Traditional Treatments:
Mesothelioma is an uncommon cancer and, to date, a cure remains elusive. Since mesothelioma is such a rare form of cancer, it is rarely seen in most medical centers. Members of the Brigham and Women's Hospital Thoracic Surgery Division have extensive experience in treating patients with mesothelioma. It is important that patients with mesothelioma are treated at centers with expertise in MPM to maximize expertise and allow innovative treatment combinations to be implemented with the greatest chance of success.
Specialists at the International Mesothelioma Program (IMP) have more than 20 years of experience in treating mesothelioma and offer the full spectrum of conventional and novel therapies, personalized to each individual patient and cancer, in a caring and compassionate environment. Treatment includes precise diagnosis, state-of-the-art multimodality therapy, and supportive care for patients and their families.
In addition to providing state-of-the-art therapies, IMP clinicians also are committed to providing personalized care – that is, tailoring treatment strategies to address the individual disease of each patient. Two new tests will help clinicians tailor therapy for their patients. The first, known as the EDR (Extreme Drug Resistance) assay, provides information on whether an individual patient’s tumor is likely to be resistant to standard mesothelioma chemotherapeutic agents and allows doctors to adjust treatment accordingly. The second test is a research breakthrough of the IMP Thoracic Surgery Oncology Laboratory. This four gene ration test predicts whether an individualpatientis likely to benefit from standard trimodalitymesothelioma therapy based on ratio of gene expression. When combined with other patient specific information, the test allows surgeons to predict with a high degree of certainty which patient will respond favorably to surgery and which should consider for more aggressive experimental therapy. Our researchers hope to make this test available to patients in the near future.
Diagnosis
The foundation for mesothelioma treatment is precise diagnosis. The disease can be challenging to diagnose, and IMP pathologists bring a wealth of experience to the task. The evaluation process includes medical history, any history of asbestos exposure, a careful physical examination, lung function tests, and a variety of imaging techniques. If any of these tests indicates the presence of mesothelioma, a biopsy is taken to confirm the diagnosis.
Once mesothelioma is confirmed, the next step is to check for lymph node involvement to determine the extent of disease. The technique used is cervical mediastinoscopy, a surgical procedure that enables biopsy of lymph nodes from the central compartment of the chest cavity. Following diagnosis and staging, the treatment team develops personalized therapeutic strategies that may encompass surgery, chemotherapy, radiation, and palliative procedures, for every patient.
Clinical Care
There is no known cure for mesothelioma and there exists no universally accepted standard therapy.Options for therapy include surgery, chemotherapy, radiation therapyand combined approaches, utilizing multiple types of therapy. However combination approaches (named multimodality therapy) utilizing surgery, chemotherapy and radiationtreatments have shown promise in extending survival of some patients with early disease.
The goal of surgery is to remove all visible tumor. Maximal tumor removal is the primary contributor to extension of life. Surgical options include pleurectomy(P/DC), removal of the lining of the chest, or extrapleural pneumonectomy (EPP), removal of the affected lung along with the lining of the chest (pleura), portions of the covering of the heart (pericardium), and the diaphragm. Following surgery, additional treatments (adjuvant treatment) including radiation and/or chemotherapy are offered to enhance local and systemic control of disease.
Chemotherapy may be used to control cancer by killing tumor cells, slowing tumor growth, or inhibiting its spread (metastasis); to shrink tumors prior to other therapy such as surgery (neoadjuvant therapy); to destroy cancer cells that remain after another treatment (adjuvant therapy); or to relieve symptoms (palliative care).Chemotherapy drugs may be given as single agents, but often, two or more drugs are given simultaneously (combination therapy).
IMP clinician-scientists have pioneered a novel way to administer chemotherapy to improve the effectiveness of treatment. This strategy involves surgery to remove all visible disease, followed by perfusion of the chest cavity with a heated bath of the chemotherapy drug or drugs (intracavitary lavage). Heating enhances drug uptake and works synergistically with the cisplatin to increase tumor cell death. In addition, other drugs are administered to protect normal cells from the chemotherapy agents and reduce systemic side effects.
