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Incidence of Second Cancers in Patients Treated for Hodgkin's Disease

Background: Numerous studies of treatment for Hodgkin's disease have demonstrated large increases in the incidence of leukemia in the early years following chemotherapy, although the duration of effect and the specific agents involved are not well understood. Also, some, but not all, studies ha...

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Published in:JNCI : Journal of the National Cancer Institute 1995-05, Vol.87 (10), p.732-741
Main Authors: Boivin, Jean-François, Hutchison, George B., Zauber, Ann G., Bernstein, Leslie, Davis, Faith G., Michel, René P., Zanke, Brent, Tan, Charlotte T. C., Fuller, Lillian M., Mauch, Peter, Ultmann, John E.
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container_issue 10
container_start_page 732
container_title JNCI : Journal of the National Cancer Institute
container_volume 87
creator Boivin, Jean-François
Hutchison, George B.
Zauber, Ann G.
Bernstein, Leslie
Davis, Faith G.
Michel, René P.
Zanke, Brent
Tan, Charlotte T. C.
Fuller, Lillian M.
Mauch, Peter
Ultmann, John E.
description Background: Numerous studies of treatment for Hodgkin's disease have demonstrated large increases in the incidence of leukemia in the early years following chemotherapy, although the duration of effect and the specific agents involved are not well understood. Also, some, but not all, studies have indicated that the incidence of certain solid tumors increases following treatment for Hodgkin's disease. Purpose: We studied the association between treatment for Hodgkin's disease and the incidence of second cancers. Methods: We conducted a study within a cohort that included 10 472 patients from 14 cancer centers in the United States and Canada who were first diagnosed as having Hodgkin's disease at some point from 1940 through 1987. Discounting the 1st year after diagnosis, the average length of follow-up was 7.1 years per subject. Results: We observed 122 leukemias and 438 solid tumors. The relative risk (RR) of leukemia following chemotherapy, compared with no chemotherapy, was 14 (95% confidence interval [CI] = 5.6–35). Increased risks of leukemia were observed after treatment with chlorambucil (RR = 2.0; 95% CI = 1.1–3.6), procarbazine (RR = 4.9; 95% CI = 2.6–9.1), vinblastine (RR = 1.7; 95% CI = 1.1–2.8), and a group of rarely used drugs that included methotrexate, vindesine, etoposide, and 22 others (RR = 3.8; 95% CI = 1.9–7.4). RRs were also estimated for various combinations of drugs, including MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) (RR = 5.9; 95% CI = 2.9–12) and ABVD (doxorubicin, bleomycin, vinblastine, and dacar–bazine) (RR = 1.5; 95% CI = 0.7–3.4). The RR of leukemia associated with splenectomy was 1.6 (95% CI = 1.0–2.5). The RR of solid tumors following chemotherapy was 1.4 (95%CI = 1.1–1.8). For the group of rarely used drugs, the RR of solid tumors was 3.1 (95% CI = 1.7–5.8). Chemotherapy was associated with an increased risk of cancers of the bones, joints, articular cartilage, and soft tissues (RR = 6.0; 95% CI = 1.7–20), and cancers of the female genital system (RR = 1.8; 95% CI = 1.1–3.2). In patients followed for 10 or more years after radiotherapy, increased risks were found for cancers of the respiratory system and intrathoracic organs (RR = 2.7; 95% CI = 1.1–6.8) and for cancers of the female genital system (RR = 2.4; 95% CI = 1.1–5.4). Conclusions: Procarbazine, chlorambucil, and vinblastine are associated with increased leukemia risk. Combination drug regimens have leukemogenic effects estimated as the produ
