Risk Factors for Primary Bone Cancer After Childhood Cancer: A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study
PURPOSERadiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.METHODST...
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| Published in | Journal of clinical oncology Vol. 41; no. 21; pp. 3735 - 3746 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Wolters Kluwer Health
20.07.2023
American Society of Clinical Oncology |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0732-183X 1527-7755 1527-7755 |
| DOI | 10.1200/JCO.22.02045 |
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| Abstract | PURPOSERadiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.METHODSTwelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.RESULTSThe OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation (Ptrend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer.CONCLUSIONTo our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans. |
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| AbstractList | PURPOSERadiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.METHODSTwelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.RESULTSThe OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation (Ptrend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer.CONCLUSIONTo our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans. PURPOSE: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy. METHODS: Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship. RESULTS: The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( P trend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m 2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. CONCLUSION: To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m 2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans. Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.PURPOSERadiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.METHODSTwelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation (Ptrend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer.RESULTSThe OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation (Ptrend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer.To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.CONCLUSIONTo our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans. Childhood cancer survivors face a 5- to 10-fold risk of bone cancer after exposure of bone tissue to cumulative radiation doses 1-9 Gy and a 7-to 8-fold risk with alkylating agent doses over 10,000 mg/m2. Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy. Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship. The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m , the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans. |
| Author | Cole, Trevor Hjorth, Lars Kaatsch, Peter Haddy, Nadia Bárdi, Edit Fauchery, Romain Gudmundsdottir, Thorgerdur Nordenfelt, Susanne Maule, Milena M. Kremer, Leontien C.M. Byrne, Julianne Zadravec Zaletel, Lorna Winther Gunnes, Maria Haupt, Riccardo Linge, Helena Zrafi, Wael Reulen, Raoul C. Allodji, Rodrigue S. van der Pal, Helena J.H. Jakab, Zsuzsanna Grabow, Desiree van Leeuwen, Flora E. Høgsholt, Stine Lähteenmäki, Päivi M. Wiebe, Thomas Sacerdote, Carlotta Øfstaas, Hilde Fidler-Benaoudia, Miranda M. Veres, Cristina Hawkins, Michael M. de Vathaire, Florent Michel, Gisela Kok, Judith L. Llanas, Damien Terenziani, Monica Diallo, Ibrahim Skinner, Roderick Waespe, Nicolas Falck Winther, Jeanette Ronckers, Cécile M. Bagnasco, Francesca Jenkinson, Helen Alessi, Daniela Jankovic, Momcilo Kaiser, Melanie Winter, David L. Sommer, Grit Lähteenmäki Taalas, Tuomas Kuehni, Claudia E. Teepen, Jop C. Feijen, Elizabeth A.M. Debiche, Ghazi Vu-Bezin, Giao |
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surname: Debiche fullname: Debiche, Ghazi organization: Radiation Epidemiology Team, Center for Research in Epidemiology and Population Health, INSERM U1018, University Paris Saclay, Gustave Roussy, Villejuif, France – sequence: 18 givenname: Desiree orcidid: 0000-0002-4853-3303 surname: Grabow fullname: Grabow, Desiree – sequence: 19 givenname: Thorgerdur surname: Gudmundsdottir fullname: Gudmundsdottir, Thorgerdur – sequence: 20 givenname: Romain surname: Fauchery fullname: Fauchery, Romain organization: Radiation Epidemiology Team, Center for Research in Epidemiology and Population Health, INSERM U1018, University Paris Saclay, Gustave Roussy, Villejuif, France – sequence: 21 givenname: Wael orcidid: 0000-0003-4289-6821 surname: Zrafi fullname: Zrafi, Wael organization: Radiation Epidemiology Team, Center for Research in Epidemiology and Population Health, INSERM U1018, University Paris Saclay, Gustave Roussy, Villejuif, France – sequence: 22 givenname: Gisela orcidid: 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Hospital, Aarhus, Denmark – sequence: 50 givenname: Leontien C.M. surname: Kremer fullname: Kremer, Leontien C.M. organization: Emma Children's Hospital, Amsterdam UMC, Amsterdam, the Netherlands – sequence: 51 givenname: Lars orcidid: 0000-0002-8302-7174 surname: Hjorth fullname: Hjorth, Lars – sequence: 52 givenname: Florent orcidid: 0000-0002-8374-9281 surname: de Vathaire fullname: de Vathaire, Florent organization: Radiation Epidemiology Team, Center for Research in Epidemiology and Population Health, INSERM U1018, University Paris Saclay, Gustave Roussy, Villejuif, France – sequence: 53 givenname: Michael M. orcidid: 0000-0001-6496-4800 surname: Hawkins fullname: Hawkins, Michael M. organization: Centre for Childhood Cancer Survivor Studies, Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom |
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| Copyright | 2023 by American Society of Clinical Oncology Distributed under a Creative Commons Attribution 4.0 International License |
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| Language | English |
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| Notes | Raoul C. Reulen, PhD, Centre for Childhood Cancer Survivor Studies, College of Medical and Dental Sciences, University of Birmingham, Institute of Applied Health Research, Robert Aitken Building, Edgbaston, Birmingham B15 2T, United Kingdom; e-mail: r.c.reulen@bham.ac.uk. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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| PublicationTitle | Journal of clinical oncology |
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| References | Reulen, Frobisher, Winter (b1) 2011; 305 Neglia, Friedman, Yasui (b11) 2001; 93 Turcotte, Liu, Yasui (b4) 2017; 317 Kuritz, Landis (b17) 1987; 125 StataCorp: Stata Statistical Software: Release 17. College Station, TX, StataCorp LLC, 2021 Preston D, Lubin J, Pierce D: Epicure User's Guide. Seattle, WA, Hirosoft International Corporation, 1991 Grabow, Kaiser, Hjorth (b14) 2018; 33 Ketteler, Hülsenbeck, Frank (b26) 2020; 133 Byrne, Alessi, Allodji (b13) 2018; 103 Tucker, D'Angio, Boice (b8) 1987; 317 Gaspar, Venkatramani, Hecker-Nolting (b27) 2021; 22 Schwartz, Benadjaoud, Cléro (b6) 2014; 53 Green, Nolan, Goodman (b16) 2014; 61 Dommering, Marees, van der Hout (b25) 2012; 11 Henderson, Rajaraman, Stovall (b10) 2012; 84 Wong, Boice, Abramson (b23) 1997; 278 Hawkins, Wilson, Burton (b7) 1996; 88 Veres, Allodji, Llanas (b15) 2014; 90 Olsen, Möller, Anderson (b2) 2009; 101 Kleinerman, Schonfeld, Sigel (b22) 2019; 37 Abramson, Frank (b21) 1998; 105 Le Vu, de Vathaire, Shamsaldin (b9) 1998; 77 Fidler, Reulen, Winter (b12) 2018; 110 Cologne, Cullings, Furukawa (b18) 2010; 99 Moll, Imhof, Schouten-Van Meeteren (b24) 2001; 108 Berrington de Gonzalez, Kutsenko, Rajaraman (b5) 2012; 2 Teepen, van Leeuwen, Tissing (b3) 2017; 35 b10 b12 b11 b14 b13 b16 b15 b18 b17 Preston D (b20) 1991 b1 b2 b3 b4 b5 b7 b8 b9 b21 b23 b22 b25 b24 b27 Schwartz B (b6) 2014; 53 b26 StataCorp (b19) 2021 |
| References_xml | – volume: 84 start-page: 224 year: 2012 end-page: 230 ident: b10 article-title: Risk factors associated with secondary sarcomas in childhood cancer survivors: A report from the childhood cancer survivor study publication-title: Int J Radiat Oncol Biol Phys – volume: 2 start-page: 18 year: 2012 ident: b5 article-title: Sarcoma risk after radiation exposure publication-title: Clin Sarcoma Res – volume: 101 start-page: 806 year: 2009 end-page: 813 ident: b2 article-title: Lifelong cancer incidence in 47,697 patients treated for childhood cancer in the Nordic countries publication-title: J Natl Cancer Inst – volume: 93 start-page: 618 year: 2001 end-page: 629 ident: b11 article-title: Second malignant neoplasms in five-year survivors of childhood cancer: Childhood cancer survivor study publication-title: J Natl Cancer Inst – volume: 305 start-page: 2311 year: 2011 end-page: 2319 ident: b1 article-title: Long-term risks of subsequent primary neoplasms among survivors of childhood cancer publication-title: JAMA – volume: 110 start-page: 183 year: 2018 end-page: 194 ident: b12 article-title: Risk of subsequent bone cancers among 69 460 five-year survivors of childhood and adolescent cancer in Europe publication-title: J Natl Cancer Inst – volume: 90 start-page: 1216 year: 2014 end-page: 1224 ident: b15 article-title: Retrospective reconstructions of active bone marrow dose-volume histograms publication-title: Int J Radiat Oncol Biol Phys – volume: 103 start-page: 238 year: 2018 end-page: 248 ident: b13 article-title: The PanCareSurFup consortium: Research and guidelines to improve lives for survivors of childhood cancer publication-title: Eur J Cancer – volume: 317 start-page: 814 year: 2017 end-page: 824 ident: b4 article-title: Temporal trends in treatment and subsequent neoplasm risk