Dr. James Stevenson, M.D.
The Importance of Mesothelioma Research
Mesothelioma is a rare cancer that has around 3,000 newly diagnosed cases in the United States each year. Due to its rarity, there isn’t as much data around mesothelioma as there is for other, more common cancers, such as lung cancer. Malignant mesothelioma research plays a crucial role for patients for a variety of reasons.
Improved Diagnostic Tools
Early detection can strongly influence prognosis for mesothelioma patients. If the disease is caught in the early stages, more treatment options are available. Treatments can also be more aggressive, and patients typically face better survival rates than those diagnosed at stage 3 or stage 4.
Blood Tests and Biomarkers
One of the largest improvements in diagnostic tools has been blood tests and biomarkers. Researchers continue to find biomarkers, or substances in the blood, that can suggest a mesothelioma diagnosis, show symptoms of mesothelioma or demonstrate a history of asbestos exposure, the only known cause of the disease. One of the newest biomarkers is HMGB1, with one study distinguishing between those with mesothelioma, those with a history of asbestos exposure but no mesothelioma and those with a history of asbestos exposure with mesothelioma. While blood tests cannot diagnose the cancer on their own, they can prompt physicians to conduct imaging scans and biopsies.
Mesothelioma Breath Test
Researchers continue to look for improved early diagnostic tools, one of which has been a mesothelioma breath test. More research is required, but a collection of case studies has found that the gas chromatography-mass spectrometry is a component of the breath test that can differentiate between at-risk, asbestos-exposed individuals and malignant pleural mesothelioma patients with 97% accuracy.
Emerging Treatments and Clinical Trials
Most malignant mesothelioma patients face survival of less than one year. However, advancements in treatment offer hope in improving prognosis. Before becoming a treatment option, newer treatments are tested in clinical trials. Patients must meet certain criteria to participate, but clinical trials are often an option for those not responding to the standard of care. If successful, clinical trials have the potential to gain FDA approval and status as a first- or second-line treatment option.
Newer treatments that have shown some success include gene therapy, immunotherapy and photodynamic therapy. Photodynamic therapy, in particular, has been a focus of many recent studies, showing success in extending survival of stage 3 patients to up to 7.3 years after diagnosis when used intraoperatively, in combination with surgery and chemotherapy.
Improved Standard Treatments
Advancements have also been made to existing standards of care, including surgery, chemotherapy and radiation, and how they are used together. Mesothelioma specialists continue to test and improve efficacy of these treatment plans.
Chemotherapy and Immunotherapy
The National Comprehensive Cancer Network (NCCN) recently updated their guidelines to include a combination of Alimta®, cisplatin and bevacizumab as a first-line treatment, combining chemotherapy drugs with a drug that targets tumor blood vessels. The NCCN recognizes that this is only an option for patients not eligible for surgery. In a recent study of 448 patients, half treated with all three drugs and half treated without bevacizumab, overall survival improved for those treated with the full combination. The combination of three extended survival to 18.8 months on average, while the combination of just Alimta® and cisplatin had an average survival of 16.1 months. Immunotherapy drugs such as pembrolizumab and nivolumab/ipilimumab have also shown effectiveness as second-line options for patients whose mesothelioma has progressed after front-line treatment, and are now included as recommended therapies in current NCCN guidelines.
Innovative Radiation Therapies
Researchers of radiotherapy and mesothelioma have also looked into how it can be used more effectively when combined with surgery. Studies have shown that Surgery for Mesothelioma After Radiation Therapy (SMART) with intensity-modulated radiation therapy has been able to extend survival to 51 months, on average. This treatment plan begins with radiation therapy and follows with surgery, an extrapleural pneumonectomy. Researchers and advocates of SMART continue to try and improve the efficacy of this option, also finding success in the combination of radiation therapy and immunotherapy prior to surgery. Radiation therapy, called IMRT, applied to the pleural surfaces after lung-sparing pleurectomy has also been investigated and found to be safe with promising effectiveness.
Resources for Mesothelioma Patients
Improved Palliative Care
Palliative care plays an important role in mesothelioma treatment, helping reduce symptoms for patients. As cancer cells spread throughout the body, patients typically experience more symptoms, as well as side effects from treatments. Palliative care can offer symptomatic relief and a higher quality of life.
Mesothelioma case studies continue to analyze the effectiveness of particular palliative treatments for both mesothelioma patients and mesothelioma survivors. For example, recent studies have looked into the palliative effects of radiation therapy on pleural mesothelioma patients. In one study, palliative radiotherapy was reported to help with pain management and improve quality of life for 50 – 60% of mesothelioma patients. Researchers continue to look into how radiation therapy can be used palliatively on its own and in combination with other treatment techniques.
Pleural mesothelioma is the most common type, making up around 80 – 90% of all cases, followed by peritoneal with 15 – 20%, pericardial with 1 – 2% and testicular mesothelioma with less than 1%. There are also rare cell types that affect even fewer individuals. Case studies most commonly cover malignant pleural mesothelioma, but research is still limited.
