Mesothelioma Research Program
By BRENDA O’SULLIVAN, Research Coordinator,
Mesothelioma Research Program, University Health Network
Following is an update of the progress
which has been made over the past six months in the Mesothelioma Research
Program at the Princess Margaret Hospital/University Health Network. Three
distinct but inter-related projects are encompassed within the program.
Progress in each of these will be summarized individually.
THE EARLY DETECTION PROGRAM
This study was launched in March 2005 and,
in the first year, has enrolled over 263 individuals with either a strong
history of asbestos exposure at least 20 years previous or chest x-ray evidence
of asbestos exposure.
Enrolment has been brisk, thanks mainly to
the support of the Sarnia Occupational Health Clinic, the Insulation and
Asbestos Workers Union, Local 95 of Ontario and the Research Program
coordinator. Each person enrolled in the study undergoes a comprehensive
interview questionnaire focusing on asbestos exposure history and other
possible contributing factors. A small sample of blood is then obtained to be
used for future biomarker studies, followed by a low-dose computer tomography
(CT) scan of the chest.
Results from the first 120 people in the
study were presented at the International Mesothelioma Symposium in
Cappadocia-Antalya Turkey. Out of 120 CT scans, three required immediate
intervention resulting in the diagnosis of one mesothelioma, one lung cancer
and one benign fluid collection.
Because of suspicious findings in the
airways of two individuals, repeat CT scans will be obtained in three months.
Finds on 35 scans were worrisome enough because of changes either in the lung
or on the pleura to warrant repeat scans in six months. Ten of those repeat
scans have been done and fortunately show no evidence of progression. Eight
scans, or two-thirds of the total, had no worrisome features and these people
will undergo a repeat scan in one year.
The program will continue to enrol subjects
at a rapid rate and actively recruit individuals from other high risk
occupations.
THE TRI-MODALITY TREATMENT TRIAL
As a pilot study over the past five years,
the Princess Margaret Hospital has treated 39 patients with pleural
mesothelioma with potentially curative therapy. This very aggressive treatment
regimen includes three cycles of chemotherapy followed by an extensive surgical
procedure in which the entire lining of the chest cavity (the pleura) is
removed, along with the lung, and portions of the diaphragm and pericardium.
Following recovery from the surgery the
patient then undergoes radiation to the entire side of the chest originally
involved with the cancer. Results from these first 39 patients have been
accepted for publication in the Journal of Thoracic and Cardiovascular Surgery.
They show that 40 per cent of patients responded to chemotherapy, with 15 per
cent having major side effects. Of the 38 patients who underwent surgery, the
tumour was too extensive to remove in five, but in the 33 who were resected, 31
(94 per cent) had removal of all visible cancer. Three of the 33 died from
complications of the surgery and 25 went on to receive radiation therapy. In
those patients who had complete resection of their tumour, over 40 per cent
were alive after four years of follow-up.
BASIC RESEARCH STUDIES
A variety of basic research studies are now
underway or in the advanced planning stages. A soluble protein in the blood,
named mesothelin, has been reported to be elevated in patients with known
mesothelioma and look for elevated levels in the blood of patients enrolled in
the early detection study.
It is hoped that this protein, along with
others that have recently been identified, can accentuate the sensitivity of
low-dose CT scanning for diagnosing early tumours. Another project takes the
tumour tissue from patients with mesothelioma and implants this tissue in the
pleural space (chest) and peritoneal space (abdomen) of laboratory mice.
These mice have poorly developed immune
systems and therefore do not reject the foreign tumour. If the tumour grows in
a reproducible fashion, the tumour can be transplanted into more mice and
studies can be conducted to evaluate new treatment methods, such as drugs or
immunotherapy. The genomic difference between tumour cells and normal mesothelial
cells can also be researched. Currently, the projgram was two mesothelioma
tumour lines growing in mice and are planning to add more as tumour tissue
becomes available.
