close

Вход

Забыли?

вход по аккаунту

?

88

код для вставкиСкачать
948
Incidence of Malignant Pleural Mesothelioma after
Thoracic Radiotherapy
Alfred I. Neugut, M.D., Ph.D.1,2
Habibul Ahsan, M.B.B.S., M.Med.Sc.2
Karen H. Antman, M.D.1
BACKGROUND. Although usually associated with asbestos exposure, a number of
case reports have noted the occurrence of malignant pleural mesothelioma in
patients who received radiotherapy (RT) to the thorax.
METHODS. The authors performed a retrospective cohort study utilizing 251,750
1
Department of Medicine, Columbia University
College of Physicians and Surgeons, New York,
New York.
2
School of Public Health, Columbia University
College of Physicians and Surgeons, New York,
New York.
women registered with breast carcinoma in the Surveillance, Epidemiology, and
End Results Program of the U.S. National Cancer Institute from 1973–1993, 24.8%
of whom received RT as part of their initial management, and 13,743 people with
Hodgkin’s disease, 50.6% of whom received RT as part of their initial management.
RESULTS. Six cases of malignant pleural mesothelioma were found: two in breast
carcinoma patients treated with RT and four found in women not treated with RT.
No cases occurred in the patients with Hodgkin’s disease. The overall estimated
relative risk for malignant pleural mesothelioma after RT was 1.56 (95% confidence
interval, 0.18–5.63).
CONCLUSIONS. To the authors’ knowledge, this is the first controlled study to investigate thoracic radiation exposure and malignant pleural mesothelioma, and no
association was found. Cancer 1997;80:948–50. q 1997 American Cancer Society.
KEYWORDS: mesothelioma, breast carcinoma, Hodgkin’s disease, radiotherapy, radiation effect, etiology, second neoplasms.
M
Address for reprints: Alfred I. Neugut, M.D.,
Ph.D., Division of Oncology, Columbia-Presbyterian Medical Center, 630 West 168th Street,
New York, NY 10032.
Received January 17, 1997, accepted April 16,
1997.
ost cases of malignant mesothelioma have been shown to be
causally related to asbestos exposure. Because these exposures
are primarily but not exclusively occupational, the incidence of malignant mesothelioma has been much higher in men than in women.1
A number of case reports have indicated an association between
therapeutic radiation and malignant mesothelioma. These pleural and
peritoneal neoplasms have been reported to occur after radiotherapy
for Hodgkin’s disease,2 – 5 testicular carcinoma,6,7 cervical carcinoma,8
Wilms’ tumor,9,10 and breast carcinoma,6,11 – 13 as well as after radiation
for nonmalignant disease6 and after Thorotrast exposure.14 The time
interval between the radiation exposure and the diagnosis of mesothelioma has ranged from several years to 35 years.
In addition, animal studies have found that radiation is carcinogenic to the pleura and peritoneum.15 In addition to its role as an
independent carcinogen, animal studies indicate that radiation and
asbestos may also have an interactive effect in inducing mesothelioma.16
All the evidence to date regarding radiation exposure and malignant mesothelioma in humans stems from case reports. No systematic
controlled study has been conducted. In this article, population –
based tumor registry data were used to conduct a retrospective cohort
analysis of the incidence of malignant pleural mesothelioma after
thoracic radiotherapy for breast carcinoma and Hodgkin’s disease.
q 1997 American Cancer Society
/ 7b5f$$1251
08-09-97 07:19:58
cana
W: Cancer
Thoracic RT and Mesothelioma/Neugut et al.
949
TABLE 1
Malignant Pleural Mesothelioma Occurring in Patients with Breast Carcinoma or Hodgkin’s Disease Registered
in the SEER Program, 1973–1993.
First primary
Radiation
No.
Person-years
Observed
Expected
RR(O/E)
95% CI
Breast carcinoma
Yes
No
62,453
189,297
226,961.3
845,138.1
2
4
1.125
4.409
1.78
0.91
0.20–6.42
0.24–2.32
Yes
No
3686
4067
24,315.0
16,272.8
0
0
0.133
0.151
—
—
—
—
Yes
No
Yes
No
3275
2720
69,414
196,084
21,847.1
10,668.5
273,123.4
872,080.1
0
0
0
0
0.024
0.019
1.282
4,579
—
—
1.56
0.91
—
—
0.18–5.63
0.24–2.24
Hodgkin’s
disease
(men)
Hodgkin’s
disease
(women)
Overall
SEER: Surveillance, Epidemiology, and End Results; RR: relative risk; O: observed; E: expected; CI: confidence interval.
METHODS
The Surveillance, Epidemiology, and End Results
(SEER) program of the U.S. National Cancer Institute
collects information from several population – based
cancer registries, comprising approximately 10% of the
U.S. population. For each case, SEER collects clinical