As more cases of mesothelioma emerge, new case studies are conducted and the number of cases analyzed increases, researchers can better understand mesothelioma statistics, cancer progression, successful treatments, risk factors and other information that will improve the diagnosis and treatment of the disease.
Mesothelioma and Genetics
One study of interest is genetics and mesothelioma. Studies throughout the past decade have looked into how genetics may be able to identify individuals that are more at risk to develop mesothelioma and other asbestos cancers. During histology, specialists can look at patient DNA to observe chromosomal losses and gains, pinpointing connections in cases of patients with malignant mesothelioma. More research is needed to determine their efficacy in assisting with diagnosis and prognosis of the disease.
The BAP1 gene is a tumor suppressor gene that has shown links to pancreatic cancer, ovarian cancer, breast cancer and malignant mesothelioma. Studies have found a large number of malignant mesothelioma cases have demonstrated mutation of the BAP1 gene. One recent study looked at both benign and malignant mesothelioma tumors and was able to detect malignancy with 100% accuracy using a BAP1 immunostain, offering much promise to help with early detection. Over the past few years, researchers have also seen a connection with BAP1 gene mutations and prognosis, demonstrating poor survival in mesothelioma patients with no gene expression, though more research is needed.
Along with other types of cancer, p53 gene loss has assisted with detection of malignancies and research for a cure continues to look into how repairing damages to the gene sequence may be able to help treat the disease. Another study took pleural fluid samples from a series of patients and found a loss of chromosome 9 expression (CDKN2A/ARF) in 72% of mesothelioma cases and a deletion of 9p in all cases of patients that had a history of asbestos exposure, suggesting that these genes can help identify patients that are at-risk of developing the disease.
Chromosomal Losses Linked to Mesothelioma
- Chromosome 14q
- Chromosome 13q
- Chromosome 11q23
- Chromosome 4q
- Chromosome 6q
- Chromosome 22q (NF2 and Merlin protein)
The Need for Continued Mesothelioma Research
Diagnostic tools and treatment options for mesothelioma, as well as understanding of the disease have improved throughout the years. However, there is still a large need for more data, tools to help with early detection, better treatment options and a cure for the cancer, stressing the importance of continued mesothelioma cancer research.
Research is crucial not just for physicians when addressing and treating the disease, but for patients and their loved ones seeking to better understand their diagnosis, treatment options and prognosis.
The mesothelioma community is comprised of many survivors, patients, loved ones, specialists, researchers, organizations and foundations dedicated to raising awareness of the disease and funding to continue research efforts.
Selected Mesothelioma Research Studies
- 2018 Update on Mesothelioma Diagnosis, Staging and Treatment Guidelines
- A retrospective cohort study to evaluate patient survival in sarcomatoid mesothelioma receiving best supportive care, chemotherapy and palliative radiotherapy
- ASCO: Study Confirms Pemetrexed-Platinum Activity in Malignant Mesothelioma
- Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin®Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial.
- First-in-human Phase 1 CRISPR Gene Editing Cancer Trials:Are We Ready?
- High-Quality Results of Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy Perfusion for Carcinomatosis at a Low Volume Institution
- Induction radiotherapy and mesothelioma surgery
- Malignant pleural mesothelioma: a comprehensive review.
- Malignant pleural mesothelioma in pregnancy.
- Mesothelioma and lung tumors attributable to asbestos among petroleum workers.
- Mesothelioma diagnosis and prognosis, are we moving beyond histology and performance status towards circulating biomarkers?
- Mesothelioma in patients with nonoccupational asbestos exposure. An evidence-based approach to causation assessment.
- New Concepts in the Treatment of Malignant Pleural Mesothelioma
- Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial
- Nintedanib shows promise for malignant pleural mesothelioma
- Perineural spread of malignant mesothelioma resulting in an intradural spinal cord mass: case report.
- Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.
- Photodynamic Therapy for Lung Cancer and Malignant Pleural Mesothelioma
- Photodynamic therapy for malignant pleural mesothelioma: the future of treatment?
- Probability of Cancer in Pulmonary Nodules Detected on First Screening CT
- Prognostic value of FDG PET imaging in malignant pleural mesothelioma.
- Sex difference in diffuse malignant peritoneal mesothelioma.
- Surgery in Malignant Pleural Mesothelioma
- Targeted next-generation sequencing of malignant pleural mesothelioma identifies recurrent NRAS oncogene mutations
- The genetic susceptibility in the development of malignant pleural mesothelioma
- The Impact of Malignant Pleural Mesothelioma Histology on the Use of Surgery and Survival in a Population-Based Analysis
- Tyler Asbestos Workers: Mortality Experience in a Cohort Exposed to Amosite
- Updates in the diagnosis and treatment of malignant pleural mesothelioma