Prophylactic cranial irradiation of acute lymphoblastic leukemia in childhood: Outcomes of late effects on pituitary function and growth in long-term survivors

Hata, Masaharu; Ogino, Ichiro; Aida, Noriko; Saito, Kimihiko; Omura, Motoko; Kigasawa, Hisato; Toyoda, Yasunori; Tachibana, Kunihide; Matsubara, Sho; Inoue, Tomio

doi:10.1002/ijc.10348

Cited by 37 publications

(28 citation statements)

References 26 publications

(28 reference statements)

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“…4 Cranial irradiation in patients with acute lymphoblastic leukemia has long been suggested to play a role in hypothyroidism, 3,4,26 although a few authors have argued that the impact of prophylactic cranial radiation is controversial. 3,5,7,27 However, those earlier studies should be interpreted with caution because of the small numbers of patients included, the retrospective nature of the studies and/or the short follow-up periods. In the current study, our results support the hypothesis that the risk of hypothyroidism is significantly lower in patients who received only central nervous system irradiation (adjusted HR=0.27, P=0.02) compared with that in the reference population (i.e., patients treated with hematopoietic stem cell transplantation without any history of irradiation).…”

Section: Discussionmentioning

confidence: 99%

Late thyroid complications in survivors of childhood acute leukemia. An L.E.A. study

Oudin¹,

Auquier²,

Bertrand³

et al. 2016

Haematologica

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T hyroid complications are known side effects of irradiation. However, the risk of such complications in childhood acute leukemia survivors who received either central nervous system irradiation or hematopoietic stem cell transplantation is less described. We prospectively evaluated the incidence and risk factors for thyroid dysfunction and tumors in survivors of childhood acute myeloid or lymphoid leukemia. A total of 588 patients were evaluated for thyroid function, and 502 individuals were assessed for thyroid tumors (median follow-up duration: 12.6 and 12.5 years, respectively). The cumulative incidence of hypothyroidism was 17.3% (95% CI: 14.1-21.1) and 24.6% (95% CI: 20.4-29.6) at 10 and 20 years from leukemia diagnosis, respectively. Patients who received total body irradiation (with or without prior central nervous system irradiation) were at higher risk of hypothyroidism (adjusted HR: 2.87; P=0.04 and 2.79, P=0.01, respectively) as compared with transplanted patients who never received any irradiation. Patients transplanted without total body irradiation who received central nervous system irradiation were also at higher risk (adjusted HR: 3.39; P=0.02). Patients irradiated or transplanted at older than 10 years of age had a lower risk (adjusted HR: 0.61; P=0.02). Thyroid malignancy was found in 26 patients (5.2%). Among them, two patients had never received any type of irradiation: alkylating agents could also promote thyroid cancer. The cumulative incidence of thyroid malignancy was 9.6% (95% CI: 6.0-15.0) at 20 years. Women were at higher risk than men (adjusted HR: 4.74; P=0.002). In conclusion, thyroid complications are frequent among patients who undergo transplantation after total body irradiation and those who received prior central nervous system irradiation. Close monitoring is thus warranted for these patients.

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Section: Discussionmentioning

confidence: 99%

Late thyroid complications in survivors of childhood acute leukemia. An L.E.A. study

Oudin¹,

Auquier²,

Bertrand³

et al. 2016

Haematologica

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“…The association of pCRT with secondary brain tumors as well as impairment of endocrinologic and neurocognitive functions has frequently been described in the literature. [59][60][61][62][63][64] However, these trials refer to irradiation doses of 18 Gy and higher, and little is known about the impact of 12 Gy cranial irradiation with respect to CNS-related late effects. The updated results from ALL-BFM 90 showed a CI of brain tumors of 3.4% plus or minus 1.6% after 16 years among the patients who had received 12 Gy pCRT demonstrating that even Isol.…”

Section: Discussionmentioning

confidence: 99%

Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95

Möricke

Reiter

Zimmermann

et al. 2008

Blood

504

284

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The trial ALL-BFM 95 for treatment of childhood acute lymphoblastic leukemia was designed to reduce acute and longterm toxicity in selected patient groups with favorable prognosis and to improve outcome in poor-risk groups by treatment intensification. These aims were pursued through a stratification strategy using white blood cell count, age, immunophenotype, treatment response, and unfavorable genetic aberrations providing an excellent discrimination of risk groups.

