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© 2000 American Society for Clinical Oncology Second Malignant Neoplasms After Treatment for Hodgkin’s Disease in Childhood or AdolescenceFrom the Departments of Pediatrics, Cancer Prevention, Epidemiology and Biostatistics, Pathology, Radiation Medicine, and Psychology, Roswell Park Cancer Institute; Departments of Pediatrics and Social and Preventive Medicine, School of Medicine and Biomedical Sciences, and Department of Natural Sciences, Roswell Park Graduate Division, University at Buffalo, State University of New York, Buffalo, NY. Address reprint requests to Daniel M. Green, MD, Department of Pediatrics, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY 14263; email daniel.green{at}roswellpark.org
PURPOSE: To determine the frequency of and risk factors for second malignant neoplasms (SMNs) after treatment for Hodgkin’s disease diagnosed in children and adolescents. PATIENTS AND METHODS: One hundred eighty-two consecutive, previously untreated patients with Hodgkin’s disease who were younger than 20 years of age at diagnosis and who were referred to Roswell Park Cancer Institute (Buffalo, NY) for treatment between January 1, 1960, and December 31, 1989, were studied. Sex-specific standardized incidence ratios (SIRs) were calculated. Kaplan-Meier survival estimates and Cox regression analyses were performed to determine the relationship of several demographic and treatment variables to SMN incidence. RESULTS: Twenty-eight patients developed an SMN at a mean of 14.93 ± 8.09 years (range, 2.65 to 29.88 years) after diagnosis of Hodgkin’s disease. The cumulative percentage of patients who developed an SMN was 26.27 ± 6.75% at 30 years after diagnosis. The SIR was 9.39 (95% confidence interval [CI], 4.05 to 18.49) for male patients and 10.16 (95% CI, 5.56 to 17.05) for female patients. The most frequent SMNs were thyroid cancer, breast cancer, nonmelanoma skin cancer, non-Hodgkin’s lymphoma, and acute leukemia. Multivariate analysis of sex, treatment with any alkylating agent, treatment with doxorubicin, splenectomy, and relapse (as a time-dependent covariate) with time to SMN onset gave nonsignificant results. CONCLUSION: Successfully treated children and adolescents with Hodgkin’s disease have a substantial risk for the occurrence of subsequent neoplasms. The most frequent SMNs (skin, thyroid, and breast) are readily detected by physical examination and available screening procedures.
THE TREATMENT OF Hodgkin’s disease in adults and children has become quite successful with the introduction of modern radiation therapy techniques1,2 and the identification of effective combination chemotherapy regimens.3,4 The 5-year survival rate for children with Hodgkin’s disease now exceeds 90%.5 The prolonged survival of patients with Hodgkin’s disease has permitted the identification of an important complication of these successful treatment strategies: the occurrence of treatment-induced second (and subsequent) malignant neoplasms (SMNs). These have been reported after treatment of adults6-8 and children and adolescents.9-17 Although solid tumors that occur after the completion of treatment are considered to be a complication produced by radiation therapy, the occurrence of acute leukemia after treatment is almost always associated with prior treatment with combination chemotherapy.18-21 We undertook the present study to evaluate the frequency of and risk factors for the occurrence of SMNs in a well-characterized cohort of children and adolescents who were treated between 1960 and 1990 for Hodgkin’s disease at a single institution in accordance with cooperative group protocols.
The Long-Term Follow-Up Project is a comprehensive study of a cohort of consecutive, previously untreated patients who were younger than 20 years of age at diagnosis. The methods used for this study have been reported previously.22 One hundred eighty-two of the members of the cohort were diagnosed with Hodgkin’s disease. Annual contact with the patients who survived was maintained through clinic visits or by mail. Mail contact was maintained for many patients through participation in the Long-Term Follow-Up Project. Others were contacted directly by the central follow-up clerk of the Medical Records Department of Roswell Park Cancer Institute (Buffalo, NY), who maintained a file of contact persons for each patient. No patient with Hodgkin’s disease included in this cohort has been lost to follow-up. Of the 119 surviving patients, two were last contacted in 1996; six through March 18, 1997; 22 between March 19, 1997, and March 18, 1998; and 89 between March 19, 1998, and March 18, 1999.
