The clinical significance of inflammatory mediators in predicting obesity and progression-free survival in patients with adult-onset Craniopharyngioma.

BACKGROUND: Craniopharyngioma (CP) is a rare malformational tumor characterized by high rates of recurrence and morbid obesity. However, the role of inflammatory mediators in obesity and the prognosis of patients with CP remains unknown. Therefore, the present study aimed to analyze associations of inflammatory mediators with weight-related outcomes and the prognosis of patients with CP. METHODS: A total of 130 consecutive patients with CP were included in this study. The expression levels of seven inflammatory mediators and the plasma leptin concentration were investigated. Clinical parameters, weight changes, new-onset obesity, and progression-free survival (PFS) were recorded. The relationships between inflammatory mediators, clinicopathologic parameters, weight-related outcomes, and PFS were explored. RESULTS: Compared with those in normal pituitary tissue, the expressions of inflammatory mediators in tumor tissue were higher. Higher expression levels of CXCL1 and CXCL8 were identified as independent risk factors for significant weight gain, and CXCL1 and TNF were identified as independent risk factors for new-onset postoperative obesity. Poor PFS was associated with higher expression levels of CXCL1, CXCL8, IL1A, IL6, and TNF. CONCLUSION: The present study revealed that inflammatory mediators are associated with morbid obesity in patients with CP. Inflammatory mediators may be the critical bridge between elevated leptin and weight-related outcomes. Additionally, PFS was associated with the expression of inflammatory mediators. Further research is needed to elucidate the underlying mechanisms of inflammatory mediators and their potential as targets for novel therapies for CP.

Craniopharyngioma in the Elderly: A Multicenter and Nationwide Study in Spain.

BACKGROUND: Craniopharyngioma (CP) is a rare tumor in the elderly whose clinical features and prognosis are not well known in this population. AIM: To evaluate the clinicopathological features and therapeutic outcomes of CP diagnosed in the elderly. PATIENTS AND METHODS: This was a retrospective, multicenter, national study of CP patients diagnosed over the age of 65 years and surgically treated. RESULTS: From a total of 384 adult CP patients, we selected 53 (13.8%) patients (27 women [50.9%], mean age 72.3 ± 5.1 years [range 65-83 years]) diagnosed after the age of 65 years. The most common clinical symptoms were visual field defects (71.2%) followed by headache (45.3%). The maximum tumor diameter was 2.9 ± 1.1 cm. In most patients, the tumor was suprasellar (96.2%) and mixed (solid-cystic) (58.5%). The surgical approach most commonly used was transcranial surgery (52.8%), and more than half of the patients (54.7%) underwent subtotal resection (STR). Adamantinomatous CP and papillary CP were present in 51 and 45.1%, respectively, with mixed forms in the remaining. Surgery was accompanied by an improvement in visual field defects and in headaches; however, pituitary hormonal hypofunction increased, mainly at the expense of an increase in the prevalence of diabetes insipidus (DI) (from 3.9 to 69.2%). Near-total resection (NTR) was associated with a higher prevalence of DI compared with subtotal resection (87.5 vs. 53.6%, p = 0.008). Patients were followed for 46.7 ± 40.8 months. The mortality rate was 39.6% with a median survival time of 88 (95% CI: 57-118) months. DI at last visit was associated with a lower survival. CONCLUSION: CP diagnosed in the elderly shows a similar distribution by sex and histologic forms than that diagnosed at younger ages. At presentation, visual field alterations and headaches are the main clinical symptoms which improve substantially with surgery. However, surgery, mainly NTR, is accompanied by worsening of pituitary function, especially DI, which seems to be a predictor of mortality in this population.

Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid).