among 5-year survivors of childhood cancer, 1970-2015 publication-title: JAMA – volume: 133 start-page: 47 year: 2020 end-page: 55 ident: b26 article-title: The impact of RB1 genotype on incidence of second tumours in heritable retinoblastoma publication-title: Eur J Cancer – reference: StataCorp: Stata Statistical Software: Release 17. College Station, TX, StataCorp LLC, 2021 – volume: 317 start-page: 588 year: 1987 end-page: 593 ident: b8 article-title: Bone sarcomas linked to radiotherapy and chemotherapy in children publication-title: N Engl J Med – volume: 77 start-page: 370 year: 1998 end-page: 377 ident: b9 article-title: Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during childhood publication-title: Int J Cancer – volume: 11 start-page: 225 year: 2012 end-page: 233 ident: b25 article-title: RB1 mutations and second primary malignancies after hereditary retinoblastoma publication-title: Fam Cancer – volume: 99 start-page: 603 year: 2010 end-page: 612 ident: b18 article-title: Attributable risk for radiation in the presence of other risk factors publication-title: Health Phys – volume: 108 start-page: 1109 year: 2001 end-page: 1114 ident: b24 article-title: Second primary tumors in hereditary retinoblastoma: A register-based study, 1945-1997 publication-title: Ophthalmology – volume: 125 start-page: 324 year: 1987 end-page: 328 ident: b17 article-title: Attributable risk ratio estimation from matched-pairs case-control data publication-title: Am J Epidemiol – volume: 53 start-page: 381 year: 2014 end-page: 390 ident: b6 article-title: Risk of second bone sarcoma following childhood cancer: Role of radiation therapy treatment publication-title: Radiat Environ Biophys – volume: 33 start-page: 335 year: 2018 end-page: 349 ident: b14 article-title: The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer: A cohort from 12 European countries publication-title: Eur J Epidemiol – volume: 37 start-page: 3436 year: 2019 end-page: 3445 ident: b22 article-title: Bone and soft-tissue sarcoma risk in long-term survivors of hereditary retinoblastoma treated with radiation publication-title: J Clin Oncol – volume: 278 start-page: 1262 year: 1997 end-page: 1267 ident: b23 article-title: Cancer incidence after retinoblastoma. 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Seattle, WA, Hirosoft International Corporation, 1991 – volume: 53 start-page: 381 year: 2014 ident: b6 publication-title: Radiat Environ Biophys – ident: b8 doi: 10.1056/NEJM198709033171002 – ident: b21 doi: 10.1016/S0161-6420(98)94006-4 – ident: b3 doi: 10.1200/JCO.2016.71.6902 – ident: b22 doi: 10.1200/JCO.19.01096 – ident: b12 doi: 10.1093/jnci/djx165 – ident: b27 doi: 10.1016/S1470-2045(21)00387-9 – ident: b2 doi: 10.1093/jnci/djp104 – ident: b15 doi: 10.1016/j.ijrobp.2014.08.335 – ident: b23 doi: 10.1001/jama.1997.03550150066037 – ident: b26 doi: 10.1016/j.ejca.2020.04.005 – ident: b16 doi: 10.1002/pbc.24679 – ident: b24 doi: 10.1016/S0161-6420(01)00562-0 – ident: b13 doi: 10.1016/j.ejca.2018.08.017 – volume-title: Stata Statistical Software: Release 17 year: 2021 ident: b19 – ident: b25 doi: 10.1007/s10689-011-9505-3 – ident: b11 doi: 10.1093/jnci/93.8.618 – ident: b18 doi: 10.1097/HP.0b013e3181db29fd – volume-title: Epicure User’s Guide year: 1991 ident: b20 – ident: b7 doi: 10.1093/jnci/88.5.270 – ident: b1 doi: 10.1001/jama.2011.747 – ident: b10 doi: 10.1016/j.ijrobp.2011.11.022 – ident: b9 doi: 10.1002/(SICI)1097-0215(19980729)77:3<370::AID-IJC11>3.0.CO;2-C – ident: b14 doi: 10.1007/s10654-018-0370-3 – ident: b5 doi: 10.1186/2045-3329-2-18 – ident: b4 doi: 10.1001/jama.2017.0693 – ident: b17 doi: 10.1093/oxfordjournals.aje.a114533 |
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| Snippet | PURPOSERadiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty... Childhood cancer survivors face a 5- to 10-fold risk of bone cancer after exposure of bone tissue to cumulative radiation doses 1-9 Gy and a 7-to 8-fold risk... Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty... PURPOSE: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is... |
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| SubjectTerms | Adolescent Alkylating Agents Bone Neoplasms Cancer Cancer and Oncology Cancer och onkologi Cancer Survivors Case-Control Studies Child Clinical Medicine Cyclophosphamide Dose-Response Relationship, Radiation Follow-Up Studies Humans Ifosfamide Klinisk medicin Life Sciences Medical and Health Sciences Medicin och hälsovetenskap Neoplasms, Second Primary - chemically induced Neoplasms, Second Primary - epidemiology Osteosarcoma - epidemiology Pediatrics Pediatrik Procarbazine Risk Factors |
| Title | Risk Factors for Primary Bone Cancer After Childhood Cancer: A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study |
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