Search

Background: Primary intraocular lymphoma (PIOL) is an uncommon subset of primary central nervous system lymphoma. Because it is rare and difficult to diagnose, the natural history and optimal management are unknown. Patients and methods: A retrospective study of 83 HIV negative, immunocompetent PIOL patients was assembled from 16 centers in seven countries. Results: Median age at diagnosis was 65. Median ECOG performance status was 0. Presenting symptoms included blurred vision, decreased visual acuity, and floaters. Median time to diagnosis was 6 months. Diagnosis was made by vitrectomy (74), choroidal/retinal biopsy (6) and ophthalmic exam (3). Eleven percent had positive CSF cytology. Initial treatment was categorized as focal in 23 (intra-ocular methotrexate, ocular radiotherapy) or extensive in 53 (systemic chemotherapy, whole brain radiotherapy). Six received none; details are unknown in one. Forty-seven relapsed: brain 47%, eyes 30%, brain and eyes 15%, and systemic 8%. Median time to relapse was 19 months. Focal therapy alone did not increase risk of brain relapse. Median progression free (PFS) and overall survival (OS) were 29.6 and 58 months, respectively, and unaffected by treatment type. Conclusion: Treatment type did not affect relapse pattern, median PFS or OS. Focal therapy may minimize treatment toxicity without compromising disease control. [ABSTRACT FROM AUTHOR]

Purpose: Pituitary neuroendocrine tumors (pitNETs) are benign tumors that may recur after surgical resection or persist following medical management. The objective of this study was to evaluate outcomes and toxicities of patients with pitNETs treated with stereotactic radiosurgery (SRS) at a single institution., Methods: We completed a retrospective, single-institution study of patients with pitNETs treated with frame-based, single-fraction, cobalt-60 SRS between September 2005 and June 2023. The primary endpoint was local tumor control. Secondary endpoints included endocrine control (for functional tumors), overall survival, and toxicities., Results: A total of 88 lesions in 83 patients were treated with SRS. Most lesions (70%) were non-functional tumors. Of the 26 functioning tumors, 6 patients achieved endocrine remission with SRS alone (23%), and the remainder achieved remission with combined medical management. With a median patient follow-up of 4.7 years, no local tumor recurrences were observed with an estimated local control probability of 100%. Two- and five-year overall survival estimates were 97% (95% confidence interval [CI] 89-99) and 95% (95% CI 84-98), respectively. Causes of death were unrelated to PitNET or SRS. Twelve patients (14%) developed hypopituitarism after SRS. Despite the 34 lesions that were ≤ 3 mm from optic structures, no patients developed any optic neuropathy or visual decline post SRS., Conclusions: SRS is a highly effective modality for recurrent or residual pitNETs. This study observed a local control of 100% with no cases of optic toxicities after a median follow-up of 4.7 years. These observed findings suggest that dose de-escalation may be possible for future treatment of pitNETs., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The majority of patients diagnosed with glioblastoma are >60 years. Three randomized trials addressed the roles of radiotherapy (RT) and temozolomide (TMZ) for elderly patients. NORDIC and NOA-08 compared RT versus TMZ, while CE.6 randomized between hypofractionated RT and RT + TMZ. All showed significant benefits for the TMZ arms, especially for those patients with O 6 -methylguanine DNA methyltransferase ( MGMT ) promoter-methylated tumors. This pooled analysis aimed at identifying additional factors that could improve individualized treatment recommendations., Methods: Analyses were performed separately in the RT and TMZ arms of the pooled NORDIC and NOA-08 data, and in the RT and TMZ/RT arms of CE.6. The prognostic value of baseline clinical factors, comorbidities, and quality of life (QoL) scores were assessed., Results: NORDIC + NOA-08 (NN) included 715 patients and CE.6 included 562 patients. Median age for NN was 71 and 73 years for CE.6. In NN and CE.6 respectively, 66.2% versus 70.5% underwent resection and 50.9% and 75.3% were on steroids. In NN, 401 patients received RT alone and 281 in CE.6, while 314 were randomized to TMZ alone in NN and 281 to concomitant RT + TMZ in CE.6. Known clinical prognostic factors, such as extent of resection and WHO performance status