Abstract
Aim
People with occupational exposure to asbestos demonstrate a high incidence of lung cancer. Asbestos medical examination for those at risk was implemented as a national policy in Japan. This study aimed to characterize patients with asbestos‐related lung cancer who were diagnosed by these examinations.
Methods
We retrospectively investigated 120 individuals exposed to asbestos who were examined from 2008 to 2016 at our institution. Clinical data, including CT findings and time‐related exposure variables, were evaluated. Each asbestos‐related change was assigned 1 point if present, and the scores were compared between patients with and without asbestos‐related lung cancer using the Mann‐Whitney U test and Fisher's exact test.
Results
Five patients were diagnosed with lung cancer, and four underwent surgical treatment. At the time of writing, three of four operated patients were alive without recurrence, with a similar prognosis to patients with lung cancer unrelated to asbestos. Average scores for asbestos‐related findings on CT Scan were 1.8 (9/5) for patients with lung cancer and 0.79 (91/115) for those without lung cancer.
Conclusion
Patients with lung cancer had significantly more asbestos‐related changes on CT scan than those without lung cancer. Concurrent calcified plaque and interstitial changes might be a predictor of lung cancer incidence. Although further investigation with a larger study group is needed, regular medical examination and CT scan every 6 months might contribute to the early detection of lung cancer with asbestos‐related changes on CT.
Keywords: asbestos, asbestosis, asbestos‐related diseases, lung cancer, occupational exposure
1. INTRODUCTION
Asbestos was determined by Japanese law to be carcinogenic in 1975 and is now a well‐known cause of malignant mesothelioma and lung cancer.1, 2, 3, 4, 5, 6 In particular, the risk of lung cancer is increased synergistically by the combination of asbestos and tobacco, the latter of which is an established carcinogen associated with a variety of malignant tumors.7, 8, 9
The volume of asbestos imported into Japan increased with the country's rapid economic growth. The harmful effects of asbestos exposure became a serious social problem in Japan beginning around 2000, and its use was restricted in stages and then forbidden.10, 11 Laws relevant to asbestos are still being established and enacted. The Act on Asbestos Health Damage Relief was enacted in 2006, and this law stipulated that asbestos medical examinations should be performed in individuals throughout Japan who were occupationally exposed to asbestos. In Japan, asbestos medical examinations are considered to have an established role as they identify cases of asbestos‐related lung cancer nationwide.12, 13 This study investigated the clinical features of patients with asbestos‐related lung cancer who were diagnosed by biannual asbestos medical examination.
2. MATERIALS AND METHODS
2.1. Study design
We retrospectively investigated individuals who underwent asbestos medical examinations from January 2008 to June 2016 at our institution. We compared the clinical characteristics of subjects with asbestos‐related lung cancer diagnosed by asbestos medical examination with those who did not have lung cancer. The whole cohort initially came to our institution for screening in the absence of respiratory symptoms, and were evaluated by sputum cytology, chest radiograph, and CT scan every 6 months; the biannual examinations were charged on the national treasury. Gender, age, smoking history, occupational history, and radiological and CT findings of asbestos‐related changes were examined retrospectively. The slice thickness of CT scans was 5 mm. Subjects who were found to have lung cancer and who underwent surgical treatment were also examined for histological type of lung cancer, clinical/pathological stage, therapeutic procedures, and prognosis. Patient follow‐up ended at death or on December 31, 2016, whichever occurred first.
Lung cancer diagnosed by the medical examination was defined as asbestos related because all study subjects had occupational asbestos exposure and asbestos‐related abnormalities on chest radiograph. The types of asbestos and quantity of asbestos particles or fibers were unknown because the number of asbestos particles was not counted at our institution.
CT results of every subject were evaluated, and findings considered to be induced by inhaled particles of asbestos, such as calcified plaque, fibrotic pulmonary changes, diffuse pleural thickening, pleural effusion, and round atelectasis, were noted.14, 15 Each of these findings was assigned 1 point if present. We calculated the total score for each participant and compared scores between patients with and without asbestos‐related lung cancer.
We also obtained employment data of all subjects from medical records and calculated several time‐related exposure variables, including time since first exposure, duration working at an asbestos‐related job, and time since cessation of exposure.
