DÄ internationalArchive18/2019The Postoperative Quality of Life in Children and Adolescents with Craniopharyngioma

Original article

The Postoperative Quality of Life in Children and Adolescents with Craniopharyngioma

Results of a prospective multicenter study

Dtsch Arztebl Int 2019; 116(18): 321-8; DOI: 10.3238/arztebl.2019.0321

Eveslage, M; Calaminus, G; Warmuth-Metz, M; Kortmann, R; Pohl, F; Timmermann, B; Schuhmann, M U; Flitsch, J; Faldum, A; Müller, H L

Background: Craniopharyngioma is a tumor of low histological malignancy resulting from an anomaly of embryonic development. Affected children and adolescents are being studied with respect to their quality of life, progression-free survival, and overall survival in the framework of the ongoing KRANIOPHARYNGEOM 2007 project.

Methods: This prospective, multicenter project consists of a randomized trial with an adaptive design combined with a purely observational study. The randomized, unblinded trial includes patients whose tumors have been incompletely resected and is intended to compare the outcomes of immediate postoperative radiotherapy versus radiotherapy on progression. Its primary endpoint is quality of life as assessed subjectively by the patients themselves with the “Pediatric Quality of Life” questionnaire (PEDQOL). In exploratory analyses, linear mixed models were used to study the effect of further factors on quality of life.

Results: An interim intention-to-treat analysis of the randomized trial revealed only minor differences between the treatment arms with respect to quality of life (n = 24). The exploratory analyses (n = 131) showed that preoperative involvement of, or operative damage to, the anterior and posterior regions of the hypothalamus was associated with a lower quality of life. Complete resection was followed by a lower quality of life than incomplete resection. Radiotherapy, a common treatment for tumors that progress after incomplete resection, was also associated with a lower quality of life.

Conclusion: Hypothalamus-sparing treatment approaches are recommended to optimize the quality of life of children and adolescents with cranio-pharyngioma. The available evidence does not support any recommendation as to when radiotherapy should be performed after incomplete resection so that the best quality of life can be achieved.

LNSLNS

Craniopharyngioma is a tumor of the sellar region that arises because of an anomaly in embryonic development. It is treated with neurosurgical procedures and radiotherapy. Because tumors of this type lie in the immediate vicinity of the optic chiasm, pituitary gland, and hypothalamus, the patient’s quality of life can be impaired over the long term by dysfunction of these structures induced either by the tumor itself or by its treatment; hypothalamic obesity is a particular problem (1). Complete resection was once considered the goal of surgery, but neurosurgeons now increasingly prefer incomplete resection in order to avoid surgical damage to the anatomical structures of the hypothalamic-pituitary axis.

The KRANIOPHARYNGEOM 2007 study (Clinical Trials.gov, identifier NCT01272622) is a prospective multicenter study of children and adolescents with craniopharyngioma. Its goal is to investigate the quality of life, progression-free survival, and overall survival of the affected patients as a function of the treatment. The study is based on a multidisciplinary approach involving all the medical specialties that collaborate in these patients’ diagnostic evaluation, treatment, and long-term care. For patients whose tumors have been incompletely resected, the KRANIOPHARYNGEOM 2007 project also includes a randomized substudy that was intended to determine the optimal timing of postoperative radiotherapy.

Methods

Study design

Recruitment for the KRANIOPHARYNGEOM 2007 study began in 2007 and includes children and adolescents from across Germany who received an initial diagnosis of craniopharyngioma before their 18th birthday. In the randomized trial, patients who were at least five years old and had undergone radiologically confirmed incomplete tumor resection were randomized to receive postoperative radiotherapy either right after surgery or only on progression of disease. Patients were not included in the randomized trial if they did not meet the inclusion criteria or did not consent to randomization, but these patients’ further course was nonetheless longitudinally observed and documented.

