Effects of stereotactic radiosurgery versus conventional

CLINICAL ARTICLEJ Neurosurg Pediatr 28:43–49, 2021

Craniopharyngiomas are histologically benign in-tracranial neoplasms, accounting for 1%–3% of all intracranial pediatric tumors. In the general

population, the incidence of craniopharyngioma is 0.5 to 2 cases per million people per year.1 It is believed that the embryological origin of craniopharyngiomas is the rem-nant of Rathke’s pouch. These neoplasms are associated with a variety of neurological symptoms and endocrino-

logical deficits. They are usually located in the suprasellar region and can lead to compression of critical neurovascu-lar structures, such as the optic apparatus, pituitary gland, pituitary stalk, internal carotid arteries, hypothalamus, and third ventricle.

Among the endocrinological deficits caused by cra-niopharyngioma (related to tumor compression or treat-ment), hypothalamic obesity is associated with significant

ABBREVIATIONS FRT = fractionated radiotherapy; GKRS = Gamma Knife radiosurgery.SUBMITTED March 6, 2020. ACCEPTED December 7, 2020.INCLUDE WHEN CITING Published online May 14, 2021; DOI: 10.3171/2020.12.PEDS20165.

Effects of stereotactic radiosurgery versus conventional radiotherapy on body mass index in patients with craniopharyngiomaChun-Lung Chou, MD,1 Hsin-Hung Chen, MD,1,3 Huai-Che Yang, MD,1,3 Yi-Wei Chen, MD, PhD,3,5 Ching-Jen Chen, MD,6 Yu-Wei Chen, MS,1 Hsiu-Mei Wu, MD,3,4 Wan-Yuo Guo, MD, PhD,3,4 David Hung-Chi Pan, MD,1,3,7 Wen-Yuh Chung, MD,1,3 Tai-Tong Wong, MD,1,3,8 and Cheng-Chia Lee, MD, PhD1–3

1Department of Neurosurgery, Neurological Institute, 4Department of Radiology, and 5Cancer Center, Taipei Veterans General Hospital, Taipei; 2Brain Research Center and 3School of Medicine, National Yang Ming Chiao Tung University, Taipei;

7Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, Taipei; 8Department of Neurosurgery, Taipei Medical University Hospital, Taipei, Taiwan; and 6Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia

OBJECTIVE Hypothalamic obesity is common among patients with craniopharyngioma. This study examined whether precise stereotactic radiosurgery reduces the risk of hypothalamic obesity in cases of craniopharyngioma with expected long-term survival.METHODS This cohort study included 40 patients who had undergone Gamma Knife radiosurgery (GKRS; n = 22) or fractionated radiotherapy (FRT; n = 18) for residual or recurrent craniopharyngioma. Neurological presentations, tumor volume changes, and BMI values were meticulously reviewed. The median clinical follow-up durations were 9.7 years in the GKRS group and 10.8 years in the FRT group.RESULTS The median ages at the time of GKRS and FRT were 9.0 years and 10.0 years, respectively. The median margin dose of GKRS was 12.0 Gy (range 10.0–16.0 Gy), whereas the median dose of FRT was 50.40 Gy (range 44.1–56.3 Gy). Prior to GKRS or FRT, the median BMI values were 20.5 kg/m2 in the GKRS cohort and 20.0 kg/m2 in the FRT cohort. The median BMIs after radiation therapy at final follow-up were 21.0 kg/m2 and 24.0 kg/m2 for the GKRS and FRT cohorts, respectively. In the FRT cohort, BMI curves rapidly increased beyond the 85th percentile of the upper limit of the general population. BMI curves in the GKRS cohort increased more gradually, and many of the patients merged into the normal growth curve after adolescence. However, the observed difference was not statistically significant (p = 0.409).CONCLUSIONS The study compared the two adjuvant radiation modalities most commonly used for recurrent and residual craniopharyngioma. The authors’ results revealed that precise radiosurgery dose planning can mediate the sub-sequent increase in BMI. There is every indication that meticulous GKRS treatment is an effective approach to treating craniopharyngioma while also reducing the risk of hypothalamic obesity.https://thejns.org/doi/abs/10.3171/2020.12.PEDS20165KEYWORDS body mass index; craniopharyngioma; Gamma Knife radiosurgery; fractionated radiotherapy; oncology