2.2. Definition of asbestos‐related changes
We adopted fibrotic pulmonary changes, diffuse pleural thickening, plaque, round atelectasis, and benign pleural effusion as indicators of asbestos‐related changes, as all have been reported as typical radiological changes attributable to inhaled asbestos (Figure 1). Fibrotic pulmonary changes of the lung, defined as interstitial findings such as honeycomb lung and small nodular or linear shadows under the pleura, were deemed to be caused by occupational exposure to asbestos if no other etiology was identified. We defined diffuse pleural thickening as a bilateral area of soft tissue density involving more than one‐quarter of the lateral chest wall, with the thickest portion >2 mm on CT.16 Plaque was defined as localized planar protrusion. However, because plain CT was used for radiographic assessment at medical examinations, it was difficult to discriminate plaque from intercostal vessels or pleural effusion if the protrusion area was relatively small. Therefore, in this study, we defined plaque as localized planar protrusion accompanied by calcification. Pleural effusion was identified as fluid density area on CT and defined as asbestos‐related benign effusion when no other etiology was suggested by thoracentesis and after observation for more than 1 year. We intended to detect round atelectasis by identifying nodules with the comet tail sign on CT, but no suspicious nodules were seen in any of the study participants.
Figure 1.
Asbestos related changes on CT: A, calcified plaque is seen as localized, plane‐shaped prostration along chest wall (arrow). B, fibrotic pulmonary change is recognized as micronodular or linear shadow. C, Diffuse pleural thickening is seen as soft tissue density area widely spread along chest wall (arrow). D, Pleural thickening is recognized as fluid density area in dorsal part of thoracic cavity (arrow). E, Comet tail sign is often present in patients with round atelectasis (arrow)
2.3. Statistics
Clinical data were statistically compared using the Mann–Whitney U test and Fisher's exact test. P values <0.05 were regarded as statistically significant.
2.4. Institutional approval
This study was reviewed and accepted by our institutional investigational review board, and the approval number was 2016‐3.
3. RESULTS
3.1. Baseline characteristics of the study group
The present cohort included 120 individuals (119 men, 1 woman) who were certified to have a history of occupational exposure to asbestos. Of the 103 participants whose occupational histories could be determined, 41 worked in construction, 13 were involved in asbestos processing, 12 worked in shipyards, 12 were exposed while manufacturing asbestos‐containing products, and the remainder were employed in other asbestos‐related work (Table 1).
Table 1.
Asbestos‐related occupations
| Area of Occupation | n |
|---|---|
| Construction | 41 |
| Asbestos processing | 13 |
| Shipbuilding | 12 |
| Asbestos product making | 12 |
| Electrician | 6 |
| Warehousing | 5 |
| Metal making | 4 |
| Manufacturing transportation facilities | 4 |
| Petroleum refining | 2 |
| Others | 4 |
The characteristics of all individuals who underwent asbestos medical examinations at our institution are shown in Table 2. No significant differences were detected between the 2 groups. Age at initial exposure to asbestos ranged from 14 to 56 years with a mean of 25.8 years. The duration of asbestos exposure ranged from 2 to 42 years with a mean of 21.4 years. Age at first examination ranged from 35 to 90 years with a mean of 68.1 years. Duration between first exposure and first examination ranged from 13 to 74 years with a mean of 42.3 years. The follow‐up period ranged from 6 to 102 months with a mean of 70.6 months. Twenty‐one participants were non‐smokers and 90 were smokers or ex‐smokers. Pack‐years smoked ranged from 0 to 150 with a mean of 28.6. No participants died of respiratory failure due to advanced asbestosis.
Table 2.
Characteristics of asbestos‐related lung cancer and non‐lung cancer patients
| Factors | Asbestos‐Related Lung Cancers (n = 5) | Non‐Lung Cancers (n = 115) | P Value |
|---|---|---|---|
| Gender | |||
| Male | 5 | 114 | 0.95 (F) |
| Female | 0 | 1 | |
| Exposure period (years) | 24 ± 11.61 | 21 ± 11.26 | 0.31 (U) |
| <10 | 1 | 19 | 0.63 (F) |
| >10 | 4 | 87 | |
| Age at first exposure | 28 ± 9.79 | 26 ± 8.45 | 0.58 (U) |
| Period from the first exposure to the first examination (years) | 39 ± 10.72 | 42 ± 9.94 | 0.59 (U) |
| <30 | 4 | 78 | 0.63 (F) |
| >30 | 1 | 26 | |
| Age at first examination | 67 ± 3.31 | 68 ± 7.79 | 0.88 (U) |
| Observation period (years) | 4.4 ± 3.14 | 5.9 ± 2.69 | 0.29 (U) |
| <3 | 2 | 19 | 0.23 (F) |
| >3 | 3 | 87 | |
| Pack‐years | 50 ± 28.43 | 28 ± 24.57 | 0.054 (U) |
| Never smoker | 0 | 21 | |
| Smoker | 5 | 85 | |
| Pack‐years >50 | 1 | 15 |
Data are absolute numbers or means ± standard error of the mean.
