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Results
Objectives
Methods
A systematic review and meta-
analysis were conducted to
examine the effect of GHRT on the
recurrence of craniopharyngioma
among pediatric patients who
underwent a surgical resection.
Conclusions
Discussion
Strengths and Limitations
Comparison of Physiologic Growth Hormone Replacement
Therapy with No Replacement on the Recurrence of
Craniopharyngioma in Pediatric Patients: a Meta-analysis.
Nawaf M. Alotaibi†, B.Pharm, MSc2, Nadia Noormohamed†, Pharm D2, Salman Alharthy, MSc, B.Pharm2, Joanne Doucette, MS2, Hassan Zaidi, MD1, Rania A. Mekary‡, MSc, PhD1,2, Timothy R. Smith‡, MD, PhD, MPH1,2
†Co-first authors; ‡Co-senior authors1Brigham and Women’s Hospital, Boston, Massachusetts; 2MCPHS University, Boston, Massachusetts
Introduction
•Surgical resection of
craniopharyngiomas can result in
hypopituitarism
•In the pediatric population,
postoperative growth hormone
deficiency can result in an
impaired organ maturation.
•Significant controversy exists on
whether growth hormone
replacement therapy (GHRT)
contributes to the recurrence of
craniopharyngiomas in the
pediatric population and may
place patients at a higher risk of
residual tumor growth.
•PubMed, EMBASE, and Cochrane
databases were searched through
October 28, 2015 for comparative
studies (n≥ 5 patients) that
evaluated the effect of GHRT on
the recurrence of pediatric
(newborn- 18 years old)
craniopharyngiomas. Pooled effect
estimates were calculated using
fixed- and random-effects models.
•Heterogeneity, in the analysis,
was evaluated by the Q statistic
and I2 statistic.
•Potential sources of heterogeneity
were explored using sub-group
analyses by categorical covariates
(growth hormone replacement
therapy, country, international
journal Impact factor, Newcastle-
Ottawa Scale –to assess study
quality-; and center).
•Covariates such as age range and
type of surgery could not be
assessed for heterogeneity
sources as information was NA.
•Potential publication bias was
assessed by using funnel plots,
Egger’s linear regression test, and
Begg’s correlation test.
•If publication bias was indicated,
the # of missing studies in a meta-
analysis was evaluated by the trim
and fill method.
Articles were found in PubMed (n=404)
Articles were found in Embase (n=694)
Articles were found in Cochrane Library (n=2)
Total Articles (n=1100)
Ide
nti
fica
tio
n
Duplicates articles (n=303)
Articles screened (n=797)
Scre
en
ing
(n=719) articles were excluded as the title or abstract was not relevant
Full-text articles assessed for eligibility (n=78)
Elig
ibili
ty
In
clu
de
d
(n=56) Not English (n=5)
Conference Abstracts and review articles.
(n=10)
Age > 18 years (n=11)
No information about recurrence and
GHRT (n=22)
Not craniopharingoma (n=3)
Case report (n=2)
Errata (n=1)
Comment to article (n=1)
Inter Library Loan (ILL) (n=1)
Articles included in qualitative synthesis (n=22)
Articles included in quantitative synthesis (meta‐analysis) (n=8)
(n=14) Abstracts and missing data (n=8)
Can’t extract event number (n=2)
Mix adults with children (n=1)
Erratum to another study (n=1)
Not for Craniopharingoma (n=2)
Figure 1: Study selection process of the identified articles
Author, Year
Journal Impact Factor Study Design Country Center
Intervention arm n/N for
GHRT
Control arm n/N for no
GHRTAge range,
year % Male Surgery typeStudy duration (Year X - Year Y)
Intervention type (Name[HGH vs rGH], Dose & Frequency) Frequency
Route of Admin GH
Time after diagnosis when GH treatment
was started
GH treatment duration
Newcastle-Ottawa
Scale
Alev Ozon, Z, 2015 1.538Retrospective
case seriesOutside the USA
Single 11/24 na na naGross totalresection
na GH na na 2.7 years na 2
Arslanian, S, 1985 7.148Retrospective
cohortUSA Single 4/13 0/5 3.9-17.8 na
Subfrontal and transphenoidal
1970-1983Somatotropin,
0.1 unit/kg.3x/week IM/SC na na 6
Darendeliler, F, 2006 1.674Retrospective
case seriesUSA Multiple 121/1038 na 4.3-14.9 N/A Not specified
Start on Jan 2004
Genotropin , 0.17 mg/kg/wk
NA IM/SC na 1.9 yr 3
Kanev,P. M, 1991 3.737Retrospective
case seriesUSA Single 0/5 na na na Subfrontal 1985 - 1987
Protropin,0.1 mg/kg each, or daily injections of 0.05 mg/kg.