were confirmed, as was MGMT promoter methylation status for TMZ-treated patients. TMZ-treated patients with 2 or 3 comorbidities; hypertension, diabetes, and/or stroke had worse survival, both in NN ( P  = .022) and CE.6 ( P  = .022). Baseline QoL had a minor association with outcome., Conclusion: Consideration of comorbidities allows improved personalized treatment decisions for elderly glioblastoma patients., Competing Interests: A.M., F.B.O., C.O.C., N.L., T.G., E.C., G.R., C.M., and J.P. none. M.W. has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Novartis, Novocure, Orbus, Philogen, Roche, and Servier. R.H. has since the start of the Nordic study received honoraria for lectures or advisory board participation or consulting from Novocure, MSD, Roche, Astra Zeneca, and BrainCool. W.W. Honoraria for consultation or non-financial clinical trial support from Apogenix, Bayer, Merck Sharp & Dome, AstraZeneca, Merck Serono, Novartis, Roche and Mundipharma, with compensation paid to the Medical Faculty at Heidelberg University. B.H.G. research funding from AstraZeneca and Roche, and honoraria from MSD, AstraZeneca, Pfizer, Janssen, Sanofi, Takeda, Eli Lilly, BMS, Gilead and Debiopharm. W.M. consultant for Merck, Servier, Novocure, Boehringer Ingelheim, and chairs a data monitoring committee for Ono Therapeutics. M.P. has received research grants and support from Bayer, Merck, Pfizer and Roche, and advisory board participation compensation from Cellula Therapeutics., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background/objectives: Around 20% of cancer patients will develop brain metastases (BrMs), with 15-25% occurring in the posterior fossa (PF). Although the effectiveness of systemic therapies is increasing, surgery followed by stereotactic radiosurgery (S+SRS) versus definitive SRS remains the mainstay of treatment. Given the space restrictions within the PF, patients with BrMs in this location are at higher risk of brainstem compression, hydrocephalus, herniation, coma, and death. However, the criteria for treating large PF BrMs with S+SRS versus definitive SRS remains unclear., Methods: We reviewed a prospective registry database (2009 to 2020) and identified 64 patients with large PF BrMs (≥4 cc) treated with SRS or S+SRS. Clinical and radiological parameters were analyzed. The two endpoints were overall survival (OS) and local failure (LF)., Results: Patients in the S+SRS group were more highly symptomatic than patients in the SRS group. Gait imbalance and intracranial pressure symptoms were 97% and 80%, and 47% and 35% for S+SRS and SRS, respectively. Radiologically, there were significant differences in the mean volume of the lesions [6.7 cm 3 in SRS vs. 29.8 cm 3 in the S+SRS cohort, ( p < 0.001)]; compression of the fourth ventricle [47% in SRS vs. 96% in S+SRS cohort, ( p < 0.001)]; and hydrocephalus [0% in SRS vs. 29% in S+SRS cohort, ( p < 0.001)]. Patients treated with S+SRS had a higher Graded Prognostic Assessment (GPA). LF was 12 and 17 months for SRS and S+SRS, respectively. Moreover, the S+SRS group had improved OS (12 vs. 26 months, p = 0.001)., Conclusions: A higher proportion of patients treated with S+SRS presented with hydrocephalus, fourth-ventricle compression, and larger lesion volumes. SRS-alone patients had a lower KPS, a lower GPA, and more brain metastases. S+SRS correlated with improved OS, suggesting that it should be seriously considered for patients with large PF-BrM.

Primary basal cell carcinoma (BCC) of the conjunctiva is a rare tumor with only six cases reported in literature. We present the case of an 81-year-old male complaining of a slow-growing lesion in his right eye for the past 3 years. The lesion in the temporal bulbar conjunctiva was gelatinous and firmly adherent to sclera. Ultrasound biomicroscopy revealed apparent scleral thinning without invasion. Our provisional diagnosis was ocular surface squamous neoplasia; however, incisional biopsy for histopathological diagnosis revealed that it was a BCC. Due to scleral adhesion and thinning, the lesion was not amenable for surgical resection. Plaque brachytherapy was used to successfully treat the lesion. To the best of our knowledge, this is the first report of brachytherapy administration for treatment of this rare cancer. Previously reported cases were all nodular or pedunculated and treated with surgical excision. For flat, adherent, or invasive lesions, plaque brachytherapy is an effective primary treatment modality.

