Long-term outcomes of neuroendoscopic cyst partial resection combined with stereotactic radiotherapy for craniopharyngioma.

PURPOSE: The aim of this study was to evaluate the treatment outcomes of neuroendoscopic cyst partial resection (ECPR) combined with stereotactic radiotherapy (SRT) for cystic craniopharyngiomas. METHODS: In this retrospective study, 22 craniopharyngioma patients undergoing ECPR combined with SRT were included. This combination therapy was indicated for suprasellar cystic craniopharyngiomas in patients whose pituitary function was preserved but would be difficult to preserve in direct surgery. The outcomes of combination therapy, including tumor control and postoperative visual and pituitary functions, were investigated. RESULTS: ECPR was safely performed, and cyst shrinkage was accomplished in all cases. After ECPR, visual function improved in 12 of 13 patients (92%) with visual field disturbance and did not deteriorate in any patients. Pituitary function was preserved in 14 patients (64%) and deteriorated in eight patients (36%) after ECPR. As a complication of ECPR, meningitis occurred because of a wound infection in one patient. In 18 of 22 patients (82%), the tumor was controlled without further treatment 19 - 87 months (median, 33 months) after SRT. Hypopituitarism was an adverse event after SRT in two of the 18 patients who achieved tumor control. Four patients (18%) had enlarged cysts after SRT. Postoperative pituitary function was significantly more likely to deteriorate in cases of extensive detachment from the ventricular wall, and retreatment was significantly more common in cases with hypothalamic extension. CONCLUSION: Although limited to some cases, ECPR combined with SRT is a less invasive and useful therapeutic option for suprasellar cystic craniopharyngiomas. However, its long-term prognosis requires further evaluation.

Fractionated stereotactic radiotherapy in craniopharyngiomas: A systematic review and single arm meta-analysis.

INTRODUCTION: Numerous studies have demonstrated Fractionated Stereotactic Radiotherapy's (FSRT) effectiveness in tumor control post-resection for craniopharyngiomas. Nevertheless, past literature has presented conflicting findings particularly regarding endocrine and visual function outcomes. This study aims to elucidate FSRT's efficacy and safety for this population. METHODS: Adhering to PRISMA, a systematic review and meta-analyses was conducted. Included studies had to report the effects of FSRT for treating craniopharyngiomas in a sample greater than four patients, addressing at least one of the outcomes of interest: improvement in visual acuity or field, new-onset hypopituitarism, effectiveness, and tumor progression. Relative risk with 95% confidence intervals were used to assess the outcomes. RESULTS: After retrieving a total of 1292 studies, 10 articles met the predefined criteria and thus were finally selected, amounting to a total of 256 patients. The improvement in visual acuity was estimated at 45% (95% CI: 6-83%), while the improvement in the visual field was 22% (95% CI: 0-51%). Regarding endocrine function, the new-onset hypopituitarism rate was found to be 5% (95% CI: 0-11%). Relative to FSRT effectiveness, the pooled estimate of the complete tumor response rate was 17% (95% CI: 4-30%), and the tumor progression rate was 7% (95% CI: 1-13%). Also, a 3-year progression-free survival rate of 98% (95% CI: 95-100%) was obtained. CONCLUSION: Despite limitations and risks, FSRT shows promise as a viable therapeutic option for craniopharyngiomas, offering notable benefits for visual functions and tumor control. Further research is required to better understand the associated risks, benefits, and clinical utility.

Encouraging Experience with Image-Guided Pencil Beam Scanning Proton Therapy in Craniopharyngioma-First Case Series From India.