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C. ; Fuller, Lillian M. ; Mauch, Peter ; Ultmann, John E.</creator><creatorcontrib>Boivin, Jean-François ; Hutchison, George B. ; Zauber, Ann G. ; Bernstein, Leslie ; Davis, Faith G. ; Michel, René P. ; Zanke, Brent ; Tan, Charlotte T. C. ; Fuller, Lillian M. ; Mauch, Peter ; Ultmann, John E.</creatorcontrib><description>Background: Numerous studies of treatment for Hodgkin's disease have demonstrated large increases in the incidence of leukemia in the early years following chemotherapy, although the duration of effect and the specific agents involved are not well understood. Also, some, but not all, studies have indicated that the incidence of certain solid tumors increases following treatment for Hodgkin's disease. Purpose: We studied the association between treatment for Hodgkin's disease and the incidence of second cancers. Methods: We conducted a study within a cohort that included 10 472 patients from 14 cancer centers in the United States and Canada who were first diagnosed as having Hodgkin's disease at some point from 1940 through 1987. Discounting the 1st year after diagnosis, the average length of follow-up was 7.1 years per subject. Results: We observed 122 leukemias and 438 solid tumors. The relative risk (RR) of leukemia following chemotherapy, compared with no chemotherapy, was 14 (95% confidence interval [CI] = 5.6–35). Increased risks of leukemia were observed after treatment with chlorambucil (RR = 2.0; 95% CI = 1.1–3.6), procarbazine (RR = 4.9; 95% CI = 2.6–9.1), vinblastine (RR = 1.7; 95% CI = 1.1–2.8), and a group of rarely used drugs that included methotrexate, vindesine, etoposide, and 22 others (RR = 3.8; 95% CI = 1.9–7.4). RRs were also estimated for various combinations of drugs, including MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) (RR = 5.9; 95% CI = 2.9–12) and ABVD (doxorubicin, bleomycin, vinblastine, and dacar–bazine) (RR = 1.5; 95% CI = 0.7–3.4). The RR of leukemia associated with splenectomy was 1.6 (95% CI = 1.0–2.5). The RR of solid tumors following chemotherapy was 1.4 (95%CI = 1.1–1.8). For the group of rarely used drugs, the RR of solid tumors was 3.1 (95% CI = 1.7–5.8). Chemotherapy was associated with an increased risk of cancers of the bones, joints, articular cartilage, and soft tissues (RR = 6.0; 95% CI = 1.7–20), and cancers of the female genital system (RR = 1.8; 95% CI = 1.1–3.2). In patients followed for 10 or more years after radiotherapy, increased risks were found for cancers of the respiratory system and intrathoracic organs (RR = 2.7; 95% CI = 1.1–6.8) and for cancers of the female genital system (RR = 2.4; 95% CI = 1.1–5.4). Conclusions: Procarbazine, chlorambucil, and vinblastine are associated with increased leukemia risk. Combination drug regimens have leukemogenic effects estimated as the product of RRs for individual drugs. Chemotherapy and radiotherapy increase the risk of selected solid tumors, and the effect of chemotherapy on solid tumor risk is weaker than the leukemogenic effect. Implications: Without doubt, the benefits of treatment of Hodgkin's disease outweigh the risk of a subsequent malignancy, but data on the carcinogenic effects of radiation and drugs beyond 10 years after treatment continue to be sparse, and future analyses should be directed at long-term survivors. [J Natl Cancer Inst 87:732–741, 1995]</description><identifier>ISSN: 0027-8874</identifier><identifier>EISSN: 1460-2105</identifier><identifier>DOI: 10.1093/jnci/87.10.732</identifier><identifier>PMID: 7563150</identifier><identifier>CODEN: JNCIEQ</identifier><language>eng</language><publisher>Cary, NC: Oxford University Press</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Biological and medical sciences ; Canada - epidemiology ; Case-Control Studies ; Chemotherapy ; Child ; Child, Preschool ; Cohort Studies ; Disease ; Female ; Follow-Up Studies ; Hematologic and hematopoietic diseases ; Hodgkin Disease - drug therapy ; Hodgkin Disease - radiotherapy ; Hodgkin Disease - surgery ; Hodgkin Disease - therapy ; Humans ; Incidence ; Infant ; Leukemia ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical research ; Medical sciences ; Middle Aged ; Neoplasms, Second Primary - chemically induced ; Neoplasms, Second Primary - epidemiology ; Neoplasms, Second Primary - etiology ; Odds Ratio ; Radiotherapy - adverse effects ; Risk ; Splenectomy - adverse effects ; Time Factors ; United States - epidemiology</subject><ispartof>JNCI : Journal of the National Cancer Institute, 1995-05, Vol.87 (10), p.732-741</ispartof><rights>1995 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) May 17, 1995</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-a6a02d1512901c1ad32848d7f698bc5d742b0a29a042bb152b1f27f6032925233</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=3609449$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7563150$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Boivin, Jean-François</creatorcontrib><creatorcontrib>Hutchison, George B.