Statistical Procedures
One hundred eighty-two previously untreated patients with Hodgkin’s disease are included in this analysis. One hundred patients were male, and 176 were white. Eighty-three had one or more recurrences of Hodgkin’s disease. The mean age at diagnosis (± SD) was 15.30 ± 3.67 years. The mean age at last follow-up or death was 32.59 ± 10.27 years. The mean duration of follow-up was 17.28 ± 9.79 years (median, 17.12 years; range, 0.29 to 37.68 years). The male patients had accumulated 1,614.96 years and the female patients had accumulated 1,419.94 years of survival. Twenty-eight patients developed 36 subsequent neoplasms (Table 1). Nine patients who developed SMNs died; seven as a result of the SMN, one because of respiratory failure, and one because of progressive Hodgkin’s disease.
All SMNs The cumulative percentage of patients who developed an SMN was 3.82% ± 1.53% at 10 years after diagnosis, 8.02% ± 2.35% at 15 years after diagnosis, 12.71% ± 3.20% at 20 years after diagnosis, 16.11% ± 3.88% at 25 years after diagnosis, and 26.27% ± 6.75% at 30 years after diagnosis of Hodgkin’s disease (Fig 1). There was no difference in the frequency of SMNs by the variables of sex (P = .3069), race (P = .4611), age group (0 to 9 years or 10 to 19 years; P = .7986), treatment with radiation therapy (P = .4795), treatment with chemotherapy (P = .4408), treatment with any alkylating agent (P = .4051), treatment with doxorubicin (P = .4116), splenectomy (P = .0546), or relapse (P = .7666).
Breast Cancer Four of 82 women developed breast cancer 12.79 to 26.07 years after diagnosis of Hodgkin’s disease. Three women were postmenopausal when breast cancer was diagnosed, and one was perimenopausal. Three had received hormone replacement therapy for 12 (one patient) to 60 (two patients) months. Two tumors were located in the upper-outer quadrant, one was located in the lower-outer quadrant, and one was located in the inner half of the breast. Two tumors were estrogen receptor-positive and two were estrogen receptor-negative. Both estrogen receptor–positive tumors were also progesterone receptor-positive. The cumulative percentage of patients who developed breast cancer was 11.89% ± 6.05% at 30 years after diagnosis of Hodgkin’s disease.
Non-Hodgkin’s Lymphoma
Thyroid Cancer
Leukemia
SIR
The SIR for female patients for an SMN at any site was 10.16 (Table 3). The SIRs were significantly elevated for female patients who were 30 to 34 and 40 to 44 years of age after adjustment for the nine age groups evaluated (P < .0055; .05/9) (data not shown). The SIRs were increased for those treated with an alkylating agent, for those treated with doxorubicin, for those who had undergone splenectomy, and for those treated with radiation therapy and chemotherapy, but not for those treated with radiation therapy only (Table 3)
Non-Hodgkin’s lymphoma. The SIR for male patients for non-Hodgkin’s lymphoma was 14.3 (95% CI, 1.73 to 51.66; P = .02). The SIRs were not significantly elevated for male patients in any of the age groups after adjustment for the 12 age groups evaluated (data not shown). The SIRs were increased for those who had undergone splenectomy (data not shown). The SIR for female patients for non-Hodgkin’s lymphoma was 22.95 (95% CI, 0.58 to 127.84; P = .09). The SIR was not significantly elevated for female patients in any of the age groups after adjustment for the nine age groups evaluated (data not shown). The SIR was increased for those treated with radiation therapy only (data not shown). Thyroid cancer. The SIR for male patients for thyroid cancer was 158.75 (95% CI, 32.74 to 463.93; P < .00001). The SIRs were significantly elevated for male patients who were 15 to 19 and 30 to 34 years of age after adjustment for the 12 age groups evaluated (data not shown). The SIRs were increased for those who had undergone a splenectomy and for those treated with radiation therapy only (data not shown). The SIR for female patients for thyroid cancer was 38.02 (95% CI, 7.84 to 111.11; P = .00015). The SIRs were not significantly elevated for female patients in any of the age groups after adjustment for the nine age groups evaluated (data not shown). The SIRs were increased for those treated with an alkylating agent, for those who had undergone splenectomy, and for those treated with radiation therapy and chemotherapy (data not shown). Leukemia. The SIR for male patients for leukemia was 18.94 (95% CI, 0.48 to 105.55; P = .10). The SIR was not significantly elevated for male patients in any of the age groups after adjustment for the 12 age groups evaluated (data not shown). The SIRs were not elevated for male patients with any of the treatment exposures evaluated. The SIR for female patients for leukemia was 24.99 (95% CI, 0.63 to 139.25; P = .08). The SIR was not significantly elevated for female patients in any of the age groups after adjustment for the nine age groups evaluated (data not shown). The SIR was increased for those treated with doxorubicin. Breast cancer. The SIR for breast cancer was 7.77 (95% CI, 2.12 to 19.89; P = .00389). The SIR for breast cancer was significantly elevated for female patients who were 30 to 34 years of age after adjustment for the nine age groups evaluated (data not shown). The SIRs were increased for those treated with an alkylating agent, those who had undergone splenectomy, and those treated with radiation therapy and chemotherapy (data not shown).