OBJECTIVE: We report our early clinical experience with image-guided, pencil beam scanning proton beam therapy (PBS-PBT) for residual and recurrent craniopharyngioma. METHODS: Between September 2019 and January 2023, 19 consecutive patients with residual or recurrent craniopharyngioma, suitable for radiotherapy and treated with image-guided PBS-PBT were analyzed. We documented detailed dosimetric data, acute toxicities, early outcomes, and imaging response on follow-up magnetic resonance imaging scans. RESULTS: A total of 19 patients (11 males and 8 females) with residual or recurrent craniopharyngioma were treated during the study period. The median age of the cohort was 14 years (range, 3-33 years). The histology of most lesions was the adamantinomatous subtype (95%). The most common clinical presentation (before PBT) and most common endocrine deficit was visual disturbance (79%) and hypocortisolism (74%), respectively. Of the 19 patients, 13 had recurrent craniopharyngioma, and 5 had undergone radiotherapy previously. Five patients (26%) had undergone surgery ≥3 times before proton therapy. The median dose delivered was 54 GyE. The most common acute toxicity was grade 1 alopecia (63%). No patient experienced grade ≥3 acute toxicity. With a median follow-up of 18 months (range, 3-40 months), 12 patients showed shrinkage of the residual tumor and/or cyst, and 4 showed a dramatic cyst reduction at 3-9 months of follow-up. Two patients experienced a reduction in both solid and cystic components, with the remaining experiencing a reduction in the cystic component only. The remaining 8 patients had stable disease on magnetic resonance imaging, with 100% disease control and overall survival. Visual function remained stable after treatment. CONCLUSIONS: Our preliminary experience with modern PBS-PBT and image guidance for craniopharyngioma is encouraging. Proton therapy in our cohort was well tolerated, resulting in limited toxicity and promising early outcomes.

Long-term outcomes of multidisciplinary treatment combining surgery and stereotactic radiotherapy with Novalis for craniopharyngioma.

Craniopharyngiomas are difficult to resect completely, recurrence is frequent, and hypothalamic/pituitary function may be affected after surgery. Therefore, the ideal treatment for craniopharyngiomas is local control with preservation of hypothalamic and pituitary functions. The purpose of this study is to retrospectively evaluate the long-term efficacy and adverse events of stereotactic radiotherapy (SRT) with Novalis for craniopharyngioma. This study included 23 patients with craniopharyngiomas who underwent surgery between 2006 and 2021 and underwent SRT as their first irradiation after surgery. The median post-irradiation observation period was 88 months, with the overall survival rates of 100 % at 10 years and 85.7 % at 20 years. One patient died of adrenal insufficiency 12 years after irradiation. The local control rate of the cystic component was 91.3 % at 5 years, 83.0 % at 15 years, with no increase in the solid component. No delayed impairment of visual or pituitary function due to irradiation was observed. No new hypothalamic dysfunction was observed after radiation therapy. No delayed adverse events such as brain necrosis, cerebral artery stenosis, cerebral infarction, or secondary brain tumors were also observed. SRT was safe and effective over the long term in patients irradiated in childhood as well as adults, with no local recurrence or adverse events. We believe that surgical planning for craniopharyngioma with stereotactic radiotherapy in mind is effective in maintaining a good prognosis and quality of life.

Benefits and limitations of a dual faculty neurosurgeon approach to resection of pediatric craniopharyngioma.

PURPOSE: The utility and safety of including two neurosurgeons for tumor resections is unknown. This study compares outcomes among pediatric patients with craniopharyngiomas operated on with a dual or single surgeon approach (DSA, SSA). METHODS: A single-center review identified all craniopharyngioma transsphenoidal or craniotomy resections from 2000 to 2020. Surgical years of experience (YOE) and rates of 5-year reoperations, complications, recurrence, and postoperative radiotherapy were analyzed. RESULTS: Twenty-six transsphenoidal and 68 craniotomies were identified among 62 patients. Eleven transsphenoidal (42.3%) utilized DSA and 15 utilized (57.7%) SSA. Eight craniotomies (11.8%) were DSA and 60 (88.2%) were SSA. The surgeon for SSA transsphenoidal procedures had a median of 10.7 YOE (IQR: 9.9-13.7) versus 6.6 (IQR: 2.7-16; p = 0.058) for the lead surgeon in DSAs. The co-surgeon in transsphenoidal DSAs had a median of 27 YOE (IQR: 11.8-35.7). The surgeon for SSA craniotomies had a median of 19.3 YOE (IQR: 12.1-26.4) versus 4.5 years (IQR: 1.3-15.3; p = 0.017) for the lead surgeon in DSA cases. The co-surgeon in DSA craniotomies had a median of 23.2 YOE (IQR: 12.6-31.4). Case complexity was similar across transsphenoidal groups. DSA transsphenoidal resections had fewer complications (18% DSA vs. 33% SSA), reoperations (45% vs. 53%), and radiation therapy (9.1% DSA vs. 33% SSA) than SSA. CONCLUSION: Lead surgeons in DSAs are frequently junior surgeons while SSAs typically employ senior surgeons. Outcomes did not significantly differ between DSA and SSA. Mentorship through DSAs does not negatively affect patient care.