</creatorcontrib><creatorcontrib>Zauber, Ann G.</creatorcontrib><creatorcontrib>Bernstein, Leslie</creatorcontrib><creatorcontrib>Davis, Faith G.</creatorcontrib><creatorcontrib>Michel, René P.</creatorcontrib><creatorcontrib>Zanke, Brent</creatorcontrib><creatorcontrib>Tan, Charlotte T. C.</creatorcontrib><creatorcontrib>Fuller, Lillian M.</creatorcontrib><creatorcontrib>Mauch, Peter</creatorcontrib><creatorcontrib>Ultmann, John E.</creatorcontrib><title>Incidence of Second Cancers in Patients Treated for Hodgkin's Disease</title><title>JNCI : Journal of the National Cancer Institute</title><addtitle>J Natl Cancer Inst</addtitle><description>Background: Numerous studies of treatment for Hodgkin's disease have demonstrated large increases in the incidence of leukemia in the early years following chemotherapy, although the duration of effect and the specific agents involved are not well understood. Also, some, but not all, studies have indicated that the incidence of certain solid tumors increases following treatment for Hodgkin's disease. Purpose: We studied the association between treatment for Hodgkin's disease and the incidence of second cancers. Methods: We conducted a study within a cohort that included 10 472 patients from 14 cancer centers in the United States and Canada who were first diagnosed as having Hodgkin's disease at some point from 1940 through 1987. Discounting the 1st year after diagnosis, the average length of follow-up was 7.1 years per subject. Results: We observed 122 leukemias and 438 solid tumors. The relative risk (RR) of leukemia following chemotherapy, compared with no chemotherapy, was 14 (95% confidence interval [CI] = 5.6–35). Increased risks of leukemia were observed after treatment with chlorambucil (RR = 2.0; 95% CI = 1.1–3.6), procarbazine (RR = 4.9; 95% CI = 2.6–9.1), vinblastine (RR = 1.7; 95% CI = 1.1–2.8), and a group of rarely used drugs that included methotrexate, vindesine, etoposide, and 22 others (RR = 3.8; 95% CI = 1.9–7.4). RRs were also estimated for various combinations of drugs, including MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) (RR = 5.9; 95% CI = 2.9–12) and ABVD (doxorubicin, bleomycin, vinblastine, and dacar–bazine) (RR = 1.5; 95% CI = 0.7–3.4). The RR of leukemia associated with splenectomy was 1.6 (95% CI = 1.0–2.5). The RR of solid tumors following chemotherapy was 1.4 (95%CI = 1.1–1.8). For the group of rarely used drugs, the RR of solid tumors was 3.1 (95% CI = 1.7–5.8). Chemotherapy was associated with an increased risk of cancers of the bones, joints, articular cartilage, and soft tissues (RR = 6.0; 95% CI = 1.7–20), and cancers of the female genital system (RR = 1.8; 95% CI = 1.1–3.2). In patients followed for 10 or more years after radiotherapy, increased risks were found for cancers of the respiratory system and intrathoracic organs (RR = 2.7; 95% CI = 1.1–6.8) and for cancers of the female genital system (RR = 2.4; 95% CI = 1.1–5.4). Conclusions: Procarbazine, chlorambucil, and vinblastine are associated with increased leukemia risk. Combination drug regimens have leukemogenic effects estimated as the product of RRs for individual drugs. Chemotherapy and radiotherapy increase the risk of selected solid tumors, and the effect of chemotherapy on solid tumor risk is weaker than the leukemogenic effect. Implications: Without doubt, the benefits of treatment of Hodgkin's disease outweigh the risk of a subsequent malignancy, but data on the carcinogenic effects of radiation and drugs beyond 10 years after treatment continue to be sparse, and future analyses should be directed at long-term survivors. [J