Purpose: The capacity for machine learning (ML) to facilitate radiation therapy (RT) planning for primary brain tumors has not been described. We evaluated ML-assisted RT planning with regard to clinical acceptability, dosimetric outcomes, and planning efficiency for adults and children with primary brain tumors., Methods and Materials: In this prospective study, children and adults receiving 54 Gy fractionated RT for a primary brain tumor were enrolled. For each patient, one ML-assisted RT plan was created and compared with 1 or 2 plans created using standard ("manual") planning procedures. Plans were evaluated by the treating oncologist, who was blinded to the method of plan creation. The primary endpoint was the proportion of ML plans that were clinically acceptable for treatment. Secondary endpoints included the frequency with which ML plans were selected as preferable for treatment, and dosimetric differences between ML and manual plans., Results: A total of 116 manual plans and 61 ML plans were evaluated across 61 patients. Ninety-four percent of ML plans and 93% of manual plans were judged to be clinically acceptable (P = 1.0). Overall, the quality of ML plans was similar to manual plans. ML plans comprised 34.5% of all plans evaluated and were selected for treatment in 36.1% of cases (P = .82). Similar tumor target coverage was achieved between both planning methods. Normal brain (brain minus planning target volume) received an average of 1 Gy less mean dose with ML plans (compared with manual plans, P < .001). ML plans required an average of 45.8 minutes less time to create, compared with manual plans (P < .001)., Conclusions: ML-assisted automated planning creates high-quality plans for patients with brain tumors, including children. Plans created with ML assistance delivered slightly less dose to normal brain tissues and can be designed in less time., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Emerging evidence suggests proton radiation therapy may offer cognitive sparing advantages over photon radiation therapy, yet dosimetry has not been compared previously. The purpose of this study was to examine dosimetric correlates of cognitive outcomes in children with medulloblastoma treated with proton versus photon radiation therapy., Methods and Materials: In this retrospective, bi-institutional study, dosimetric and cognitive data from 75 patients (39 photon and 36 proton) were analyzed. Doses to brain structures were compared between treatment modalities. Linear mixed-effects models were used to create models of global IQ and cognitive domain scores., Results: The mean dose and dose to 40% of the brain (D40) were 2.7 and 4.1 Gy less among proton-treated patients compared with photon-treated patients (P = .03 and .007, respectively). Mean doses to the left and right hippocampi were 11.2 Gy lower among proton-treated patients (P < .001 for both). Mean doses to the left and right temporal lobes were 6.9 and 7.1 Gy lower with proton treatment, respectively (P < .001 for both). Models of cognition found statistically significant associations between higher mean brain dose and reduced verbal comprehension, increased right temporal lobe D40 with reduced perceptual reasoning, and greater left temporal mean dose with reduced working memory. Higher brain D40 was associated with reduced processing speed and global IQ scores., Conclusions: Proton therapy reduces doses to normal brain structures compared with photon treatment. This leads to reduced cognitive decline after radiation therapy across multiple intellectual endpoints. Proton therapy should be offered to children receiving radiation for medulloblastoma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Children who require radiation therapy (RT) should ideally be treated awake, without anaesthesia, if possible. Audiovisual distraction is a known method to facilitate awake treatment, but its effectiveness at keeping children from moving during treatment is not known. The aim of this study was to evaluate intrafraction movement of children receiving RT while awake., Methods: In this prospective study, we measured the intrafraction movement of children undergoing treatment with fractionated RT, using pre- and post-RT cone beam CT (CBCT) with image matching on bony anatomy. Study CBCTs were acquired at first fraction, weekly during RT, and at last fraction. The