Patterns of Care in Craniopharyngioma: Clinical Outcomes After Surgery and Radiation Therapy in a Real-World Setting.

OBJECTIVE: Craniopharyngioma (CP) is a benign neuroepithelial tumor generally treated with maximal safe resection and radiation therapy (RT) in incompletely resected CP or in recurrent tumors to achieve long-term control. We analyzed the clinical outcomes of patients with CPs treated with a multimodality approach. PATIENTS AND METHODS: A retrospective clinical audit of histologically proven CPs registered between 2008 and 2019 at a specialized neuro-oncology center in India was performed. Time-to-event outcomes (overall survival [OS] and progression-free survival [PFS]) were analyzed. RESULTS: One hundred and twenty-two patients with CP were analyzed. The median age of the population was 14 years (interquartile range [IQR], 8-26) with a significant male preponderance. Gross total resection was achieved in only 25% of patients. At a median follow-up of 57.1 months (IQR, 27.8-87.8), 5-year estimates of PFS and OS were 52% (95% confidence interval, 46%-63.4%) and 85.8% (95% confidence interval, 78.6%-93%), respectively. Recurrence or progression was observed in 48 of 122 patients (39.3%) at a median time of 84.4 months (IQR, 24.7-174.8). On multivariate analysis, the absence of residual disease (P = 0.004), near-total resection (P = 0.035), and use of up-front adjuvant RT (P < 0.001) significantly improved the 5-year PFS, whereas the absence of extracavernous extension (P = 0.058) and any use of postoperative RT (P = 0.026) significantly improved the 5-year OS. CONCLUSIONS: This study represents one of the largest single-institutional series of CPs, showing improved PFS with up-front adjuvant RT in most cases of CP. Deferring adjuvant RT should be considered only in patients with no evidence of residual disease (as shown on dedicated sellar imaging) after primary surgery.

Management of first recurrence or progression of craniopharyngioma after resection alone: A systematic review and individual-participant data meta-analysis.

The initial management of craniopharyngioma is generally either gross total resection (GTR) or subtotal resection (STR) with adjuvant radiotherapy (RT). However, the optimal management strategy for recurrent/progressive craniopharyngioma remains unclear. In this systematic review and individual participant data meta-analysis, we aimed to compare the outcomes of surgery and/or RT for the first recurrence/progression of craniopharyngioma after resection alone. The exposure was the treatment that was administered for the first recurrence/progression, and the outcomes were tumor regrowth and overall survival (OS). Subgroup analyses were performed by age at the treatment for the first recurrence/progression (<18 or ≥ 18 years old), duration between the first treatment and the first recurrence/progression (<2 or ≥ 2 years), and the initial treatment that was administered (STR or GTR). Of the 2932 studies screened, 11 studies reporting a total of 80 patients were included. Across almost all subgroups, patients who received RT for the first recurrence/progression had a significantly lower risk of tumor regrowth than those who did not, regardless of whether surgery was performed and the extent of resection. There was no significant association between the treatment administered for the first recurrence/progression and OS, except for patients with a recurrence/progression < 2 years after the first treatment, where GTR was associated with a higher risk of mortality. For patients with the first recurrence/progression of craniopharyngioma after resection alone, RT should be considered for better local control. In cases where RT is not administered, GTR is preferred over STR provided it can be safely performed, for improved local control.

[Radiotherapy for Pituitary Tumors:An Overview of the Current Evidence].

Various tumors, such as pituitary neuroendocrine tumors(PitNETs)and craniopharyngiomas, can arise in the sellar/parasellar region. Although surgical removal is the standard therapeutic modality for these pathologies, a single surgery may not be sufficient to provide durable tumor control, given the surrounding critical neurovascular structures. Therefore, adjunctive radiotherapy has a substantial role in treating these neoplasms. There are wide variety of radiotherapy modalities, including photon-based fractionated radiotherapy, stereotactic radiosurgery/radiotherapy, and proton- and carbon-ion beam-based radiotherapies. All modalities have their own advantages and disadvantages and thus need to be selectively used after consideration of their characteristics and existing evidence. In addition, the radiation sensitivity of normal anatomies should be kept in mind. In particular, the optic apparatus is very sensitive to ionizing radiation; thus, meticulous care needs to be taken when creating a radiation plan to avoid optic neuropathy. Overall, if properly used, radiotherapy can provide excellent durable tumor control for PitNETs, craniopharyngiomas, and even chordomas. A judicious combination of surgery and radiotherapy plays a key role in functional preservation without affecting tumor control or overall survival.

