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The most effective therapeutic approaches to managing mesothelioma combine multiple treatment modalities. Since mesothelioma is often not diagnosed until very advanced stages, using aggressive strategies can be risky yet lead to higher survival times and increased overall quality of life. The benefits as well as drawbacks of using different modalities must be weighed against stage, histology, performance status, etc. before creating a treatment plan.
The three standard mesothelioma treatment modalities are: surgery, chemotherapy and radiation therapy. If the patient’s condition allows, surgical resection will be the first intervention before others are introduced. For surgical cytoreduction to be a feasible option, certain criteria must be met:
1. Overall patient health must indicate that surgery can be performed safely, including nutritional health, performance status, pulmonary function levels, extent of disease and histology subtype
2. Malignancy is localized, increasing chances of complete tumor removal
3. Informed patient consent, including understanding of risks and investigational versus curative nature of procedures
For pleural malignancies such as mesothelioma, surgery usually includes extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) followed by either radiation or chemotherapy. EPP involves removal of the thin membrane of tissue that covers the lungs and heart, the lung, and surrounding diaphragm muscle. Best results are seen with single incision of the 6th rib, pericardial and diaphragmatic reconstruction and epithelial types of mesothelioma. EPP is almost always followed with adjuvant therapy of chemotherapy using cisplatin-gemcitabine and/or external beam radiation.
P/D is a less intense surgical procedure that leaves the lung intact and only involves removal of the tumor and pleura. The procedure of separating the tumor from the lung versus complete removal takes more time yet carries a lower mortality rate while still enhancing quality of life.
The best way to minimize surgical complications and improve patient outcome is to ensure good patient selection, attention to detail during surgery, and awareness and immediate treatment of any postoperative complications if they occur. Recurrence is known to occur, with the most common site being the thoracic cavity. Aggressive adjuvant therapies are needed to lower the high local recurrence rates.
Despite risks, survival benefit makes surgical cytoreduction combined with post-adjuvant therapies worth considering for anyone diagnosed with mesothelioma, especially early stage disease. For current clinical trials being conducted at the National Cancer Institute involving surgery for eligible patients visit: http://clinicaltrials.gov/ct2/show/NCT01134146.
In most cases where malignant pleural mesothelioma, a cancer that begins in the lining of the lung, is diagnosed, thoracentesis is the first step toward not only verifying the diagnosis but also relieving painful symptoms. One of the main symptoms of mesothelioma is pleural effusion, a painful build-up of fluid between the layers of the pleura that line the lungs and inside of the chest cavity.
Pleural effusion is often experienced as chest pain, dry cough, shortness of breath, and/or difficulty breathing. Several methods are used to evaluate pleural effusions:
· CT Scan (computed tomography scan) of the chest
· Xray or Ultrasound of the chest
· Thoracentesis
· Analysis and examination of pleural fluid
· Thoracoscopic surgery (also referred to as VATS – video assisted thoracoscopic surgery)
Thoracentesis is one diagnostic procedure where a needle is inserted between the ribs and into the pleural cavity to retrieve a sample of fluid. During this time, palliation of fluid build-up can also be performed, helping to relieve symptoms of lung constriction.
If the cancer has progressed to the point where it is compressing the lung and fluid removal does not lead to increased expansion, then other long term treatment options for palliative care will be introduced as thorancentesis will be ineffective at providing symptom relief.
In some cases, serial thorancenteses will be recommended as part of a systemic treatment, however such a plan is rare as other risks are created with repeated procedures. Consult with your medical team to discuss all possible palliative options that are best suited for your particular stage and type of mesothelioma.
One of the main symptoms of pleural mesothelioma is difficulty breathing and lung compression due to fluid build up and tumor growth in the chest cavity. This symptom is known as pleural effusion and can cause serious pain and dyspnea. When the first line of palliative treatment, often a thoracentesis, is ineffective at providing symptom relief, two other procedures may be tried: a pleurodesis or placement of an intrapleural catheter (Pleurx).
