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.

Stereotactic radiosurgery for nonfunctioning pituitary tumor: A multicenter study of new pituitary hormone deficiency.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency. METHODS: Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves. RESULTS: A total of 869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR): 18.9]) were treated using a median margin dose of 14Gy (IQR: 4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio [HR]:0.33, 95% CI: 0.18-0.60, P < 0.001). The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI: 11-19.4) at 5 and 10 years, respectively. A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR: 3.47, 95% CI: 1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph, and growth hormone deficiency was 8% (95% CI: 3.9-11.9), 8.3% (95% CI: 3.9-12.5), 3.5% (95% CI: 1.7-5.2), and 4.7% (95% CI: 1.9-7.4), respectively at 10 years. CONCLUSIONS: SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.

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.

Surgical Strategies in the Treatment of Giant Pituitary Adenomas.

BACKGROUND AND OBJECTIVES: The management of giant pituitary adenomas (GPAs) is challenging due to associated endocrinopathies and the close proximity of these tumors to critical structures, such as the optic nerves, structures of the cavernous sinus, and hypothalamus. The objective of this review article was to summarize the current management strategies for giant pituitary adenomas, including the role of open and endoscopic surgical approaches and the role of medical and radiation therapy in conjunction with surgery. METHODS: We conducted a retrospective review of GPAs operated at our institute between January 2010 and March 2023. Surgical approaches, extent of resection, and associated complications were documented. Furthermore, we conducted a thorough literature review to identify relevant studies published in the past decade, which were incorporated along with insights gained from our institutional case series of GPAs to analyze and integrate both the existing knowledge base and our institution's firsthand experience in the management of GPAs. RESULTS: A total of 46 giant pituitary adenomas (GPAs) were operated on, using various surgical approaches. Transsphenoidal approach was used in 25 cases and a staged approach using transsphenoidal and pterional was used in 15 cases. Other approaches included transcortical-transventricular, transcallosal, pterional/orbitozygomatic, and subfrontal approaches. Complications and technical nuances were reported. CONCLUSION: The management of giant pituitary adenomas remains complex, often involving several modalities-open or endoscopic resection, radiosurgery, and medical management of both the tumor and associated endocrinopathies. Surgical resections are often challenging procedures that require careful consideration of several factors, including patient characteristics, tumor location, and size, and the experience and skill of the surgical team.

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.

Radiotherapy and Mortality in Pituitary Adenomas.

BACKGROUND: Pituitary adenomas (PA), comprising 10-20% of intracranial tumors, are classified as functioning and non-functioning and are further divided by size. Non-functioning tumors cause mechanical symptoms while functioning ones result in hormonal hypersecretion syndromes. Initial treatment involves surgery, with medical treatment for prolactinomas. Radiotherapy (RT) is employed as an adjuvant treatment, with various modalities including conventional, stereotactic radiosurgery (SRS), and fractionated stereotactic RT (FSRT). Although effective, RT is associated with complications and toxicities such as hypopituitarism, optic neuritis, secondary CNS tumors, and neurocognitive deficits. AIM: Describe the information on mortality from radiotherapy as treatment of functioning PA. METHODS: A PubMed search spanning 2000-2017 was conducted for articles on pituitary RT. RESULTS: Conventional RT entails high-energy radiation over multiple sessions, while SRS delivers precise high doses in a single session. FSRT offers enhanced precision using a linear accelerator, delivering multiple doses. Optic structure proximity and tumor volume dictate RT modality. Studies have shown SRS and FSRT's efficacy in tumor and endocrine control, with variable risks and complications. Mortality rates in pituitary adenomas treated with RT have been evaluated, revealing complexities. Acromegaly, associated with increased mortality due to cerebrovascular disease, may result from RT. Irradiation of non-functioning pituitary macroadenomas also elevates cerebrovascular risk, while radiotherapy-induced hypopituitarism is associated with increased cardiovascular mortality. RT-induced damage is attributed to microvascular lesions and arteriolar changes. CONCLUSION: Modern techniques mitigate complications, and although safer, long-term studies are needed. Multidisciplinary evaluation guides the treatment decision, optimizing efficacy and minimizing risk, ultimately improving the patient's quality of life.

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.

Early Versus Delayed Fractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma.

BACKGROUND: Fractionated stereotactic radiotherapy (FSRT) is a common modality used to treat pituitary adenomas with good control rates. It is not known whether FSRT should be performed early or delayed until progression occurs. We compared FSRT in treating nonfunctional pituitary adenomas (NFPA) as an adjuvant (ADJ) or on-progression (PRG) therapy. METHODS: A retrospective review of patients who underwent FSRT for an NFPA between January 2004 and December 2022 at a single institution was performed. We compared endocrinologic, ophthalmologic, and radiographic outcomes in FSRT delivered as ADJ and PRG treatment. RESULTS: Seventy-five patients were analyzed, with a median follow-up of 53 months. FSRT was administered to 35 and 40 patients as ADJ and PRG, with a median time to treatment of 5.5 and 40 months, respectively. The tumor control rate was 94.3% for ADJ and 95.0% for PRG. Treatment resulted in 4 (11.4%) versus 7 (17.5%) new endocrinopathies and 2 (5.7%) versus 1 (2.5%) new visual deficits for ADJ versus PRG. A survival analysis of time to new endocrinopathy showed no difference between the 2 cohorts. The median time from surgery to new endocrinopathy was significantly different between ADJ and PRG, at 15.5 and 102.0 months, respectively. CONCLUSIONS: FSRT is effective in treating NFPA for residual and progressive tumors, with excellent tumor control rates and a low risk of developing new endocrinopathies and visual deficits. Delaying treatment delayed the development of new endocrinopathies, suggesting that observation with FSRT on tumor progression may delay the onset of hypopituitarism and maintain similar effectiveness in tumor 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.

