Kimura T, Koyama K, Kudoh S, Kawabe J, Yoshimura N, Mitsuoka S, Shiomi S, Hirata K.

Department of Respiratory Medicine, Osaka City University, Osaka. kimutats@med.osaka-cu.ac.jp

Abstract

We report a 56-year-old man who underwent monitoring of the response to chemotherapy of malignant pleural mesothelioma (MPM). ⁸F-fluoro-2-deoxy-_D-glucose positron emission tomography (FDG-PET) and computed tomography (CT) were performed prior to chemotherapy and after the first and second courses of chemotherapy. The tumor lesion exhibited shrinkage on CT and a decrease in the standardized uptake value (SUV) max after the first course of chemotherapy, but exhibited size enlargement and an increase in SUV max after the second course of chemotherapy. These findings suggest that results of quantification of metabolic response by FDG-PET are related to the objective response as determined by CT in patients with MPM.

Keywords: FDG-PET, mesothelioma, SUV, response

Glossary

lesion

(lee-zhun) a change in body tissue; sometimes used as another word for tumor.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

tumor

an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

Saito Y, Furukawa T, Arano Y, Fujibayashi Y, Saga T.

Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 263-8555, Japan.

Abstract

Introduction: Various techniques are available for in vivo imaging, and precise understanding of their characteristics is essential for effective use of the imaging results. We established human mesothelioma cell lines expressing red fluorescent protein (RFP) and examined their fluorescence intensity and uptake of positron emission tomography (PET) tracer analogs to compare their characteristics and assess their usefulness in the evaluation of therapeutics.

Method: A human mesothelioma cell line was stably transfected to express RFP. Fluorescence, cell number and protein amount were measured during cell growth and treatment with cytotoxic reagents. In in vivo experiments, RFP-expressing cells were injected subcutaneously or into the pleural cavity of nude mice, and fluorescence images were taken with or without pemetrexed treatment. The uptake of [³H]3′-deoxy-3′-fluorothymidine ([³H]FLT) and [¹⁴C]2-fluoro-2-deoxy-d-glucose ([¹⁴C]FDG) under treatment with the above reagents in vitro and in vivo were examined.

Results: Strong correlation was observed between fluorescence intensity and total cell number with or without cytotoxic treatment. The uptake of [³H]FLT and [¹⁴C]FDG decreased rapidly after the initiation of treatment with actinomycin D or cycloheximide. When treated with pemetrexed, the uptake of [³H]FLT temporarily increased. The cells formed subcutaneous and orthotopic tumors, with fluorescence intensity correlating with tumor volume. The correlation was sustained under pemetrexed treatment. The uptake of [³H]FLT in vivo increased significantly early after pemetrexed treatment.

Conclusion: Fluorescence imaging could be used to semiquantitatively monitor tumor size, whereas PET could be used to monitor tumor response to therapeutic treatments, and especially, FLT might be a good marker of the response to anti-folate chemotherapeutics.

Keywords: Mesothelioma; Mouse tumor model; Fluorescence imaging; PET; FLT

Glossary

imaging

any method used to produce a picture of internal body structures. Some imaging methods used to detect cancer are x-rays (including mammograms and CT scans), magnetic resonance imaging (MRI), scintigraphy, and ultrasound.

cytotoxic

(site-o-tox-ik) toxic to cells; cell-killing.

cell

the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.

tumor

an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

Sørensen JB, Ravn J, Loft A, Brenøe J, Berthelsen AK; Nordic Mesothelioma Group.

Aaseboe U, Billing B, Bjørck T, Brodin O, Brunsvig P, Forsløw U, Frank H, Hansen O, Harving H, Hillerdal G, Jakobsen KD, Johansson A, Ladegaard L, Lindh B, Melgaard P, Mygind N, Månsson T, Palshof T, Sundstrøm S, Sørensen P, Vigander T.