Craniopharyngioma
Craniopharyngioma
Box
Craniopharyngioma

Endpoints

Quality of life was assessed with the “Pediatric Quality of Life” questionnaire (PEDQOL) (4, 5), which yields a numerical score reflecting the subjective assessment—by the patients themselves and their parents—of quality of life in seven distinct domains. The subscore in each area can range from 25 to 100 points, with a low score reflecting a higher quality of life (for details, cf. eMethods). The primary endpoint for the randomized trial was the change in the PEDQOL physical function subscore from a first time point three months after surgery to another time point three years after surgery. The secondary endpoints were progression-free and overall survival. For the entire patient group, the PEDQOL score in all domains was analyzed one year and three years after surgery in order to assess long-term quality of life after the patients’ postoperative condition had become stable.

Neuroradiological diagnostic studies

The degree of preoperative hypothalamic involvement (HI) and of operative hypothalamic damage (HD) was determined neuroradiologically according to published criteria (5, 6). In brief, a score of 0 corresponded to no demonstrable HI or HD, a score of 1 corresponded to involvement or damage of anterior hypothalamic structures not including the mammillary bodies, and a score of 2 corresponded to involvement or damage of anterior and posterior hypothalamic areas including the mammillary bodies (Figure 1).

MRI on diagnosis and 36 months after surgery in three children with craniopharyngioma with different degrees of preoperative hypothalamic involvement and operative hypothalamic damage
MRI on diagnosis and 36 months after surgery in three children with craniopharyngioma with different degrees of preoperative hypothalamic involvement and operative hypothalamic damage
Figure 1
MRI on diagnosis and 36 months after surgery in three children with craniopharyngioma with different degrees of preoperative hypothalamic involvement and operative hypothalamic damage

Statistical methods

The primary evaluation of the results of the randomized trial was carried out with an intention-to-treat analysis. The main hypothesis was tested in an adaptive study design with a two-tailed significance level set at 5%. All further analyses, including the analysis of quality of life in the overall patient cohort, can only be considered exploratory; the significance level was, therefore, not adjusted for multiple testing. P-values less than or equal to 0.05 were considered statistically noticeable. Based on the data from the overall patient cohort, exploratory analyses employing linear mixed models were carried out to study the effects of age, sex, degree of resection, radiotherapy, preoperative HI, and operative HD on self-assessed quality of life (for details of the statistical methods, see eMethods).

Results

Randomized trial

24 patients were included in the analysis of the primary endpoint (Figure 2, eFigure 1). The PEDQOL physical function subscore in the 10 patients who underwent radiotherapy immediately after surgery increased by +2.1 ± 16.6 points (mean ± standard deviation), reflecting a mild worsening. The change in the 14 patients who only underwent radiotherapy on progression was −0.9 ± 15.5 (two-tailed p-value by the Mann–Whitney U test = 0.63). Seven of these 14 patients underwent radiotherapy within three years of surgery. Randomization was terminated in September 2016, as required by the underlying adaptive design, because the probability of detecting a significant difference would then have been too low even if recruitment had been extended for the longest practically achievable time (“stop for futility”). Since the end of recruitment, the project has been continued as a purely observational study. The analysis of progression-free survival (PFS) reveals good tumor control after primary radiotherapy: the estimated PFS at one year is 93.3% (95% confidence interval [81.5; 100]), as opposed to 45.0% [27.7; 73.1]) in the patients who did not undergo radiotherapy immediately after surgery (eFigure 2). This difference had been anticipated in the planning of the study; the central question of the randomized trial was the extent to which delayed radiotherapy might provide a benefit with respect to quality of life. None of the randomized patients died, so there was no evidence of any difference in overall survival. Further details of the analysis of the randomized part of the study are provided in the eMethods section.

Flowchart of recruitment and randomization in the KRANIOPHARYNGEOM 2007 study.
Flowchart of recruitment and randomization in the KRANIOPHARYNGEOM 2007 study.
Figure 2
Flowchart of recruitment and randomization in the KRANIOPHARYNGEOM 2007 study.
CONSORT flowchart for the randomized part of the study.
CONSORT flowchart for the randomized part of the study.
eFigure 1
CONSORT flowchart for the randomized part of the study.
Kaplan–Meier estimate of progression-free survival p = 0.0013 (log-rank test).
Kaplan–Meier estimate of progression-free survival p = 0.0013 (log-rank test).
eFigure 2
Kaplan–Meier estimate of progression-free survival p = 0.0013 (log-rank test).