Craniopharyngiomas (CPs) are histologically benign tumors that are associated with high levels of morbidity. Two clinicopathological variants - adamantinomatous (ACP) and papillary (PCP) - have been described. They differ in their molecular features, whereby activating mutations in BRAF (V600E) and CTNNB1 genes characterize PCP and ACP, respectively. Recently, both variants have been shown to express elevated PD-L1 protein expression, but ACP also exhibited tumor cell-intrinsic PD-1 expression. In this study we analyze these molecular alterations in 52 cases with a long follow-up and examine their associations with immunohistochemical and clinical characteristics. ACPs comprise 73.1% of cases, while 21.2% are PCPs. Aberrant nuclear immunoreactivity for ß-catenin was observed in all ACPs. BRAF p.V600E mutations were observed in 90.9% of PCPs. Only one ACP case featured both alterations. Both types of CP exhibited strong nuclear staining for p63 with diffuse and basal distribution. ACP and PCP consistently expressed PD-L1, most in a substantial percentage of tumor cells, with a distinctive spatial distribution of expression in each subtype; only ACP demonstrated PD-1 expression. There was no evidence of differences in clinical prognosis between ACPs and PCPs. The identification of hallmark molecular signatures in the two CP variants is useful for sub-categorization in routine histopathology reporting. It is also pertinent to personalized therapy and for the development of improved non-invasive therapeutic strategies in this disease.

Clinical outcomes following proton therapy for adult craniopharyngioma: a single-institution cohort study.

BACKGROUND: Craniopharyngioma is a benign tumor that commonly develops within the suprasellar region. The tumor and treatment can have debilitating consequences for pediatric and adult patients, including vision loss and pituitary/hypothalamic dysfunction. Most craniopharyngioma series focus on treatment of the pediatric population. We evaluated the outcomes of all adult craniopharyngioma patients treated at our institution using proton therapy to report outcomes for disease control, treatment-related toxicity, and tumor response. METHODS: We analyzed 14 adult patients (≥ 22 years old). All patients had gross disease at the time of radiotherapy. Five were treated for de novo disease and 9 for recurrent disease. Patients received double-scattered conformal proton therapy to a mean dose of 54 GyRBE in 1.8 GyRBE/fraction (range 52.2-54 GyRBE). Weekly magnetic resonance imaging (MRI) helped to evaluate tumor changes during radiotherapy. RESULTS: With median clinical and radiographic follow-up of 29 and 26 months, respectively, the 3-year local control and overall survival rates were both 100%. There were no grade 3 or greater acute or late radiotherapy-related side effects. There was no radiotherapy-related vision loss or optic neuropathy. No patients required intervention or treatment replanning due to tumor changes during radiotherapy. Two patients experienced transient cyst expansion at their first post-radiotherapy MRI. Both patients were followed closely clinically and radiographically and had subsequent dramatic tumor/cyst regression, requiring no interventions. CONCLUSIONS: Our data support the safety and efficacy of proton therapy in the treatment of adult craniopharyngioma as part of primary or salvage treatment. We recommend early consideration of radiotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03224767.

The implication of giant tumor size on surgical resection, oncological, and functional outcomes in craniopharyngioma.

OBJECTIVE: Implication of the tumor size on oncological and functional outcomes of craniopharyngioma is inconsistently reported. The aim of this study is to assess the postoperative outcome of giant craniopharyngiomas (> 4 cm in diameter) and to elucidate the impact of tumor size on various outcome parameters and survival. MATERIAL AND METHODS: Forty-four patients (children aged ≤ 18 years: 25; adults: 16) with giant craniopharyngioma, operated between January 2001 and December 2015, were included in this study. Various outcomes, progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: Gross total resection (GTR) was achieved in 17 (39%) and subtotal resection (STR) in 27 (61%) patients. Eleven patients (25%) received radiotherapy (RT) after STR. Postoperatively, new cranial nerve and motor deficits were noted in 12 (27%) and 9 (20%) patients, respectively. Tumor recurrence following GTR and STR without adjuvant RT was diagnosed in 3 (17%), and 5 (38%) patients, respectively. Following STR with RT, one (9%) experienced recurrence. PFS at 5-, and 10- year following GTR, STR, and STR + RT was 80.8%, 45.4%, and 90%, respectively. At 5- and 10- year, OS was 86.5%, 77.9% and 100% following GTR, STR, and STR + RT, respectively. The rate of GTR was significantly lower in patients with giant tumors (39% vs. 62%; Chi-square test, p value 0.008). Postoperatively, neurological deficit (20%), hypopituitarism (95%) and hypothalamic dysfunction (26%) were significantly higher for giant craniopharyngiomas. Hazards of recurrence were not significant between giant and non-giant tumors (hazard ratio 1.86; 95% CI 0.94-3.68; p 0.07). There was no significant difference in OS between the patients with giant and non-giant tumors (log-rank test 2.1; p value 0.14). CONCLUSION: Tumor size should be considered as an important predictor of the postoperative functional outcome. Although the rate of GTR is less than that of small tumors, the recurrence rate, progression-free survival, and overall survival of the patients with giant tumor are comparable to non-giant tumors.