primary endpoint was the magnitude of vector change between the pre- and post-RT scans. Our hypothesis was that 90 % of CBCT acquisitions would have minimal movement, defined as <3 mm for head-and-neck (HN) treatments and <5 mm for non-HN treatments., Results: A total of 65 children were enrolled and had evaluable data across 302 treatments with CBCT acquisitions. Median age was 11 years (range, 2-18; 1st and 3rd quartiles 7 and 14 years, respectively). Minimal movement was observed in 99.4 % of HN treatments and 97.2 % of non-HN treatments. The study hypothesis of >90 % of evaluations having minimal movement was met. Children who were age >11 years moved less at initial evaluation but tended to move more as a course of radiation progressed, as compared to children who were younger., Conclusion: Children receiving RT with audiovisual distraction while awake had small magnitudes of observed intrafraction movement, with minimal movement in >97 % of observed RT fractions. This study validates methods of anaesthesia avoidance using audiovisual distraction for selected children., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Stereotactic radiosurgery (SRS) marginal dose is associated with successful obliteration of cerebral arteriovenous malformations (AVM). SRS dose rate-how old the cobalt-60 sources are-is known to influence outcomes for some neurological conditions and benign tumors. The objective of this study was to determine the association between cobalt-60 treatment dose rate and cerebral AVM obliteration in patients treated with SRS., Methods: We performed a retrospective cohort study of 361 patients undergoing 411 AVM-directed SRS treatments between 2005 and 2019 at a single institution. Lesion characteristics, SRS details, obliteration dates, and post-treatment toxicities were recorded. Univariate and multivariate regression analyses of AVM outcomes regarding SRS dose rate (range 1.3-3.7 Gy, mean = 2.4 Gy, median = 2.5 Gy) were performed., Results: At 10 years post-SRS, 68% of AVMs were obliterated on follow-up imaging. Dose rates >2.9 Gy/min were found to be significantly associated with AVM obliteration compared with those <2.1 Gy/min ( P = .034). AVM size, biologically effective dose, and SRS marginal dose were also associated with obliteration, with obliteration more likely for smaller lesions, higher biologically effective dose, and higher marginal dose. Higher dose rates were not associated with the development of post-SRS radiological or symptomatic edema, although larger AVM volume was associated with both types of edema., Conclusion: Patients with cerebral AVMs treated with higher SRS dose rates (from newer cobalt-60 sources) experience higher incidences of obliteration without a significant change in the risk of post-treatment edema., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as standard-of-care adjuvant treatment following surgery for brain metastasis (BrM). Concomitant with the adoption of adjuvant SRS, a new pattern of failure termed "Pachymeningeal failure" (PMF) has emerged., Methods: We reviewed a prospective registry of 264 BrM patients; 145 and 119 were treated adjuvantly with WBRT and SRS, respectively. The Cox proportional hazards model was used to identify variables correlating to outcomes. Outcomes were calculated using the cumulative incidence (CI) method. Univariate (UVA) and multivariate analyses (MVA) were done to identify factors associated with PMF., Results: CI of PMF was 2 % and 18 % at 12 months, and 2 % and 23 % at 24 months for WRBT and SRS, respectively (p < 0.001) . The CI of classic leptomeningeal disease (LMD) was 3 % and 4 % at 12 months, and 6 % and 6 % at 24 months for WBRT and SRS, respectively (P = 0.67). On UVA, adjuvant SRS [HR 9.75 (3.43-27.68) (P < 0.001)]; preoperative dural contact (PDC) [HR 6.78 (1.64-28.10) (P = 0.008)]; GPA score [HR 1.64 (1.11-2.42) (P = 0.012)]; and lung EGFR/ALK status [HR 3.11 (1.02-9.45) (P = 0.045)]; were associated with PMF risk. On MVA, adjuvant SRS [HR 8.15 (2.69-24.7) (P < 0.001)]; and PDC [HR 6.28 (1.51-26.1) (P = 0.012)] remained associated with PMF., Conclusions: Preoperative dural contact and adjuvant SRS instead of adjuvant WBRT were associated with an increased risk of PMF. Strategies to improve pachymeningeal radiation coverage to sterilize at risk pachymeninges should be investigated., (© 2024 The Author(s).)