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“…While cranial radiotherapy can affect growth hormone secretion, especially at doses ≥24 Gy (16,21,22), the evidence for growth hormone deficiency following 18 Gy doses has been inconsistent (9,23). The duration of the pubertal growth spurt and peak growth velocity may also be decreased following cranial radiotherapy as a result of growth hormone deficiency (8).…”

Section: Discussionmentioning

confidence: 99%

“…Growth deficits have been reported consistently following doses of ≥24 Gy cranial radiotherapy, but the data are less consistent for doses <20 Gy (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). The effect on loss of stature was greater in children who also received radiotherapy to the spine, secondary to direct inhibition of vertebral growth (13).…”

Section: Introductionmentioning

confidence: 99%

Decreased Adult Height in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

Chow

Friedman

Yasui

et al. 2007

The Journal of Pediatrics

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Objectives-To determine risk factors associated with reduced adult height in survivors of childhood acute lymphoblastic leukemia (ALL).Study design-Cross-sectional study. Attained adult height was determined among 2,434 ALL survivors participating in the Childhood Cancer Survivor Study, a cohort of five-year survivors of common pediatric cancers diagnosed from [1970][1971][1972][1973][1974][1975][1976][1977][1978][1979][1980][1981][1982][1983][1984][1985][1986], and compared with 3,009 siblings.Results-All survivor treatment exposure groups (chemotherapy alone, chemotherapy with cranial or craniospinal radiotherapy) had decreased adult heights and an increased risk of adult short stature (height standard deviation score < −2) compared with siblings (p<0.001). Compared with siblings, the risk of short stature for survivors treated with chemotherapy alone was elevated (OR 3.4, 95% CI 1.9, 6.0). Among survivors, significant risk factors for short stature included diagnosis of ALL prior to puberty, higher dose cranial radiotherapy (≥20 Gy versus <20 Gy), any radiotherapy to the spine, and female sex.Conclusions-Survivors of childhood ALL are at increased risk of adult short stature, including those treated with chemotherapy alone. Risk is highest for those treated with cranial and craniospinal radiotherapy at a young age. PO Box 19024, Seattle, WA 98109-1024. Phone (206) 667-7724, Fax (206) 667-5948, email: ericchow@u.washington.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.The authors disclose no potential conflicts of interest. Cranial and craniospinal radiotherapy were commonly used in the 1970s and early 1980s to treat as well as to prevent the spread of acute lymphoblastic leukemia (ALL) to the central nervous system (CNS) in children. While radiotherapy was effective, it was associated with adverse endocrine and neurocognitive outcomes(1). As a result, over the past three decades, radiotherapy doses have been reduced or eliminated in an attempt to decrease these adverse long-term outcomes, and have been replaced by more intensive chemotherapy.Several studies have examined growth in ALL survivors. Growth deficits have been reported consistently following doses of ≥24 Gy cranial radiotherapy, but the data are less consistent for doses <20 Gy(2-17). The effect on loss of stature was greater in children who also received radiotherapy to the spine, secondary to direct inhibition of vertebral growth(13). For most studies in which the impact of chemotherapy without radiotherapy was examined, growth suppression during treatment was followed by catch-up growth (...

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Prophylactic cranial irradiation of acute lymphoblastic leukemia in childhood: Outcomes of late effects on pituitary function and growth in long-term survivors

Abstract: SUMMARY It is well known that prophylactic cranial irradiation is highly effective in preventing central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL).

Cited by 37 publications

References 26 publications

Late thyroid complications in survivors of childhood acute leukemia. An L.E.A. study

Late thyroid complications in survivors of childhood acute leukemia. An L.E.A. study

Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95

Decreased Adult Height in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

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