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morbidity and can affect patient survival. Cardiovascular mortality among craniopharyngioma patients with hy-pothalamic obesity is 19-fold higher than that found in the general population.2–4 Resection remains the first-line therapy for patients with craniopharyngiomas. However, complete resection may be challenging, and this must be weighed against neurological and endocrinological complications associated with aggressive resection. For those with recurrent or residual disease, there are several treatment options, including conventional fractionated radiotherapy (FRT), intensity-modulated radiation ther-apy, Gamma Knife radiosurgery (GKRS), CyberKnife radiosurgery, fractionated proton therapy, and intracavi-tary irradiation. The optimal salvage or adjuvant therapy for recurrent or residual disease remains unclear. In this study, we compared the safety and efficacy of GKRS ver-sus FRT in the treatment of recurrent or residual cranio-pharyngiomas.

MethodsPatient Selection

This was a retrospective review of consecutive patients with craniopharyngiomas treated at the Taipei Veterans General Hospital between 1988 and 2018. This study was approved by the institutional review board, and patient consent was waived due to the retrospective nature of the study. Patients who underwent GKRS or FRT for recur-rent or residual craniopharyngiomas after resection were included. Patients with less than 3 years of imaging and clinical follow-up, comorbid congenital disease, or other metabolic disorder were excluded from the study. Patients were then categorized into GKRS and FRT cohorts if they underwent GKRS or FRT as salvage or adjuvant therapy for recurrent or residual craniopharyngioma.

Data CollectionData collected included patient demographics, neuro-

imaging findings, tumor pathology, GKRS and FRT treat-ment parameters, and outcomes. Patient demographics in-

cluded patient age and sex, prior treatments, and BMI (kg/m2). Craniopharyngiomas were classified as solid, cystic, and mixed on neuroimaging, and tumor extensions were classified as suprasellar, third ventricular, and retrosellar. Tumor pathology was categorized as papillary or adaman-tinomatous. GKRS treatment parameters included radia-tion volume and maximum, mean, and margin doses. For FRT, total dose, number of fractions, and length of treat-ment were also recorded.

GKRS TechniqueThe detailed procedure description was published in

2015.5 The patient’s head was fixed using pins within the Leksell frame under local anesthesia for adult patients and under general anesthesia for pediatric patients. Stereo-tactic MRI was performed to delineate tumor margin as part of the pre-GKRS planning. Multiple isocenters were placed over the solid components of the tumor for better conformation and to avoid radiation injury to surround-ing normal brain parenchyma (case example illustrated in Fig. 1A). GKRS was performed using the Leksell Gamma Knife Kula system from 1993 to 1996, model 3C from 1996 to 2006, model 4C from 2006 to 2012, and Perfexion after 2013 (Elekta Instruments AB). A radiation dose < 12 Gy was suggested for radiosensitive structures such as the optic apparatus.