Background: Aside from surgical resection, the only standard of care treatment modality for meningiomas is radiotherapy (RT). Despite this, few studies have focused on identifying clinical covariates associated with failure of fractionated RT following surgical resection (fRT), and the timing of fRT following surgery still remains controversial (adjuvant versus salvage fRT). We assessed the outcomes of the largest, multi-institutional cohort of surgically resected meningiomas treated with subsequent adjuvant and salvage fRT to identify factors associated with local freedom from recurrence (LFFR) over 3-10 years post-fRT and to determine the optimal timing of fRT., Methods: Patients with intracranial meningiomas who underwent surgery and fRT between 1997 and 2018 were included. Primary endpoints were radiographic recurrence/progression and time to progression from the completion of fRT., Results: 404 meningiomas were included for analysis. Of these, 167 (41.3%) recurred post-fRT. Clinical covariates independently associated with worse PFS post-fRT included receipt of previous RT to the meningioma, having a WHO grade 3 meningioma or recurrent meningioma, the meningioma having a higher MIB1-index or brain invasion on pathology, and older patient age at diagnosis. Subgroup analysis identified higher MIB1-index as a histological factor associated with poorer LFFR in WHO grade 2 meningiomas. 179 patients underwent adjuvant RT shortly after surgery whereas 225 patients had delayed, salvage fRT after recurrence/progression. Following propensity score matching, patients that underwent adjuvant fRT had improved LFFR post-fRT compared to those that received salvage fRT., Conclusion: There is a paucity of clinical factors that can predict a meningioma's response to fRT following surgery. Adjuvant fRT may be associated with improved PFS post-fRT compared to salvage fRT. Molecular biomarkers of RT-responsiveness are needed to better inform fRT treatment decisions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To understand the natural history and optimal treatment strategy for pituitary gland metastasis., Methods: We performed both a retrospective chart review of patients treated at our institution and a scoping review of the topic., Results: The retrospective review identified seven patients with an average age of 59.6 years. Primary histologies included breast cancer (4), melanoma (1), renal cell carcinoma (1), and sarcoma (1). Two patients had anterior pituitary endocrine dysfunction, one of whom was the only patient with visual symptoms. All patients were treated with radiosurgery and two also underwent surgical resection. Overall survival ranged from 6.5 to 117 months. Literature review identified 166 patients from 71 studies. The most common primary cancer was lung (27.7%), followed by breast (18.7%) and renal (14.5%) cancer. 107 presented with endocrine dysfunction, including 41 cases of diabetes insipidus and 55 cases of hypopituitarism. 110 presented with visual compromise. 107 patients received radiotherapy, 96 underwent surgical resection and 44 received systemic chemotherapy/immunotherapy. Surgery was significantly associated with an increased likelihood of vision improvement and a decreased likelihood of endocrine normalization. Radiographic regression predicted visual improvement. Median overall survival was 9.9 months (range: 0.2-96)., Conclusions: This scoping review showed that both radiosurgery and surgical resection have been frequently used to treat pituitary metastases with good response. Vision improvement is more likely to happen following surgical resection, likely at the expense of endocrine dysfunction. Despite treatment and radiographic response, patient survival remains less than a year., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

At our institution, patients diagnosed with choroidal melanoma requiring external beam radiation therapy are treated with two 6 MV volumetric-modulated arcs delivering 50 Gy over 5 daily fractions. The patient is immobilized using an Orfit head and neck mask and is directed to look at a light emitting diode (LED) during CT simulation and treatment to minimize eye movement. Patient positioning is checked with cone beam computed tomography (CBCT) daily. Translational and rotational displacements greater than 1 mm or 1° off the planned isocenter position are corrected using a Hexapod couch. The aim of this study is to verify that the mask system provides adequate immobilization and to verify our 2-mm planning target volume (PTV) margins are sufficient. Residual displacements provided by pretreatment verification and post-treatment CBCT data sets were used to assess the impact of patient mobility during treatment on the reconstructed delivered dose to the target and organs at risk. The PTV margin calculated using van Herk's method 1 was used to assess patient motion plus other factors that affect treatment position, such as kV-MV isocenter