Comparing survival outcomes of gross total resection and subtotal resection with radiotherapy for craniopharyngioma: a meta-analysis.

BACKGROUND: Recent studies suggest that subtotal resection (STR) followed by radiation therapy (RT) is an appealing alternative to gross total resection (GTR) for craniopharyngioma, but it remains controversial. We conducted a meta-analysis to determine whether GTR is superior to STR with RT for craniopharyngioma. MATERIALS AND METHODS: A systematic search was performed for articles published until October 2017 in the PubMed, Embase, and Cochrane Central databases. The endpoints of interest are overall survival and progression-free survival. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using a fixed or random-effects model. The data were analyzed using Review Manager 5.3 software. RESULTS: A total of 744 patients (seven cohort studies) were enrolled for analyses. There were no significant differences between the GTR and STR with RT groups when the authors compared the pooled HRs at the end of the follow-up period. Overall survival (pooled HR = 0.76, 95% CI: 0.46-1.25, P = 0.28) and progression-free survival (pooled HR = 1.52, 95% CI: 0.42-5.44, P = 0.52) were similar between the two groups. CONCLUSIONS: The current meta-analysis suggests that GTR and STR with RT have the similar survival outcomes for craniopharyngioma.

Outcome of Surgical Resection of Craniopharyngioma:Single Center 12 Years' Experience.

Background Craniopharyngiomas (CPs) are rare epithelial tumors arising from the Rathke's pouch remnant located along the path of the craniopharyngeal duct accounting for 1.2-4% of all primary intracranial brain tumors, the primary treatment of which is surgery. Objective Whether radical surgical resection or partial resection followed by radiotherapy is a topic of debate. We presented our 12 years single center experience on surgical resection of craniopharyngioma. Method This was a descriptive cross-sectional study conducted among forty-five patients who underwent transcranial resection of craniopharyngioma during a period of 12 years. Data were collected from medical record archives. Glassgow outcome score (GOS), electrolyte imbalance and visual complications were assessed as outcome measure. GOS > 3 was considered favorable while score ≤ 3 was considered unfavorable. Recurrence of tumors were analyzed. Result Out of 45 patients, 28 patients were male with male to female ration of 1.64. Mean age was 32.22±16.42 years. Supra-sellar craniopharyngioma were the most common location. Gross total resection was accomplished in 32 patients (71.1%) while subtotal resection among 13 patients (28.9%). Post-operative Diabetes Insipidus was developed among 35 patients (77.7%). Adamantinomatous craniopharyngioma was the most common histopathological type. Postoperative MRI with contrast was repeated to ascertain the completeness of resection. All patient with subtotal resection received radiotherapy. Follow up period ranged from 3 months to 8 years with mean of 4.2 years. Favorable outcome (GOS>3) was seen among 41 patients while unfavorable among 4 patients. Recurrence seen among 4 patients (8.9%). Overall mortality was 4 (8.8%). Conclusion Gross total excision of craniopharyngioma has a favorable outcome with acceptable morbidity.

[Radiotherapy and radiosurgery in treatment of craniopharyngiomas]. / Luchevaia terapiia i radiokhirurgiia v lechenii kraniofaringiom.