Proton therapy and limited surgery for paediatric and adolescent patients with craniopharyngioma (RT2CR): a single-arm, phase 2 study.

BACKGROUND: Compared with photon therapy, proton therapy reduces exposure of normal brain tissue in patients with craniopharyngioma, which might reduce cognitive deficits associated with radiotherapy. Because there are known physical differences between the two methods of radiotherapy, we aimed to estimate progression-free survival and overall survival distributions for paediatric and adolescent patients with craniopharyngioma treated with limited surgery and proton therapy, while monitoring for excessive CNS toxicity. METHODS: In this single-arm, phase 2 study, patients with craniopharyngioma at St Jude Children's Research Hospital (Memphis TN, USA) and University of Florida Health Proton Therapy Institute (Jacksonville, FL, USA) were recruited. Patients were eligible if they were aged 0-21 years at the time of enrolment and had not been treated with previous radiotherapeutic or intracystic therapies. Eligible patients were treated using passively scattered proton beams, 54 Gy (relative biological effect), and a 0·5 cm clinical target volume margin. Surgical treatment was individualised before proton therapy and included no surgery, single procedures with catheter and Ommaya reservoir placement through a burr hole or craniotomy, endoscopic resection, trans-sphenoidal resection, craniotomy, or multiple procedure types. After completing treatment, patients were evaluated clinically and by neuroimaging for tumour progression and evidence of necrosis, vasculopathy, permanent neurological deficits, vision loss, and endocrinopathy. Neurocognitive tests were administered at baseline and once a year for 5 years. Outcomes were compared with a historical cohort treated with surgery and photon therapy. The coprimary endpoints were progression-free survival and overall survival. Progression was defined as an increase in tumour dimensions on successive imaging evaluations more than 2 years after treatment. Survival and safety were also assessed in all patients who received photon therapy and limited surgery. This study is registered with ClinicalTrials.gov, NCT01419067. FINDINGS: Between Aug 22, 2011, and Jan 19, 2016, 94 patients were enrolled and treated with surgery and proton therapy, of whom 49 (52%) were female, 45 (48%) were male, 62 (66%) were White, 16 (17%) were Black, two (2%) were Asian, and 14 (15%) were other races, and median age was 9·39 years (IQR 6·39-13·38) at the time of radiotherapy. As of data cutoff (Feb 2, 2022), median follow-up was 7·52 years (IQR 6·28-8·53) for patients who did not have progression and 7·62 years (IQR 6·48-8·54) for the full cohort of 94 patients. 3-year progression-free survival was 96·8% (95% CI 90·4-99·0; p=0·89), with progression occurring in three of 94 patients. No deaths occurred at 3 years, such that overall survival was 100%. At 5 years, necrosis had occurred in two (2%) of 94 patients, severe vasculopathy in four (4%), and permanent neurological conditions in three (3%); decline in vision from normal to abnormal occurred in four (7%) of 54 patients with normal vision at baseline. The most common grade 3-4 adverse events were headache (six [6%] of 94 patients), seizure (five [5%]), and vascular disorders (six [6%]). No deaths occurred as of data cutoff. INTERPRETATION: Proton therapy did not improve survival outcomes in paediatric and adolescent patients with craniopharyngioma compared with a historical cohort, and severe complication rates were similar. However, cognitive outcomes with proton therapy were improved over photon therapy. Children and adolescents treated for craniopharyngioma using limited surgery and post-operative proton therapy have a high rate of tumour control and low rate of severe complications. The outcomes achieved with this treatment represent a new benchmark to which other regimens can be compared. FUNDING: American Lebanese Syrian Associated Charities, American Cancer Society, the US National Cancer Institute, and Research to Prevent Blindness.

Frameless Hypofractionated Gamma Knife Radiosurgery for Residual or Recurrent Craniopharyngioma.

