Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study

Child, Christopher J.; Zimmermann, Alan G.; Woodmansee, Whitney W.; Green, Daniel M.; Li, Jian J; Jung, Heike; Erfurth, Eva Marie; Robison, Leslie L.

doi:10.1530/eje-11-0286

Cited by 53 publications

(58 citation statements)

References 22 publications

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“…Despite extended person years of follow-up, the average time of follow-up in HypoCCS remains relatively short (mean 4.8 years for all GH-treated patients). However, the SIRs for both GH-treated and untreated patients have reduced with increased follow-up since the previous analysis, from 0.88 (0.74-1.04) previously (14) to 0.82 (0.71-0.93) for GH-treated patients in this report. Cancer/tumour induction time was not used to adjust our analyses.…”

Section: Discussioncontrasting

confidence: 52%

“…Additionally, the SIR for primary cancers in US patients with CO GHD was significantly elevated. As reported previously from the HypoCCS database it is reasonable to conclude that a proportion of these patients have a higher risk of second neoplasms associated with survival of childhood neoplastic disease (14,34). The updated analysis presented here included 28 patients with history of malignancy prior to HypoCCS entry, including 12 with history of intracranial tumours or leukaemia and mean age at second cancer onset of 32.6 years, and ten of whom had CO GHD.…”

Section: Discussionmentioning

confidence: 85%

“…As concerns have remained that GH treatment may be associated with increased cancer risk since GH replacement in adult hypopituitary patients was first approved in 1995 (1), detailed analysis of neoplasia risk is of critical importance. Initial analysis on incidence of primary cancer from this database indicated no increased risk for primary cancers in GH-treated adult hypopituitary patients in HypoCCS (14). At study close, and with an increment to over 40 500 person-years for GH-treated and 4476 for untreated patients, compared with 25 034 and 2688, respectively, in the previous analysis, there remained no evidence of increased risk for primary cancers in GH-treated adult patients across all countries when comparing with general population cancer rates.…”

Section: Discussionmentioning

confidence: 99%

“…Data from an interim analysis of the Hypopituitary Control and Complications Study (HypoCCS) and a US-specific subset indicated no increased risk of primary cancers or recurrence of intracranial tumours in GH-treated adults, but were limited by a short period of follow-up and/or small number of patients (14,15). Earlier retrospective studies of GH-treated cohorts in general had not indicated increased risk for malignancy (16,17,18,19), although in the study of Swerdlow et al (18) in patients treated with human cadaveric GH during childhood, the occurrence of colorectal cancer was significantly elevated vs general population rates.…”

Section: Introductionmentioning

confidence: 99%

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Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study

Child¹,

Conroy

Zimmermann

et al. 2015

European Journal of Endocrinology

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Objective: Speculation remains that GH treatment is associated with increased neoplasia risk. Studies in GH-treated childhood cancer survivors suggested higher rates of second neoplasms, while cancer risk data for GH-treated and untreated hypopituitary adults have been variable. We present primary cancer risk data from the Hypopituitary Control and Complications Study (HypoCCS) with a focus on specific cancers, and assessment of recurrence rates for pituitary adenomas (PA) and craniopharyngiomas (CP). Design: Incident neoplasms during HypoCCS were evaluated in 8418 GH-treated vs 1268 untreated patients for primary malignancies, 3668 GH-treated vs 720 untreated patients with PA history, and 956 GH-treated vs 102 untreated patients with CP history. Methods: Using population cancer rates, standardised incidence ratios (SIRs) were calculated for all primary cancers, breast, prostate, and colorectal cancers. Neoplasm rates in GH-treated vs untreated patients were analysed after propensity score adjustment of baseline treatment group imbalances. Results: During mean follow-up of 4.8 years, 225 primary cancers were identified in GH-treated patients, with SIR of 0.82 (95% CI 0.71-0.93). SIRs (95% CI) for GH-treated patients were 0.59 (0.36-0.90) for breast, 0.80 (0.57-1.10) for prostate, and 0.62 (0.38-0.96) for colorectal cancers. Cancer risk was not statistically different between GH-treated and untreated patients (relative risk (RR)Z1.00 (95% CI 0.70-1.41), PZ0.98). Adjusted RR for recurrence was 0.91 (0.68-1.22), PZ0.53 for PA and 1.32 (0.53-3.31), PZ0.55 for CP. Conclusions: There was no increased risk for all-site cancers: breast, prostate or colorectal primary cancers in GH-treated patients during HypoCCS. GH treatment did not increase the risk of PA and CP recurrences.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study