Craniopharyngiomas are benign epithelial tumors having a dysembryogenetic origin, which are usually located in the sellar/parasellar and/or third ventricle regions. Gross total resection is the modern standard of treatment for these tumors because of a low recurrence rate. However, this surgery in some patients with craniopharyngioma often leads to the development or worsening of diencephalic disorders poorly responding to treatment. Perhaps, in these cases, subtotal or partial tumor resection or implantation of an Ommaya reservoir into the tumor cyst followed by stereotactic radiotherapy/radiosurgery may provide better functional outcomes and higher life quality in patients, with tumor growth control being reasonable (according to the published data, the mean 10-year disease-free survival is 66.9% after total tumor resection and 79.6% after combined treatment). The paper presents a review of the literature on radiological treatment of craniopharyngiomas. We discuss the issues of indications, optimal timing of radiotherapy/radiosurgery, its efficacy, and treatment outcomes in terms of complications and quality of life. Particular attention is paid to enlargement of craniopharyngioma cysts during and after radiological treatment.

Aberrant membranous expression of ß-catenin predicts poor prognosis in patients with craniopharyngioma.

The objective of this study is to investigate ß-catenin expression in craniopharyngioma patients and determine its significance in predicting the prognosis of this disease. Fifty craniopharyngioma patients were enrolled in this study. Expression of ß-catenin in tumor specimens collected from these patients was examined through immunostaining. In addition, mutation of exon 3 in the ß-catenin gene, CTNNB1, was analyzed using polymerase chain reaction, denaturing high-pressure liquid chromatography, and DNA sequencing. Based on these results, we explored the association between membranous ß-catenin expression, clinical and pathologic characteristics, and prognoses in these patients. Of all craniopharyngioma specimens, 31 (62.0%) had preserved membranous ß-catenin expression, whereas the remaining 19 specimens (38.0%) displayed aberrant expression. Statistical analysis showed a significant correlation between aberrant membranous ß-catenin expression and CTNNB1 exon 3 mutation, as well as between aberrant membranous ß-catenin expression and the histopathologic type of craniopharyngioma and type of resection in our patient population. Furthermore, aberrant membranous ß-catenin expression was found to be associated with poor patient survival. Results of Kaplan-Meier survival analysis and Cox regression analysis further confirmed this finding. In conclusion, our study demonstrated that aberrant membranous ß-catenin expression was significantly correlated with poor survival in patients with craniopharyngioma. This raises the possibility for use of aberrant membranous ß-catenin expression as an independent risk factor in predicting the prognosis of this disease.

Childhood craniopharyngioma - changes of treatment strategies in the trials KRANIOPHARYNGEOM 2000/2007.

BACKGROUND: Prognosis in childhood cranio-pharyngioma, is frequently impaired due to sequelae. Radical surgery was the treatment of choice for decades. Even at experienced facilities radical surgery can result in hypothalamic disorders such as severe obesity. OBJECTIVE: We analyzed, whether treatment strategies for childhood craniopharyngioma patients recruited in GPOH studies have changed during the last 12 years. MATERIALS AND METHODS: We compared the grade of pre-surgical hypothalamic involvement, treatment, degree of resection and grade of surgical hypothalamic lesions between patients recruited in KRANIOPHARYNGEOM 2000 (n=120; 2001-2007) and KRANIOPHARYNGEOM 2007 (n=106; 2007-2012). RESULTS: The grade of initial hypothalamic involvement was similar in patients treated 2001-2007 and 2007-2012. The realized treatment was more radical (p=0.01) in patients recruited 2001-2007 (38%) when compared with patients treated 2007-2012 (18%). In patients with pre-surgical involvement of anterior/posterior hypothalamic areas, the rate of hypothalamus-sparing operations resulting in no (further) hypothalamic lesions was higher (p=0.005) in patients treated 2007-2012 (35%) in comparison with the 2001-2007 cohort (13%). Event-free-survival rates were similar in both cohorts. CONCLUSIONS: A trend towards less radical surgical approaches is observed, which was accompanied by a reduced rate of severe hypothalamic lesions. Radical surgery is not an appropriate treatment strategy in patients with hypothalamic involvement. Despite previous recommendations to centralize treatment at specialized centers, a trend towards further decentralization was seen.