Mesothelioma Surgery and Staging
Chemotherapy
Adjuvant Therapy
Palliative Therapy
Radiation Therapy
Pleurodesis - One of the most common, first symptoms of mesothelioma is shortness of breath. This is usually caused by the buildup of fluid (pleural effusion) between the tissue covering the lung and lining the chest wall (pleura). The fluid stops the lung from fully expanding , so as it builds up, the collected fluid will cause shortness of breath.
A surgical procedure, called a pleurodesis, can stop this fluid from building up and help relieve the symptoms. It seals the space between pleura with either sterile talc or an antibiotic. The idea is to put in something that will irritate the pleura causing them to stick together, preventing fluid buildup.
Pleurodesis is a palliative surgical procedure since it treats a symptom of mesothelioma, but does not treat the disease.
Mediastinoscopy
A surgical procedure that enables visualization and biopsyof lymph nodesin themediastinum .
Mediastinoscopy is often used for staging (The process used to find out if cancer has spread outside the pleurais called staging).
Mediastinoscopy procedure involves making an incision approximately 1 cm above the suprasternal notch of the sternum(breast bone). After dissection,a scope (mediastinoscope) isadvanced into the created tunnel which provides a view of the mediastinum (direct visualization or may be attached to a video monitor).
Mediastinoscopy provides access to mediastinal lymph node levels 2, 4, and 7.
MesotheliomaStaging
The information gathered from the staging process determines the stage of the disease.Thetreatment plan is based on the spreading of the cancer. The following tests and procedures may be used in the staging process: Chest x-ray,CT scan,Pet, MRI (magnetic resonance imaging), mediastinoscopy, Endoscopic ultrasound (EUS) may be used to guide fine-needle aspiration (FNA) biopsy of the lung, lymph nodes, or other areas.
Pneumonectomy - Traditional pneumonectomy involves removing only the diseased lung. Most often, a pneumonectomy is done to remove lung cancer. Patients with mesothelioma generally are candidates for an extrapleural pneumonectomy.
Extrapleural Pneumonectomy - Extrapleural pneumonectomy (EPP) is a surgical procedure that involves the removal of the lung along with its coverings and the associated coverings of the heart and diaphragm. Of all treatment approaches attempted, extrapleural pneumonectomy has been most consistently associated with long-term disease-free survival and has provided for the greatest amount of cytoreduction. Also, with the lung removed, a higher amount of radiation can be delivered.
EPP Procedure - Once the patient is under complete general anesthesia, an incision will be made extending from below the shoulder blade, around the side along the curvature of the ribs to the front of the chest on the side of the diseased lung (thoracotomy). The surgeon also may remove the sixth rib to help expose the lung and to obtain enough working space.
Next, the surgeon will collapse the diseased lung and tie off its major blood vessels. The lung's main bronchial tube (air tube) will be clamped and cut and the lung removed. The cut end of the bronchial tube either is closed with staples or tied off with sutures (stitches).
Next, the pleura will be carefully removed from the chest wall. Parts of the pericardium and diaphragm will be cut away on the affected side and replaced with patches made of Gore-Tex, a safe, synthetic material. After confirming that the closed end of the bronchial tube is not leaking air, the surgeon will close the chest incision with sutures, leaving a temporary drain in the chest cavity.
After surgery, the patient will be taken to the surgical intensive care unit (ICU). For the first 24 hours, a respirator may assist breathing, although many patients do not require it, and a chest drainage tube will remain in place. Once considered stable, usually within a few days, the patient will be transferred to a regular hospital room. Patients will be hospitalized between one and two weeks. All patients receive an epidural to control their pain.
Pleurectomy - The goal of pleurectomy is to remove the tumor while preserving the lung. Pleurectomy involves the removal of the tumor and the lining around the lung (visceral pleura) and chest wall (parietal pleura) and can include removal of the lining around the heart and the diaphragm.
Pleurectomy Procedure - An identical thoracotomy is performed as in an EPP. The parietal pleura is first dissected off the chest wall and then the mediastinum. The visceral pleura (surrounding the lung) is then opened and removed. Although the procedure can allow extensive debulking (removal of tumor), it is not generally possible to attain complete removal of all tumor with this procedure.
A pleurectomy can control fluid accumulation and decrease pain. The treatment is generally considered to be palliative, that is, it decreases pain but is not a cure. In early stages of mesothelioma, when a pleurectomy is combined with other treatments such as radiation and chemotherapy, it may improve the length of survival.
