Influence of growth hormone therapy on the occurrence of a second neoplasm in survivors of childhood cancer

in European Journal of Endocrinology
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  • 1 Cancer and Radiation, CESP, Unit 1018 INSERM, Villejuif, France
  • 2 University Paris-Saclay, Villejuif, France
  • 3 Department of Pediatric Endocrinology, AP-HP, Université Paris Saclay, site Bicetre, Le Kremlin Bicêtre, France
  • 4 Department of Pediatric Endocrinology, Children Hospital, Toulouse, France
  • 5 Department of Pediatrics Oncology, Institut Curie, Paris, France
  • 6 Department of Pediatrics Oncology, Institut Gustave Roussy, Villejuif, France
  • 7 Department of Research Gustave Roussy, Villejuif, France
  • 8 Department of Radiotherapy Oncology, Institut Gustave Roussy, Villejuif, France
  • 9 Centre Claudius Régaud, Toulouse, France
  • 10 Department of Pediatrics Oncology, CHU Angers, Angers, France

Correspondence should be addressed to C Thomas-Teinturier; Email: cecile.teinturier@aphp.fr
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Context:

Growth hormone (GH) deficiency is a common late effect of cranial irradiation. However, concerns have been raised that GH treatment might lead to an increased risk of a second neoplasm (SN).

Objective:

To study the impact of GH treatment on the risk of SN in a French cohort of survivors of childhood cancer (CCS) treated before 1986.

Design and setting:

Cohort study and nested case–control study.

Participants:

Of the 2852 survivors, with a median follow-up of 26 years, 196 had received GH therapy (median delay from cancer diagnosis: 5.5 years).

Main outcome measures:

Occurrence of SN

Results:

In total, 374 survivors developed a SN, including 40 who had received GH therapy. In a multivariate analysis, GH treatment did not increase the risk of secondary non-meningioma brain tumors (RR: 0.6, 95% CI: 0.2–1.5, P = 0.3), secondary non-brain cancer (RR: 0.7, 95% CI: 0.4–1.2, P = 0.2), or meningioma (RR: 1.9, 95% CI: 0.9–4, P = 0.09). Nevertheless, we observed a slight non-significant increase in the risk of meningioma with GH duration: 1.6-fold (95% CI: 1.2–3.0) after an exposure of less than 4 years vs 2.3-fold (95% CI: 0.9–5.6) after a longer exposure (P for trend = 0.07) confirmed by the results of a case–control study.

Conclusion:

This study confirms the overall safety of GH use in survivors of childhood cancer, which does not increase the risk of a SN. The slight excess in the risk of meningioma in patients with long-term GH treatment is non-significant and could be due to difficulties in adjustment on cranial radiation volume/dose and/or undiagnosed meningioma predisposing conditions.

Supplementary Materials

    • Supplementary Table 1: Details on all patients with secondary neoplasms occurring after GH therapy

 

     European Society of Endocrinology

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  • 1

    Constine LS, Woolf PD, Cann D, Mick G, McCormick K, Raubertas RF, Rubin P. Hypothalamic-pituitary dysfunction after radiation for brain tumors. New England Journal of Medicine 1993 328 8794. (https://doi.org/10.1056/NEJM199301143280203)

    • Search Google Scholar
    • Export Citation
  • 2

    Sklar CA, Constine LS. Chronic neuroendocrinological sequelae of radiation therapy. International Journal of Radiation Oncology, Biology, Physics 1995 31 11131121. (https://doi.org/10.1016/0360-3016(94)00427-M)

    • Search Google Scholar
    • Export Citation
  • 3

    Hudson MM, Ness KK, Gurney JG, Mulrooney DA, Chemaitilly W, Krull KR, Green DM, Armstrong GT, Nottage KA & Jones KE Clinical ascertainment of health outcomes among adults treated for childhood cancer. JAMA 2013 309 23712381. (https://doi.org/10.1001/jama.2013.6296)