Long-term outcomes for adult craniopharyngioma following radiation therapy.

BACKGROUND: We report long-term outcomes in adult patients with craniopharyngioma following surgery and radiation therapy (RT). MATERIAL AND METHODS: Fifty-three patients treated with RT (median, 50 Gy in 25 fractions) between 1980 and 2009 with pathologically confirmed craniopharyngioma were reviewed (53% solid and 47% cystic/solid). The median age was 53 years (range, 22-76), 53% were female, 83% were sub-totally resected, 6% were gross totally resected and 11% had a biopsy and/or cyst aspiration alone. RT was delivered adjuvantly in 53% of patients as opposed to salvage intent upon progression. RESULTS: Median follow-up was seven years (86 months, range, 8-259). The 5- and 10-year progression-free survival (PFS) rates were 85% and 69%, overall survival (OS) rates were 76% and 70%, and cause-specific survival (CSS) rates were both 88%, respectively. Both univariable and multivariable analysis identified age (<53 or ≥53) as a prognostic factor for OS (p =0.0003) and CSS (p =0.05). PFS was observed to be worse in patients with >2 surgeries prior to RT (p =0.01). Neither the intent of radiation or tumor type (cystic vs. solid/cystic) were prognostic or predictive. New endocrinopathies and visual dysfunction were observed in 53% and 17% of patients post-surgery, and in 11% and 6% post-RT, respectively. CONCLUSION: We report long-term favorable PFS, CSS and OS for craniopharyngioma post-RT. We observe age as a significant prognostic factor, however, timing of radiation was not.

Mortality and morbidity in adult craniopharyngioma.

A craniopharyngioma (CP) is an embryonic malformation of the sellar and parasellar region. The annual incidence is 0.5-2.0 cases/million/year and approximately 60 % of CP are seen in adulthood. Craniopharyngiomas have the highest mortality of all pituitary tumors. Typical initial manifestations at diagnosis in adults are visual disturbances, hypopituitarism and symptoms of elevated intracranial pressure. The long-term morbidity is substantial with hypopituitarism, increased cardiovascular risk, hypothalamic damage, visual and neurological deficits, reduced bone health, and reduction in quality of life and cognitive function. Therapy of choice is surgery, followed by cranial radiotherapy in about half of the patients. The standardised overall mortality rate varies 2.88-9.28 in cohort studies. Patients with CP have a 3-19 fold higher cardiovascular mortality in comparison to the general population. Women with CP have an even higher risk.

The superiority of conservative resection and adjuvant radiation for craniopharyngiomas.

The purpose of this study is to evaluate the roles of resection extent and adjuvant radiation in the treatment of craniopharyngiomas. We reviewed the records of 122 patients ages 11-52 years who received primary treatment for craniopharyngioma between 1980 and 2009 at the University of California, San Francisco (UCSF). Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints were development of panhypopituitarism, diabetes insipidus (DI), and visual field defects. Of 122 patients, 30 (24%) were treated with gross total resection (GTR) without radiation therapy (RT), 3 (3%) with GTR + RT, 41 (33.6%) with subtotal resection (STR) without RT, and 48 (39.3%) with STR + RT. Median age at diagnosis was 30 years, with 46 patients 18 years or younger. Median follow-up for all patients was 56.4 months (interquartile range 18.9-144.2 months) and 47 months (interquartile range 12.3-121.8 months) for the 60 patients without progression. Fifty six patients progressed, 10 have died, 6 without progression. Median PFS was 61.1 months for all patients. PFS rate at 2 years was 61.5% (95% CI: 52.1-70.9). OS rate at 10 years was 91.1% (95% CI 84.3-97.9). There was no significant difference in PFS and OS between patients treated with GTR vs. STR + XRT (PFS; p = 0.544, OS; p = 0.735), but STR alone resulted in significantly shortened PFS compared to STR + RT or GTR (p < 0.001 for both). STR was associated with significantly shortened OS compared to STR + RT (p = 0.050) and trended to shorter OS compared to GTR (p = 0.066). GTR was associated with significantly greater risk of developing DI (56.3 vs. 13.3% with STR + XRT, p < 0.001) and panhypopituitarism (54.8 vs. 26.7% with STR + XRT, p = 0.014). In conclusion, for patients with craniopharyngioma, STR + RT may provide superior clinical outcome, achieving better disease control than STR and limiting side effects associated with aggressive surgical resection.