FRT TechniquePatients were maintained in a static position using a

head immobilizer. Until 1990, all treatment plans at our facility were based entirely on the results of CT scan-ning. Since that time, treatment planning has relied on CT scans as well as MRI. Image fusion was first performed to permit delineation of the target volume and at-risk or-gans in each 3D voxel. In the current study, we defined gross tumor volume as the solid lesion measurable on contrast-enhanced T1-weighted MR images, including the cystic tumor components (e.g., cyst wall) measurable on T2-weighted MR images. Note that the clinical target volume of craniopharyngiomas is generally close to the gross tumor volume. The radiotherapy planning target vol-ume enclosed the gross tumor volume with an anisotropic safety margin of 2 mm to account for potential misalign-ment. Beam’s eye view–based treatment planning for field optimization was performed using the Voxelplan/dkfz 3D treatment planning system (Virtuoso/Fa. Leibinger) since 1990. A multileaf collimator (5 mm thick at the isocenter) was used to shape 3–5 noncoplanar isocentric fields. In ac-cordance with the International Commission on Radiation Units and Measurements (ICRU 50 and 62), the isocentric dose prescription method delivered a median dose of 50.4 Gy (range 44.1–56.3 Gy). The isodose line encompassed 95% of the target volume. Note that in all cases, the doses delivered to the brainstem and optic apparatus were less than 54.0 Gy, as shown in Fig. 1B.

Clinical and Imaging Follow-UpClinical follow-ups were conducted at an average of 6

months after GKRS or FRT treatment. Each patient’s BMI was recorded at every clinical follow-up. BMI is defined

FIG. 1. Radiation dose plans for GKRS and FRT. A: GKRS: the tumor margin (pink) is covered by the 11-Gy isodose line (yellow). The radia-tion exposure of the optic apparatus (blue) was usually less than 10 Gy. The 10-, 12-, and 16-Gy isodose lines are shown in green. B: FRT: Gross tumor volume, clinical target volume, and planning target volume are shown in pink, green, and red, respectively. The dose of 5300 cGy was prescribed to the PTV, and the blue-cloud area is the region larger than 5330 cGy. The hot spot was 5333.8 cGy, located in the center of the craniopharyngioma. Figure is available in color online only.


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based on the weight and height of a person. The formula for BMI is weight divided by the square of the body height (kg/m2). For patients with a craniopharyngioma, BMI is a good index for hypothalamic dysfunction.

Neuroimaging follow-ups were performed at 6-month intervals after GKRS or FRT treatment. Tumor growth was defined as an increase in solid tumor volume ≥ 10% compared with tumor volume at the time of GKRS or FRT treatment. Tumor shrinkage was defined as a decrease in tumor volume ≥ 10% compared with tumor volume at the time of GKRS or FRT treatment. A tumor that remained within 10% of its volume at the time of GKRS or FRT treatment was defined as stable.

Statistical AnalysisStatistical analysis was performed using SAS version

9.4 (SAS Institute Inc.). Patients were categorized into GKRS and FRT cohorts. Fisher’s exact test and the chi-square test were used to assess differences between the two cohorts. Continuous variables are reported as the me-dian, mean, and range. Categorical variables are presented as frequencies and percentages. A linear mixed model was used to estimate changes in BMI following GKRS or FRT. The reference BMI of the general population was normal-ized according to local demographic records.6 Prognostic factors were analyzed using a logistic regression model. Probability values < 0.05 were considered statistically sig-nificant.

ResultsAmong the 165 patients treated for craniopharyngioma

at our institution, 57 patients underwent total resection without any further adjuvant therapy. Of the remaining 108 patients with residual or recurrent craniopharyn-gioma, 52 patients underwent subsequent FRT, and 56 patients underwent subsequent GKRS for recurrent or re-sidual disease. After excluding patients with other comor-bidities and insufficient clinical and imaging follow-up, 22 patients remained in the GKRS cohort and 18 in the FRT cohort. Table 1 compares the baseline characteristics be-tween the two cohorts. The median ages of patients at the time of diagnosis were 8.7 and 9.1 years for the GKRS and FRT groups, respectively. The median ages at the time of treatment were 9.0 years and 10.0 years for the GKRS and FRT groups, respectively. Males were predominant, repre-senting 59.1% and 61.1% in the GKRS and FRT cohorts, respectively. The median tumor volumes were 3.5 mL for the GKRS cohort and 9.95 mL for FRT cohort.