coincidence. Patient position variations were small and were shown to not cause significant dose variations between the planned and reconstructed dose to the target and organs at risk. The PTV margin analysis showed patient translational motion alone required a PTV margin of 1 mm. Given other factors that affect treatment delivery accuracy, a 2-mm PTV margin was shown to be sufficient for treatment of 95% of our patients with 100% of dose delivered to the GTV. The mask immobilization with LED focus is robust and we showed a 2-mm PTV margin is adequate with this technique., Competing Interests: Conflicts of Interest The authors declare no conflicts of interest., (Copyright © 2023 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO)., Methods: From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan-Meier method., Results: Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11-0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 - 9.1)., Conclusion: The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Purpose: Brain radiotherapy (cnsRT) requires reproducible positioning and immobilization, attained through redundant dedicated imaging studies and a bespoke moulding session to create a thermoplastic mask (T-mask). Innovative approaches may improve the value of care. We prospectively deployed and assessed the performance of a patient-specific 3D-printed mask (3Dp-mask), generated solely from MR imaging, to replicate a reproducible positioning and tolerable immobilization for patients undergoing cnsRT., Material and Methods: Patients undergoing LINAC-based cnsRT (primary tumors or resected metastases) were enrolled into two arms: control (T-mask) and investigational (3Dp-mask). For the latter, an in-house designed 3Dp-mask was generated from MR images to recreate the head positioning during MR acquisition and allow coupling with the LINAC tabletop. Differences in inter-fraction motion were compared between both arms. Tolerability was assessed using patient-reported questionnaires at various time points., Results: Between January 2020 - July 2022, forty patients were enrolled (20 per arm). All participants completed the prescribed cnsRT and study evaluations. Average 3Dp-mask design and printing completion time was 36 h:50 min (range 12 h:56 min - 42 h:01 min). Inter-fraction motion analyses showed three-axis displacements comparable to the acceptable tolerance for the current standard-of-care. No differences in patient-reported tolerability were seen at baseline. During the last week of cnsRT, 3Dp-mask resulted in significantly lower facial and cervical discomfort and patients subjectively reported less pressure and confinement sensation when compared to the T-mask. No adverse events were observed., Conclusion: The proposed total inverse planning paradigm using a 3D-printed immobilization device is feasible and renders comparable inter-fraction performance while offering a better patient experience, potentially improving cnsRT workflows and its cost-effectiveness., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: Neurosurgery (NS) is an essential modality for large brain metastases (BM). Postoperative stereotactic radiosurgery (SRS) is the standard of care adjuvant treatment. Pachymeningeal failure (PMF) is a newly described entity, distinct from classical leptomeningeal failure (LMF), that is uniquely observed in postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS + SRS., Methods: From a prospective registry (2009 to 2021), we identified all patients treated with NS + SRS. Clinical, imaging, pathological, and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model., Results: 144 Patients were identified. The median age was 62 (23-90). PMF occurred in 21.5% (31/144). Female gender [Hazard Ratio (HR) 2.65, p = 0.013], higher Graded Prognostic Assessment (GPA) index (HR 2.4, p < 0.001), absence of prior radiation therapy (HR N/A, p = 0.018), controlled extracranial disease (CED) (HR 3.46, p = 0.0038), and pia/dura contact (PDC) (HR 3.30, p = 0.0053) were associated with increased risk for PMF on univariate analysis. In patients with PDC, wider target volumes correlated with reduced risk of PMF. Multivariate analysis indicated PDC (HR 3.51, p = 0.0053), piecemeal resection (HR 2.38, p = 0.027), and CED (HR 3.97, p = 0.0016) independently correlated with PMF risk. PMF correlated with reduced OS (HR 2.90, p < 0.001) at a lower rate compared to LMF (HR 10.15, p < 0.001)., Conclusion: PMF correlates with tumor PDC and piecemeal resection in patients treated with NS + SRS. For unclear reasons, it is also associated with CED. In tumors with PDC, wider dural radiotherapy coverage was associated with a lower risk of PMF., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Surgery is the primary treatment for most meningiomas. However, primary fractionated radiotherapy (fRT) remains an option for patients with larger meningiomas in challenging anatomic locations or patients at