Department of Oncology, Finsen Centre/National University Hospital, Copenhagen, Denmark. jens.benn.soerensen@rh.regionh.dk

Abstract

Objectives: Extrapleural pneumonectomy (EPP) in MPM may be confined with both morbidity and mortality and careful preoperative staging identifying resectable patients is important. Staging is difficult and the accuracy of preoperative CT scan, 18F-FDG PET/CT scan (PET/CT), and mediastinoscopy is unclear. The objectives were to compare these staging techniques to each other and to surgical–pathological findings.

Methods: Patients had epithelial subtype MPM, age ≤70 years, and lung function test allowing pneumonectomy. Preoperative staging after 3–6 courses of induction chemotherapy included conventional CT scan, PET/CT, and mediastinoscopy. Surgical–pathological findings were compared to preoperative findings.

Results: Forty-two consecutive patients were without T4 or M on CT scan. PET/CT showed inoperability in 12 patients (29%) due to T4 (7 patients) and M1 (7 patients). Among 30 patients with subsequent mediastinoscopy, including 10 with N2/N3 on PET/CT, N2 were histologically verified
in 6 (20%). Among 24 resected patients, T4 occurred in 2 patients (8%), and N2 in 4 (17%), all being PET/CT negative. PET/CT accuracy of T4 and N2/N3 compared to combined histological results of mediastinoscopy and EPP showed sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios of 78% and 50%, 100% and 75%, 100% and 50%, 94% and 75%, not applicable and 5.0, and 0.22 and 0.67, respectively.

Conclusions: Non-curative surgery is avoided in 29% out of 42 MPM patients by preoperative PET/CT and in further 14% by mediastinoscopy. Even though both procedures are valuable, there are false negative findings with both, urging for even more accurate staging procedures.

Keywords: Mesothelioma; Staging; PET/CT scan; Mediastinoscopy; Extrapleural pneumonectomy

Glossary

staging

the process of finding out whether cancer has spread and if so, how far. There is more than one system for staging. The TNM system, described below, is one used often. The TNM system for staging gives three key pieces of information: T refers to the size of the Tumor N describes how far the cancer has spread to nearby Nodes M shows whether the cancer has spread (Metastasized) to other organs of the body Letters or numbers after the T, N, and M give more details about each of these factors. To make this information somewhat clearer, the TNM descriptions can be grouped together into a simpler set of stages, labeled with Roman numerals. In general, the lower the number, the less the cancer has spread. A higher number means a more serious cancer.

scan

a study using either x-rays or radioactive isotopes to produce images of internal body organs.

oncology

(on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.

morbidity

a measure of the new cases of a disease in a population; the number of people who have a disease.

mortality

a measure of the rate of death from a disease within a given population.

mediastinoscopy

(me-dee-as-tin-OS-ko-pee) examination of the chest cavity using a lighted tube replaced under the chest bone (sternum). This allows the doctor to see the lymph nodes in this area and remove samples to check for cancer.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

CT scan

computed tomography (tom-og-ruh-fee), an imaging test in which many x-rays are taken of a part of the body to produce cross-sectional pictures of internal organs. Except for the injection of a dye (needed in some but not all cases), this is a painless procedure that can be done in an outpatient clinic. It is often referred to as a "CT" or "CAT" scan.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

extrapleural pneumonectomy

(EPP) surgery to remove the pleura, diaphragm, pericardium, and entire lung involved with the tumor. You can view a web cast from Brigham and Women's Hospital in Boston of this procedure being done by Dr. David Sugarbaker: see the extrapleural pneumonectomy (EPP) web cast here.

Plathow C, Staab A, Schmaehl A, Aschoff P, Zuna I, Pfannenberg C, Peter SH, Eschmann S, Klopp M.

Department of Diagnostic Radiology, University of Tuebingen, Tuebingen, Germany. christian.plathow@uniklinik-freiburg.de

Abstract

Objective: To evaluate and compare the role of computed tomography (CT), positron emission tomography (PET), PET/CT, and magnetic resonance imaging (MRI) in the correct staging of patients with limited malignant pleural mesothelioma (MPM).