Time After Diagnosis of Hodgkin’s Disease The SIRs for all sites for female patients were significantly elevated 0 to 4 and 25 to 29 years after diagnosis after adjustment for the six groups evaluated (P < .0083; .05 divided by six comparisons) (data not shown). The SIR for breast cancer was significantly elevated 15 to 19 years after diagnosis (data not shown). The SIR for thyroid cancer was elevated 20 to 24 years after diagnosis (data not shown).
Multivariate Analysis
The present study was conducted to estimate the frequency of and risk factors for the occurrence of SMNs in a well-characterized cohort of previously untreated children and adolescents with Hodgkin’s disease who were treated at a single institution with complete follow-up. We identified 36 new cancers in 28 patients. The 10-, 15-, 20-, and 30-year actuarial estimates for SMNs in the present series are 3.8%, 8.0%, 12.7%, and 26.3%, respectively. The 15-year percentage is similar to that reported by Saint Jude Children’s Research Hospital (SJCRH; 7.7%)11 and by the Late Effects Study Group (LESG; 7.0%),14 both of which are lower than the rate of 18.7% at 15 years reported by Memorial Sloan-Kettering Cancer Center.9 The percentages are higher than those reported from the Nordic countries, which were 1.9%, 6.9%, and 18% at 10, 20, and 30 years, respectively.12 The reasons for this difference cannot be determined, because the Nordic series did not report the distribution of different treatment modalities within their cohort. The Nordic series, as well as those from SJCRH11 and The Hospital for Sick Children/Princess Margaret Hospital,13 included nonmelanoma skin cancer in the actuarial estimates of SMN frequency. This will produce higher SMN frequency estimates than those reported by centers that excluded nonmelanoma skin cancer from consideration. The SIRs for male and female patients in the present series were 9.39 (95% CI, 4.05 to 18.49) and 10.16 (95% CI, 5.56 to 17.05), respectively. The SIRs for male patients in previous series have been 18 (95% CI, 6 to 42),10 6.5 (95% CI, 4.3 to 9.6),12 and 10.6 (95% CI, 6.6 to 16).15 The SIRs for female patients in previous series have been 57 (95% CI, 27 to 105),10 8.9 (95% CI, 6.2 to 12),12 and 15.4 (95% CI, 10.6 to 21.5).15 Thus, as in the present series, the 95% CIs for the SIRs for male and female patients have overlapped, suggesting that there is not a sex difference in overall SMN incidence. The SIR for breast cancer in the present series (7.77; 95% CI, 2.12 to 19.89), although elevated significantly, was not as dramatically increased as in other series, such as that from Stanford University Medical Center (SUMC; 26.2; 95% CI, 15 to 42.6),15 SJCRH (33.2; 95% CI, 12.1 to 72.4),16 the LESG (75.3; 95% CI, 44.9 to 118.4),14 the Statistics, Epidemiology and End Results Program (60.57; 95% CI, 22.1 to 132),17 or the Nordic countries (17; 95% CI, 9.9 to 28).12 Truncated follow-up of healthy female survivors and aggressive reporting by survivors of subsequent cases of cancer could produce substantial errors in SIR estimates. All of the surviving women in the present cohort have been contacted in 1997 or 1998, assuring that such reporting bias is not a factor in the present analysis. In addition, it is difficult to estimate the effect that mammographic screening has on both the frequency of breast cancer diagnosed in survivors of Hodgkin’s disease and the frequency of breast cancer in various population-based registries, such the Statistics, Epidemiology and End Results registry. Failure to obtain pathology reports that confirm the diagnosis of invasive breast carcinoma and/or comparison of recently diagnosed cases with population rates obtained before the widespread use of mammographic screening in the general population are additional sources of error in estimation of the relative risk of breast cancer in cohorts of Hodgkin’s disease survivors. Differences in breast cancer rates in Hodgkin’s disease survivors may be related to treatment differences. The mantle radiation therapy dose used at Roswell Park Cancer Institute during the period of this review was lower than that used at other centers.29 The data of the LESG suggest that the risk of breast cancer may be lower when doses of 20 to 40 Gy are used.14 However, breast cancer is a known complication of low-dose breast radiation.30 Thus breast cancer may remain a risk among adolescent women