F, Fisher's exact test; U, Mann‐Whitney U test.
3.2. Characteristics of asbestos‐related lung cancer patients
Five subjects were diagnosed with asbestos‐related lung cancer by regular asbestos medical check‐ups during the observation period (Table 3). No lung cancer diagnoses were made by any other means. The incidence rate of lung cancer as detected by asbestos medical examinations was 71 cases per 10 000 person‐years, and the discovery rate of lung cancer was 4.2%. In the five lung cancer cases, the pack‐years smoked ranged from 30 to 100 with a mean of 50, the number of years performing asbestos‐related jobs ranged from 8 to 40 years with a mean of 24 years, and the duration between initial asbestos exposure and first asbestos‐related examination ranged from 30 to 55 years with a mean of 39 years.
Table 3.
Clinicopathological data for patients with asbestos‐related lung cancer
| Age at Diagnosis/Sex, y | Period of Exposure, y | Period from First Exposure to First Examination, y | Pack‐Years Smoked | Occupation | Tumor Location/Surgical Procedure | Histological Type | Tumor Size, cm | TNM |
Outcome |
|---|---|---|---|---|---|---|---|---|---|
| 74/male | 27 | 30 | 47 | Construction |
RLL VATS wedge resection |
Squamous cell ca. | 5.8 | pT2bNXM0 | No recurrence for 77 wks |
| 72/male | 30 | 44 | 100 | Construction |
RUL VATS lobectomy, ND2a‐1 + #3a |
Adenocarcinoma | 1.2 | pT1aN0M0 | No recurrence for 235 wks |
| 65/male | 28 | 37 | 30 | Metalworking |
LLL Open lobectomy, ND2a‐1 |
Squamous cell ca. | 1.4 | pT1aN0M0 | No recurrence for 23 wks |
| 65/male | 40 | 45 | 35 | Shipbuilding | RUL open lobectomy, ND2a‐2 |
Squamous cell ca. Adenocarcinoma |
5.2
3.0 |
pT3N2M0
pT1bN2M0 |
Cancer death |
| 75/male | 8 | 55 | 40 | Shipbuilding |
RLL ‐ |
Small cell ca. | 3.3 | cT2aN2M1b | Cancer death |
Abbreviations: ca., carcinoma; LLL, left lower lobe; ND, node dissection; RLL, right lower lobe; RUL, right upper lobe; VATS, video‐assisted thoracic surgery.
One patient exhibited adenocarcinoma, and three had squamous cell carcinoma. The final patient had small cell carcinoma with multiple metastases, diagnosed by transbronchial lung biopsy; this patient received the best available supportive care but died 1 month after diagnosis. Surgery was indicated for the other four patients based on the clinical stage. One patient with squamous cell carcinoma underwent partial resection due to poor respiratory function, while the other three patients underwent lobectomy and systematic lymph node dissection.
Three of the four patients who underwent surgery were alive without recurrence at the time of this writing after observation periods of 77, 23, and 235 weeks, respectively. The patient with squamous cell carcinoma who underwent partial resection was pathologically staged as N2 and died of multiple metastasis at 6 weeks after surgery. Thus the 1‐year postoperative survival rate was 50%.
3.3. Asbestos‐related changes
Regarding asbestos‐related changes on CT scan, 49 subjects (41%) exhibited fibrotic pulmonary changes, 4 (3.5%) demonstrated diffuse pleural thickening, and 35 (30%) showed calcified plaque. Seven (6.1%) had pleural effusion. Round atelectasis was not observed in any subject. Scoring of CT findings is shown in Table 4. The total scores were 9 and 91 in the lung cancer group and no‐lung‐cancer group, respectively. The average scores were 1.8 and 0.79, respectively, which were significantly different (P = 0.0091, U‐test) (Table 4). The number of subjects with both asbestosis and calcified plaque was 3 of 5 (60%) in the lung cancer group and 9 of 114 (8%) in the no‐lung‐cancer group, indicating a significant difference (P = 0.007, Fisher's exact test) (Table 5).
Table 4.
Cumulative point totals for asbestos‐related findings on CT scan
| Findings | Asbestos‐Related Lung Cancers (n = 5) | Non‐Lung Cancers (n = 115) | P Value |
|---|---|---|---|
| Calcified plaque | 4 | 35 | 0.038 (F) |
| Fibrotic pulmonary change | 4 | 46 | 0.095 (F) |
| Diffuse pleural thickening | 0 | 4 | 0.84 (F) |
| Pleural effusion | 1 | 6 | 0.26 (F) |
| No findings (no points) | 0 | 40 | 0.12 (F) |
| Total points | 9 | 91 | |
| Average score | 1.8 (9/5) | 0.79 (91/115) | 0.0091 (U) |
| NS = not significant |
F, Fisher's exact test; U, U test.