    • Search Google Scholar
    • Export Citation
  • 4

    Brauner R, Rappaport R, Prevot C, Czernichow P, Zucker JM, Bataini P, Lemerle J, Sarrazin D, Guyda HJ. A prospective study of the development of growth hormone deficiency in children given cranial irradiation, and its relation to statural growth. Journal of Clinical Endocrinology and Metabolism 1989 68 346351. (https://doi.org/10.1210/jcem-68-2-346)

    • Search Google Scholar
    • Export Citation
  • 5

    Clayton PE, Shalet SM. Dose dependency of time of onset of radiation-induced growth hormone deficiency. Journal of Pediatrics 1991 118 226228. (https://doi.org/10.1016/s0022-3476(05)80487-1)

    • Search Google Scholar
    • Export Citation
  • 6

    Orme SM, Menally RJQ, Cartwright RA, Belchetz PE. Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. Journal of Clinical Endocrinology and Metabolism 1998 83 27302734. (https://doi.org/10.1210/jcem.83.8.5007)

    • Search Google Scholar
    • Export Citation
  • 7

    Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M. Plasma insulin-like growth factor 1 and prostate cancer risk: a prospective study. Science 1998 279 563566. (https://doi.org/10.1126/science.279.5350.563)

    • Search Google Scholar
    • Export Citation
  • 8

    Zhang R, Xu GL, Li Y, He LJ, Chen LM, Wang GB, Lin SY, Luo GY, Gao XY, Shan HB. The role of insulin-like growth factor 1 and its receptor in the formation and development of colorectal carcinoma. Journal of International Medical Research 2013 41 12281235. (https://doi.org/10.1177/0300060513487631)

    • Search Google Scholar
    • Export Citation
  • 9

    Sklar CA, Mertens AC, Mitby P, Occhiogrosso G, Qin J, Heller G, Yasui Y, Robison LL. Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: a report from the childhood cancer survivor study. Journal of Clinical Endocrinology and Metabolism 2002 87 31363141. (https://doi.org/10.1210/jcem.87.7.8606)

    • Search Google Scholar
    • Export Citation
  • 10

    Ergun-Longmire B, Mertens AC, Mitby P, Qin J, Heller G, Shi W, Yasui Y, Robison LL, Sklar CA. Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor. Journal of Clinical Endocrinology and Metabolism 2006 91 34943498. (https://doi.org/10.1210/jc.2006-0656)

    • Search Google Scholar
    • Export Citation
  • 11

    Patterson BC, Chen Y, Sklar CA, Neglia J, Yasui Y, Mertens A, Armstrong GT, Meadows A, Stovall M & Robison LL Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the Childhood Cancer Survivor Study. Journal of Clinical Endocrinology and Metabolism 2014 99 20302037. (https://doi.org/10.1210/jc.2013-4159)

    • Search Google Scholar
    • Export Citation
  • 12

    Bell J, Parker KL, Swinford RD, Hoffman AR, Maneatis T, Lippe B. Long term safety of recombinant human growth hormone in children. Journal of Clinical Endocrinology and Metabolism 2010 95 167177. (https://doi.org/10.1210/jc.2009-0178)

    • Search Google Scholar
    • Export Citation
  • 13

    Woodmansee WW, Zimmermann AG, Child CJ, Rong Q, Erfuth EM, Beck-Peccoz P, Blum WF, Robison LL & GeNeSIS and HypoCCS International Advisory Boards. Incidence of second neoplasm in childhood cancer survivors treated with GH: an analysis of GeNeSIS and HypoCCS. European Journal of Endocrinology 2013 168 565573. (https://doi.org/10.1530/EJE-12-0967)

    • Search Google Scholar
    • Export Citation
  • 14

    De Vathaire F, Hawkins M, Cambell S, Oberlin O, Raquin MA, Schlienger JY, Shamsaldin A, Diallo I, Bell J & Grimaud E Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment. British Journal of Cancer 1999 79 18841893. (https://doi.org/10.1038/sj.bjc.6690300)

    • Search Google Scholar
    • Export Citation
  • 15

    Birch JM, Marsden HB. A classification scheme for childhood cancer. International Journal of Cancer 1987 40 620624. (https://doi.org/10.1002/ijc.2910400508)