who receive any dose of thoracic irradiation for Hodgkin’s disease, as the available data show a linear relation of dose to breast cancer incidence and the highest SIR of breast cancer among those who are irradiated before they are 20 years old.31 Thyroid cancer was the most frequently diagnosed SMN in the present cohort. The SIR was 158.75 (95% CI, 32.74 to 463.93) among male patients and 38.02 (95% CI, 7.84 to 111.11) among female patients. The SIR for thyroid cancer in the five Nordic countries study was 55 (95% CI, 15 to 140) among male patients and 25 (95% CI, 8 to 57) among female patients.12 The SIR for male and female patients combined was 9.7 (95% CI, 2.4 to 26.4) for those who were treated at SUMC15 and 32.7 (95% CI, 15.3 to 55.3) for those reported by the LESG.14 The SIR for thyroid cancer was not estimated in the remaining studies of SMNs in survivors of Hodgkin’s disease diagnosed during childhood or adolescence. Thyroid neoplasia is a well-recognized complication of incidental neck irradiation.30 The risk of thyroid cancer increases linearly with increasing radiation dose and is largest among those irradiated at the younger ages.32 Radiation doses greater than 2 Gy increase the risk of thyroid cancer by a factor of 13.33 Non-Hodgkin’s lymphoma was identified in three survivors of Hodgkin’s disease. The SIRs for male and female patients in the present series were 14.3 (95% CI, 1.73 to 51.66) and 22.95 (95% CI, 0.58 to 127.84), respectively. Previous reports provided SIRs for both sexes combined. The reported SIRs were 15 (95% CI, 4.9 to 35),12 11.3 (95% CI, 1.3 to 40.8),16 11.2 (95% CI, 2.3 to 32.9),15 and 20.9 (95% CI, 7.7 to 42).14 Two of the three cases in the present series were T-cell–rich, B-cell lymphoma.34 We observed only two cases of leukemia as an SMN, despite the substantial exposure of our cohort to alkylating agents. The SIRs for leukemia among male and female patients in the present series were 18.94 (95% CI, 0.48 to 105.55) and 24.99 (95% CI, 0.63 to 139.25), respectively. Neither estimate was statistically significant. The SIRs reported in other series were 29.0 (95% CI, 7.8 to 74.2),16 17 (95% CI, 6.9 to 35),12 78.8 (95% CI, 56.6 to 123.2),14 and 40.9 (95% CI, 17.7 to 80.7).15 The most significant factors previously associated with leukemia as an SMN have been treatment with the combination of nitrogen mustard, vincristine, procarbazine, and prednisone,18,19 intensity of alkylating-agent treatment,14,20 and splenectomy.6,21,35 The increasing use of topoisomerase II inhibitors in chemotherapy regimens for children and adolescents with Hodgkin’s disease may lead to an increase in the frequency of treatment-related myelodysplastic syndrome and acute leukemia.36,37 We were not able to identify any risk factor that significantly increased the risk of any SMN or of specific SMNs (thyroid, breast, non-Hodgkin’s lymphoma, leukemia) because the 95% CIs for each of the variables examined (treatment with or without an alkylating agent, treatment with or without doxorubicin, splenectomy, and treatment with radiation therapy only or treatment with radiation therapy and chemotherapy) overlapped, although the risks in most of these groups were significantly elevated compared with those in the Connecticut population. We did not identify an effect of age at diagnosis on the risk of developing an SMN. Older age at diagnosis was identified as a risk factor for SMNs in one previous series11 but not in a subsequent analysis from the same institution.16 The failure to identify an effect of age at diagnosis on the risk of an SMN may also be related to the small number of patients in the youngest group (0 to 9 years of age), the number of events, and/or the duration of follow-up. Of the published single-institution series,9,10,11,13,15 only that from SUMC included a larger number of new cancers.15 The median follow-up of the patients in the current series is 16.7 years, compared with 9.0 years for the patients from SJCRH11 and 12.3 years for the patients from SUMC.15 Two large multi-institutional series included 5712 and 7914 SMNs in pediatric Hodgkin’s disease patients. The patients who were included in one large multi-institutional series had a median follow-up period of 11.4 years,14 and the median was not reported in the other.12 We did not demonstrate an effect of disease recurrence on the risk of an SMN. Such an effect has been