Patient cohort for exploratory analyses

As the randomized comparison yielded no conclusion about the optimal timing of radiotherapy for the patients’ subjectively assessed quality of life (QoL), further parameters were studied in the overall patient cohort for their possible effect on postoperative QoL. 240 patients had been recruited as of June 2018, of whom 230 had a craniopharyngioma. PEDQOL responses one and/or three years after surgery were available from 131 patients; data from these patients were included in the analysis (Figure 2, eFigure 3).

Results of the exploratory analses of self-assessed quality of life in the overall cohort (n = 131).
Results of the exploratory analses of self-assessed quality of life in the overall cohort (n = 131).
Figure 3
Results of the exploratory analses of self-assessed quality of life in the overall cohort (n = 131).

Information on the investigated patient cohort is presented in the Table. The documentation of some variables was incomplete; e.g., the extent of resection was unknown for some patients. It was decided, however, to carry out each QoL analysis with the largest possible number of patients. The median age at diagnosis was 10 years (range, 1–18), and 66 of 131 patients (50%) were female. Only 6% of the patients had no hypothalamic involvement at the time of diagnosis; 21% had anterior HI, and 73% had both anterior and posterior HI. Tumor resection was complete in 18% and incomplete in 82%. Radiotherapy was documented for 41 of the 91 patients who had undergone incomplete resection; one additional patient underwent radiotherapy after complete resection. The type of radiotherapy was not predetermined in the study protocol. 47% of the patients who underwent radiotherapy had photon radiotherapy, and another 47% had proton-beam radiotherapy.

Patient cohort for exploratory analysis of the quality of life*
Patient cohort for exploratory analysis of the quality of life*
Table
Patient cohort for exploratory analysis of the quality of life*

To check whether the PEDQOL responses of these 131 patients were representative of the overall cohort, the groups with and without PEDQOL values at one or three years were descriptively compared. The two groups displayed no statistically noticeable differences in any of the main baseline characteristics (age on diagnosis, sex, tumor site, hypothalamic involvement or hypothalamic damage). A small difference was seen with respect to treatment: information on quality of life was available for 72% (94/131) of the patients who underwent incomplete resection, but for only 50% (21/42) of those who underwent complete resection (p = 0.014).

Factors affecting patients’ postoperative quality of life

Patients who were aged seven years or older when craniopharyngioma was diagnosed rated their own quality of life one or three years after surgery worse than younger children did, in six of the seven domains of assessment (eFigure 4). Male and female patients differed only slightly in self-assessed quality of life.

Results of the linear mixed model for self-assessed quality of life in the overall patient cohort (n = 131).
Results of the linear mixed model for self-assessed quality of life in the overall patient cohort (n = 131).
eFigure 4
Results of the linear mixed model for self-assessed quality of life in the overall patient cohort (n = 131).

Patients who preoperatively had anterior and posterior HI rated their quality of life markedly worse than patients without HI or with only anterior HI (Figure 3, eFigure 5). For example, the PEDQOL body image subscore in patients with second-degree HI was 16.9 points higher than in those without HI ([4.4; 29.5], p = 0.009). When interpreting such differences, one should bear in mind that different responses to a single domain-specific question can lead to an approximately five-point difference in the corresponding subscore, with higher scores indicating a lower quality of life. In both comparisons, patients with anterior and posterior HI had higher PEDQOL subscores relating to body image and to social behavior (as determined from questions about friendships); a comparison of first- and second-degree HI revealed statistically noticeable differences in three further domains. On the other hand, no relevant difference was seen between patients with anterior HI and patients without any preoperative HI.

The degree of postoperative hypothalamic damage also affects the quality of life. The self-assessed QoL of patients with anterior and posterior HD was worse in all domains than that of patients with only anterior HD or no HD; the difference was statistically noticeable in four of the seven domains. Patients with anterior HD did not differ from patients without HD in their self-assessed QoL.