Materials and Methods: Fifty-four patients with an epithelial MPM (34 men and 20 women) were included in this study. Patients were referred to our department for staging in a predicted resectable state (stage II/III). Within 3 days, PET/CT and MRI was performed in all patients. Images were evaluated by 3 specialists in the field of PET/CT and MRI. The subexaminations of PET/CT, PET, and CT were independently evaluated with respect to tumor stage. Subexaminations were compared with each other, with MRI and PET/CT. N-stage was verified by mediastinoscopy. Afterward, consensus reading was performed.

In 52 patients, surgery served as gold standard. In 2 patients, follow-up control served as gold standard as an inoperable situation with distant metastases was found. Additionally, interobserver variability ([kappa] value) was calculated.

Results: In stage II, accuracy was 0.77 (CT), 0.86 (PET), 0.8 (MRI), 1.0 (PET/CT), and in stage III 0.75, 0.83, 0.9, 1.0. PET/CT was significantly more accurate (P < 0.05) in stages II and III compared with all other techniques. CT and MRI were not able to detect distant metastases in 2 patients, which changed therapy (operable vs. inoperable). Interobserver variability was 0.7, 0.9, 0.8, 1.0 in stage II and 0.9, 0.9, 0.9, 1.0 in stage III.

Conclusion: PET/CT makes it possible to stage patients with limited MPM with high accuracy and low interobserver variability.

Glossary

therapy

any of the measures taken to treat a disease. Unproven therapy is any therapy that has not been scientifically tested and approved. Use of an unproven therapy instead of standard (proven) therapy is called alternative therapy. Some alternative therapies have dangerous or even life-threatening side effects. For others, the main danger is that a patient may lose the opportunity to benefit from standard therapy. Complementary therapy, on the other hand, refers to therapies used in addition to standard therapy. Some complementary therapies may help relieve certain symptoms of cancer, relieve side effects of standard cancer therapy, or improve a patient's sense of well-being. The ACS recommends that patients considering use of any alternative or complementary therapy discuss this with their health care team.

staging

the process of finding out whether cancer has spread and if so, how far. There is more than one system for staging. The TNM system, described below, is one used often. The TNM system for staging gives three key pieces of information: T refers to the size of the Tumor N describes how far the cancer has spread to nearby Nodes M shows whether the cancer has spread (Metastasized) to other organs of the body Letters or numbers after the T, N, and M give more details about each of these factors. To make this information somewhat clearer, the TNM descriptions can be grouped together into a simpler set of stages, labeled with Roman numerals. In general, the lower the number, the less the cancer has spread. A higher number means a more serious cancer.

mediastinoscopy

(me-dee-as-tin-OS-ko-pee) examination of the chest cavity using a lighted tube replaced under the chest bone (sternum). This allows the doctor to see the lymph nodes in this area and remove samples to check for cancer.

MRI

Stands for magnetic resonance imaging. A method of taking pictures of the inside of the body. Instead of using x-rays, MRI uses a powerful magnet and transmits radio waves through the body; the images appear on a computer screen as well as on film. Like x-rays, the procedure is physically painless, but some people find it psychologically uncomfortable to be in the small core of the MRI machine.

imaging

any method used to produce a picture of internal body structures. Some imaging methods used to detect cancer are x-rays (including mammograms and CT scans), magnetic resonance imaging (MRI), scintigraphy, and ultrasound.

tumor

an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

Miles SE, Sandrini A, Johnson AR, Yates DH.

Dust Diseases Board Research & Education Unit, Sydney, NSW, Australia. Deborahy88@hotmail.com.