Usually after a thoracentesis and determination of what is causing pleural effusion, a thoracic surgeon is recommended to perform a chemical pleurodesis. The chemical, a sclerosing agent, is introduced through a chest tube and inserted between the two layers covering the lung. Sclerosing agents, such as talc, bleomycin, and providone iodine, are intended to cause irritation which creates an obliteration in the space, preventing fluid from being able to re-accumulate in that space.
A pleurodesis can be performed at the bedside or in the operating room, under local anesthesia and/or sedatives. A chest tube is then inserted that allows fluid to drain. After adequate drainage, a chemical solution is added and then the patient is asked to alter positions to allow the agent to be fully distributed within the cavity. The goal is to expand the lung and prevent fluid from continually filling the space.
An additional treatment is a tunneled intrapleural catheter, where a small drainage tube is inserted by the surgeon. The tube is then connected to a Pleurx, a suction bulb device. The patient is instructed on how to drain the fluid from the Pleurx until the lung re-expands, which usually takes 2 to 3 weeks. Ideally, the tube can then be removed with little chance of reaccumulation of fluid. If the lung is entrapped, the surgeon may opt to keep the tube in place versus remove it.
There are some risks involved in either procedure that patients should be made aware of so that they can weigh the benefits and make informed choices with the help of their surgeon. Both can be extremely effective at providing symptom and pain relief.
Pleural effusions are a common occurrence, causing dyspnea and great chest pain. Treatments are purely palliative and not curative in intent, although some clinical trials are searching for more definitive methods.
Assessment usually begins with a thoracentesis if the patient shows signs of pleural effusion. If any suspicion of prior asbestos exposure or malignancy is present, the treating clinician will then perform a surgical biopsy of the pleura. This procedure is performed by an oncologist in a hospital under general anesthesia by making a small incision that allows a video thoracoscope to be inserted into the chest cavity for visual investigation, aspiration of any fluid buildup, and biopsies of the pleural lining. The procedure is performed not only for the purpose of diagnosis but also to palliate fluid to relieve painful symptoms. In instances where this type of biopsy is not possible, core needle and incisional biopsies may be performed.
Once a diagnosis of malignant pleural mesothelioma has been rendered, the health care team will create a treatment plan with a palliative approach in mind. Palliative means relieving symptoms versus removing or curing the cancer completely. Intent is to extend survival times with improved quality of life.
If you are experiencing any symptoms of mesothelioma, consult with an oncologist immediately. Increased treatment options exist with earliest possible diagnosis. You can visit the National Cancer Institute for more information and for the latest listing of clinical trials being conducted in your area.
Immunotherapy is one avenue being explored through clinical trials as one way to manage and treat mesothelioma. This method uses an agent to trigger, induce or enhance the body’s natural immune response system in defense against tumors. Immuno cell therapy combined with other standard forms can destroy tumor cells, thereby slowing progression of the cancer and prolonging survival times.
Data from previous clinical trials have shown that adenoviral vector expressing interferon-beta (Ad.IFN-beta), when administered into the pleural cavity, has resulted in gene transfer and led to antitumor immune responses for patients diagnosed with mesothelioma. A recent study researched whether giving two doses versus one would be safe and more effective at inducing an immune response and stabilizing the cancer.
The phase I trial involved ten patients diagnosed with malignant pleural mesothelioma, each given two doses of IFN-beta within a period of seven days or longer. Interferon-beta is a protein made and released by white blood cells as an immune response to tumor cells. IFN’s cause cells to communicate, activate immune cells, and can trigger a response that interrupts tumor cell replication.
Interferon therapy is usually used in combination with chemotherapy and radiation as a treatment for mesothelioma, with some evidence of successful effect. For pleural mesothelioma, IFNs are administered through a catheter into the pleura. Most common side effects are general flu-like symptoms, such as fatigue, nausea, temperature, dizziness and muscle pain. Pharmaceutical forms of interferon betas can come in liquid, lyophilized or biogeneric forms.
Data from this clinical trial showed that multiple doses were well tolerated; however the gene transfer process was blocked by preexisting anti-AAV neutralizing antibodies (NABs). AAV stands for adeno-associated virus vectors, which have become main vehicles in gene therapy. Anti-AAV antibodies are naturally acquired by human infections, and can be used as part of cancer therapy by way of gene transfer.