The effects of preoperative HI and operative/postoperative HD on patients’ quality of life cannot be assessed independently, because these two entities are strongly correlated with each other (p<0.0001, eTable 1). For example, all 48 patients with second-degree postoperative HD had second-degree HI before surgery.

The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: Comparison of preoperative hypothalamic involvement and postoperative hypothalamic damage*
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: Comparison of preoperative hypothalamic involvement and postoperative hypothalamic damage*
eTable 1
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: Comparison of preoperative hypothalamic involvement and postoperative hypothalamic damage*

The temporal dependence of radiotherapy was considered in the analysis of treatment modalities: PEDQOL responses were assigned to the “Radiotherapy” category if the patient had undergone radiotherapy before answering the corresponding questions (Table). Whether or not they were treated with radiotherapy, patients who underwent incomplete resection uniformly rated their quality of life better than those who underwent complete resection. The effects of the extent of resection and of HD could not be assessed independently, as these two parameters were closely linked (p = 0.0001, eTables 2, 3). Thus, most (16/21) patients who underwent complete resection had second-degree hypothalamic damage thereafter.

The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of preoperative hypothalamic involvement and extent of resection*
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of preoperative hypothalamic involvement and extent of resection*
eTable 2
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of preoperative hypothalamic involvement and extent of resection*
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of extent of resection and postoperative hypothalamic damage*
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of extent of resection and postoperative hypothalamic damage*
eTable 3
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of extent of resection and postoperative hypothalamic damage*

Quality of life after incomplete tumor resection

Among the 94 patients whose tumors were incompletely resected, those who underwent radiotherapy had a marginally lower self-assessed quality of life than those who did not, with statistically noticeable differences in two PEDQOL subscores—body image and physical function (Figure 3). Radiotherapy was performed after progression in most cases (27/41). The analysis was repeated with simultaneous consideration of possible hypothalamic damage and adjustment for age. The deleterious effect of anterior and posterior hypothalamic damage was confirmed and was found to be even stronger in patients who had also received radiotherapy (eFigure 6). Quality of life as a function of the radiotherapeutic modality (eFigure 7) was also investigated. A statistically noticeable worsening of the quality of life in the domains of autonomy, body image, and physical function was found after photon radiotherapy, but a direct comparison of photon radiotherapy versus proton-beam radiotherapy revealed no statistically noticeable difference. The degree of hypothalamic damage could not be considered in this analysis because of the small number of cases. The patient cohorts who underwent photon radiotherapy and proton-beam radiotherapy were compared in descriptive fashion with respect to their main features. There were no relevant differences other than the year of diagnosis: the patients who underwent proton-beam radiotherapy received their diagnosis two years earlier (comparison of medians, p = 0.047). Despite this, an analysis of the effect of radiotherapeutic modality adjusted for year of diagnosis or age at the time of diagnosis (not shown), confirmed the results of the unadjusted analyses.

Results of the linear mixed models for the self-assessed quality of life for patients who underwent incomplete resection (n = 94).
Results of the linear mixed models for the self-assessed quality of life for patients who underwent incomplete resection (n = 94).
eFigure 7
Results of the linear mixed models for the self-assessed quality of life for patients who underwent incomplete resection (n = 94).

Discussion

Treatment strategies for craniopharyngioma in childhood and adolescence are a matter of controversy (8, 9). Radical neurosurgical procedures with the goal of complete resection of the tumor often have serious long-term adverse effects because of operative damage to the hypothalamus (1, 10, 11). One complication, in particular, that markedly impairs the quality of life of the surviving patients is severe obesity as part of a hypothalamic syndrome (12, 13). More conservative surgical strategies intended to preserve the integrity of hypothalamic structures are often associated with the need for further surgery or for postoperative radiotherapy after incomplete primary resection of the craniopharyngioma (1, 14).