Fifteen patients underwent GKRS for recurrence (me-dian time from operation to GKRS: 21 months, range 6–45 months), and the other 7 patients underwent GKRS for residual craniopharyngioma (median time from opera-tion to GKRS: 4 months, range 3–12 months). Twelve pa-tients underwent FRT because of recurrence (median time from operation to FRT: median 15 months, range 8–56 months), and the other 6 patients underwent FRT for re-sidual craniopharyngioma (median time from operation to FRT: 5 months, range 3–9 months).

Among the 22 patients in the GKRS cohort, a median margin dose of 12.0 Gy (range 10.0–16.0 Gy) was deliv-

ered to a median isodose line of 55% (range 20%–60%). The median maximum dose was 21.8 Gy (range 20.0–32.0 Gy), and the median mean dose was 16.4 Gy (range 13.4–21.4 Gy). Among the 18 patients in the FRT cohort, a median dose of 50.4 Gy (range 44.1–56.3 Gy) was deliv-ered in 27 fractions (range 22–32) over a median treatment length of 37.7 days (range 30–50 days).

Tumor ControlTable 2 compares the neuroimaging outcomes between

two cohorts. The median neuroimaging follow-up times were 6.7 years for the GKRS cohort and 7 years for the FRT cohort. Good tumor control was observed in 9 pa-tients (40.9%) in the GKRS cohort and 8 patients (44.4%) in the FRT cohort. Tumor growth was noted in 9 patients (40.9%) in the GKRS cohort and 1 patient (5.6%) in the FRT cohort. New observed lesions were found in 4 pa-tients in the GKRS cohort and 1 patient in the FRT cohort. In the FRT cohort, 5 patients (27.8%) had initial tumor regression followed by regrowth. Regardless of the type of tumor growth (e.g., direct tumor growth, initial shrinkage/regrowth, and new lesion development), treatment fail-ure was observed in 13 patients (59.1%) and 10 patients (55.6%) in the GKRS and FRT cohorts, respectively.

Neurological and Endocrinological OutcomesThe median clinical follow-up times were 8.7 years for

the GKRS cohort and 9.1 years for the FRT cohort. In the GKRS cohort, 17 patients (77.3%) presented with visual field deficits and 2 had improvement following GKRS. No patient had visual field deterioration after GKRS. All 16 patients (72.7%) with hypopituitarism prior to GKRS re-mained unchanged after GKRS. Among the 18 patients (81.8%) with diabetes insipidus prior to GKRS, 17 had no deterioration. Among the 14 patients (63.6%) with hypo-thalamic dysfunction before GKRS, 2 had improvement after GKRS and 11 remained stable. None of the 3 patients (13.6%) with cranial nerve deficit before GKRS had dete-rioration after GKRS.

Among the 12 patients (66.7%) with visual field deficit in the FRT cohort, 10 patients remained unchanged af-ter FRT. Among the 11 patients (61.1%) with hypopituita-rism, 10 patients remained stable after FRT. Among the 9 patients (50%) with diabetes insipidus, 7 patients had no worsening after FRT. Among the 7 patients (38.9%) with hypothalamus dysfunction, 1 patient had improvement after FRT, and 4 patients remained stable. None of the 3 patients (16.7%) with cranial nerve deficits had worsening deficits after FRT.

The adverse effects of radiation were observed in both the GKRS and FRT cohorts, including new-onset visual deterioration in 2 patients (9.1%) in the GKRS cohort and 2 patients (11.1%) in the FRT cohort. One patient in the FRT group had a cerebrovascular accident with no direct anatomical relation to the previous FRT field.