reported in some series,11,13,15 but not in others.10 Inclusion of patients with Hodgkin’s disease who were referred to an institution only for management of disease relapse in analyses of risk factors for SMN occurrence may overestimate the significance of relapse as a risk factor. Although we were not able to identify treatment with radiation therapy as a risk factor for the occurrence of SMNs after treatment for Hodgkin’s disease in the multivariate analysis, this does not imply that there is not a radiation effect. Most patients in the present and previous studies have been treated with radiation therapy, with or without chemotherapy. Most solid SMNs occur within prior areas of radiation treatment. A minority of patients were treated with chemotherapy only. The failure to demonstrate an effect of radiation therapy may be an artifact due to the small sample of patients treated with chemotherapy only. Treatment with an alkylating agent, with doxorubicin, with radiation therapy and chemotherapy, or splenectomy were each associated with significant increases in the SIRs of all SMNs among female patients. Doxorubicin was shown to be a significant risk factor for the occurrence of SMNs.38 Independent effects of radiation therapy and treatment with doxorubicin on the SIR of SMNs were reported by the National Wilms Tumor Study Group39 and are consistent with experimental40,41 and clinical42 findings of modulation of effective radiation dose by administration of doxorubicin. In addition, the present data are consistent with that of a previous report of independent effects of radiation therapy dose and intensity of treatment with alkylating agents on the risk of treatment-related bone sarcomas.43 Splenectomy, treatment with an alkylating agent, and treatment with radiation therapy and chemotherapy were associated with increased SIRs for all SMNs among male patients. The finding that splenectomy status may be associated with an increased risk of SMNs is consistent with a previous report in adults.7 Previous reports of SMNs in pediatric patients showed no effect of splenectomy on SMN11,15 or leukemia incidence.14 These differences may be partly explained by temporal trends, with splenectomy being less likely to have been performed on more recently treated patients.15 The results of the present study suggest that careful attention to skin, breast, and thyroid examination, in addition to the use of cost-effective screening techniques, are most likely to facilitate early detection of three of the most frequent treatment-related SMNs in Hodgkin’s disease survivors. Routine mammography has been recommended starting 844,45 or 1046 years after radiation treatment for Hodgkin’s disease that includes part or all of the breast, although there are no data that rigorously demonstrate the efficacy of such an approach.47 Routine high-resolution real-time ultrasound screening of the thyroid gland after neck irradiation has not been evaluated prospectively in an irradiated population. The role for this intervention is thus not known.48 In the future, genetic screening for cancer predisposition genes may allow screening interventions to be focused on those who are at highest risk. As these patients return to the care of community physicians, both the patients and their physicians must be educated regarding the future health risks related to the prior diagnosis and treatment of Hodgkin’s disease.
Supported by a 1997 Developmental Funds award from the Roswell Park Alliance Foundation. We thank Diane Piacente for her assistance with this research.
1. Carmel RJ, Kaplan HS: Mantle irradiation in Hodgkin’s disease. Cancer 37:2813-2825, 1976[Medline] 2. Kaplan HS: Hodgkin’s Disease (ed 2). Cambridge MA,Harvard University Press, 1980, pp 426-429 3. DeVita VT, Serpick AA, Carbone PP: Combination chemotherapy in the treatment of advanced Hodgkin’s disease. Ann Intern Med 73:881-895, 1970 4. Bonadonna G, Zucali R, Monfardini S, et al: Combination chemotherapy of Hodgkin’s disease with Adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer 36:252-259, 1975[Medline] 5. Ries LA, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics Review: 1973-1995. Bethesda, MD, National Institutes of Health, 1998 6. Abrahamsen JF, Andersen A, Hannisdal E, et al: Second malignancies after treatment of Hodgkin’s disease: The influence of treatment, follow-up time and age. Oncol 11:255-261, 1993
7.