BACKGROUND: The management of craniopharyngiomas is challenging, usually requiring multidisciplinary care. Gamma Knife radiosurgery (GKRS) is an essential technique for residual/recurrent craniopharyngiomas. OBJECTIVE: To evaluate the efficacy of frameless hypofractionated GKRS (hfGKRS) for craniopharyngioma and factors which affect tumor control and complications. METHODS: This retrospective study involved 24 patients managed with hfGKRS. Clinical and radiological data, tumor characteristics, and procedural details were analyzed. RESULTS: There were 15 (62.5%) female patients. The median age was 38.5 years (range, 3-66 years). The mean tumor volume was 2.4 (1.93) cm 3 , with a mean solid volume of 1.6 (1.75) cm 3 . The median marginal dose was 20 Gy (range, 18-25 Gy) delivered in a median of 5 fractions (range, 3-5). During a median radiological follow-up of 23.5 months (range, 12-50 months), tumor progression was noted in 5 (20.8%) patients. The 2-year and 4-year progression-free survival were 81.8% and 61.4%, respectively. No deaths were identified at a median clinical follow-up of 31.3 months (range, 12-54 months). Visual deficits attributable to progression were noted in 3 (12.5%) patients with pre-GKRS visual field defects. An additional 4 (16.7%) patients with pre-GKRS visual deficit developed new minor visual field defects. Four (16.7%) patients showed improvement of vision after GKRS. There were no new-onset post-GKRS hormonal deficits. CONCLUSION: The management of craniopharyngioma requires a multidisciplinary approach, and irradiation represents effective treatment option for residual/recurrent tumors after surgery. To the best of our knowledge, this is the first study that addresses the efficacy of frameless hfGKRS in managing craniopharyngiomas over sufficient follow-up.

Is Postoperative Radiotherapy Needed in the Management of Adult Craniopharyngiomas?

BACKGROUND: The optimal treatment of adult craniopharyngioma (CP) remains controversial. Although benign, these tumors tend to recur locally. The choice between gross total resection (GTR) versus subtotal resection (STR) with adjuvant or delayed radiotherapy (RT) is debated. The objective of this study is to review our experience with adult CPs over a 20-year period and identify an optimal management strategy. METHODS: From 1999 to 2020, we reviewed all patients diagnosed with CP at our institution. We collected data regarding tumor characteristics, treatments, and toxicity. Disease progression was defined as growth on imaging. Descriptive statistics were used to assess patient characteristics. The Kaplan Meier method was used to assess progression-free survival (PFS) and corresponding 95% confidence intervals (CI) from the time since treatment initiation. RESULTS: Twenty-four patients with a median age of 50 were included in this study. The median follow-up was 85 months. Seven patients had initial GTR, 10 STR, and 7 STR + RT. The overall 5-year PFS was 56% (95% CI: 38-83%): 100% in the STR + RT group, 69% in the GTR group, and 18% in the STR group (p = 0.01). Of the 17 patients initially treated with surgery alone, 3 with GTR and 6 with STR required salvage RT at a median of 46 months, with no further progression after salvage RT. CONCLUSIONS: Our study underscores the importance of RT for local control and suggests that STR + RT should be considered a viable option in the management of these tumors as it may be associated with improved PFS compared to surgery alone.

Pediatric Craniopharyngioma: The Effect of Visual Deficits and Hormone Deficiencies on Long-Term Cognitive Outcomes After Conformal Photon Radiation Therapy.

PURPOSE: Pediatric patients with craniopharyngioma risk cognitive deficits when treated with radiation therapy. We investigated cognitive outcomes after conformal photon radiation therapy (CRT) and the effect of visual deficits and hormone deficiencies. METHODS AND MATERIALS: One hundred one pediatric patients were enrolled on a single institutional protocol beginning in 1998 (n = 76) or followed a similar nonprotocol treatment plan (n = 25). CRT (54 Gy) was administered using a 1.0- or 0.5-cm clinical target volume margin. Median age at CRT was 9.50 years (range, 3.20-17.63 years). Patients were followed for 10 years with assessment of hearing, vision, hormone deficiencies, and cognitive performance. RESULTS: Intellectual functioning (intelligence quotient) was significantly lower in children treated at a younger age and those who received higher doses to temporal lobes and hippocampi. Black race (-17.77 points, P = .002) and cerebrospinal fluid shunting (-11.52 points, P = .0068) were associated with lower baseline intelligence quotient. Reading scores were lower over time in models incorporating age, shunt, and dose to specific brain structures. Patients treated for growth hormone deficiency within 12 months of CRT had better intelligence and attention outcomes. Among patients with normal baseline vision, the 10-year cumulative incidence of change in visual acuity was 4.00% ± 2.82% and in visual field 10.42% ± 4.48%. Reading scores decreased after treatment (0.7873 points/y, P = .0451) in those with impaired baseline vision. CONCLUSIONS: Cognitive outcomes are selectively affected by dose to brain subvolumes, comorbidities of visual deficits, and treatment of endocrinopathy in pediatric craniopharyngioma. Improved treatment selection, normal tissue sparing methods of irradiation, and posttreatment management of endocrinopathy should be considered.