Radical surgery was the treatment of choice for decades, with tumor control rates of 65–90%, compared to 10–50% after incomplete resection (1518). Yet the radical neurosurgical approach, even in expert hands, carries the risk of postoperative damage to hypothalamic-pituitary structures, which can become clinically manifest as endocrine deficits, obesity as part of a hypothalamic syndrome, neurocognitive deficits, and behavioral abnormalities (1). For this reason, more conservative, hypothalamus-sparing surgical strategies with subsequent radiotherapy are now being increasingly used (5, 6, 1926). Our randomized trial unfortunately yielded no answer to the question of the ideal timing of radiotherapy after the incomplete resection of a craniopharyngioma. Good tumor control was seen after primary radiotherapy, but the data do not support any conclusion about possible differences between the randomized groups with respect to quality of life. The interim analysis enabled a check of the assumptions under which the study was planned, leading to a cessation of randomization because of the low chance of success. Thus, despite low case numbers and little advance knowledge, the use of an adaptive design permitted a randomized trial to be performed with the option of premature termination of the study or adaptation of case numbers after an interim analysis. The structured, prospective acquisition of data also made it possible to draw conclusions about the quality of life of children and adolescents with craniopharyngioma as a function of various factors, in both the randomized and the observational cohort.

The special prognostic significance of the posterior hypothalamic area is also indicated by experimental studies in animals, which have shown that changes in posteriorly located hypothalamic nuclei (the dorsomedial nucleus, the dorsal hypothalamic nucleus, and the ventromedial nucleus) are primarily responsible for the hypothalamic syndrome (27). Roth et al. (24) confirmed these results in a study of imaging findings in patients with sellar masses of various types and their association with the outcome. In contrast, the preoperative involvement of, or operative damage to, anterior hypothalamic areas has a much less deleterious effect on the postoperative quality of life. In view of these facts and the beneficial effect of restricted surgical strategies (i.e., incomplete tumor resection) on quality of life, hypothalamus-sparing surgery is now recommended as a means of avoiding posterior hypothalamic damage. Moreover, our analyses of the subgroup of craniopharyngioma patients who underwent incomplete tumor resection confirmed the deleterious effect of posterior hypothalamic damage on quality of life. The particular radiotherapeutic modality used (photon vs. proton-beam radiotherapy) was not found to make any detectable difference; in any case, no such difference could have been expected in view of the short follow-up interval.

Our study has certain limitations that affect the interpretation of the results. Because of the rarity of the disease, the case numbers were small, despite the near-completeness of the study sample. Because of the short follow-up interval, analyses and conclusions about late sequelae and long-term impairment of patients’ quality of life are not yet possible. Other studies have shown, however, that comorbidites and risk factors for impaired quality of life in craniopharyngioma patients generally exert their lasting prognostic effects early on, i.e., in the first three years after diagnosis (28). A fully reliable assessment of the long-term quality of life will only be possible in future analyses. Moreover, it must be kept in mind that the analyses presented here are based on the patients’ own assessments of their quality of life; a repeated analysis based on information supplied by their parents did, however, yield very similar results (not shown). There was also a very high correlation between self-assessed quality of life in the domains of body image and physical function and the body-mass index (an objectively measurable quantity) (eFigure 8); this supports the validity of the results with respect to quality of life.

Association between subjectively self-assessed quality of life and body-mass index Correlation between subjective quality of life (self-assessment by the patient in the seven domains of the PEDQOL) and body-mass index (BMI, kg/m²) for the overall patient cohort (n = 131).
Association between subjectively self-assessed quality of life and body-mass index Correlation between subjective quality of life (self-assessment by the patient in the seven domains of the PEDQOL) and body-mass index (BMI, kg/m²) for the overall patient cohort (n = 131).
eFigure 8
Association between subjectively self-assessed quality of life and body-mass index Correlation between subjective quality of life (self-assessment by the patient in the seven domains of the PEDQOL) and body-mass index (BMI, kg/m²) for the overall patient cohort (n = 131).
Conditional error function for the randomized trial component of the KRANIOPHARYNGEOM 2007 project
Conditional error function for the randomized trial component of the KRANIOPHARYNGEOM 2007 project
eFigure 9
Conditional error function for the randomized trial component of the KRANIOPHARYNGEOM 2007 project
Results of the interim assessment of the primary endpoint of the randomized trial. A negative difference indicates improvement of the quality of life, and a positive difference indicates worsening
Results of the interim assessment of the primary endpoint of the randomized trial. A negative difference indicates improvement of the quality of life, and a positive difference indicates worsening
eFigure 10
Results of the interim assessment of the primary endpoint of the randomized trial. A negative difference indicates improvement of the quality of life, and a positive difference indicates worsening