Dietrich P-Y, Henry-Amar M, Cosset J-M, et al: Second primary cancers in patients continuously disease-free from Hodgkin’s disease: A protective role for the spleen? Blood 84:1209-1215, 1994
8.
Mauch PM, Kalish LA, Marcus KC, et al: Second malignancies after treatment for laparotomy staged IA-IIIB Hodgkin’s disease: Long-term analysis of risk factors and outcome. Blood 87:3625-3632, 1996 9. Kushner BH, Zauber A, Tan CTC: Second malignancies after childhood Hodgkin’s disease: The Memorial Sloan-Kettering Cancer Center experience. Cancer 62:1364-1370, 1988[Medline] 10. Tarbell NJ, Gelber RD, Weinstein HJ, et al: Sex differences in risk of second malignant tumours after Hodgkin’s disease in childhood. Lancet 341:1428-1432, 1993[Medline]
11.
Beatty O III, Hudson MM, Greenwald C, et al: Subsequent malignancies in children and adolescents after treatment for Hodgkin’s disease. J Clin Oncol 13:603-609, 1995
12.
Sankila R, Garwicz S, Olsen JH, et al: Risk of subsequent malignant neoplasms among 1,641 Hodgkin’s disease patients diagnosed in childhood and adolescence: A population-based cohort study in the five Nordic countries. J Clin Oncol 14:1442-1446, 1996 13. Jenkin D, Greenberg M, Fitzgerald A: Second malignant tumours in childhood Hodgkin’s disease. Pediatr Oncol 26:373-379, 1996
14.
Bhatia S, Robision LL, Oberlin O, et al: Breast cancer and other second neoplasms after childhood Hodgkin’s disease. J Med 334:745-751, 1996 15. Wolden SL, Lamborn KR, Cleary SF, et al: Second cancers following pediatric Hodgkin’s disease. J Clin Oncol 16:536-544, 1998[Abstract] 16. Hudson MM, Poquette CA, Lee J, et al: Increased mortality after successful treatment for Hodgkin’s disease. Oncol 16:3592-3600, 1998
17.
Travis LB, Curtis RE, Boice JD Jr: Late effects of treatment for childhood Hodgkin’s disease. N Engl J Med 335:352-353, 1996 (letter) 18. Blayney DW, Longo DL, Young RC, et al: Decreasing risk of leukemia with prolonged follow-up after chemotherapy and radiotherapy for Hodgkin’s disease. N Engl J Med 316:710-714, 1987[Abstract] 19. Pedersen-Bjergaard J, Specht L, Larsen SO, et al: Risk of therapy-related leukaemia and pre-leukaemia after Hodgkin’s disease: Relation to age, cumulative dose of alkylating agents, and time from chemotherapy. Lancet 11:83-88, 1987 20. Andrieu J-M, Ifrah N, Payen C, et al: Increased risk of secondary acute nonlymphocytic leukemia after extended-field radiation therapy combined with MOPP chemotherapy for Hodgkin’s disease. J Clin Oncol 8:1148-1154, 1990[Abstract]
21.
Tura S, Fiacchini M, Zinzani PL, et al: Splenectomy and the increasing risk of secondary acute leukemia in Hodgkin’s disease. J Clin Oncol 11:925-930, 1993
22.
Green DM, Hyland A, Chung CS, et al: Cancer and cardiac mortality among 15-year survivors of cancer diagnosed during childhood or adolescence. J Clin Oncol 17:3207-3215, 1999 23. Heaston JF, Kelly JAB, Meigs JW, et al: Forty-five years of cancer incidence in Connecticut: 1935-79. Natl Cancer Inst Monogr 70:1-706, 1986 24. National Cancer Institute: SEER Cancer Incidence Public-Use Database, 1973-1995, August 1997 Submission. Bethesda, MD, United States Department of Health and Human Services National Institutes of Health, National Cancer Institute, Cancer Statistics Branch, 1998 25. Breslow NE, Day NE: Statistical Methods in Cancer Research (vol 2): The Design and Analysis of Cohort Studies. Lyon, France, International Agency for Research on Cancer, 1987, pp 69-72 26. Neter J, Wasserman W, Kutner MH: Applied Linear Statistical Models (ed 3): Simultaneous Inferences and Other Topics in Regression Analysis. Homewood, IL, Richard D. Irwin, Inc, 1990 27. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457-481, 1958 28. Kalbfleisch JD, Prentice RL: The Statistical Analysis of Failure Time Data. New York, NY,Wiley, 1980, p 159
29.