Limited utility despite accuracy of the national SEER dataset for the study of craniopharyngioma.

Craniopharyngioma is histologically benign and associated with high survival rates but poor quality of life. The SEER Program is among the most cited data sources regarding malignancies in the United States. SEER began collecting data regarding craniopharyngiomain 2004. SEER-STAT v7.0.5 was utilized to identify patients (January 1, 2004-December 31, 2008) with ICD-O-3 codes for craniopharyngioma. Age was categorized into 3 groups: ≤19, 20-34, and ≥35 years, as was surgical intervention: none, subtotal resection, and gross total/radical resection. Demographic, initial treatment, and follow-up data were collected. 635/662 (95.9 %) patients had complete data. Incidence per million patient-years by age group was 1.9, 1.1, and 1.9, respectively (p < 0.0001). There was bimodal incidence, with peaks at 5-9 and 60-74 years. Surgery occurred in 528 patients (83.1 %), without association between age group and extent of surgery (p = 0.14). Radiation was delivered in 139 (21.9 %) cases, with no association between treatment and extent of surgery (p = 0.73) or age group (p = 0.14). Median follow-up was 23 months. Overall and Cause-specific Survival were 87.9 and 94.5 %, respectively. Neither was associated with extent of surgery but both were positively associated with radiation (p = 0.0003 and 0.0007, respectively). There was no difference in OS or CSS when comparing STR ± RT versus GTR alone (p = 0.38 and 0.56, respectively). SEER provides reliable demographic and survival data regarding craniopharyngioma. SEER's focus on mortality statistics limits utility for outcomes studies in tumors with high survival rates, such as craniopharyngioma. Initial treatment data from SEER varies somewhat from current literature, meriting further investigation.

Transient enlargement of craniopharyngioma after radiation therapy: pattern of magnetic resonance imaging response following radiation.

Clinical experience suggests that craniopharyngiomas may temporarily increase in size after radiation therapy (RT). The study goal is to determine the incidence and natural history of this response in a cohort of patients managed at Children's Healthcare of Atlanta (CHOA) or Emory Healthcare (EHC). Between 08/1998 and 06/2009, 41 children and young adults were diagnosed with craniopharyngioma at CHOA and/or EHC. Of these, 21 received external-beam radiation and were included in our analysis. Serial magnetic resonance imaging (MRI) studies were evaluated volumetrically to assess response to RT. Median age at diagnosis was 8.2 years (range 3.2-23.5 years). Median radiation dose was 54.0 Gy using standard fractionation (1.8-2.0 Gy/day). With median follow-up of 41.3 months (range 7.2-121.8 months), actuarial local control and overall survival rates at 5 years were 78.7 % and 100 %, respectively. Of subjects, 52.4 % of subjects (11 of 21) were noted on serial MRI evaluation to have tumor enlargement (mostly cystic component) after radiation before eventual shrinkage without further intervention. For tumors that expanded, the median volume increase was 33.9 % (range 15.6-224.4 %). Median time to maximal tumor/cyst expansion was 1.5 months (range 1.0-5.0 months). Finally, nearly all patients (20 of 21) showed a measurable objective response to therapy by MRI regardless of ultimate disease control. Median time to maximal response post-radiation, as defined by MRI, was 9.5 months (range 3.5-39.9 months). In summary, RT is effective for managing craniopharyngioma. However, despite good ultimate responses, approximately 50 % of the patients show tumor/cyst expansion on MRI over the first few months post-radiation. Caution should be taken not to subject these patients to "salvage surgery" or cyst aspiration during this early time unless there are other overriding surgical indications. Understanding the natural history of this phenomenon could potentially help guide the management of these craniopharyngioma patients.

Sleep dysfunction in long term survivors of craniopharyngioma.