Additional Management After GKRS or FRTAmong the 15 patients with tumor progression or re-

growth after GKRS or FRT, 9 patients underwent resec-tion, and 3 patients were managed conservatively. There


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TABLE 1. Characteristics of 40 craniopharyngioma patients who underwent either GKRS or FRT

GKRS (n = 22) FRT (n = 18) p Value

Median age at time of diagnosis, yrs 8.68 (0.6–16.0) 9.10 (1.9–22.4) 0.30Median age at time of GKRS or FRT, yrs 9.00 (1.5–16.4) 10.0 (1.9–27.8) 0.32Female sex 9 (40.9) 7 (38.9) 0.90Median tumor vol, ml 3.5 (0.3–20.3) 9.95 (0.2–50.0) 0.10Classification 0.50 Solid 7 (31.8) 3 (16.7) Cystic 9 (40.9) 8 (44.4) Mixed 6 (27.3) 7 (38.9)Pathology 0.01 Papillary 12 (54.5) 17 (94.4) Adamantinomatous 10 (45.5) 1 (5.6)Tumor extension Suprasellar 20 (90.9) 12 (66.7) 0.69 3rd ventricle 7 (31.8) 1 (5.6) 1.00 Retrosellar 3 (13.6) 1 (5.6) 0.40 Missing data 5 (27.8)No. of prior resections 4 1 (4.5) 0 0.56 3 1 (4.5) 2 (11.1) 2 3 (13.6) 1 (5.6) 1 15 (68.2) 15 (83.3) 0 2 (9.1) 0No. of patients w/ prior biopsy 9 (40.9) 1 (5.6) 0.001No. of patients w/ prior cyst aspiration 3 (13.6) 3 (16.7) 0.56No. of patients w/ prior Ommaya shunt replacement 2 (9.1) 3 (16.7) 0.40No. of patients w/ prior intracavity Tx (RT or chemo) 1 (4.5) 3 (16.7) 0.23No. of patients w/ prior VP shunt replacement 4 (18.2) 4 (22.2) 0.53Pre-GKRS/FRT visual field deficits 17 (77.3) 12 (66.7) 0.86Pre-GKRS/FRT hypopituitarism 16 (72.7) 11 (61.1) 0.44Pre-GKRS/FRT diabetes insipidus 18 (81.8) 9 (50.0) 0.03Pre-GKRS/FRT hypothalamic dysfunction 14 (63.6) 7 (38.9) 0.12Pre-GKRS/FRT CN deficits 3 (13.64) 3 (16.7) 0.56Median clinical follow-up, yrs 9.7 (5.2–16.3) 10.8 (5.6–20.4)Median imaging follow-up, yrs 6.7 (3.4–12.5) 7 (4.3–16.7)Radiation parameters Median radiation vol, mL 3.75 (0.58–24.2) Median margin radiation dose, Gy 12.0 (10–16) Median maximum radiation dose, Gy 21.8 (20–32) Median margin radiation dose, % 55 (20–60) Median mean dose, Gy 16.4 (13.4–21.4) Median FRT dose, Gy 50.40 (44.1–56.3) Median fractionation 27.0 (22–32) Median days 37.7 (30–50)

Chemo = chemotherapy; CN = cranial nerve; RT = radiotherapy; Tx = treatment; VP = ventriculoperitoneal.Values represent the number of patients (%) unless stated otherwise. Median values are presented as the median (range).



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were 8 instances of Ommaya shunts, 4 aspirations, 3 fen-estrations, 3 intracavity bleomycin injections, and 5 cases of repeat GKRS among these 15 patients. All 4 patients with new lesions underwent resection, followed by GKRS (Table 2).

Prognostic Factors of Craniopharyngioma Patients With BMI Elevations

Hypothalamic obesity was found in 32 (73%) of 44 pa-tients with craniopharyngioma. In the univariable model of this study, including age, sex, margin dose, maximum dose, tumor volume, suprasellar extension, third ventricle extension, retrosellar extension, pathology type, and ex-istence of hypopituitarism, no predictor was found to be associated with hypothalamic obesity (Table 3).