Further clinical research is supported to verify the antitumor efficacy of this agent in controlling and/or eradicating mesothelioma tumors.
Malignant mesothelioma is a rare, aggressive cancer that is difficult to diagnose and manage, with the majority of cases carrying a prognosis ranging from 9 to 17 months. Mesothelioma tumors arise from the mesothelial cells of serosal surfaces of the abdomen, lungs, or heart. Mesothelioma is caused by exposure to asbestos and has a long latency period of 10 to 40 years between initial exposure and development of symptoms. Standard therapies have not been very effective at treating mesothelioma, whose cells are considered to be highly resistant to apoptosis.
Due to such characteristics of mesothelioma, new targeted therapies are constantly being developed and researched. In this article, we discuss two current clinical trials that show some success in offering disease control in mesothelioma tumors.
One trial studied whether a metabolite, 3-O-Methylfunicone (OMF), produced by Penicillium pinophilum, could slow cell proliferation by stopping cell division and affect motility in solid mesothelioma tumors. The researchers concluded that OMF might have the potential to be an anti-tumor drug for treating mesothelioma.
Metabolites are small molecules that are a natural product of metabolism. Metabolites can also in the form of chemical compounds, such as OMF. Such metabolites, when introduced into the body, can prevent cell life and growth, including that of malignant cells. OMF is, in a sense, a metabolic poison for malignant cells but not normal ones.
Another trial investigated the utility of Zoledronate (ZOL) and two forms of interleukin (IL-2 and IL-18) combined as anti-tumor agents that could act as a treatment strategy for mesothelioma. What the researchers discovered was that with the addition of IL-18, gamma delta T cells expanded, creating a substantial antitumor effect.
More studies will be done to continue to develop and test alternative treatments in search of more effective therapeutic interventions. Hopefully, one day, not only will treatments lead to longer prognosis and higher quality of life, but also to a cure.
A recently published report from researchers at Harvard explores the viability of using transcription factor PAX8 as a marker for malignant pleural mesothelioma. Mesothelioma is a rare form of cancer caused by asbestos in which tumors form in the mesothelium, the protective sac that covers the hearts, lungs, and abdomen.
The study explored a marker that has been used in detecting ovarian serous neoplasms as they have been shown to have morphologic overlap with malignant mesothelioma. Mesothelioma generally has a very poor prognosis of less than a year from time of diagnosis. The hope is to find a sensitive and specific marker so that mesothelioma can be detected at earlier stages, thereby improving overall survival times.
Researchers were looking to see if PAX8 could reliably distinguish mesothelioma separate from Mullerian tumors, a type of serous ovarian cancer. PAX8 and the presence of h-caldesmon has been proven to be effective markers in the differential diagnosis of breast and ovarian cancers, and the goal was to determine if it could be as successful in identifying mesothelioma tumors.
Unfortunately, the conclusion of the study was that the presence of staining for PAX8 h-caldesmon was weak and therefore not recommended as being useful in the differential diagnosis of mesothelioma. Research will continue to search for effective markers. The full article is published in May edition of The American Journal of Surgical Pathology.
Mesothelioma has a poor prognosis, with a median survival rate of less than nine months from time of diagnosis. Beyond being difficult to diagnose in early stages, mesothelioma has been shown to be resistant to standard therapies. Research continues to focus of finding new diagnostic methods and more effective treatments to extend survival times and improve quality of life for patients diagnosed with mesothelioma.
Recent research from Genoa, Italy suggests that a better understanding of the biology of mesothelioma may lead to new therapeutic strategies for treating the disease. The goal of the study was to examine cell lines that could differentiate tumors and provide gene expression profiles that would aid in diagnosing pleural meosthelioma.
Using human pleural mesothelioma cell tissue in vitro, the researchers were able to identify several markers that had strong positive correlation with mesothelioma. The four main markers were:
· Mesothelin (MSLN)
· Calretinin (CALB2)
· BMI-1, a stemness marker, and
· DKK1, a WNT inhibitor
The scientist suggest further research into the biology properties of mesothelioma tumor cell lines as these could be useful markers for the diagnosis and prognosis of mesothelioma. The full study results are published in the latest edition of BioMed Central.