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Letter to the Editor Re: “Mesothelioma and asbestos”
Regulatory Toxicology and Pharmacology 52 (2008) 353–354
Contents lists available at ScienceDirect
Regulatory Toxicology and Pharmacology journal homepage: www.elsevier.com/locate/yrtph
Letter to the Editor
Letter to the Editor Re: ‘‘Mesothelioma and asbestos” q In a review of malignant mesothelioma (MM) and asbestos by Gibbs and Berry (2008), the authors indicated, without citing specific investigations, that limited studies to date have not supported an association between MM and antecedent therapeutic irradiation. The authors did note, however, that anecdotal evidence suggests that therapeutic irradiation is ‘‘highly likely to be an occasional cause of mesothelioma.” We would like to bring to the authors’ attention that an increasing number of epidemiologic studies published in the last few years have reported an association between high-dose radiation and the subsequent development of MM (Travis et al., 2005; Brown et al., 2006, 2007; Tward et al., 2006; Deutsch et al., 2007; Hodgson et al., 2007; Teta et al., 2007). In a Surveillance Epidemiology and End Results (SEER) program-based study (1973–1993) of 62,453 breast cancer survivors initially treated with radiation (Neugut et al., 1997), a non-statistically significant excess of pleural MM was reported (relative risk [RR] = 1.8, N = 2 cases), while no excess was observed among breast cancer survivors who did not receive radiation (RR = 0.9, N = 4 cases). No cases of pleural MM occurred among irradiated Hodgkin lymphoma (HL) survivors, but the authors pointed out that the study was limited by a relatively short follow-up period. In 2005, Travis et al. reported a significantly elevated fourfold RR for pleural MM in a large, international population-based study of nearly 13,000 testicular cancer patients initially treated with radiotherapy alone. These results were interpreted with the understanding that, in the past, supra-diaphragmatic irradiation was delivered in high-doses (on the order of 30 gray) to the mediastinum to treat testicular cancer. In a subsequent population-based study of 21,111 irradiated survivors of non-Hodgkin lymphoma (NHL) reported to the SEER program, Tward et al. (2006) reported a significantly elevated risk of MM (standardized incidence ratio [SIR] = 2.3, N = 9 cases). In contrast, the risk among over 55,000 NHL patients who did not initially receive radiotherapy was not elevated (SIR = 0.9, N = 9 cases). In another SEER program-based investigation (1973–2003), Teta et al. (2007) reported a statistically significant excess of MM among male HL patients whose initial treatment included radiotherapy (SIR = 6.6, N = 4 cases); no excess of MM was observed among male HL patients whose initial treatment did not include radiotherapy (SIR = 1.3, N = 1 case). In an international study of HL survivors, Hodgson et al. (2007) found a significantly increased 20-fold risk of pleural MM among over 18,000 five-year HL survivors reported to population-based registries in Europe and the SEER program (1973–1995), although treatment type was not specifically addressed.
q
See Gibbs and Berry (2008).