Peritoneal Mesothelioma - Complete surgical removal of peritoneal mesothelioma is rarely possible, and most commonly, operative intervention is used to provide palliation (treatment aimed at relieving the symptoms and pain) for intestinal obstruction (blockage of the bowel preventing the passage of material).
If there is no evidence of obstruction, then significant palliative and possible curative cytoreductive surgery in combination with intraoperative, intraperitoneal heated chemotherapy at the time of surgery may be performed. This technique permits the administration of high concentrations of selected drugs into the abdominal and pelvic surfaces. The drug makes contact with all the peritoneal surfaces of the tumor-resected areas. This procedure is used to kill any of the cancer cells left behind while minimizing harm to the normal body cells.
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Chemotherapy uses drugs that interfere with the cancer cells' ability to divide and reproduce. Depending upon the kind of cancer and its stage of development, chemotherapy can be used to control the cancer by preventing its spread or slowing its growth; by shrinking tumors prior to other treatments, such as surgery (neoadjuvant therapy); by destroying tumor cells left behind after surgery (adjuvant therapy )by relieving symptoms, such as pain (palliative therapy)
The most common method of delivery of chemotherapy drugs is by injection into a vein; however, depending on the type of cancer and the drug used, delivery can be by mouth, into the muscle, or into the skin or by placing them directly into a body cavity (intracavitary chemotherapy)
Most chemotherapy drugs cause fatigue or even exhaustion. Other side effects may include nausea, vomiting and hair loss. Specific side effects will depend upon the drug(s) prescribed, the dosage, and the length of treatment. Medications can be given to minimize these effects.
Combination Chemotherapy - Various combination chemotherapy regimens have been reported to have higher response rates in small phase II trials. Raltitrexed combined with oxaliplatin has also been shown to be effective, and gemcitabine--applied as a single agent or in combination with cisplatin--as well as vinorelbine appear to improve quality of life in patients presenting with mesothelioma. The most active and best-studied drug combination for the treatment of mesothelioma that has emerged is the combination of Alimta and Platinol® (cisplatin) and will probably be adopted as a “standard” for comparing other treatments. The only phase III randomized study of chemotherapy for mesothelioma ever performed was the comparison of Alimta® and cisplatin to cisplatin alone.
Alimta® and Platinol® (cisplatin)
In this study, a total of 456 patients were enrolled from April 1999 to March 2001. Patients were randomized to receive either the combination Alimta® and cisplatin or cisplatin alone. Patients treated with the Alimta®/cisplatin combination lived longer (12 months vs. 9 months) and experienced a longer time gap before the cancer progressed. The average survival and time to cancer progression was further improved by giving a vitamin supplementation of B12 and folic acid. In addition to a longer survival time and the ability to control the disease, patients assigned to the Alimta® /cisplatin combination reported an improvement in quality of life and symptom relief (including pain, shortness of breath, fatigue, weight loss and cough) when compared with cisplatin alone.
While many regimens are being tested for the treatment of mesothelioma, there is still room for development of new agents or combinations of agents. Currently, the addition of Gemzar® to Alimta® is being evaluated in clinical trials and could be compared to Alimta® and cisplatin or Alimta® and Paraplatin®. Other combinations, including cisplatin and gemcitabine, have also shown encouraging response rates and clinical activity.
Targeted agents, developed through a better understanding of the biology of the disease either used alone or as part of multimodal therapy, may provide major clinical advances in the next few years. Studies are also underway for second line chemotherapy treatment regimens for those patients who fail chemotherapy the first time.
Patients evaluated at the Brigham and Women’s Hospital and Dana-Farber Cancer Institute are offered multiple treatment options. Patients are offered chemotherapy alone. If eligible for surgery, patients will be offered a combined modality approach, including surgery, chemotherapy and radiation. Our most important consideration is to tailor the best treatment for every patient.
