss, and flu-like symptoms.
Usually, doctors would prescribe drugs to reduce many of these side effects.
It means a combination of all the possible forms of treatment. As a rule, multimodal therapy is the golden standard for treating cancer. Using any single type of therapeutic approach is extremely rare in such a life-threatening condition like cancer.
In most cases, doctors would try to treat the patient by combining surgery, radiation therapy, chemotherapy and use of other modalities. It not only increases the chances of a cure or long-term survival but also results in better quality of life.
Clinical trials and emerging therapies
In recent year cancer treatment is getting more and more attention. Though survival rate in mesothelial cancer is still not very high, nevertheless on the brighter side, things are improving fast. Thus one of the ways is to give clinical trials and emerging therapies a try. Many people have already benefited by participating in the clinical trials, in the process getting access to the latest drugs that are still not available in usual clinics.
Below we discuss some of the therapies that may also be used to improve survival and quality of life in mesothelioma.
It is emerging as one of the most promising branches of cancer therapy. Immunotherapy may combine various methods to train our immune system in fighting the cancer cells. Some of the methods used are vaccines, cell therapy, drugs, and antibodies.
Immune therapy is encouraging in a way that it does not have the kind of widespread toxic effect related to surgery, chemotherapy, and radiation. And even better that it has much broader outreach. After all immune system can reach almost any part of our body.
At present there are many drugs and immunotherapy agents in an advanced stage of clinical trials, if not a complete cure, they are promising to improve the survival rates significantly, with a minimum amount of toxic effects.
One example of such drug that is under investigation is tremelimumab. It has already shown its safety and effectiveness in the phase 2 trials. If all goes well, there are chances that many such drugs would be added to the arsenal of cancer specialists in their fight against mesothelioma.
As no two people are same, similarly all cases of mesothelioma differ from each other. In some cases, it is possible to find a treatment that would be effective in that particular case. In some advanced treatment centers, specialists would carry out detailed genetic or molecular study of the mesothelioma to identify the weak spot.
Notwithstanding the difficulties, it is impressive to see the numerous drugs and therapies being tested to better the outcomes in mesothelioma. Here is the list of some of the drugs being tested, that may possibly change the way we treat mesothelioma in the future.
- EGFR (epidermal growth factor) is overexpressed in mesothelioma. Gefitinib a novel EGFR tyrosine kinase inhibitor has shown to inhibit mesothelioma in lab conditions. Another drug erlotinib from the same group is also under investigation.
- PDGF (platelet-derived growth factor) inhibitor imatinib though failed to show results in phase 2 trial, have shed light on many important factors.
- VGEF (Vascular endothelial growth factor) inhibitors like sorafenib, vatalanib, and thalidomide are other possible candidates that may improve the response of drug therapy.
- Bevacizumab an anti-VEGF monoclonal antibody is being tested by the University of Chicago. It is used in combination with gemcitabine plus cisplatin and is already in phase 2 trial.
- Src kinase inhibitor dasatinib is being tested in previously treated patients.
- Class I and II histone deacetylases inhibitor called Suberoylanilide hydroxamic acid (SAHA) has demonstrated potent inhibitory activity against mesothelioma in vitro. It is a drug that is in a phase 3 trial. It is expected to improve the survival rate in mesothelioma.
- Bortezomib the proteasome inhibitor is being studied in two clinical trials in the Europe, it is intended to be used in combination with cisplatin.
- Many studies are looking for a drug that could inhibit mesothelin, a surface glycoprotein find in mesothelium cells.
Thus one can see that mesothelioma is no more a neglected condition by researchers, and a considerable number of drugs are in the pipeline.
Nutrition, exercise, and complementary medicine
Mesothelioma is an aggressive type of cancer with poor outcomes in the majority of cases. In a bitter fight against such aggressive and malignant opponent every single tool must be deployed. Complimentary medicine along with better nutrition and exercise may help to boost immunity, improve quality of life, and contribute to prolonging survival. Moreover, who said that miracles do not happen, or everything has been discovered in the world.
Mesothelioma treatment in nutshell
- If the prognosis is good, which means a person has been diagnosed at early stage and patient is in good health, multimodal treatment would work best. It is a combination of surgical removal of the tumor, followed by neutralization of cancer cells with the help of radiation therapy and chemotherapy.
- If surgical treatment is not possible or carries too much risk, radiation therapy and chemotherapy can still help to shrink cancer, prolong life, and better the quality of life.
- No two cancers including mesothelioma are similar, sometimes after thorough molecular study of disease, a specialist may propose personalized treatment.
- There are numerous drugs in the pipeline, with many in the end stage of trials. Thus survival would improve in near future.
- Alternative medicine or complementary medicine would not cure mesothelioma but could play a role in improving symptoms and quality of life.
Prognosis in mesothelioma
It is the very aggressive type of cancer, treating it still remains challenging for modern medicine. Unfortunately, in most cases, life is only prolonged at best by few years. However, in some instances when mesothelioma has been caught in early stages, long-term remission has been achieved. There is a small number of cases that can achieve either long-term remission or even permanent remission of the disease.
How long can a person survive would depend on the stage, age, performance status, and histology.
Given below are the characteristics of mesothelioma associated with poor prognosis:
- Being male
- WBC count >8.3 × 109/L.
- If the known as ECOG PS is ≥ as 1.
- An older patient
- Having a non-epithelioid histology.
Some people may expect better outcomes with aggressive multimodal treatment, characteristics of long-term survivors are:
- Epithelioid histology.
- Negative lymph nodes.
- Negative surgical margins.
Would surgery indeed prolong life in mesothelioma?
Unlike 30-40 years back, surgical procedures are quite safe nowadays, yet in mesothelioma surgical treatment is a bit controversial as it is only shown to prolong life in early stages of cancer. In the advanced stage, it may either not help or may cause unnecessary discomfort for the patient.
Do women live longer with mesothelioma?
Yes, though the prevalence of mesothelioma is less in women, however, statistics indicate that women have much higher survival rate. Thus in one of the studies, 14,228 cases of mesothelioma were analyzed to find that after five years, the survival rate in women was 13.4%, while in men it was mere 4.5%. That is almost thrice more women were living after five years of diagnosis.
What other factors result are related to better outcomes?
Not all cases of mesothelioma are similar. Thus some types of mesothelioma have much better outcomes than other. It is something that a specialist would be able to tell after the histological and molecular analysis report of cancer. Thus, for example, a patient with mesothelioma belonging to germline BAP1 mutations have seven-fold higher survival rate.
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