Particularly with respect to the posterior hypothalamic region, our findings support the recommendation for a hypothalamus-sparing neurosurgical approach. In case of progression of the residual tumor after incomplete resection, conservative treatment is recommended, e.g., radiotherapy, in order to achieve effective tumor control while avoiding further surgery, which would carry a high risk of further hypothalamic damage adversely affecting the clinical outcome. Children and adolescents with craniopharyngioma should only be treated by experienced multidisciplinary teams.

Funding

KRANIOPHARYNGEOM 2007 is supported financially by the German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung), Bonn, Germany.

Data sharing

The data cannot yet be made available because the study has not yet been concluded. Moreover, the small number of cases would likely make it difficult to preserve the full anonymity of the data.

Conflict of interest statement
Prof. Müller has received reimbursement of participation fees for scientific meetings and continuing medical education events from the following companies: Ferring, Lilly, Pfizer, Sandoz/Hexal, Novo Nordisk, Ipsen, and Merck Serono. He has received reimbursement of travel expenses from Ipsen and lecture honoraria from Pfizer.

The other authors state that they have no conflict of interest.

Manuscript submitted on 9 November 2018 and accepted after revision on 7 March 2019.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Hermann Müller
Klinik für Allgemeine Kinderheilkunde,
Hämatologie/Onkologie
Universitätsklinik für Kinder- und Jugendmedizin
Klinikum Oldenburg AöR
Rahel-Straus-Str. 10
D-26133 Oldenburg, Germany
mueller.hermann@klinikum-oldenburg.de

Cite this as:
Eveslage M, Calaminus G, Warmuth-Metz M, Kortmann RD,
Pohl F, Timmermann B, Schuhmann MU, Flitsch J, Faldum A,
Müller HL: The postoperative quality of life in children and
adolescents with craniopharyngioma—results of a prospective
multicenter study. Dtsch Arztebl Int 2019; 116: 321–8.
DOI: 10.3238/arztebl.2019.0321

Supplementary material
For eReferences please refer to:
www.aerzteblatt-international.de/ref1819

eMethods, eFigures, and eTables:
www.aerzteblatt-international.de/19m0321

Reproduced and modified with permission from Nature (2)