Volumetric Assessment of Nonfunctional Pituitary Adenoma Treated With Stereotactic Radiosurgery: An Assessment of Long-Term Response.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is widely used to manage recurrent or residual nonfunctioning pituitary adenomas (NFPAs). Studies on the long-term volumetric response of NFPAs to SRS are lacking. Such a post-SRS volumetric study will allow us to set up appropriate radiographic follow-up protocols and predict tumor volumetric response. METHODS: Two providers independently performed volumetric analyses on 54 patients who underwent single-session SRS for a recurrent/residual NFPA. In the case of discrepancy between their results, the final volume was confirmed by an independent third provider. Volumetry was performed on the 1-, 3-, 5-, 7-, and 10-year follow-up neuroimaging studies. RESULTS: Most patients showed a favorable volumetric response, with 87% (47/54) showing tumor regression and 13% (7/54) showing tumor stability at 10 years. Year 3 post-SRS volumetric results correlated (R 2 = 0.82, 0.63, 0.56) with 5-, 7-, and 10-year outcomes. The mean interval volumetric reduction was 17% on year 1; further interval volumetric reduction was 17%, 9%, 4%, and 9% on years 3, 5, 7, and 10, respectively. CONCLUSION: Year 3 post-SRS volumetric response of patients with residual or recurrent NFPAs is predictive of their 7-10-year follow-up response. For patients demonstrating NFPA regression in the first 1-3 years, interval follow-up MRI's can likely be performed at 2-year periods unless otherwise clinically indicated. Further studies are needed to better define the volumetric response to adenomas more than a decade after SRS.

Health-related quality of life analyses in nonfunctioning pituitary macroadenoma patients identifies at-risk populations.

PURPOSE: The quality of life (QoL) impact of multidisciplinary treatment for patients with nonfunctioning pituitary macroadenomas (NFPMA) is unclear. We sought to investigate associations between patient factors, clinical data, and patient-reported QoL in patients with NFPMA. METHODS: Patients with treated NFPMA and > 1 year of follow up after transsphenoidal surgery (TSS) and with no evidence of progressive disease were evaluated utilizing the following patient-reported outcome measures: RAND-36-Item Health Survey, Multidimensional Fatigue Inventory, Cognitive Failures Questionnaire. RESULTS: 229 eligible patients completed QoL questionnaires a median of 7.7 years after initial transsphenoidal surgery (TSS). 25% of participants received radiation therapy (RT) a median of 2.0 years (0.1-22.5) after initial TSS. Patients who received RT were younger (median age 46 v 58, p < 0.0001), had larger tumors (28 mm v 22 mm, p < 0.0001), were more likely to have visual symptoms (65% v 34%, p = 0.0002), and were more likely to have hypopituitarism (93% v 62%, p < 0.0001). Patients with hypopituitarism reported worse energy and fatigue and cognitive function (p < 0.03). Patients who received RT reported significantly worse general health, physical health, physical fatigue and cognitive functioning (p < 0.05). The largest QoL differences were in patients who experienced a financial stressor, independent of treatment type. CONCLUSION: Hypopituitarism, radiation therapy after TSS, and financial stressors are associated with more impaired QoL in patients with NFPMA. Awareness of these factors can better guide use and timing of radiation therapy in addition to identifying patients who can benefit from multidisciplinary surveillance.

Postsurgical outcomes of nonfunctioning pituitary adenomas: a patient-level meta-analysis.

BACKGROUND: Surgical resection is the main treatment for symptomatic nonfunctioning pituitary adenomas (NFPA). We aimed to analyze the impact of surgical approach, completeness of resection, and postoperative radiotherapy on long-term progression-free survival (PFS) of NFPA, using individual patient data (IPD) meta-analysis. METHODS: An electronic literature searched was conducted on PubMed, EMBASE, and Web of Science from database inception to 6 November 2022. Studies describing the natural history of surgically resected NFPA, with provision of Kaplan-Meier curves, were included. These were digitized to obtain IPD, which was pooled in one-stage and two-stage meta-analysis to determine hazard ratios (HRs) and 95%CIs of gross total resection (GTR) versus subtotal resection (STR), and postoperative radiotherapy versus none. An indirect analysis of single-arm data between endoscopic endonasal (EES) and microscopic transsphenoidal (MTS) surgical technique was also performed. RESULTS: Altogether, eleven studies (3941 patients) were retrieved. PFS was significantly lower in STR than GTR (shared-frailty HR 0.32, 95%CI 0.27-0.39, p < 0.001). Postoperative radiotherapy significantly improved PFS compared to no radiotherapy (shared-frailty HR 0.20, 95%CI 0.15-0.26, p < 0.001), including in the subgroup of patients with STR (shared-frailty HR 0.12, 95%CI 0.08-0.18, p < 0.001). Similar PFS was observed between EES and MTS (indirect HR 1.09, 95%CI 0.92-1.30, p = 0.301). CONCLUSIONS: This systematic review and patient-level meta-analysis provides a robust prognostication of surgically treated NFPA. We reinforce current guidelines stating that GTR should be the standard of surgical resection. Postoperative radiotherapy is of considerable benefit, especially for patients with STR. Surgical approach does not significantly affect long-term prognosis. REGISTRATION: PROSPERO CRD42022374034.