Craniopharyngiomas are slow growing tumors of the sellar and parasellar region and may also involve the hypothalamus. Treatment involves maximal surgical excision or subtotal resection followed by focal radiation therapy. Late effects of treatment include endocrinopathies, cognitive deficits, behavioral changes, obesity and sleep dysfunction. We conducted a retrospective review of all patients with craniopharyngioma more than 2 years off treatment and who were evaluated in the neuro-oncology survivorship clinic between 2003 and 2007. Clinical data, extent of resection, treatment modalities, endocrine status, patient symptom report and sleep study results were collected to evaluate the presence of patient reported daytime sleepiness and sleep disturbance and to determine possible risk factors. 28 patients were identified (25 %) female. 19/28 self-reported daytime fatigue or sleep disturbance; this included 4/6 patients with gross total resection and 15/22 with subtotal resection. 16/22 patients treated with cranial irradiation reported sleep-related abnormalities, compared to 3/6 patients who did not receive radiation. All but one patient had pituitary dysfunction requiring hormonal replacement. Patients with more than ≥2 sleep related complaints had a higher BMI (44.6 vs. 32.6, p = 0.0192). 8 patients underwent formal sleep evaluation. 3 patients had documented central or obstructive sleep apnea. The mean arousal index was 11.0/h (normal <5). Two patients were treated with melatonin for sleep disturbance and 2 were treated with stimulants for excessive daytime sleepiness. A majority of patients with craniopharyngioma have self-reported daytime fatigue and/or sleep dysfunction after treatment. Extent of resection did not increase the likelihood of patient-reported daytime sleepiness and/sleep dysfunction; however, patients who received radiation more frequently reported daytime sleepiness and/or sleep dysfunction. Patients with a higher BMI were more likely to experience sleep disturbance. Formal sleep evaluations should be considered in all patients with craniopharyngioma.

Single and hypofractionated stereotactic radiotherapy with CyberKnife for craniopharyngioma.

Craniopharyngiomas are slow-growing tumors found in the suprasellar region, with especially high incidence in Japanese children. Due to the location, proximity and adhesiveness of the tumor to adjacent critical structures, these tumors remain a significant clinical challenge. The purpose of this study was to evaluate the clinical outcome of single and hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for craniopharyngioma. Forty-three patients (21 men and 22 women; median age 44 years; range 3-85 years) were treated at two institutions. Three cases were treated in a single fraction to a marginal dose of 13-16 Gy. The other 40 cases were treated in 2-5 fractions to a marginal dose of 13-25 Gy. Tumor volumes ranged from 0.09 to 20.8 cm(3) (median 2.0 cm(3)). Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period was 40 months (range 12-92 months). The 3-year overall survival and local control rates were 100 and 85%, respectively. In-field cyst enlargement was observed in 9 patients. These tumors had significantly larger volumes (mean 6.9 cm(3); 95% confidence interval, CI, 2.8-10.9 cm(3)) than the 34 controlled tumors (2.9 cm(3); CI 1.5-4.3 cm(3)) (P = 0.02). Out-field tumor regrowth was observed in 4 patients. No radiation-induced symptomatic visual disorder or brain necrosis was observed. Hypopituitarism was observed in only 1 patient. Single and hypofractionated SRT using CyberKnife produced high tumor control rates with minimal complications. Hypofractionated SRT may be useful for protecting the visual nerve and neuroendocrine function, especially for tumors located near the optic pathways and for large tumors.

Management of craniopharyngioma: the Liverpool experience following the introduction of the CCLG guidelines. Introducing a new risk assessment grading system.