Mixed Model Evaluation of BMI Post-GKRS and Post-FRTBMIs for patients with craniopharyngioma were higher

than those in the general population prior to radiation ther-apy. The median BMIs before radiation therapy were 20.5 kg/m2 and 20.0 kg/m2 for the GKRS and FRT cohorts, respectively. The median BMIs after radiation therapy at final follow-up were 21.0 kg/m2 and 24.0 kg/m2 for the GKRS and FRT cohorts, respectively. Figure 2 illustrates the changes in BMI of craniopharyngioma patients treat-ed with GKRS or FRT. Generally speaking, there was an increase in BMI with increasing age for both the GKRS

and FRT cohorts. For BMIs in the FRT cohort, the in-crease was more rapid compared with BMIs in the GKRS cohort, and there was a high proportion of BMI values that exceeded the 85% upper limit of the general popula-tion. BMIs in the GKRS cohort increased more gradually with increasing age, and, after adolescence, many of the patients merged into the normal growth curve. Note that the observed difference was not statistically significant (p = 0.409).

DiscussionHypothalamic invasion and treatment-related hypo-

thalamus injury have both been associated with obesity among patients with craniopharyngioma. The effects are more pronounced in younger individuals, leaving more time for the development of obesity-related diseases. Obe-sity during childhood tends to continue into adulthood, resulting in early morbidity and mortality.7–9 In a previ-ous series of 26 pediatric and 34 adult craniopharyngioma patients who underwent resection (median follow-up 12 years), there was a fivefold increase in overall mortality, which was primarily related to cardiovascular and cere-brovascular conditions.10 Obesity has also been linked to low self-esteem and unsatisfactory peer relationships, par-ticularly among adolescents. Numerous studies have re-ported high incidences of psychopathological difficulties among craniopharyngioma patients, including depression, anxiety, withdrawal, and reduced functional capacity.11,12 Despite the wide range of symptoms associated with cra-niopharyngiomas,13–17 hypothalamic dysfunction appears to be the single most important risk factor for the severe impairment of physical function, social functionality, and body image perception.15,16,18

Hypothalamic obesity control is generally beyond the scope of lifestyle modification. Its pathophysiology is re-lated to imbalances in central sympathetic output, energy expenditure, and the dysregulation of appetite. Several medications have been used for the management of these issues, including dextroamphetamine,19 methylpheni-date,20 octreotide,21 GLP-1 analogs,22 and oxytocin. Vari-ous forms of bariatric surgery have also been performed to treat hypothalamic obesity, including laparoscopic ad-justable gastric banding, Roux-en-Y gastric bypass, sleeve gastrectomy, and biliopancreatic diversion.23 In the early era of treatment for hypothalamic obesity, none of these methods have been proven to be effective in long-term weight loss.24 There is considerable controversy regarding the use of nonreversible surgical techniques in the pedi-atric population due to legal, medical, and ethical rami-fications.24 However, current studies have shown that the

TABLE 2. Imaging outcomes of craniopharyngioma patients after GKRS or FRT

Tumor Vol Change GKRS FRT Additional Management

Shrinkage & stable 9 8Growth 9 1 Resection ×9, Ommaya ×8, aspiration ×4, fenestration

×3, re-GKRS ×5, observation ×3, bleomycin ×3Initial shrinkage/regrowth 0 5New lesion development 4 1 Resection ×4, GKRS ×4, biopsy ×1, Ommaya ×1

TABLE 3. Prognostic factors of patients with hypothalamic obesity

Logistic Univariatep Value OR (95% CI)

Age (child or teenage vs adult)* 0.43 0.22 (0.01–9.4)Sex (female vs male) 0.60 0.70 (0.18–2.7)Margin dose (>12 vs <12 Gy) 0.89 0.91 (0.24–3.4)Maximum dose (>21.8 vs <21.8 Gy) 0.73 0.79 (0.20–3.07)Tumor volume (<5.5 vs >5.5 mL) 0.97 1.02 (0.26–4.0)Tumor extension Suprasellar (yes vs no) 0.11 6.48 (0.64–65) Third ventricle (yes vs no) 0.33 0.40 (0.06–2.5) Retrosellar extension (yes vs no) 0.27 0.21 (0.01–3.2)Pathology (adamantinomatous vs papillary)

0.52 1.61 (0.38–6.8)

Hypopituitarism (yes vs no) 0.33 2.13 (0.47–9.60)

* The cutoff value between child and adult is 18 years.