Endoscopic treatment of cystic craniopharyngiomas in elderly patients. Report of three cases with a review.

Craniopharyngiomas are rare tumors with peak incidence between 5-14 and between 65-74 years of age. Treatment of choice is surgical resection, sometimes associated with radiation therapy. Complete tumor resection may be challenging. Radical surgery is particularly risky in older patients. Authors evaluate three cases of large cystic craniopharyngioma in patients in their 7th and 8th decade of life operated with the use of endoscopic technique. The postoperative follow-up period in which out- patient controls with imaging examinations were performed was up to 6 years. Symptoms of intracranial hypertension resolved in all patients in the immediate postoperative period. Visual acuity improved in two patients. No cases of aseptic meningitis have been reported. One patient underwent subsequent radio- therapy. The well-being of the operated patients continued. Endoscopic transventricular approach to cystic craniopharyngiomas may be a safe and effective approach in older patients, being an alternative to microsurgical procedures.

Upfront adjuvant irradiation versus postoperative surveillance following incomplete surgical resection of craniopharyngiomas in children and young adults.

OBJECTIVE: Incomplete surgical removal of craniopharyngiomas frequently results in suboptimal oncological control. Radiation therapy is usually offered in these cases to prevent local recurrence of disease; however, the efficacy of radiation is limited by its potential adverse effect, particularly in younger patients. This study was undertaken to compare long-term outcomes and rates of postoperative obesity and endocrinopathy in patients undergoing either upfront adjuvant radiation after surgery, or postoperative surveillance with progression-contingent intervention. METHODS: Thirty-seven patients aged <25 years who had undergone primary incomplete surgical resection of craniopharyngiomas were retrospectively identified and categorized according to the prescribed treatment strategy. Recurrence rates, functional status, neuro-ophthalmologic, and endocrine outcomes were studied in both groups of patients. RESULTS: Twenty-three patients received upfront adjuvant radiation, and 14 patients underwent postoperative surveillance. Adjuvant radiation in the former group was delivered using either conventional (n=10), 3D-conformal (n=4), or fractionated stereotactic (n=9) techniques using a linear accelerator. The mean follow-up duration was 64.7 months (range 14-134 months). Disease progression was significantly higher in patients undergoing surveillance as compared to those undergoing upfront adjuvant radiation (71.4 versus 17.4%; p=0.002). Median progression-free survival times were 129 months and 27 months in the upfront adjuvant radiation and surveillance groups, respectively (p=0.007). In patients undergoing surveillance, 50% ultimately required irradiation, and the median radiation-free survival time in this subgroup was 57 months. Two children in the adjuvant radiation group developed asymptomatic radiation-related vasculopathies on follow-up; however, there were no statistically significant differences between the two groups in terms of visual, functional, or pituitary-hypothalamic function at last follow-up. CONCLUSIONS: In comparison to upfront adjuvant radiation following incomplete craniopharyngioma resection significantly, a strategy of postoperative surveillance resulted in less durable disease control but allowed radiation therapy to be delayed by a median time of 57 months, without significant detriment to global functional, visual, and neuro-endocrinological outcomes. The merits and demerits of either strategy should be carefully considered in the post-surgical management of these patients.

Physical function, body mass index, and fitness outcomes in children, adolescents, and emerging adults with craniopharyngioma from proton therapy through five years of follow-up.