prohibitively high surgical risk. Outcome prediction for these patients is uncertain and cannot be guided by histopathology without available tumor tissue from surgery. Therefore, we aimed to assess the clinical factors that contribute to treatment failure in a large cohort of meningiomas consecutively treated with fRT as primary therapy, with the goal of identifying predictors of response., Methods: Patients treated with primary fRT for intracranial meningiomas from 1998 to 2017 were reviewed. Those who received primary surgical resection, radiosurgery, previous fRT, or had <6 months of clinical follow-up were excluded. We applied logistic regression and Cox regression modeling to ascertain key predictors of treatment failure, progression-free survival (PFS), and adverse events (AE) following fRT., Results: Our cohort included 137 meningiomas, 21 of which progressed after fRT (median PFS 3.45 years). Progressive meningiomas had a larger median gross tumor volume (GTV) compared to those that remained stable (19.1 cm 3 vs 9.6 cm 3 , p = 2.86 × 10 -2 ). GTV > 11.27 cm 3 was independently predictive of progression and larger GTV was associated with higher risk of significant (grades 3/4) AE following fRT. Cavernous sinus and optic nerve sheath meningiomas had overall excellent outcomes post-fRT., Conclusions: We present a large cohort of meningiomas treated with primary fRT and find GTV and anatomic location to be key predictors of outcome, adding to the complex treatment considerations for this heterogeneous disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Justin Z. Wang was funded by the Vanier Scholarship from the Canadian Institutes for Health Research (CIHR) and the Neurosurgery Research Educational Fund (NREF) & Southeastern Brain Tumor Foundation Research Fellowship., (© 2023 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Purpose: To determine long-term outcomes of a cohort of children with germinoma treated with chemotherapy and radiation therapy without primary tumor boost even in the absence of complete response to chemotherapy METHODS: This retrospective study analyzed the outcome of patients with germinoma consecutively diagnosed and treated at a tertiary care center from January 2000 to December 2021. MRIs were reviewed by two radiologists, blinded to patient data. Tumor location at diagnosis, tumor response to chemotherapy and at completion of radiation therapy and site of relapse were assessed. Tumor response was assessed radiologically by determining the tumor size and response on diffusion-weighted imaging, in addition to biochemical, cytological parameters and neurological status., Results: Of 46 pediatric germinoma patients, 29 children (14 male; median age 12.8 years) received no primary tumor boost. Median follow-up was 63 months (range 9-187 months). Twenty-five children had localized disease and tumor location was suprasellar (n = 11), pineal (n = 10), bifocal (n = 3) and basal ganglia (n = 1) while 4 children had metastatic disease at presentation. All patients completed multi-agent chemotherapy followed by either ventricular irradiation (VI) (23.4 Gy) (n = 23), whole brain (WBI) (23.4 Gy) (n = 5) or craniospinal radiation (CSI) (23.4 Gy) (n = 1). Two children, who had localized disease at presentation and received VI after chemotherapy, relapsed 9 months and 32 months after completion of treatment respectively. No patient had a local relapse. Location of relapse was distant, outside (n = 1) and out- and inside (n = 1) the irradiation field. Five-year progression free survival (PFS) was 91% and overall survival (OS) was 100%., Conclusions: In this case series, excellent 5-year PFS and OS rates were achieved with chemotherapy followed by radiation therapy of 23.4 Gy delivered without primary tumor boost. No local relapse was observed despite omitting primary tumor boost in patients with localized and metastatic germinoma., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As frameless stereotactic radiosurgery increase in use, the aim of this study was to evaluate intra-fraction motion through cone-beam CT (CBCT) and high-definition motion management (HDMM) systems. Intra-fraction motion measured between localization, repeat localization and post-treatment CBCTs were correlated to intra-faction motion indicated by the HDMM files using the Pearson coefficient (r). A total of 302 plans were reviewed from 263 patients (114 male, 149 female); 216 pairs of localization-repeat localization, and 260 localization-post-treatment CBCTs were analyzed against HDMM logs. We found the magnitude of intra-fraction motion detected by the HDMM system were larger than the corresponding CBCT results., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was partially supported through a research grant from Elekta and the Canadian Institutes of Health Research (CIHR); the principal investigators of the grants were Dr. David Jaffray and Dr. Caroline Chung., (© 2023 The Authors.)