information regarding the cancer diagnosis and follow-up information, including subsequent malignancies. The authors utilized data on the set of 2.0 million
newly diagnosed cancer patients registered in SEER
between 1973 and 1993.17
To estimate the relative risk (RR) of developing a
malignant pleural mesothelioma among patients with
an initial cancer compared with patients without cancer, the authors calculated the gender specific standardized incidence ratio, adjusting for age and calendar year. This methodology has been described previously.18 Briefly, the authors estimated the expected
number of second primary mesotheliomas by applying
gender, age (every 5 years), and calendar year (within
the given year) specific SEER incidence rates to the
person-year experiences of respective categories. The
number of observed malignant mesotheliomas after
breast carcinoma or Hodgkin’s disease, with or without radiotherapy treatment, was compared with the
expected number to give an estimate of the RR. A 95%
confidence interval (CI) was calculated around the estimated RR using Byar’s limits, assuming a Poisson
distribution.19
Cases diagnosed at autopsy or through death certificates, cases in which the date of diagnosis was unknown, and cases of carcinoma in situ were excluded.
The authors also excluded malignant mesotheliomas
diagnosed within 60 months after the diagnosis of the
first cancer to minimize diagnostic bias (these cases
/ 7b5f$$1251
08-09-97 07:19:58
cana
may have been diagnosed due to a diagnostic workup
related to the first malignancy).
RESULTS
The main results of the current study are shown in
Table 1. Approximately 25% of the breast carcinoma
patients underwent primary radiotherapy, constituting 27% of the person-years of follow-up. Six cases of
malignant mesothelioma were observed among almost 252,000 women with breast carcinoma: 2 cases
occurred in women who had received radiotherapy for
their breast carcinoma, whereas 4 cases occurred in
women who did not receive radiotherapy.
Of the Hodgkin’s disease patients, approximately
51% underwent primary radiotherapy, constituting
63% of the person-years of follow-up. There were no
cases of pleural mesothelioma that occurred in the
follow-up of this cohort.
Overall, as can be seen in Table 1, the RR of developing a pleural mesothelioma after thoracic radiotherapy was 1.6 (95% CI, 0.2 – 5.6) whereas the RR without
radiotherapy treatment was 0.9 (95% CI, 0.2 – 2.2).
DISCUSSION
Several case reports have indicated a possible elevation in the risk of malignant pleural mesothelioma
after radiotherapy for breast carcinoma or Hodgkin’s
disease.2 – 6,11 – 13 These studies have been uncontrolled.
To the authors’ knowledge, this was the first controlled
study to investigate the risk of mesothelioma after radiation exposure, and no elevation in risk was found.
Although asbestos is a very powerful etiologic
agent for mesothelioma, no specific information is
available regarding asbestos exposure in the cases in
the current study. Animal data have suggested there
W: Cancer
950
CANCER September 1, 1997 / Volume 80 / Number 5
may be an interactive effect between asbestos and radiation exposure.16 In truth, malignant mesothelioma
is a type of soft tissue sarcoma and a considerable
body of evidence has established radiation exposure
as a risk factor for the development of sarcomas.20
Thus, it would come as no surprise to learn that radiotherapy raises the risk of malignant mesotheliomas as
well.
One limitation of this study was the relatively short
follow-up time available (maximum, 20 years). In the
case reports that have been published to date, several
of the malignant mesotheliomas occurred after an 18 –
35-year time interval. Thus, the cases observed herein
represent an underestimate of what may ultimately be
expected. In addition, it is possible, if not likely, that
a significant number of pleural effusions were misdiagnosed as breast carcinoma or Hodgkin’s disease
rather than as new primary malignant mesotheliomas.
Again, this is likely to make the authors’ RR estimate
a conservative underestimation of the truth.
Radiotherapy for breast carcinoma has been previously shown to be carcinogenic to the lung.21,22 However, it does not appear to raise the risk of leukemia
or contralateral breast carcinoma.23,24 All of these studies of breast carcinoma radiotherapy, including the
current one, have described the cancer incidence experience after postmastectomy radiotherapy. The carcinogenic effects of whole breast RT after lumpectomy
are currently unknown.
Radiotherapy for Hodgkin’s disease also has been