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Roux-en-Y bypass will result in at least a 75% reduction in the excess body weight for size within about 2 years, which reduces the risk of the development of diabetes mellitus and subsequent late manifestations in such pa-tients.25,26

GKRS is a salvage or adjuvant therapy for recurrent or residual craniopharyngiomas. It is associated with a rela-tively low risk of treatment-related hypothalamic injury.5 The sharp margin dose attenuation and highly focused ra-diation energy of GKRS reduce the risk of injury to adja-cent neurovascular tissue. Compared with FRT, treatment with GRKS was associated with a trend toward slower BMI increase in craniopharyngioma patients over time, and this BMI increase eventually fell within the normal range of the general population.

Several limitations were recognized in this study. This cohort was derived from retrospective data comprising a relatively small number of patients at a single medical cen-ter. There is inherent selection bias as the choice between GKRS and FRT was at the discretion of the treating phy-sician, and the patients were not randomized. Given the small sample size of the study and the rarity of the disease, we could not adequately adjust for differences in baseline characteristics and selection bias. Given these limitations, we have provided longitudinal data on BMI changes over the years. In addition, the latency period between surgery and radiation treatment was not controlled. Therefore, it is conceivable that the amount of time was not sufficient to observe the effects of surgery on BMI. Further analysis using a larger, more diverse cohort is required to fully elu-cidate the benefits of GKRS.

ConclusionsCompared with FRT, GRKS was associated with a

slower BMI increase over time in craniopharyngioma pa-tients. This BMI increase in the GKRS cohort eventually fell within the normal range of the general population. Both GKRS and FRT offered reasonable tumor control rates for recurrent or residual craniopharyngiomas.

AcknowledgmentsThis work was supported by the Ministry of Science and Tech-

nology, Taiwan (MOST108-2321-B-010-012-MY2). The funding sources had no role in the design and conduct of the study; collec-tion, management, analysis, or interpretation of the data; prepara-tion, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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FIG. 2. BMI values from all patients plotted according to patient age. Mixed model linear regression curves in the GKRS cohort (GKS) increased more gently than those in the FRT cohort. BMI values presented the most profound increase during childhood and adolescence; therefore, we depicted the local general population’s BMI (5th–85th percentile, gray area) based on the growth chart provided in Chen et al.6 BMI curves in the FRT cohort consistently exceeded the 85% upper limit of the general population. BMI curves in the GKRS cohort tended to merge into normal growth curves after adolescence.



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DisclosuresThe authors report no conflict of interest concerning the materi-als or methods used in this study or the findings specified in this paper.

Author ContributionsConception and design: Lee. Acquisition of data: Lee, Chou. Analysis and interpretation of data: Lee, Yang. Drafting the article: Lee, Chou. Critically revising the article: Lee, HH Chen, Yang, Yi-Wei Chen, CJ Chen. Reviewed submitted version of manuscript: Lee, HH Chen, Yang, Yi-Wei Chen, CJ Chen, Wu. Approved the final version of the manuscript on behalf of all authors: Lee. Statistical analysis: Lee, Chou, Yu-Wei Chen. Administrative/technical/material support: Lee, HH Chen, Yang, Wu, Pan, Wong. Study supervision: Lee, Yi-Wei Chen, Wu, Guo, Pan, Chung, Wong.

CorrespondenceCheng-Chia Lee: Neurological Institute, Taipei Veterans Gen-eral Hospital, Taipei, Taiwan. [email protected]; [email protected].


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