Child¹,

Conroy

Zimmermann

et al. 2015

European Journal of Endocrinology

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“…[25]. rates of general population, standardized by country, gender, and age [30]. Bunderen et al played a review to discuss the long-term efficacy and safety of GH treatment in AGHD patients with emphasis on morbidity [31].…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone Replacement Therapy in Adult Growth Hormone Deficiency and Risk of Cancer: A Meta-Analysis

Zeng¹,

Song²,

Lin³

et al. 2017

OJEMD

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The growth hormone (GH) replacement therapy in adult growth hormone deficiency (AGHD) is now well developed, nevertheless, the safety of GH replacement, especially the incidence of cancer in these patients remains to be further clarified. To summarize the evidence on the safety of using GH in AGHD, we conduct this meta-analysis to assess the relationship between the risk of cancer and GH replacement therapy. Randomized controlled trials and cohort studies involved in GH therapy for AGHD were selected. Meta-analysis was performed and risk ratio (RR) was pooled with 95% confidence interval (CI) to investigate the relationship between GH replacement and the risk of cancer. The result indicated that there was no evidence to draw a conclusion that GH replacement therapy will increase the risk of cancer (P = 0.001, RR = 0.77, 95% CI [0.65, 0.90]). Meanwhile, according to the calculated analysis, the replacement therapy might even reduce the risk of cancer. Furthermore, subgroup analysis demonstrated that there was no correlation between replacement therapy of GH and the risk of cancer both in prospective and retrospective cohort design research, and in prospective group, the risk of cancer even decreased (P = 0.0002, RR = 0.71, 95%CI [0.59, 0.85]). In conclusion, our study corroborates evidence from previous studies showing that GH replacement therapy in AGHD patients would not increase the risk of cancer; instead, it might be even decrease cancer risk. The results suggested that GH replacement therapy in AGHD patients was safe.#These authors contributed equally to this work.

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Adult mortality or morbidity is not increased in childhood-onset growth hormone deficient patients who received pediatric GH treatment: an analysis of the Hypopituitary Control and Complications Study (HypoCCS)

Hardin

Erfurth

et al. 2013

Pituitary

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BackgroundThe French Safety and Appropriateness of Growth Hormone treatments in Europe (SAGhE) cohort has raised concern of increased mortality risk during follow-up into adulthood in certain patients who had received growth hormone (GH) treatment during childhood. The Hypopituitary Control and Complications Study monitored mortality and morbidity of adult GH-deficient patients including those with childhood-onset GH deficiency (COGHD) who received GH treatment as children.PurposeEvaluate risk of mortality, cancer, myocardial infarction (MI) and stroke in a prospective observational study.MethodsCOGHD patients [n = 1,204, including 389 diagnosed with idiopathic COGHD (ICOGHD)] had received pediatric GH treatment. Standardized mortality ratios (SMRs), and cancer standardized incidence ratios (SIRs) in patients without a prior cancer were estimated relative to reference populations. Crude incidence rates were estimated for MI and stroke.ResultsNo increased mortality or cancer incidence was observed, as compared with reference populations, during a follow-up of 3.7 ± 3.3 years (mean ± SD). The overall SMR for COGHD was 1.14 [95 % confidence interval (CI) 0.55–2.10], and for ICOGHD, 0.33 (0.01–1.84). The overall cancer SIR for COGHD was 0.27 (0.01–1.50), and for ICOGHD, 0.00 (0.00–2.45). No incident case of MI was reported. The crude stroke incidence rate [181.3 per 100,000 person-years] in COGHD patients was consistent with the rates reported in reference populations. No incident case of stroke was identified in ICOGHD patients who are presumed to have no increased stroke risk factors.ConclusionsThe results indicate no increased risk of mortality or incidence of cancer, stroke, or MI in adult GH-deficient patients who had previously received pediatric GH treatment.

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Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study

Cited by 53 publications

References 22 publications

Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study

Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study

Growth Hormone Replacement Therapy in Adult Growth Hormone Deficiency and Risk of Cancer: A Meta-Analysis

Adult mortality or morbidity is not increased in childhood-onset growth hormone deficient patients who received pediatric GH treatment: an analysis of the Hypopituitary Control and Complications Study (HypoCCS)

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