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Radiotherapy


Table 1: Summary of Studies Evaluating Growth Hormone Deficiency After Cranial and Craniospinal Irradiation Author


Patients Enrolled/ Malignancy Patients Tested


Melin et al., 199816


Gurney et al., 20038


35/35 Xu et al., 200418


Medulloblastoma 329/unknown, ependymoma 108/unknown 7/7


Laughton et al., 88/70 200814


Bahl et al., 200915


70/unknown Leukaemia


Proportion with GH Deficiency


63%


Medulloblastoma/PNET Medulloblastoma 39%, and ependymoma


ependymoma 24%


Medulloblastoma Embryonal brain tumours


Medulloblastoma (48), ependymoma (22)


100% 94%,


4-year CI 93% 52%,


5-year CI among CSI 68% Comments


Patients treated with 18Gy of cranial radiation and routinely evaluated 5 years after therapy


Data are based on patient report and are not derived from prospective surveillance for endocrine dysfunction During this time period, ependymoma was treated with whole-brain radiation or CSI at most institutions Patients treated with 18Gy of CSI


Patients assessed for endocrine conditions in a systematic, prospective manner


Data obtained retrospectively so data on endocrine


dysfunction only available if patients had been referred to endocrinologist for evaluation


CI = cumulative incidence; CSI = craniospinal irradiation; GH = growth hormone; PNET = primitive neuroectodermal tumour. Table 2: Summary of Studies Evaluating Hypothyroidism After Cranial and Craniospinal Irradiation


Author


Patients Enrolled/ Malignancy Patients Tested


Livesey et al., 144/119 19909


Chin et al., 199719


Proportion with Hypothyroidism Comments


Paediatric brain tumour 41% PH among CSI, 5% PH not involving HP axis


among cranial radiation, 3.4% TSH deficiency


34/34 conventional, Medulloblastoma 14/14


and PNET hyperfractionated


Schmiegelow 71/71 et al., 200323


62% PH with conventional fractionation, 14% PH with hyperfractionated radiation


Paediatric brain tumour 41% PH among CSI, not involving HP axis


Patients were not evaluated for endocrine dysfunction in a systematic manner


Patients treated with conventionally fractionationated radiation were compared to hyperfractionated (1Gy per fraction twice per day)


Patients treated with cranial radiation


12% PH among cranial radiation, (either whole brain or focal) or CSI ± tumour boost no cases of TSH deficiency among CSI, 6% TSH deficiency among cranial radiation


Gurney et al., Medulloblastoma Medulloblastoma/PNET Medulloblastoma 30%, 20038


Xu et al., 200418


329/unknown, ependymoma 108/unknown 7/7


Laughton et al., 88/87 200814


Bahl et al., 200915


70/unknown and ependymoma Medulloblastoma


Embryonal brain tumours


Medulloblastoma (48), Ependymoma (22)


ependymoma 12% 14% hypothyroidism PH: 51% 4-year CI 65%


TSH deficiency: 10% 4-year CI 23%


Data are based on patient report and are not derived from prospective surveillance for endocrine dysfunction Primary hypothyroidism not differentiated from TSH deficiency


Patients treated with 18Gy of craniospinal radiation. Unclear whether this is PH or TSH deficiency Patients assessed for endocrine conditions in a systematic, prospective manner


33%, 5-year CI among CSI 52% Patients who received cranial radiation were routinely ependymoma (22)


tested for thyroid hormone dysfunction Authors did not differentiate between primary hypothyroidism and TSH deficiency


CI = cumulative incidence; CSI = craniospinal irradiation; HP = hypothalamic–pituitary; PH = primary hypothyroidism; PNET = primitive neuroectodermal tumour; TSH = thyroid-stimulating hormone.


The relatively low cumulative incidence of endocrinopathies (18%) among patients treated with focal radiation without craniospinal treatment is almost certainly related to the lower dose received by the hypothalamus and pituitary gland as a result of the absence of whole-brain radiation given as part of CSI. In addition, the fact that only the tumour bed was treated in these patients as opposed to the whole posterior fossa as in the medulloblastoma patients may contribute further to the reduced cumulative incidence of endocrinopathies. Ongoing evaluation will document the actual radiation dose delivered to the hypothalamus among the patients in this study.


Growth Hormone Deficiency The studies on GH deficiency are presented in Table 1. Both the research performed at the Hospital for Sick Children and at St Jude demonstrates a very high risk of GH deficiency in patients treated with


50 CSI.14,15 GH deficiency is known to develop after relatively low doses of


It is therefore not surprising that even when conformal radiation is used to deliver the posterior fossa radiation, thereby reducing a portion of the dose delivered to the hypothalamus, patients remain at high risk of GH deficiency. The radiation dose below which patients will not develop GH deficiency is not known. There have even been reports of GH deficiency in patients who received just 12Gy of total-body irradiation as conditioning for bone marrow transplant.17 Melin et al. described a prevalence of 63% of GH deficiency five years after receiving 18Gy of cranial radiation for therapy for leukemia.16


cranial radiation.16 Even


in the study by Xu et al., where patients with medulloblastoma received a craniospinal dose of only 18Gy, all patients developed GH deficiency.18 In this study, since the boost doses were not given using conformal radiation it is likely that a large proportion of the posterior fossa dose reached the hypothalamic–pituitary axis. CSI doses used in the studies


EUROPEAN ONCOLOGY & HAEMATOLOGY


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