Background: We sought to identify variates correlating with overall survival (OS) in patients treated with surgery (S) plus adjuvant stereotactic radiosurgery (SRS) versus definitive SRS for large (&gt;4 cc) brain metastases (BrM)., Methods: We used univariate (UVA) and multivariate analyses (MVA) to identify survival correlates among eligible patients identified from a prospective registry and compared definitive SRS to S+ adjuvant SRS cohorts using propensity score-matched analysis (PSMA). Secondary outcomes were measured using the cumulative incidence (CI) method., Results: We identified 364 patients; 127 and 237 were treated with S+SRS and definitive SRS, respectively. On UVA, SRS alone [HR1.73 (1.35,2.22) P &lt; .001), BrM quantity [HR 1.13 (1.06-1.22) (P &lt; .001)]; performance status (PS) [HR 2.78 (1.73-4.46) (P &lt; .001)]; extracranial disease (ECD) [HR 1.82 (1.37,2.40) (P &lt; .001)]; and receipt of systemic treatment after BrM therapy, [HR 0.58 (0.46-073) (P &lt; .001)] correlated with OS. On MVA, SRS alone [HR 1.81 (1.19,2.74) (P &lt; .0054)], SRS target volume [HR 1.03 (1.01,1.06) (P &lt; .0042)], and receipt of systemic treatment [HR 0.68 (0.50,0.93) (P &lt; .015)] correlated with OS. When PSMA was used to balance ECD, BrM quantity, PS, and SRS target volume, SRS alone remained correlated with worsened OS [HR 1.62 (1.20-2.19) (P = 0.0015)]. CI of local failure requiring resection at 12 months was 3% versus 7% for S+SRS and SRS cohorts, respectively [(HR 2.04 (0.89-4.69) (P = .091)]. CI of pachymeningeal failure at 12 months was 16% versus 0% for S+SRS and SRS., Conclusion: SRS target volume, receipt of systemic therapies, and treatment with S+SRS instead of definitive SRS correlated with improved survival in patients with large BrM., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To report the efficacy and toxicity of External beam Radiotherapy (EBRT) as a sole treatment for MALT and Follicular Primary Orbital and Ocular adnexal Lymphoma (POOAL)., Methods: Retrospective review of all POOAL patients treated with EBRT utilizing megavoltage photon or electron beam radiotherapy between 2003 and 2015. Patient demographics, tumour extent and pathology, radiotherapy techniques, and treatment outcomes were reviewed. The actuarial rates of tumour control and radiation toxicities were calculated using Kaplan-Meier estimates., Results: This study included 167 tumours, of which MALT lymphoma involved 149 (89 %). The conjunctiva and orbit were equally involved as the predominant site (48 %). Megavoltage photon radiotherapy was used in 60 % of predominantly orbital lymphoma and Electron beam with lens shielding in 77 % of the conjunctival lymphoma. The majority (95 %) were treated with a total dose of 25 Gy in 10 fractions. Local control rate was 98 % (CI: 93-100 %) at 5 years. The long-term RT toxicities included dry eye in 27 eyes (16 %) and cataract in 22 (13 %). None of the patients developed significant structural or functional radiation toxicity., Conclusion: External Beam Radiotherapy, with lens shielding whenever indicated, at a dose of 20-30 Gy delivered over 10-20 fractions is an efficacious and safe primary treatment option for POOAL lymphoma, with excellent local control and low incidence of late manageable ocular toxicities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: In addition to poor survival rates, individuals with glioblastoma (GBM) are at risk of neurocognitive impairment due to multiple factors. This study aimed to characterize neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms in newly diagnosed GBM patients; and to examine whether neurobehavioral symptoms, fatigue, sleep, and depressive symptoms influence neurocognitive performance., Methods: This study was part of a prospective, inception cohort, single-arm exercise intervention in which GBM patients underwent a neuropsychological assessment shortly after diagnosis (median 4 weeks; ie, baseline) and 3, 6, 12, and 18 months later, or until tumor progression. Here, we present baseline data. Forty-five GBM patients (mean age = 55 years) completed objective neurocognitive tests, and self-report measures of neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms., Results: Compared to normative samples, GBM patients scored significantly lower on all neurocognitive tests, with 34 (76%) patients exhibiting neurocognitive impairment. Specifically, 53% exhibited impairment in memory retention, 51% in executive function, 42% in immediate recall, 41% in verbal fluency, and 24% in attention. There were high rates of clinically elevated sleep disturbance (70%), fatigue (57%), depressive symptoms (16%), and neurobehavioral symptoms (27%). A multivariate regression analysis revealed that depressive symptoms are significantly associated with neurocognitive impairment., Conclusions: GBM patients are vulnerable to adverse outcomes including neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms shortly after diagnosis, prior to completing chemoradiation. Those with increased depressive symptoms are more likely to demonstrate neurocognitive impairment, highlighting the need for early identification and treatment of depression in this population., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)