    • Search Google Scholar
    • Export Citation
  • 16

    Alziar I, Bonniaud G, Couanet D, Ruaud JB, Vicente C, Giordana G, Ben-Harrath O, Diaz JC, Grandjean P & Kafrouni H Individual radiation therapy patient whole-body phantoms for peripheral dose evaluations: method and specific software. Physics in Medicine and Biology 2009 54 N375N383. (https://doi.org/10.1088/0031-9155/54/17/N01)

    • Search Google Scholar
    • Export Citation
  • 17

    Bezin JV, Veres A, Lefkopoulos D, Chavaudra J, Deutsch E, de Vathaire F, Diallo I. Field size dependent mapping of medical linear accelerator radiation leakage. Physics in Medicine and Biology 2015 60 21032106. (https://doi.org/10.1088/0031-9155/60/5/2103)

    • Search Google Scholar
    • Export Citation
  • 18

    Alabdoaburas MM, Mege JP, Chavaudra J, Bezin JV, Veres A, de Vathaire F, Lefkopoulos D, Diallo I. Experimental assessment of out-of-field dose components in high energy electron beams used in external beam radiotherapy. Journal of Applied Clinical Medical Physics 2015 16 435448. (https://doi.org/10.1120/jacmp.v16i6.5616)

    • Search Google Scholar
    • Export Citation
  • 19

    Benadjaoud MA, Bezin J, Veres A, Lefkopoulos D, Chavaudra J, Bridier A, de Vathaire F, Diallo I. A multi-plane source model for out-of-field head scatter dose calculations in external beam photon therapy. Physics in Medicine and Biology 2012 57 77257739. (https://doi.org/10.1088/0031-9155/57/22/7725)

    • Search Google Scholar
    • Export Citation
  • 20

    Veres C, Allodji RS, Llanas D, Vu Bezin J, Chavaudra J, Mege JP, Lefkopoulos D, Quiniou E, Deutsh E & de Vathaire F Retrospective reconstructions of active bone marrow dose-volume histograms. International Journal of Radiation Oncology, Biology, Physics 2014 90 12161224. (https://doi.org/10.1016/j.ijrobp.2014.08.335)

    • Search Google Scholar
    • Export Citation
  • 21

    Cox DR. Regression models and life tables. Journal of the Royal Statistical Society: Series B 1972 34 187202. (https://doi.org/10.1111/j.2517-6161.1972.tb00899.x)

    • Search Google Scholar
    • Export Citation
  • 22

    Zhang X, Loberiza FR, Klein JP, Zhang MJ. A SAS macro for estimation of direct adjusted survival curves based on a stratified Cox regression model. Computer Methods and Programs in Biomedicine 2007 88 95101. (https://doi.org/10.1016/j.cmpb.2007.07.010)

    • Search Google Scholar
    • Export Citation
  • 23

    Guerin S, Guibout C, Shamsaldin A, Dondon MG, Diallo I, Hawkins M, Oberlin O, Hartmann O, Michon J & Le Deley MC Concomitant chemo-radiotherapy and local dose of radiation as risk factors for second malignant neoplasms after solid cancer in childhood: a case-control study. International Journal of Cancer 2007 120 96102. (https://doi.org/10.1002/ijc.22197)

    • Search Google Scholar
    • Export Citation
  • 24

    Taylor AJ, Little MP, Winter DL, Sugden E, Ellison DW, Stiller CA, Stovall M, Frobisher C, Lancashire ER & Reulen RC Population-based risks of CNS tumors in survivors of childhood cancer: the British childhood cancer survivor study. Journal of Clinical Oncology 2010 28 52875293. (https://doi.org/10.1200/JCO.2009.27.0090)

    • Search Google Scholar
    • Export Citation
  • 25

    Tamhane S, Sfeir JG, Kittah NEN, Jasim S, Chemaitilly W, Cohen LE, Murad MH. GH therapy in childhood cancer survivors: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism 2018 103 27942801. (https://doi.org/10.1210/jc.2018-01205)

    • Search Google Scholar
    • Export Citation