0273-2300/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.yrtph.2008.07.001
Two studies of breast cancer survivors have reported excesses of MM among women whose initial therapy included radiation. Brown et al. (2007) found a significantly elevated risk of pleural MM (SIR = 1.4, N = 40) among 376,825 one-year breast cancer survivors in Sweden, Denmark, Finland, and Norway. The SIR for the subgroup of 22 pleural MM that occurred among breast cancer patients reported to registries that routinely record treatment data was significantly increased (SIR = 1.8, N = 15 cases) for women initially given radiotherapy, compared to an SIR of 0.95 (N = 7 cases) for those who did not receive radiotherapy (Brown et al., 2006). Likewise, Deutsch et al. (2007) reported a significantly increased risk (RR = 3.7, N = 3 cases) of pleural MM among 9432 breast cancer patients given radiotherapy in clinical trials, noting that none of these patients had known exposure to asbestos. In contrast, no cases of MM were observed (expected = 1.1) among the 12,798 breast cancer patients who did not receive radiation. Given the low population incidence rates of MM, it has been possible to detect elevated risks only when large numbers of patients given radiotherapy are followed long-term. Nearly all of the studies described above (Neugut et al., 1997; Travis et al., 2005; Tward et al., 2006; Brown et al., 2007; Hodgson et al., 2007; Teta et al., 2007) were conducted in population-based cancer registries, which include only initial treatment data and do not collect information related to asbestos exposure. Since decisions to administer radiotherapy for cancer, however, are unrelated to asbestos exposure, it is unlikely that confounding by asbestos exposure accounts for the reported associations. Moreover, the association of MM with antecedent radiotherapy was observed for various types of cancer (i.e., testis cancer, breast cancer, HL, and NHL), and not observed among those patients who did not receive irradiation (Neugut et al., 1997; Brown et al., 2006; Tward et al., 2006; Deutsch et al., 2007; Teta et al., 2007). Any misclassification of radiation exposure in the cancer registrybased studies would likely tend to minimize observed associations. Conflict of interest No funding was obtained for the preparation of this letter. LBT and MEW have performed consulting work for companies involved in asbestos friction product litigation since 2007 and 2006, respectively, although this work has not influenced their opinions in this letter.
References Brown, L.M., Howard, R., Travis, L.B., 2006. The risk of secondary malignancies over 30 years after the treatment of Non-Hodgkin Lymphoma. Cancer 107, 2741– 2743.
354
Letter to the Editor / Regulatory Toxicology and Pharmacology 52 (2008) 353–354
Brown, L.M., Chen, B.E., Pfeiffer, R.M., Schairer, C., Hall, P., Storm, H., Pukkala, E., Langmark, F., Kaijser, M., Andersson, M., Joensuu, H., Fosså, S.D., Travis, L.B., 2007. Risk of second non-hematological malignancies among 376,825 breast cancer survivors. Breast Cancer Res. Treat. 106, 439–451. Deutsch, M., Land, S.R., Begovic, M., Cecchini, R., Wolmark, N., 2007. An association between postoperative radiotherapy for primary breast cancer in 11 National Surgical Adjuvant Breast and Bowel Project (NSABP) studies and the subsequent appearance of pleural mesothelioma. Am. J. Clin. Oncol. 30, 294–296. Gibbs, G.W., Berry, G., 2008. Mesothelioma and asbestos. Regulatory Toxicology and Pharmacology 52, S223–S231. Hodgson, D.C., Gilbert, E.S., Dores, G.M., Schonfeld, S.J., Lynch, C.F., Storm, H., Hall, P., Langmark, F., Pukkala, E., Andersson, M., Kaijser, M., Joensuu, H., Fosså, S.D., Travis, L.B., 2007. Long-term solid cancer risk among 5-year survivors of Hodgkin’s lymphoma. J. Clin. Oncol. 25, 1489–1497. Neugut, A.I., Ahsan, H., Antman, K.H., 1997. Incidence of malignant pleural mesothelioma after thoracic radiotherapy. Cancer 80, 948–950. Teta, M.J., Lau, E., Sceurman, B.K., Wagner, M.E., 2007. Therapeutic radiation for lymphoma: risk of malignant mesothelioma. Cancer 109, 1432–1438.
Travis, L.B., Fosså, S.D., Schonfeld, S.J., McMaster, M.L., Lynch, C.F., Storm, H., Hall, P., Holowaty, E., Andersen, A., Pukkala, E., Andersson, M., Kaijser, M., Gospodarowicz, M., Joensuu, T., Cohen, R.J., Boice Jr., J.D., Dores, G.M., Gilbert, E.S., 2005. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J. Natl. Cancer Inst. 97, 1354–1365. Tward, J.D., Wendland, M.M., Shrieve, D.C., Szabo, A., Gaffney, D.K., 2006. The risk of secondary malignancies over 30 years after the treatment of non-Hodgkin lymphoma. Cancer 107, 108–115.