shown to be carcinogenic to the lung, as well as increasing the risk of leukemia and other malignancies.25 However, as observed in the current study, it does not appear
to increase the risk of mesothelioma, although previous
results have suggested that this is possible.2–5
In conclusion, it is clear that there is no significant
elevation in risk for mesothelioma after thoracic radiotherapy. However, it should be noted that the confidence limits on this estimate are wide, and that an RR
õ5 cannot be excluded.
REFERENCES
1.
2.
3.
4.
5.
McDonald AD, McDonald JC. Epidemiology of malignant
mesothelioma. In: Antman K, Aisner J, editors. Asbestosrelated malignancy. Orlando: Grune & Stratton, 1987:31–55.
Brenner J, Sordillo PP, Magill GB, Golbey RB. Malignant mesothelioma of the pleura. Review of 123 patients. Cancer
1982;49:2431–5.
Lerman Y, Learman Y, Schachter P, Herceq E, Lieberman Y,
Yellin A. Radiation associated malignant pleural mesothelioma. Thorax 1991;46:463–4.
Weismann LB, Corson JM, Neugut AI, Antman KH. Malignant mesothelioma following radiation therapy for Hodgkin’s disease. J Clin Oncol 1996;14:2098–100.
Pappo AS, Santana VM, Furman WL, Kun LE, Walter AW,
Jenkins JJ, et al. Post-irradiation malignant mesothelioma.
Cancer 1997;79:192–3.
/ 7b5f$$1251
08-09-97 07:19:58
cana
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
Antman KH, Corson JM, Li FP, Greenberger J, Sytkowski A,
Henson DE, et al. Malignant mesothelioma following radiation exposure. J Clin Oncol 1983;1:695–700.
Stock RJ, Fu YS, Carter JR. Malignant peritoneal mesothelioma following radiotherapy for seminoma of the testis. Cancer 1979;44:914–9.
Babcock TL, Powell DH, Bothwell RS. Radiation-induced
peritoneal mesothelioma. J Surg Oncol 1976;8:369–72.
Antman KH, Ruxer RL, Aisner J, Vawter G. Mesothelioma following Wilms’ tumor in childhood. Cancer 1984;54:367–9.
Anderson KA, Hurley WC, Hurley BT, Ohrt DW. Malignant
pleural mesothelioma following radiotherapy in a 16-year
old boy. Cancer 1985;56:273–6.
Kawashima A, Libshitz HI, Lukerman JM. Radiation-induced
malignant pleural mesothelioma. Can Assoc Radiol J 1990;
41:384–6.
Shannon VR, Nesbitt JC, Libshitz HI. Malignant mesothelioma after radiation therapy for breast cancer: a report of
two additional patients. Cancer 1995;76:437–41.
Cavazza A, Travis LB, Travis WD, Wolfe JT, Foo ML, Gillespie
DJ, et al. Post-irradiation malignant mesothelioma. Cancer
1996;77:1379–85.
Andersson M, Wallin H, Jonsson M, Nielsen LL, Visfeldt J,
Vyberg M, et al. Lung carcinoma and malignant mesothelioma in patients exposed to thorotrast: incidence, histology
and p53 status. Int J Cancer 1995;63:330–6.
Sanders CL, Jackson TA. Induction of mesotheliomas and
sarcomas from ‘‘hotspots’’ of 239PuO2 activity. Health Phys
1972;22:755–9.
Warren S, Brown CE, Chute RN, Federman M. Mesothelioma
relative to asbestos, radiation, and methylcholanthrene.
Arch Pathol Lab Med 1981;105:305–12.
National Cancer Institute. Surveillance, Epidemiology, and
End-Results (SEER) Public Use Tape (1973–93), [audiocassette]. National Cancer Institute, producers. Bethesda, MD:
DCPC, Surveillance Program Cancer Statistics Branch, 1996.
Neugut AI, Murray TI, Lee WC, Robinson E. The association
of breast cancer and colorectal cancer in men. An analysis
of SEER program data. Cancer 1991;68:2069–73.
Breslow NE, Day NE. Statistical methods of cancer research.
Volume 2. The design and analysis of cohort studies. IARC
Scientific Pub. No. 82. Lyon: International Agency for Research on Cancer, 1987:65–71.
Robinson E, Neugut AI, Wylie P. Clinical aspects of postirradiation sarcomas. J Natl Cancer Inst 1988;80:233–40.
Neugut AI, Robinson E, Lee WC, Murray T, Karwoski K,
Kutcher GJ. Lung cancer after radiation therapy for breast
cancer. Cancer 1993;71:3054–7.
Neugut AI, Murray T, Santos J, Amols H, Hayes MK, Flannery
JT, et al. Increased risk of lung cancer following breast cancer radiation therapy in cigarette smokers. Cancer 1994;
73:1615–20.
Curtis RE, Boice JD Jr., Stovall M, Bernstein L, Greenberg
RS, Flannery JT, et al. Risk of leukemia after chemotherapy
and radiation treatment for breast cancer. N Engl J Med
1992;326:1745–51.
Boice JD Jr., Harvey ED, Blettner M, Stovall M, Flannery
JT. Cancer in the contralateral breast after radiotherapy for
breast cancer. N Engl J Med 1992;326:781–5.
Tucker MA. Secondary cancers. In: DeVita VT Jr., Hellman
S, Rosenberg SA, editors. Cancer: principles and practice of
oncology. 4th edition. Philadelphia: J.B. Lippincott, 1993:
2407–16.
W: Cancer
Документ
Категория
Без категории
Просмотров
4
Размер файла
60 Кб
Теги
1/--страниц
Пожаловаться на содержимое документа