Single Agent Chemotherapy - Mesothelioma is relatively chemoresistant. Most single chemotherapeutic agents have demonstrated response rates less than 20% and are associated with significant toxicities. Although no single agent has been shown to have an effect on overall survival, the following single agents appear to be active against mesothelioma: 5-fluorouracil, methotrexate (high dose), timetrexate, doxorubicin, epirubicin, cyclophosphamide, ifosfamide, mitomycin C, Platinol® (cisplatin), interferon, and Alimta®. Single-agent therapy with vinorelbine may provide useful relief of symptoms with low toxicity. The accepted “standard” single agent for the treatment of mesothelioma is cisplatin. Recently, various drug combinations have been explored and appear to be more active than current single drug regimens.
Development of the chemotherapy drug Alimta® (pemetrexed) has constituted a major step forward in the treatment of mesothelioma. Alimta® is related to methotrexate and was evaluated as a single agent drug in a phase II multi-center trial carried out in the U.S., Germany, and Italy with a reported response rate of 16%.
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When radiation and/or chemotherapy are administered after surgery, they are called adjuvant therapies. Research suggests that patients in good condition with stage I-III malignant pleural mesothelioma should be treated with adjuvant chemotherapy and/or radiation therapy.
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Palliative care addresses physical, psychological, social and spiritual sources of distress for patients with advanced or life-threatening disease and their families. The goal of palliative care is to provide comfort and to maintain the highest possible quality of life for as long as life remains.
Those diagnosed with mesothelioma experience a variety of different symptoms. Often, the level of pain experienced with mesothelioma is very high. Pain control is usually one of the first symptoms addressed with mesothelioma palliative care. Palliation can include the traditional pain management programs, such as prescribing several different pain medications, but it also can focus on behavior modification, stress management, meditation, or even massage therapy. Palliative surgery can be done to reduce pain caused by the tumor or to prevent fluid from accumulating. Studies have shown that radiation therapy is useful in relieving pain due to mesothelioma. Palliative care can be a sound choice to increase the remaining quality of life for patients who suffer from mesothelioma.
At the Brigham and Women’s Hospital, patients will have the opportunity to enrol in a quality of life protocol in which patients will undergo bi-weekly palliative care assessment and symptom management. Patients will be assessed and treated by skilled palliative care practitioners, teaming with the oncology team, anesthesia pain specialists and psychologists. The techniques and methods are available to make sure that every patient with mesothelioma can have adequate pain control at any stage of the disease.
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Radiation therapy uses high-energy rays to damage or kill cells by preventing them from growing and dividing. It is delivered to the site of the tumor by machines called linear accelerators, which produce high-energy external radiation beams that penetrate the tissues deep into the areas where the cancer is located. This technique is called external beam radiation therapy (EBRT). Radiation therapy also can palliate the symptoms of mesothelioma by reducing pain, improving breathing, or relieving other side effects caused by the cancer.
Factors that can limit the application of this treatment include the volume of the tumor and how near it is to vital organs. Radiotherapy following surgical resection (adjuvant therapy) has been shown to reduce local cancer recurrence and improve the survival of patients with early-stage disease and is an essential part of the management of patients undergoing extrapleural pneumonectomy.
EBRT is delivered precisely by using computed tomography (CT) scan as well as PET scans to localize the areas at risk for tumor recurrence. Careful radiation planning allows for a higher dose of radiation to be directed at the tumor tissue and at the same time, decreasing the volume of normal tissue exposed to this high dose. Our faculty in radiation oncology has over 15 years of experience in treating mesothelioma patients with radiotherapy.
Intensity-modulated radiation therapy (IMRT) is a novel breakthrough in radiation oncology. It allows treatment of areas that were previously out of the reach of conventional radiation. IMRT for mesothelioma is availableatBWH one of the few sites in the country where this technique has been perfected. It requires a treatment team composed of radiation oncologist, physicists and radiation therapists to deliver. The state of the art machinery available hereat BWH represents the top-of the line in radiation delivery equipment. Preliminary data indicates significant improvements in local recurrences for mesothelioma patients undergoing this treatment.
New clinical trials investigating the optimum method for combining chemotherapy and radiation are underway at BWH/DFCI.
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The lack of any single consistently curative treatment for mesothelioma has led to the development of multi-modality therapy, including surgery, radiation therapy, and chemotherapy. The long-term survivors of MPM have been cured with radical surgical extirpation (EPP or PDC) often followed by radiation therapy and or adjuvant chemotherapy. Back to the Top
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