Meghan E. Wagner Lois B. Travis Exponent, Inc., Health Sciences Practice, 420 Lexington Avenue, Suite 1740, New York 10170, USA Fax: +1 212 895 8199. E-mail address: [email protected] (M.E. Wagner) Available online 17 July 2008
Contents lists available at ScienceDirect
Regulatory Toxicology and Pharmacology journal homepage: www.elsevier.com/locate/yrtph
Letter to the Editor
Letter to the Editor Re: ‘‘Mesothelioma and asbestos” q In a review of malignant mesothelioma (MM) and asbestos by Gibbs and Berry (2008), the authors indicated, without citing specific investigations, that limited studies to date have not supported an association between MM and antecedent therapeutic irradiation. The authors did note, however, that anecdotal evidence suggests that therapeutic irradiation is ‘‘highly likely to be an occasional cause of mesothelioma.” We would like to bring to the authors’ attention that an increasing number of epidemiologic studies published in the last few years have reported an association between high-dose radiation and the subsequent development of MM (Travis et al., 2005; Brown et al., 2006, 2007; Tward et al., 2006; Deutsch et al., 2007; Hodgson et al., 2007; Teta et al., 2007). In a Surveillance Epidemiology and End Results (SEER) program-based study (1973–1993) of 62,453 breast cancer survivors initially treated with radiation (Neugut et al., 1997), a non-statistically significant excess of pleural MM was reported (relative risk [RR] = 1.8, N = 2 cases), while no excess was observed among breast cancer survivors who did not receive radiation (RR = 0.9, N = 4 cases). No cases of pleural MM occurred among irradiated Hodgkin lymphoma (HL) survivors, but the authors pointed out that the study was limited by a relatively short follow-up period. In 2005, Travis et al. reported a significantly elevated fourfold RR for pleural MM in a large, international population-based study of nearly 13,000 testicular cancer patients initially treated with radiotherapy alone. These results were interpreted with the understanding that, in the past, supra-diaphragmatic irradiation was delivered in high-doses (on the order of 30 gray) to the mediastinum to treat testicular cancer. In a subsequent population-based study of 21,111 irradiated survivors of non-Hodgkin lymphoma (NHL) reported to the SEER program, Tward et al. (2006) reported a significantly elevated risk of MM (standardized incidence ratio [SIR] = 2.3, N = 9 cases). In contrast, the risk among over 55,000 NHL patients who did not initially receive radiotherapy was not elevated (SIR = 0.9, N = 9 cases). In another SEER program-based investigation (1973–2003), Teta et al. (2007) reported a statistically significant excess of MM among male HL patients whose initial treatment included radiotherapy (SIR = 6.6, N = 4 cases); no excess of MM was observed among male HL patients whose initial treatment did not include radiotherapy (SIR = 1.3, N = 1 case). In an international study of HL survivors, Hodgson et al. (2007) found a significantly increased 20-fold risk of pleural MM among over 18,000 five-year HL survivors reported to population-based registries in Europe and the SEER program (1973–1995), although treatment type was not specifically addressed.
q
See Gibbs and Berry (2008).
0273-2300/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.yrtph.2008.07.001
Two studies of breast cancer survivors have reported excesses of MM among women whose initial therapy included radiation. Brown et al. (2007) found a significantly elevated risk of pleural MM (SIR = 1.4, N = 40) among 376,825 one-year breast cancer survivors in Sweden, Denmark, Finland, and Norway. The SIR for the subgroup of 22 pleural MM that occurred among breast cancer patients reported to registries that routinely record treatment data was significantly increased (SIR = 1.8, N = 15 cases) for women initially given radiotherapy, compared to an SIR of 0.95 (N = 7 cases) for those who did not receive radiotherapy (Brown et al., 2006). Likewise, Deutsch et al. (2007) reported a significantly increased risk (RR = 3.7, N = 3 cases) of pleural MM among 9432 breast cancer patients given radiotherapy in clinical trials, noting that none of these patients had known exposure to asbestos. In contrast, no cases of MM were observed (expected = 1.1) among the 12,798 breast cancer patients who did not receive radiation. Given the low population incidence rates of MM, it has been possible to detect elevated risks only when large numbers of patients given radiotherapy are followed long-term. Nearly all of the studies described above (Neugut et al., 1997; Travis et al., 2005; Tward et al., 2006; Brown et al., 2007; Hodgson et al., 2007; Teta et al., 2007) were conducted in population-based cancer registries, which include only initial treatment data and do not collect information related to asbestos exposure. Since decisions to administer radiotherapy for cancer, however, are unrelated to asbestos exposure, it is unlikely that confounding by asbestos exposure accounts for the reported associations. Moreover, the association of MM with antecedent radiotherapy was observed for various types of cancer (i.e., testis cancer, breast cancer, HL, and NHL), and not observed among those patients who did not receive irradiation (Neugut et al., 1997; Brown et al., 2006; Tward et al., 2006; Deutsch et al., 2007; Teta et al., 2007). Any misclassification of radiation exposure in the cancer registrybased studies would likely tend to minimize observed associations. Conflict of interest No funding was obtained for the preparation of this letter. LBT and MEW have performed consulting work for companies involved in asbestos friction product litigation since 2007 and 2006, respectively, although this work has not influenced their opinions in this letter.