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Institute of Biostatistics and Clinical Research, Universtity of Münster:
Maria Eveslage
Department of PediatricHematology/Oncology, University Children’s Hospital Bonn:
Dr. med. Gabriele Calaminus
Department of Interventional and Diagnostic Neuroradiology, Universitiy Hospital Würzburg:
Prof. Dr. med. Monika Warmuth-Metz
Department of Radiation Oncology, University of Leipzig:
Prof. Dr. med. Rolf-Dieter Kortmann
Department of Radiotherapy, University Hospital Regensburg:
Dr. med. Fabian Pohl
Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen (WPE): Prof. Dr. med. Beate Timmermann
Division of Pediatric Neurosurgery within the Department of Neurosurgery, University Hospital Tübingen: Prof. Dr. med. Martin Ulrich Schuhmann
Department of Neurosurgery, University Medical Center Hamburg-Eppendorf (UKE):
Prof. Dr. med. Jörg Flitsch
Institute of Biostatistics and Clinical Research, Universtity of Münster:
Prof. Dr. rer. nat. et med. habil. Andreas Faldum
Department of General Pediatrics,Hematology/Oncology, University Children’s Hospital Oldenburg: Prof. Dr. med. Hermann L. Müller
Craniopharyngioma
Craniopharyngioma
Box
Craniopharyngioma
MRI on diagnosis and 36 months after surgery in three children with craniopharyngioma with different degrees of preoperative hypothalamic involvement and operative hypothalamic damage
MRI on diagnosis and 36 months after surgery in three children with craniopharyngioma with different degrees of preoperative hypothalamic involvement and operative hypothalamic damage
Figure 1
MRI on diagnosis and 36 months after surgery in three children with craniopharyngioma with different degrees of preoperative hypothalamic involvement and operative hypothalamic damage
Flowchart of recruitment and randomization in the KRANIOPHARYNGEOM 2007 study.
Flowchart of recruitment and randomization in the KRANIOPHARYNGEOM 2007 study.
Figure 2
Flowchart of recruitment and randomization in the KRANIOPHARYNGEOM 2007 study.
Results of the exploratory analses of self-assessed quality of life in the overall cohort (n = 131).
Results of the exploratory analses of self-assessed quality of life in the overall cohort (n = 131).
Figure 3
Results of the exploratory analses of self-assessed quality of life in the overall cohort (n = 131).
Key messages
Patient cohort for exploratory analysis of the quality of life*
Patient cohort for exploratory analysis of the quality of life*
Table
Patient cohort for exploratory analysis of the quality of life*
CONSORT flowchart for the randomized part of the study.
CONSORT flowchart for the randomized part of the study.
eFigure 1
CONSORT flowchart for the randomized part of the study.
Kaplan–Meier estimate of progression-free survival p = 0.0013 (log-rank test).
Kaplan–Meier estimate of progression-free survival p = 0.0013 (log-rank test).
eFigure 2
Kaplan–Meier estimate of progression-free survival p = 0.0013 (log-rank test).
Results of the linear mixed model for self-assessed quality of life in the overall patient cohort (n = 131).
Results of the linear mixed model for self-assessed quality of life in the overall patient cohort (n = 131).
eFigure 4
Results of the linear mixed model for self-assessed quality of life in the overall patient cohort (n = 131).
Results of the linear mixed models for the self-assessed quality of life for patients who underwent incomplete resection (n = 94).
Results of the linear mixed models for the self-assessed quality of life for patients who underwent incomplete resection (n = 94).
eFigure 7
Results of the linear mixed models for the self-assessed quality of life for patients who underwent incomplete resection (n = 94).
Association between subjectively self-assessed quality of life and body-mass index Correlation between subjective quality of life (self-assessment by the patient in the seven domains of the PEDQOL) and body-mass index (BMI, kg/m²) for the overall patient cohort (n = 131).
Association between subjectively self-assessed quality of life and body-mass index Correlation between subjective quality of life (self-assessment by the patient in the seven domains of the PEDQOL) and body-mass index (BMI, kg/m²) for the overall patient cohort (n = 131).
eFigure 8
Association between subjectively self-assessed quality of life and body-mass index Correlation between subjective quality of life (self-assessment by the patient in the seven domains of the PEDQOL) and body-mass index (BMI, kg/m²) for the overall patient cohort (n = 131).
Conditional error function for the randomized trial component of the KRANIOPHARYNGEOM 2007 project
Conditional error function for the randomized trial component of the KRANIOPHARYNGEOM 2007 project
eFigure 9
Conditional error function for the randomized trial component of the KRANIOPHARYNGEOM 2007 project
Results of the interim assessment of the primary endpoint of the randomized trial. A negative difference indicates improvement of the quality of life, and a positive difference indicates worsening
Results of the interim assessment of the primary endpoint of the randomized trial. A negative difference indicates improvement of the quality of life, and a positive difference indicates worsening
eFigure 10
Results of the interim assessment of the primary endpoint of the randomized trial. A negative difference indicates improvement of the quality of life, and a positive difference indicates worsening
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: Comparison of preoperative hypothalamic involvement and postoperative hypothalamic damage*
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: Comparison of preoperative hypothalamic involvement and postoperative hypothalamic damage*
eTable 1
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: Comparison of preoperative hypothalamic involvement and postoperative hypothalamic damage*
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of preoperative hypothalamic involvement and extent of resection*
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of preoperative hypothalamic involvement and extent of resection*
eTable 2
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of preoperative hypothalamic involvement and extent of resection*
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of extent of resection and postoperative hypothalamic damage*
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of extent of resection and postoperative hypothalamic damage*
eTable 3
The association of preoperative hypothalamic involvement, extent of surgical resection, and postoperative hypothalamic damage: comparison of extent of resection and postoperative hypothalamic damage*
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