Natl Cancer Inst 87:732–741, 1995]</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Biological and medical sciences</subject><subject>Canada - epidemiology</subject><subject>Case-Control Studies</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cohort Studies</subject><subject>Disease</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hodgkin Disease - drug therapy</subject><subject>Hodgkin Disease - radiotherapy</subject><subject>Hodgkin Disease - surgery</subject><subject>Hodgkin Disease - therapy</subject><subject>Humans</subject><subject>Incidence</subject><subject>Infant</subject><subject>Leukemia</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasms, Second Primary - chemically induced</subject><subject>Neoplasms, Second Primary - epidemiology</subject><subject>Neoplasms, Second Primary - etiology</subject><subject>Odds Ratio</subject><subject>Radiotherapy - adverse effects</subject><subject>Risk</subject><subject>Splenectomy - adverse effects</subject><subject>Time Factors</subject><subject>United States - epidemiology</subject><issn>0027-8874</issn><issn>1460-2105</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><recordid>eNo9kN1LwzAUxYMoc05ffROCCD51S26SpnmUubnBQMEJspeQNql0H60mHeh_b8bK8nJzOL_7wUHolpIhJYqN1nVRjTIZxVAyOEN9ylOSACXiHPUJAZlkmeSX6CqENYlPAe-hnhQpo4L00WQe-62rC4ebEr-7oqktHpuofcBVjd9MW7m6DXjpnWmdxWXj8ayxX5uqfgz4uQrOBHeNLkqzDe6mqwP0MZ0sx7Nk8foyHz8tkoJL1SYmNQQsFRQUoQU1lkHGMyvLVGV5IazkkBMDypD4yamAnJYQXcJAgQDGBuj-OPfbNz97F1q9bva-jis1MJFSgExEaHiECt-E4F2pv321M_5PU6IPmelDZjqTBx0ziw133dR9vnP2hHchRf-h800ozLb0MZ4qnDCWEsW5ilhyxKrQut-TbfxGp5JJoWefKz2drjioWTyE_QO3T4Ct</recordid><startdate>19950517</startdate><enddate>19950517</enddate><creator>Boivin, Jean-François</creator><creator>Hutchison, George B.</creator><creator>Zauber, Ann G.</creator><creator>Bernstein, Leslie</creator><creator>Davis, Faith G.</creator><creator>Michel, René P.</creator><creator>Zanke, Brent</creator><creator>Tan, Charlotte T. 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Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasms, Second Primary - chemically induced</topic><topic>Neoplasms, Second Primary - epidemiology</topic><topic>Neoplasms, Second Primary - etiology</topic><topic>Odds Ratio</topic><topic>Radiotherapy - adverse effects</topic><topic>Risk</topic><topic>Splenectomy - adverse effects</topic><topic>Time Factors</topic><topic>United States - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Boivin, Jean-François</creatorcontrib><creatorcontrib>Hutchison, George B.</creatorcontrib><creatorcontrib>Zauber, Ann G.</creatorcontrib><creatorcontrib>Bernstein, Leslie</creatorcontrib><creatorcontrib>Davis, Faith G.</creatorcontrib><creatorcontrib>Michel, René P.</creatorcontrib><creatorcontrib>Zanke, Brent</creatorcontrib><creatorcontrib>Tan, Charlotte T. C.</creatorcontrib><creatorcontrib>Fuller, Lillian M.</creatorcontrib><creatorcontrib>Mauch, Peter</creatorcontrib><creatorcontrib>Ultmann, John E.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><jtitle>JNCI : Journal of the National Cancer Institute</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Boivin, Jean-François</au><au>Hutchison, George B.</au><au>Zauber, Ann G.</au><au>Bernstein, Leslie</au><au>Davis, Faith G.</au><au>Michel, René P.</au><au>Zanke, Brent</au><au>Tan, Charlotte T. C.</au><au>Fuller, Lillian M.</au><au>Mauch, Peter</au><au>Ultmann, John E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Incidence of Second Cancers in Patients Treated for Hodgkin's Disease</atitle><jtitle>JNCI : Journal of the National Cancer Institute</jtitle><addtitle>J Natl Cancer Inst</addtitle><date>1995-05-17</date><risdate>1995</risdate><volume>87</volume><issue>10</issue><spage>732</spage><epage>741</epage><pages>732-741</pages><issn>0027-8874</issn><eissn>1460-2105</eissn><coden>JNCIEQ</coden><abstract>Background: Numerous studies of treatment for Hodgkin's disease have demonstrated large increases in the incidence of leukemia in the early years following chemotherapy, although the duration of effect and the specific agents involved are not well