Abstract

Asbestos-related diffuse pleural thickening (DPT), or extensive fibrosis of the visceral pleura secondary to asbestos exposure, is increasingly common due to the large number of workers previously exposed to asbestos. It may coexist with asbestos related pleural plaques but has a distinctly different pathology. The pathogenesis of this condition as distinct from pleural plaques is gradually becoming understood. Generation of reactive oxygen and nitrogen species, profibrotic cytokines and growth factors in response to asbestos is likely to play a role in the formation of a fibrinous intrapleural matrix. Benign asbestos related pleural effusions commonly antedate the development of diffuse pleural thickening. Environmental as well as occupational exposure to asbestos may also result in pleural fibrosis, particularly in geographic areas with naturally occurring asbestiform soil minerals. Pleural disorders may also occur after household exposure. High resolution computed tomography (CT) is more sensitive and specific than chest radiography for the diagnosis of diffuse pleural thickening, and several classification systems for asbestos-related disorders have been devised. Magnetic resonance imaging and fluorodeoxyglucose positron emission tomography (PET) scanning may be useful in distinguishing between DPT and malignant mesothelioma. DPT may be associated with symptoms such as dyspnoea and chest pain. It causes a restrictive defect on lung function and may rarely result in respiratory failure and death. Treatment is primarily supportive.

Glossary

pleura

(pler-uh) the membrane around the lungs and lining of the chest cavity. (Pleural mesothelioma.)

imaging

any method used to produce a picture of internal body structures. Some imaging methods used to detect cancer are x-rays (including mammograms and CT scans), magnetic resonance imaging (MRI), scintigraphy, and ultrasound.

growth factors

a naturally occurring protein that causes cells to grow and divide. Too much growth factor production by some cancer cells helps them grow quickly, and new treatments to block these growth factors are being tested in clinical trials. Other growth factors help normal cells recover from side effects of chemotherapy.

fibrosis

formation of scar-like (fibrous) tissue. This can occur anywhere in the body.

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

benign

(be-nine) not cancer; not malignant.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

visceral pleura

lining immediately surrounding the lung; the parietal pleura lines the chest wall and between the parietal and visceral pleura is the pleural space.

Hinshaw JL, Pickhardt PJ.

Department of Radiology, University of Wisconsin Medical School, Madison, WI, 53792, USA.

Abstract

Peritoneal carcinomatosis and metastatic involvement of the retroperitoneum are relatively common manifestations of many organ-based malignancies and lymphoproliferative disorders. Primary malignancies of peritoneal and retroperitoneal origin occur much less frequently, and can be difficult to distinguish from metastatic disease. In many cases, a precise diagnosis based on imaging findings alone is not possible. However, the imaging features of these primary tumors, in combination with the clinical and demographic data, can be utilized to narrow the scope of the differential diagnosis. This chapter will present the clinical and imaging features of primary peritoneal and retroperitoneal tumors arising from the various tissue components that comprise the ligaments, mesenteries and connective tissues of these anatomic spaces.

Glossary

imaging

any method used to produce a picture of internal body structures. Some imaging methods used to detect cancer are x-rays (including mammograms and CT scans), magnetic resonance imaging (MRI), scintigraphy, and ultrasound.

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

tissue

a collection of cells, united to perform a particular function.

peritoneal

(pair-uh-tuh-nee-al) the serous membrane that lines the cavity of the abdomen. (More on Peritoneal Mesothelioma.)

Park EK, Sandrini A, Yates DH, Thomas PS, Creaney J, Robinson BW, Johnson AR.

Research and Education Unit, Dust Diseases Board, Sydney, NSW, Australia.

Abstract

Rationale: Soluble mesothelin related protein (SMRP) is raised in epithelial type malignant mesothelioma (MM), but the utility of SMRP in screening for MM is unknown.

Objectives: We aimed to evaluate SMRP in asbestos exposed subjects.

Methods: 538 subjects were studied. Those with elevated SMRP (≥ 2.5nM) underwent further investigation including positron-emission tomography/computed tomography.

Measurements and Main Results: Mean (± SD) SMRP in healthy subjects exposed to asbestos (n=223) was 0.79 (± 0.45) nM. 15 subjects had elevated SMRP, of whom one had lung cancer which was successfully resected. Another with lung cancer was undetected by SMRP. No subjects were diagnosed with MM. Mean SMRP in healthy subjects was significantly lower than in subjects with PPs (p<0.01).