Hancock SL, Tucker MA, Hoppe RT: Breast cancer after treatment of Hodgkin’s disease. Cancer Inst 85:25-31, 1993 30. Boice JD Jr, Land CE, Preston DL: Ionizing radiation, in Schottenfeld D, Fraumeni JF Jr (eds): Cancer Epidemiology and Prevention (ed 2). New York, NY,Oxford University Press, 1996, pp 319-354 31. Tokunaga M, Land CE, Tokuoka S, et al: Incidence of female breast cancer among atomic bomb survivors, 1950-1985. Radiat Res 138:209-223, 1994[Medline] 32. Ron E, Lubin JH, Shore RE, et al: Thyroid cancer after exposure to external radiation: A pooled analysis of seven studies. Radiat Res 141:259-277, 1995[Medline]
33.
Tucker MA, Morris-Jones PH, Boice JD Jr, et al: Therapeutic radiation at a young age is linked to secondary thyroid cancer. Cancer Res 51:2885-2888, 1991 34. Amini R-M, Enblad G, Sundstrom C, et al: Patients suffering from both Hodgkin’s disease and non-Hodgkin’s lymphoma: A clinico-pathological and immuno-histochemical population-based study of 32 patients. J Cancer 71:510-516, 1997 35. Kaldor JM, Day NE, Clarke EA, et al: Leukemia following Hodgkin’s disease. N Engl J Med 322:7-13, 1990[Abstract] 36. Pedersen-Bjergaard J, Daugaard G, Hansen SW, et al: Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ cell tumours. Lancet 338:359-363, 1991[Medline] 37. Hawkins MM, Kinnier Wilson LM, Stovall MA, et al: Epipodophyllotoxins, alkylating agents, and radiation and risk of secondary leukaemia after childhood cancer. BMJ 304:951-958, 1992 38. Green DM, Zevon MA, Reese PA, et al: Second malignant tumors following treatment during childhood and adolescence for cancer. Med Pediatr Oncol 22:1-10, 1994[Medline] 39. Breslow NE, Takashima JR, Whitton JA, et al: Second malignant neoplasms following treatment for Wilms tumor: A report from the National Wilms Tumor Study Group. Oncol 13:1851-1859, 1995 40. Phillips TL, Wharam MD, Margolis LW: Modification of radiation injury to normal tissues by chemotherapeutic agents. Cancer 35:1678-1684, 1975[Medline] 41. Redpath JL, Colman M: The effect of Adriamycin and actinomycin D on radiation induced skin reactions in mouse feet. Int J Radiat Oncol Biol Phys 5:483-486, 1979[Medline] 42. Cassady JR, Richter MP, Piro AJ, et al: Radiation Adriamycin interactions: Preliminary clinical observations. Cancer 36:946-949, 1975[Medline] 43. Tucker MA, D’Angio GJ, Boice JD, et al: Bone sarcoma linked to radiotherapy and chemotherapy in children. N Engl J Med 317:588-593, 1987[Abstract]
44.
Goss PE, Sierra S: Current perspectives on radiation-induced breast cancer. J Clin Oncol 16:338-347, 1998 45. Yahalom J, Petrek JA, Biddinger PW, et al: Breast cancer in patients irradiated for Hodgkin’s disease: A clinical and pathologic analysis of 45 events in 37 patients. Clin Oncol 10:1674-1681, 1992 46. Cutuli B, Dhermain F, Borel C, et al: Breast cancer in patients treated for Hodgkin’s disease: A clinical and pathological analysis of 76 cases in 63 patients. Eur J Cancer 33:2315-2320, 1997
47.
Shapiro CL, Mauch PM: Radiation-associated breast cancer after Hodgkin’s disease: Risks and screening in perspective. J Clin Oncol 10:1662-1665, 1992 (editorial) 48. Sarne D, Schneider AB: External radiation and thyroid neoplasia. Am 25:181-195, 1996 Submitted December 28, 1998; accepted December 6, 1999.
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Copyright © 2000 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