References Brown, L.M., Howard, R., Travis, L.B., 2006. The risk of secondary malignancies over 30 years after the treatment of Non-Hodgkin Lymphoma. Cancer 107, 2741– 2743.
354
Letter to the Editor / Regulatory Toxicology and Pharmacology 52 (2008) 353–354
Brown, L.M., Chen, B.E., Pfeiffer, R.M., Schairer, C., Hall, P., Storm, H., Pukkala, E., Langmark, F., Kaijser, M., Andersson, M., Joensuu, H., Fosså, S.D., Travis, L.B., 2007. Risk of second non-hematological malignancies among 376,825 breast cancer survivors. Breast Cancer Res. Treat. 106, 439–451. Deutsch, M., Land, S.R., Begovic, M., Cecchini, R., Wolmark, N., 2007. An association between postoperative radiotherapy for primary breast cancer in 11 National Surgical Adjuvant Breast and Bowel Project (NSABP) studies and the subsequent appearance of pleural mesothelioma. Am. J. Clin. Oncol. 30, 294–296. Gibbs, G.W., Berry, G., 2008. Mesothelioma and asbestos. Regulatory Toxicology and Pharmacology 52, S223–S231. Hodgson, D.C., Gilbert, E.S., Dores, G.M., Schonfeld, S.J., Lynch, C.F., Storm, H., Hall, P., Langmark, F., Pukkala, E., Andersson, M., Kaijser, M., Joensuu, H., Fosså, S.D., Travis, L.B., 2007. Long-term solid cancer risk among 5-year survivors of Hodgkin’s lymphoma. J. Clin. Oncol. 25, 1489–1497. Neugut, A.I., Ahsan, H., Antman, K.H., 1997. Incidence of malignant pleural mesothelioma after thoracic radiotherapy. Cancer 80, 948–950. Teta, M.J., Lau, E., Sceurman, B.K., Wagner, M.E., 2007. Therapeutic radiation for lymphoma: risk of malignant mesothelioma. Cancer 109, 1432–1438.
Travis, L.B., Fosså, S.D., Schonfeld, S.J., McMaster, M.L., Lynch, C.F., Storm, H., Hall, P., Holowaty, E., Andersen, A., Pukkala, E., Andersson, M., Kaijser, M., Gospodarowicz, M., Joensuu, T., Cohen, R.J., Boice Jr., J.D., Dores, G.M., Gilbert, E.S., 2005. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J. Natl. Cancer Inst. 97, 1354–1365. Tward, J.D., Wendland, M.M., Shrieve, D.C., Szabo, A., Gaffney, D.K., 2006. The risk of secondary malignancies over 30 years after the treatment of non-Hodgkin lymphoma. Cancer 107, 108–115.
Meghan E. Wagner Lois B. Travis Exponent, Inc., Health Sciences Practice, 420 Lexington Avenue, Suite 1740, New York 10170, USA Fax: +1 212 895 8199. E-mail address: [email protected] (M.E. Wagner) Available online 17 July 2008