Table 5.
Number of patients presenting with both calcified plaques and interstitial changes on CT scan
| Factors |
Asbestos‐Related Lung Cancers (n = 5) |
Non‐Lung Cancers (n = 115) | P Value |
|---|---|---|---|
|
Calcified plaques + Fibrotic pulmonary changes |
3 patients | 9 patients | 0.0023 (F) |
F, Fisher's exact test.
4. DISCUSSION
Asbestos‐related lung cancer is still a deep‐rooted social problem in Japan, and to optimize prognosis, it is critical to identify lung cancer in its early stages in those who were occupationally exposed to asbestos.
The present study was undertaken to investigate asbestos‐related primary lung cancer diagnosed by regular asbestos medical examinations at our institution. Smoking habits and time‐related exposure variables were not found to be significantly different between asbestos‐related lung cancer patients and subjects without lung cancer. There was also no significant difference regarding various asbestos‐related changes on CT, but all five patients with asbestos‐related lung cancer had fibrotic pulmonary changes, calcified plaques, or pleural effusion, and the average score reflecting the total number of asbestos‐related CT changes was significantly higher in the lung cancer group than the no‐lung‐cancer group. Furthermore, the number of individuals who presented with both fibrotic pulmonary changes and calcified plaques was significantly higher in the lung cancer group. This suggests that the patients with lung cancer were likely to have relatively more asbestos‐related changes. Furthermore, it is possible that the combination of calcified plaques and fibrotic pulmonary changes could be a predictive indicator for lung cancer incidence. Taking this into consideration, chest radiograph alone might not dependably detect asbestos‐related changes or tumors masked by these changes in their early stages. CT scans are preferable to identify and evaluate these changes and ought to play a main role in regular asbestos medical examinations. Biannual medical examination with CT scan will possibly decrease the number of patients identified with advanced, inoperable lung cancer.
Regarding survival, we cannot state that the patients in this study with asbestos‐related lung cancer diagnosed by regular medical examination did not have an inferior prognosis to previously reported patients with non‐asbestos‐related lung cancer13, 17 because of small sample size. It was reported that the prognosis of asbestos‐related lung cancer patients who underwent surgical treatment was better than that of patients for whom surgery was not indicated due to advanced clinical stage,18 which is compatible with our results.
Japanese national surgery revealed that the incidence rate of lung cancer diagnosed by asbestos medical examination in this study was higher than that of lung cancer of any etiology diagnosed by regular lung cancer medical examination, the latter of which was 6.4 cases per 10 000 person‐years in males in 2009.19 Moreover, the discovery rate of lung cancer by asbestos medical examination at our institution was 4.2%, which is higher than that by regular lung cancer medical examination with CT scan.20, 21, 22 These results might be attributable to the fact that the period from first exposure to first medical examination of this cohort was 42 ± 9.2 years, which is similar to the latent development period of asbestos‐related lung cancer.23
High pack years and long incubation period from cessation of asbestos exposure increase the possibility of second primary lung cancer. Therefore, it is important to have asbestos medical examination continuously although it is another problem to make a differential diagnosis between second primary lung cancer and recurrence of first primary lung cancer.
Limitations of the present study include the small numbers of subjects who underwent asbestos medical examination and those diagnosed with asbestos‐related lung cancer, as well as the short postoperative observation period. The retrospective way of investigation is also one of the limitations. We should aim to increase the number of individuals who receive asbestos medical examinations, investigating in a prospective way in order to optimize the evaluation of prognosis regarding asbestos‐related lung cancer diagnosed by medical examination. Furthermore, optimal frequency of the examination should be evaluated from other aspects including medical economy and radiation exposure.
In conclusion, concurrent calcified plaque and interstitial changes on CT identified by asbestos medical examination might be a predictor of lung cancer incidence.
CONFLICT OF INTEREST
All authors declare that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
AUTHOR'S CONTRIBUTIONS
All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Conceptualization, T.Y., A.S. and T.F.; Methodology, T.Y. and A.S.; Investigation, T.Y.; Formal Analysis, T.Y. and A.S.; Resources, T.F.; Writing ‐ Original Draft, T.Y.; Writing ‐ Review & Editing, A.S. and T.F.; Visualization, T.Y.; Supervision, A.S. and T.F.; none.
ACKNOWLEDGEMENTS
None declared.
Yotsumoto T, Sano A, Fukuda T. Clinical study of asbestos‐related lung cancer diagnosed by asbestos medical examination. Cancer Reports. 2018;1:e1124. 10.1002/cnr2.1124
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