3x/week SC na na 3
Moshang T, 1995 9.392Retrospective
case seriesUSA Single 2/19 na 3.5-12.5 84.2 Not specified 1985-1995 rHGH na na 2.4 years na 3
Moshang T, 1996 3.79Prospective case series
USA Multiple 35/546 na na na Not specified na rHGH na na Not specified na 3
Price DA, 1997 2.48Retrospective
case seriesOutside the USA
Multiple 54/488 na 4.9-14.8 57 Not specified 1988-1996rGH, mean dose 0.49+-
0.15 IU/kg/6x/ week
(range 3-7)Injection
Median 1.56 yrs , mean 2.23+-1.88 yrs
Some patients after one year
and other patients after 5 years on GH.
2
Rohrer, RT, 2010 0.995Retrospective
case seriesOutsidethe USA
Single 11/22 4/7 1.3-15.5 65.5 Not specified na hGH, 0.025 mg/kg Daily Injection Not mentioned na 2
Table 1: The characteristics of the studies included in the meta-analysis.
•Eight studies (7 case series and 1 retrospective cohort) with 2,167
patients with craniopharyngioma were included in the final analysis.
•The fixed pooled prevalence was 11.7% (95% CI: 10.4%; 13.2%) for
GHRT+ and 43.1% (95% CI: 16.7%; 74.1%) for GHRT- (P-
interaction = 0.23)
• Among the GHRT group, the fixed pooled prevalence was 15.5%
(95% CI: 12.4%; 19.1%) for studies outside the USA and 10.4%(
95% CI: 9.0%; 12.0%) for studies conducted in the USA (P-
interaction= 0.07).
•The fixed pooled prevalence was 10.4% (95% CI: 9.10%; 11.8%) for
multiple-center studies and 37.9% (95% CI: 27.3%; 49.7%) for
single-center studies (P-interaction<0.01).
•The fixed pooled prevalence was 7.50% (95% CI: 5.60%; 10.0%) for
high impact factor journals and12.9% (95% CI: 11.3%; 14.7%) for
low impact factor (P-interaction=0.16).
•The fixed pooled prevalence was 10.4% (95% CI: 9.0%; 12.0%) for
high NOS and 15.5% (95% CI: 12.4%; 19.1%) for low NOS (P-
interaction=0.07)
Figure 2: Craniopharyngioma recurrence prevalence for growth hormone replacement
therapy (GHRT) and no GHRT.
Forest plot represents the craniopharyngioma recurrence prevalence (95% CI) after GHRT
(GHRT+) or no GHRT (GHRT-) among patients with craniopharyngioma who underwent a
surgical resection. Horizontal lines denote 95% CIs; solid squares represent the point
estimate of each study and the diamond represents the pooled estimate of the intervention
effect. The size of the solid squares is proportional to the weight of the study. (I2 for GHRT
+=88.6%; p-heterogeneity<0.01; I2 for GHRT- = 61.7%; p-heterogeneity=0.11 ; overall I2 =
87.3%; p-heterogeneity<0.01 (P-interaction comparing the two groups=0.23).
The fixed pooled prevalence is 11.7% (95% CI: 10.4%; 13.2%) for GHRT+ and 43.1% (95%
CI: 16.7%; 74.1%) for GHRT-. The overall prevalence is 11.9% (95% CI: 10.5%; 13.4%).
Figure 3: Funnel Plot of Standard Error by Logit event rate.
The vertical solid line is drawn at the pooled log odds ratio, and the other two
lines represent the expected 95% confidence interval for a given standard
error. Visually, the Funnel plot showed a slight asymmetry. Statistically, both
Begg’s rank correlation test (P = 1.00) and Egger’s linear regression test (P =
0.24) indicated no significant publication bias. Conducting the trim and fill
method resulted in an overall imputed effect estimate that dropped from 11.9
% (10.5%; 13.4%) to 11.1% (9.87%; 12.5%).
• GHRT among pediatric patients with biochemical
evidence of GH deficiency after surgical resection for
craniopharyngiomas remains a topic of controversy for
clinicians and surgeons.
• Our current meta-analysis demonstrated that pediatric
patients treated with GHRT after surgical resection of
craniopharyngioma had a lower incidence of tumor
recurrence.
• There was insufficient evidence in the current
literature to indicate that GHRT promoted growth of
craniopharyngiomas after surgical resection.
Pros Cons
Explored different sources of
heterogeneity for which the
information was available
Only studies in English were included
Publication bias was assessed Age and perioperative medical treatment modalities
were not available
Heterogeneity remained relatively high in the
subgroups reflecting some residual effect modifiers
that were not reported in all the studies.
• This meta-analysis showed that GHRT use
was not associated with the recurrence of
craniopharyngioma among carefully selected
pediatric patients
Contact Information
Email: [email protected]