understood. Also, some, but not all, studies have indicated that the incidence of certain solid tumors increases following treatment for Hodgkin's disease. Purpose: We studied the association between treatment for Hodgkin's disease and the incidence of second cancers. Methods: We conducted a study within a cohort that included 10 472 patients from 14 cancer centers in the United States and Canada who were first diagnosed as having Hodgkin's disease at some point from 1940 through 1987. Discounting the 1st year after diagnosis, the average length of follow-up was 7.1 years per subject. Results: We observed 122 leukemias and 438 solid tumors. The relative risk (RR) of leukemia following chemotherapy, compared with no chemotherapy, was 14 (95% confidence interval [CI] = 5.6–35). Increased risks of leukemia were observed after treatment with chlorambucil (RR = 2.0; 95% CI = 1.1–3.6), procarbazine (RR = 4.9; 95% CI = 2.6–9.1), vinblastine (RR = 1.7; 95% CI = 1.1–2.8), and a group of rarely used drugs that included methotrexate, vindesine, etoposide, and 22 others (RR = 3.8; 95% CI = 1.9–7.4). RRs were also estimated for various combinations of drugs, including MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) (RR = 5.9; 95% CI = 2.9–12) and ABVD (doxorubicin, bleomycin, vinblastine, and dacar–bazine) (RR = 1.5; 95% CI = 0.7–3.4). The RR of leukemia associated with splenectomy was 1.6 (95% CI = 1.0–2.5). The RR of solid tumors following chemotherapy was 1.4 (95%CI = 1.1–1.8). For the group of rarely used drugs, the RR of solid tumors was 3.1 (95% CI = 1.7–5.8). Chemotherapy was associated with an increased risk of cancers of the bones, joints, articular cartilage, and soft tissues (RR = 6.0; 95% CI = 1.7–20), and cancers of the female genital system (RR = 1.8; 95% CI = 1.1–3.2). In patients followed for 10 or more years after radiotherapy, increased risks were found for cancers of the respiratory system and intrathoracic organs (RR = 2.7; 95% CI = 1.1–6.8) and for cancers of the female genital system (RR = 2.4; 95% CI = 1.1–5.4). Conclusions: Procarbazine, chlorambucil, and vinblastine are associated with increased leukemia risk. Combination drug regimens have leukemogenic effects estimated as the product of RRs for individual drugs. Chemotherapy and radiotherapy increase the risk of selected solid tumors, and the effect of chemotherapy on solid tumor risk is weaker than the leukemogenic effect. Implications: Without doubt, the benefits of treatment of Hodgkin's disease outweigh the risk of a subsequent malignancy, but data on the carcinogenic effects of radiation and drugs beyond 10 years after treatment continue to be sparse, and future analyses should be directed at long-term survivors. [J Natl Cancer Inst 87:732–741, 1995]</abstract><cop>Cary, NC</cop><pub>Oxford University Press</pub><pmid>7563150</pmid><doi>10.1093/jnci/87.10.732</doi><tpages>10</tpages></addata></record>
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identifier ISSN: 0027-8874
ispartof JNCI : Journal of the National Cancer Institute, 1995-05, Vol.87 (10), p.732-741
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1460-2105
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source Oxford University Press Archive
subjects Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Biological and medical sciences
Canada - epidemiology
Case-Control Studies
Chemotherapy
Child
Child, Preschool
Cohort Studies
Disease
Female
Follow-Up Studies
Hematologic and hematopoietic diseases
Hodgkin Disease - drug therapy
Hodgkin Disease - radiotherapy
Hodgkin Disease - surgery
Hodgkin Disease - therapy
Humans
Incidence
Infant
Leukemia
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical research
Medical sciences
Middle Aged
Neoplasms, Second Primary - chemically induced
Neoplasms, Second Primary - epidemiology
Neoplasms, Second Primary - etiology
Odds Ratio
Radiotherapy - adverse effects
Risk
Splenectomy - adverse effects
Time Factors
United States - epidemiology
title Incidence of Second Cancers in Patients Treated for Hodgkin's Disease
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