Conclusions: This is the first large scale prospective study of SMRP for screening for malignancy in asbestos-exposed individuals. A high false positive rate was observed. SMRP seems unlikely to prove useful in screening for MM.

Keywords: soluble mesothelin related protein, mesothelioma, asbestos-related disorders, diagnostic accuracy, screening

Glossary

screening

the search for disease, such as cancer, in people without symptoms. For example, the principal screening measure for breast cancer is mammography. Screening may refer to coordinated programs in large populations.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

Mahmood S, Martinez de Llano SR.

Department of Radiology, Nuclear Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. smahmood@yahoo.com

Abstract

A 71-year-old man with newly diagnosed malignant mesothelioma was referred for an F-18 FDG PET/CT study to evaluate the extent of disease. PET showed mild FDG uptake in the right chest, corresponding to a lobulated, mass-like right pleural effusion versus thickening involving the entire right pleural space, and some mediastinal involvement, on the accompanying CT scan. In addition, marked FDG uptake was seen in the proximal left humerus, suspicious for an osseous metastasis. The corresponding CT scan findings of cortical thickening and a "Swiss cheese" appearance were most consistent with Paget disease. The intense FDG uptake in an osseous lesion on FDG-PET in our case reminds us of the variable nature of FDG uptake in Paget disease, the possibility of false-positive findings on FDG-PET in patients with cancer, and the usefulness of the fusion techniques in the evaluation of skeletal lesions, with the potential for discriminating between benign Paget disease and other pathologic bone findings.

Glossary

scan

a study using either x-rays or radioactive isotopes to produce images of internal body organs.

metastasis

(meh-tas-teh-sis) the spread of cancer cells to distant areas of the body by way of the lymph system or bloodstream.

lesion

(lee-zhun) a change in body tissue; sometimes used as another word for tumor.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

CT scan

computed tomography (tom-og-ruh-fee), an imaging test in which many x-rays are taken of a part of the body to produce cross-sectional pictures of internal organs. Except for the injection of a dye (needed in some but not all cases), this is a painless procedure that can be done in an outpatient clinic. It is often referred to as a "CT" or "CAT" scan.

benign

(be-nine) not cancer; not malignant.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

pleural effusion

an abnormal accumulation of fluid, usually caused by trauma or disease, in the pleural space.

Ceresoli GL, Castagneto B, Zucali PA, Favaretto A, Mencoboni M, Grossi F, Cortinovis D, Conte GD, Ceribelli A, Bearz A, Salamina S, De Vincenzo F, Cappuzzo F, Marangolo M, Torri V, Santoro A.

1Department of Oncology, Istituto Clinico Humanitas IRCCS, Rozzano, Milano, Italy.

Abstract

The incidence of malignant pleural mesothelioma (MPM) in elderly patients is increasing. In this study, pooled data from two phase II trials of pemetrexed and carboplatin (PC) as first-line therapy were retrospectively analysed for comparisons between age groups. Patients received pemetrexed 500 mg m^-2 and carboplatin AUC 5 mg ml^-1 min^-1 intravenously every 21 days with standard vitamin supplementation. Elderly patients were defined as those >/=70 years old. A total of 178 patients with an ECOG performance status of </=2 were included. Median age was 65 years (range 38-79), with 48 patients >/=70 years (27%). Grade 3-4 haematological toxicity was slightly worse in >/=70 vs <70-year-old patients, with neutropenia observed in 25.0 vs 13.8% (P=0.11), anaemia in 20.8 vs 6.9% (P=0.01) and thrombocytopenia in 14.6 vs 8.5% (P=0.26). Non-haematological toxicity was mild and similar in the two groups. No significant difference was observed in terms of overall disease control (60.4 vs 66.9%, P=0.47), time to progression (7.2 vs 7.5 months, P=0.42) and survival (10.7 vs 13.9 months, P=0.12). Apart from slightly worse haematological toxicity, there was no significant difference in outcome or toxicity between age groups. The PC regimen is effective and well tolerated in selected elderly patients with MPM.