Effect of pituitary-dependent hypercortisolism on the survival of dogs treated with radiotherapy for pituitary macroadenomas.

BACKGROUND: Radiotherapy (RT) is an effective treatment for dogs presented with neurologic signs caused by pituitary tumors. However, its impact on the outcome of concurrent pituitary-dependent hypercortisolism (PDH) is controversial. OBJECTIVES: Determine whether dogs with PDH have longer survival after pituitary RT compared with dogs with nonhormonally active pituitary masses and to evaluate whether clinical, imaging, and RT variables affect survival. ANIMALS: Ninety-four dogs divided into 2 groups: PDH and non-PDH, based on the presence of hypercortisolism. Forty-seven dogs were allocated to the PDH group and 47 to the non-PDH group. METHODS: Retrospective cohort study in which clinical records of dogs undergoing RT for pituitary macroadenomas between 2008 and 2018 at 5 referral centers were retrospectively evaluated. RESULTS: Survival was not statistically different between PDH and non-PDH groups (median survival time [MST], 590 days; 95% confidence interval [CI], 0-830 days and 738 days; 95% CI, 373-1103 days, respectively; P = .4). A definitive RT protocol was statistically associated with longer survival compared with a palliative protocol (MST 605 vs 262 days, P = .05). The only factor statistically associated with survival from multivariate Cox proportional hazard analysis was total radiation dose (Gy) delivered (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: No statistical difference in survival was identified between the PDH and non-PDH groups, and longer survival was associated with higher Gy delivered.

The Role of Stereotactic Radiosurgery for Functioning and Nonfunctioning Pituitary Adenomas.

Pituitary adenomas are benign brain tumors that comprise 10%-20% of all central nervous system neoplasms. In recent years, stereotactic radiosurgery (SRS) has emerged as a highly effective treatment option in the management of functioning and nonfunctioning adenomas. It is associated with tumor control rates frequently ranging from 80% to 90% in published reports. While permanent morbidity is uncommon, potential side effects include endocrine dysfunction, visual field deficits, and cranial nerve neuropathies. In patients where single fraction SRS would pose an unacceptable risk (e.g. large lesion size or close proximity to the optic apparatus), hypofractionated SRS delivered in 1-5 fractions is a potential treatment option; however, available data are limited. A comprehensive literature search of PubMed/MEDLINE, CINAHL, Embase, and the Cochrane Library was conducted to identify articles reporting on the use of SRS in functioning and nonfunctioning pituitary adenomas.

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.

Molecular Imaging of Pituitary Tumors.

Tumors of the pituitary gland, although mostly benign adenomas, are a cause of significant morbidity and even excess mortality due to local compressive effects (eg visual loss, hypopituitarism) and unregulated hormone secretion (eg acromegaly or Cushing Disease). Surgery, radiotherapy, and medical management (sometimes in combination) may be needed to mitigate the effects of tumor expansion and endocrine dysfunction. Magnetic resonance imaging (MRI) plays a central role in treatment planning for most patients. However, it does not always reliably identify the site(s) of primary or recurrent disease, especially where post-treatment remodeling results in indeterminate anatomical appearances. In these contexts, molecular imaging is a potential game-changer, allowing precise localization of sites of active disease and enabling safe and effective targeted intervention when patients would otherwise be consigned to expensive life-long medication. For pituitary and parasellar imaging, PET is the preferred modality due to its superior spatial resolution and sensitivity compared with SPECT, and an array of PET radioligands have been studied in different pituitary adenoma (PA) subtypes. While 18F-fluorodeoxyglucose (18F-FDG) is widely available, significant heterogeneity in tumoral uptake has limited its use. Instead, ligands targeting specific molecular pathways relevant to PA biology (eg somatostatin or dopamine receptor expression, amino acid uptake) are increasingly preferred and are beginning to find application in routine clinical practice. In addition, novel approaches to distinguish adenomatous tissue from normal gland (eg through comparison of images obtained with different radiotracers) and increase confidence that a suspected abnormal focus is indeed pathological (eg through subtraction imaging) have been proposed. It is likely therefore that molecular imaging will continue to find increasing application in the management of pituitary tumors just as it already does in other endocrine disorders.