Although mesothelioma is a relatively rare disease in the general population, it is not uncommon in workers—or their families—from a number of different professions, such as mining, ship building and automotive break construction and repair. Every year thousands of people are diagnosed with mesothelioma and doctors and epidemiologists know that even more will be diagnosed in the years to come. Asbestos was in heavy use during much of the 20th century and the delayed response of many countries in banning, or strictly regulating, its use means that the incidence rate of the disease’s most common forms—pleural mesothelioma and peritoneal mesothelioma— is expected to keep rising during the forseeable future. Because of these difficult facts, research dedicated to improving the traditional modalities of mesothelioma treatment continues in diverse institutions from countries all over the world.

Historically, the efficacy of the most common treatments for mesothelioma have been a great disappointment to patient and doctor alike. In many studies, median survival from time of diagnosis has been less than one year. In recent years, however, we’ve seen improvements in the surgical methods that are deployed for treatment, as well the introduction of Alimta therapy in many countries, which has increased the effectiveness of chemotherapy in treating mesothelioma. Single modality therapy has not, however, shown a general effectiveness for the curative treatment of the disease, so multimodal therapies utilizing a combination of the traditional approaches were developed and now many physicians feel that these therapies should be considered the standard approach to mesothelioma treatment.

Even as doctors have decided upon multimodal therapy as the treatement standard, there is still considerable controversy regarding which combinations are the most effective for the overall treatment of the disease and many institutions are actively exploring just this question. Researchers from the Netherlands have recently released the results of a study they conducted which compared the efficacy and morbidity results of patients who underwent some form of cytoreductive surgery—either an extrapleural pneumonectomy (EPP) or a pleurectomy/decortication (PD)—with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) then followed by radiation therapy to the thoractomy scar and drainage tracks to a cohort of patients who received an EPP and then postoperative hemithoracic radiation.

Overview of the Study

The authors compared two cohorts of patients who underwent multimodal treatment for pleural mesothelioma at their institution, the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital in Amsterdam. To be eligible for admission into either treatment cohort, patients had to meet specific admission criteria after workup, which included thoracoscopic biopsy and mediastinoscopy, as well as CT. Only patients who presented with Stage I or II disease with epitheloid or biphasic histology were allowed admission. Patients were denied these treatments if any of the following were found: “distant metastasis, mediastinal lymph node involvement and chest invasion, clinical or radiological retraction of the hemithorax, excessive weight loss... and a poor general condition.”

In the first cohort of patients, treated between January 1999 to December 2001, 20 people underwent cytoreductive surgery, HITHOC and radiation. For this cohort, 12 patients received PD and 8 received an EPP. After the actual surgery was completed, but still during the same operation, the patients received intrathoracic perfusion chemotherapy, consisting of cisplatin and adriamycin. As the final step in this process, each patient received radiotherapy with a total dose of 24 Gy to the thoractomy scar and drainage tracts.

The second cohort was treated between January 2002 and September 2005. This cohort was made up of 15 patients who were treated with EPP and then postoperative hemithoracic radiation. Unlike the Sugarbaker method, which suggests the total resection of the diaphragm and pericardium along with the affected lung and other adjacent tissues, the EPPs as performed by the authors only removed the parts of the diaphragm and pericardium where tumor was present. After the surgery was completed and the patient given ample time to heal up, external beam radiotherapy was applied to the entire hemithorax. The total dose delivered was 54 Gy, given in 1.8 Gy or 2 Gy daily fractions.

Results

The patients who received EPP with RT fared significantly better than did the patients from the other cohort. Median survival for the EPP/RT group was 29 months, while median survival for the HITHOC patients was 11 months. The EPP/RT group also scored much better on disease-free survival, with a median value of 21 months as compared to 8 months for the other group. 11 patients in the EPP/RT group experienced mesothelioma recurrence, compared to 18 in the HITHOC group. At the time of the last follow-up, 4 of the EPP/RT patients were alive. Three showed no sign of disease (23,40,54 months after surgery), while one had tumor recurrence, but was still alive 59 months after surgery. This compares to one HITHOC long-term survivor, who was still alive 65 months after surgery.

Besides the overall survival figures, recovery time and postoperative complications are another important metric of treatment utility. Here as well, the EPP/RT was better off than the HITHOC group. The EPP/RT group was a little quicker to leave ICU than was the other group, but both cohorts experienced similar days for total post-op stay. The EPP group only experienced two hospital readmissions, while seven patients from the HITHOC cohort required readmission. The EPP/RT group experienced fewer complications, 8 vs. 14, than did the HITHOC group. There were no deaths within 30 days of surgery, but two HITHOC patients died months later from complications directly linked to the surgery. 1 patient from the EPP/RT group died 6 months post-operatively, but the cause of death was never determined.

Conclusion

The authors conclude their study by summarizing a number of recent studies on the multimodal treatment of mesothelioma and they place their results within the context of those findings. The results for their EPP/RT group, where a median survival of 29 months was achieved as compared to the traditionally reported median value of 12 months, signal that this combination of therapies should be further studied. However, the same positive statement could not be made for the HITHOC cohort of patients. In fact, the authors note that the poor results returned for the HITHOC group tell them that the treatment is neither safe, nor effective and they conclude that it should be avoided in the future.

As with all research programs, further research needs to be accomplished to verify the results that were obtained in this study. However, the goal of improving upon mesothelioma treatments is slowly moving forward and doctor and patient alike can look upon the results of this study as an important step in this process.

Labels: mesothelioma