PURPOSE: Children diagnosed with craniopharyngioma are vulnerable to adverse health outcomes. Characterization of body mass index (BMI), physical function, and cardiopulmonary fitness in those treated with proton radiotherapy (PRT) will serve to design interventions to improve outcomes. METHODS: Ninety-four children with craniopharyngioma completed physical function testing prior to PRT and annually for 5 years. For each outcome, age- and sex-specific z-scores were calculated using normative values. Participants with z-scores > 1.5 or < - 1.5 were classified as impaired. Those with z-scores > 2.0 or < - 2.0 were classified as significantly impaired. Descriptive statistics were used to describe study outcomes and change in prevalence of impairments from 2 to 5 years after treatment. RESULTS: Nearly half of participants [45.2%, 95% confidence interval (CI) 39.4, 51.0] had mean BMI z-scores > 1.5 at baseline, with prevalence increasing to 66.7% (95% CI 61.5, 71.9) at 5 years. More than half of participants (54.2%, 95% CI 48.4, 60.0) had knee extension strength z-scores < - 1.5 at baseline, with prevalence increasing to 81.3% (95% CI 77.7, 84.9) at 5 years. BMI and knee extension strength had the largest proportion of participants impaired at both 2 and 5 years (53.2% and 62.3%, respectively). Resting heart rate had the highest proportion of participants not impaired at 2 years but became impaired at 5 years (26.6%). CONCLUSIONS: Children with craniopharyngioma have BMI and fitness abnormalities at diagnosis and continue 5 years after treatment. This cohort may benefit from interventions designed to improve BMI, strength, and resting indicators of cardiopulmonary fitness.

Craniopharyngiomas: Surgery and Radiotherapy.

Taking into account the benign nature of craniopharyngiomas, the main method of treatment is the resection of the tumor. However, the tendency of these tumors to invade critical structures (such as optic pathways, the hypothalamic-pituitary system, the Willis circle vessels) often limits the possibility of a radical surgery.Craniopharyngiomas of the third ventricle represent the greatest challenge for surgery. After radical surgery, hypothalamic disorders often occur, including not only obesity but also cognitive, emotional, mental, and metabolic disturbances. Metabolic disorders associated with damage to the hypothalamus progress after surgery and lead to impaired functions of the internal organs. This process is irreversible and, in many cases, becomes the direct cause of mortality. The life expectancy of patients with the surgically affected hypothalamus is significantly shorter than in patients with preserved diencephalic function. The incidence of hypothalamic disorders after surgery can reach 40%.Even with macroscopically total resection, craniopharyngiomas can recur in 10-30% of cases, and in the presence of tumor remnants and with no further radiation treatment, the risk of recurrence significantly increases to up to 50-85% according to various studies. For this reason, the observation of patients with residual tumors after surgery is an incorrect strategy.Radiation therapy significantly improves progression-free survival (PFS), and the use of stereotactic irradiation techniques ensures conformity of irradiation of tumor remnants with a complicated shape and location (Iwata H et al., J Neurooncol 106(3):571-577, 2012; Aggarwal et al., Pituitary 16(1):26-33, 2013; Savateev et al., Zh Vopr Neirokhir Im N N Burdenko 81(3):94-106; 2017), which potentially reduces the risk of undesirable postradiation effects. Therefore, the quality of life in patients with craniopharyngiomas infiltrating the hypothalamus is significantly higher after non-radical operations with subsequent stereotactic radiation than after a total or subtotal removal.

Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillance.

BACKGROUND: Radiotherapy is a valuable treatment in the management algorithm of pituitary adenomas and craniopharyngiomas. However, the risk of second brain tumour following radiotherapy is a major concern. We assessed this risk using non-irradiated patients with the same primary pathology and imaging surveillance as controls. METHODS: In this multicentre, retrospective cohort study, 4292 patients with pituitary adenoma or craniopharyngioma were identified from departmental registries at six adult endocrine centres (Birmingham, Oxford, Leeds, Leicester, and Bristol, UK and Ferrara, Italy). Patients with insufficient clinical data, known genetic predisposition to or history of brain tumour before study entry (n=532), and recipients of proton beam or stereotactic radiotherapy (n=81) were excluded. Data were analysed for 996 patients exposed to 2-dimensional radiotherapy, 3-dimensional conformal radiotherapy, or intensity-modulated radiotherapy, and compared with 2683 controls. FINDINGS: Over 45 246 patient-years, second brain tumours were reported in 61 patients (seven malignant [five radiotherapy, two controls], 54 benign [25 radiotherapy, 29 controls]). Radiotherapy exposure and older age at pituitary tumour detection were associated with increased risk of second brain tumour. Rate ratio for irradiated patients was 2·18 (95% CI 1·31-3·62, p<0·0001). Cumulative probability of second brain tumour was 4% for the irradiated and 2·1% for the controls at 20 years. INTERPRETATION: Irradiated adults with pituitary adenoma or craniopharyngioma are at increased risk of second brain tumours, although this risk is considerably lower than previously reported in studies using general population controls with no imaging surveillance. Our data clarify an important clinical question and guide clinicians when counselling patients with pituitary adenoma or craniopharyngioma on the risks and benefits of radiotherapy. FUNDING: Pfizer.