PURPOSE: The Children's Cancer Leukaemia Group (CCLG) proposed a management pathway for craniopharyngioma that advocated limited surgery followed by upfront radiotherapy (RT) for large tumours with hypothalamic involvement and a radical resection only for smaller tumours without hypothalamic involvement. This strategy is not proven to provide optimum care or to be risk-free. The aim of this study is to review our experience of the management of craniopharyngioma diagnosed since the introduction of the CCLG guidelines in 2005. METHODS: All children diagnosed with craniopharyngioma at Alder Hey Children's Hospital NHS Foundation Trust in the period between 1 January 2005 and 30 June 2011 were included. Management was based on the presence of hypothalamic syndrome, hydrocephalus, tumour size and radiological Paris grading system. Endoscopic drainage of tumour cyst was performed prior to formalising risk grade and surgical strategy. Definitive surgery was performed in 4-6 weeks time. In this respect, we developed a grading criteria. RESULTS: Twenty patients were included. Ten of the children underwent endoscopic cyst drainage prior to definitive surgery. The results of the subsequent surgical excision were complete resection, near total resection or subtotal resection in 30, 25 and 45 % patients, respectively. There was no surgical-related mortality and no new neurological deficits. Nine patients underwent RT at some stage. CONCLUSIONS: In this study, we tried to develop an advanced model for the management of craniopharyngioma with a new risk grading system. This may have a direct impact on the surgical strategy and outcome and could be able to improve morbidity.

Prognostic factors for tumor recurrence after gamma knife radiosurgery of partially resected and recurrent craniopharyngiomas.

A study was conducted to clarify the prognostic factors related to recurrence of craniopharyngioma and to improve the quality of life of patients by the treatment with intentional partial removal and gamma knife radiosurgery. One hundred cases of craniopharyngioma have been treated at Komaki City Hospital since 1991. In a mean follow-up period of 65.5 months, the tumor control rate was 79.5%. The 5- and 10-year actuarial survival rates were 94.1% and 91%, respectively. However, the recurrence-free survival rates were 73.6% at 5 years and 60.2% at 10 years. Nine factors thought to be related to the recurrence were selected from past references and previous studies, including gender, age, pediatric (< or =17 years) or adult patient, partial removal or recurrence, mean tumor diameter, tumor type (solid or cyst), pathological types (squamous cell or adamantinoma), number of previous treatments, and radiation dose. Statistical analysis was performed to determine which factors had a significant prognostic impact. Multivariate analysis showed that mean tumor diameter and radiation dose were independent predictors of outcome. To maximize the prognostic power of these factors, cut-off levels were determined using ROC analysis. These levels were 19 mm for tumor diameter and 13.2 Gy for marginal dose. Significant prognostic factors related to recurrence of craniopharyngioma are tumor diameter and radiation dose. A tumor diameter of <19 mm and a marginal dose of > or =13.2 Gy are favorable prognostic factors for gamma knife radiosurgery.

Outcomes of Gamma Knife surgery for craniopharyngiomas.

Gamma Knife surgery (GKS) has emerged as a valuable adjuvant treatment modality for recurrent or residual craniopharyngioma. However, prognostic factors pertaining to progression-free survival (PFS) remain poorly understood. A study was conducted to address this issue. A total of 37 consecutive patients undergoing 39 sessions of GKS procedures targeting the solid portions of the tumors at our institution between 1989 and 2005 were analyzed. Twenty-one male and 16 female patients comprised this study. Median age at GKS was 36 years (range, 4-78). Median tumor volume was 1.6 cm(3) (range, 0.1-18.6), median marginal dose was 14.5 Gy (range, 6-25), and median maximal dose was 30 Gy (range, 15.6-60). Median follow-up was 50 months (range, 8-212). Univariate and multivariate analyses using Cox proportional hazards model were employed to identify the potential prognostic factors including tumor volume, marginal dose, gender, age at GKS, and status of visual field defect (VFD) in terms of in-field PFS. The actuarial 3- and 5-year in-field PFS were 84.8 and 67.0%, respectively. On univariate analysis, absence of VFD at GKS was a favorable prognostic factor (hazard ratio: 0.279; 95% CI, 0.085-0.913, P = 0.035), whereas on multivariate analysis, absence of VFD at GKS, tumor volume ≤1.6 cm(3), and marginal dose >14.5 Gy related to a longer in-field PFS. GKS may offer reasonable control of recurrent or residual craniopharyngiomas. There was a consistent correlation between absence of VFD at the time of GKS and in-field PFS.