Keywords: malignant pleural mesothelioma; elderly patients; chemotherapy; carboplatin; pemetrexed

Glossary

thrombocytopenia

(throm-bo-sigh-toe-PEEN-ee-ah) a decrease in the number of platelets in the blood; can be a side effect of chemotherapy.

therapy

any of the measures taken to treat a disease. Unproven therapy is any therapy that has not been scientifically tested and approved. Use of an unproven therapy instead of standard (proven) therapy is called alternative therapy. Some alternative therapies have dangerous or even life-threatening side effects. For others, the main danger is that a patient may lose the opportunity to benefit from standard therapy. Complementary therapy, on the other hand, refers to therapies used in addition to standard therapy. Some complementary therapies may help relieve certain symptoms of cancer, relieve side effects of standard cancer therapy, or improve a patient's sense of well-being. The ACS recommends that patients considering use of any alternative or complementary therapy discuss this with their health care team.

regimen

(rej-uh-men) a strict, regulated plan (such as diet, exercise, or other activity) designed to reach certain goals. In cancer treatment, a plan to treat cancer.

oncology

(on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.

grade

The grade of a cancer reflects how abnormal it looks under the microscope. There are several grading systems for cancer, such as the Gleason score for prostate cancer. Each grading system divides cancer into those with the greatest abnormality (poorly differentiated), the least abnormality (well-differentiated), and those in between (moderately differentiated). Grading is done by the pathologist who examines the tissue from the biopsy. It is important because higher grade cancers tend to grow and spread more quickly and have a worse prognosis.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

Barone-Adesi F, Ferrante D, Bertolotti M, Todesco A, Mirabelli D, Terracini B, Magnani C.

Unit of Cancer Epidemiology, CeRMS and Center for Oncologic Prevention Piemonte, University of Turin, Turin, Italy.

Abstract

Models based on the multistage theory of carcinogenesis predict that the rate of mesothelioma increases monotonically as a function of time since first exposure (TSFE) to asbestos. Predictions of long-term mortality (TSFE >/= 40 years) are, however, still untested, because of the limited follow-up of most epidemiological studies. Some authors have suggested that the increase in mesothelioma rate with TSFE might be attenuated by clearance of asbestos from the lungs. We estimated mortality time trends from pleural and peritoneal cancer in a cohort of 3,443 asbestos-cement workers, followed for more than 50 years. The functional relation between mesothelioma rate and TSFE was evaluated with various regression models. The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalized to include a term representing elimination over time. We observed 139 deaths from pleural and 56 from peritoneal cancer during the period 1950-2003. The rate of pleural cancer increased during the first 40 years of TSFE and reached a plateau thereafter. In contrast, the rate of peritoneal cancer increased monotonically with TSFE. The model allowing for asbestos elimination fitted the data better than the traditional model for pleural (p = 0.02) but not for peritoneal cancer (p = 0.22). The risk for pleural cancer, rather than showing an indefinite increase, might reach a plateau when a sufficiently long time has elapsed since exposure. The different trends for pleural and peritoneal cancer might be related to clearance of the asbestos from the workers’ lungs.

Keywords: asbestos, mesothelioma, multi-stage model, latency, clearance

Glossary

mortality

a measure of the rate of death from a disease within a given population.

epidemiology

(ep-uh-deem-ee-AHL-uh-gee) the study of diseases in populations by collecting and analyzing statistical data. In the field of cancer, epidemiologists look at how many people have cancer; who gets specific types of cancer; and what factors (such as environment, job hazards, family patterns, and personal habits, such as smoking and diet) play a part in the development of cancer.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

peritoneal

(pair-uh-tuh-nee-al) the serous membrane that lines the cavity of the abdomen. (More on Peritoneal Mesothelioma.)