Limited surgery and conformal photon radiation therapy for pediatric craniopharyngioma: long-term results from the RT1 protocol.

BACKGROUND: Our aim was to estimate long-term disease control and complications after conformal radiation therapy (CRT) in children and adolescents with craniopharyngioma. MATERIALS AND METHODS: Pediatric patients with craniopharyngioma (n = 101) were enrolled on or treated according to a phase II single institutional protocol from 1998. Surgery was individualized, and CRT (54Gy) was administered using a 1.0 cm or 0.5 cm clinical target volume margin. Patients were followed for 10 years by serial MR imaging and MR angiography and a battery of tests to measure the effects of treatment. RESULTS: Twenty patients had tumor progression. Twelve patients who had tumor progression died due to tumor (n = 6) or complications related to tumor or treatment (n = 6). With a median follow-up of 14.94 years for survivors, the 10 year estimates (±SE) of progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) were 78.84% ± 4.10%, 77.12% ± 4.19%, and 96.02% ± 1.95%, respectively. OS, EFS, and PFS were significantly associated with race, shunt status, and tumor volume. The 10 year cumulative incidence (±SE) of the secondary tumor (1.99% ± 1.40%), secondary malignant tumor (1.0% ± 1.0%), necrosis (1.98% ± 1.39%), vasculopathy (8.47% ± 2.90%), and permanent neurologic deficits (8.28% ± 3.37%) were estimated by competing risk analysis. Three patients required revascularization surgery. Salvage therapy was successful in 13 patients using surgery and radiosurgery. CONCLUSIONS: Limited surgery and CRT using photons results in excellent tumor control. Tumor control and the incidence and severity of complications are associated with host, tumor, and treatment factors.

Endocrine outcomes after limited surgery and conformal photon radiation therapy for pediatric craniopharyngioma: Long-term results from the RT1 protocol.

BACKGROUND: To estimate the incidence of endocrinopathy in children and adolescents with craniopharyngioma after treatment with photon-based conformal and intensity-modulated radiation therapy (CRT). METHODS: One hundred one pediatric patients were enrolled on a phase II single-institution protocol beginning in 1998 (n = 76) or followed a similar non-protocol treatment plan (n = 25). Surgery was individualized. CRT (54 Gy) was administered using a 1.0-cm or ≤0.5-cm clinical target volume margin. Patients underwent baseline and serial evaluation of the hypothalamic-pituitary axis. RESULTS: The 10-year cumulative incidence (CI) of growth hormone deficiency (GHD) was 68.42% (±11.27) for black patients and 94.23% (±3.57) for white patients (P = .0286). The CI of thyroid-stimulating hormone deficiency (TSHD) was 70.94% (±8.44) at 10 years for non-shunted patients and 91.67% (±10.40) at 6 years for shunted patients (P = .0260). The CI of TSHD was 100% (±14.29) at 4 years for those with diabetes insipidus (DI) and 71.36% (±8.86) at 10 years for those without DI (P = .0008). The 10-year CI of adrenocortical hormone deficiency was 70.00% (±16.15) for those with DI and 48.39% (±9.19) for those without DI (P = .0080). The 10-year CI of LH/FSH deficiency was 43.33% (±9.32) age <7 years, 61.29% (±9.11) aged 7-10 years, and 78.95% (±6.38) age ≥10 years (P < .0001). BMI was significantly greater prior to CRT in white patients with DI (P = .0004) and preexisting GHD (P = .0275). CONCLUSIONS: Hormone deficiencies are common in pediatric patients with craniopharyngioma and are associated with host, tumor, and treatment factors. Understanding the incidence and time to onset may facilitate intervention and patient selection for treatment.