ASL, DSC, DCE perfusion MRI and 18F-DOPA PET/CT in differentiating glioma recurrence from post-treatment changes.

OBJECTIVES: To discriminate between post-treatment changes and tumor recurrence in patients affected by glioma undergoing surgery and chemoradiation with a new enhancing lesion is challenging. We aimed to evaluate the role of ASL, DSC, DCE perfusion MRI, and 18F-DOPA PET/CT in distinguishing tumor recurrence from post-treatment changes in patients with glioma. MATERIALS AND METHODS: We prospectively enrolled patients with treated glioma (surgery plus chemoradiation) and a new enhancing lesion doubtful for recurrence or post-treatment changes. Each patient underwent a 1.5T MRI examination, including ASL, DSC, and DCE PWI, and an 18F-DOPA PET/CT examination. For each lesion, we measured ASL-derived CBF and normalized CBF, DSC-derived rCBV, DCE-derived Ktrans, Vp, Ve, Kep, and PET/CT-derived SUV maximum. Clinical and radiological follow-up determined the diagnosis of tumor recurrence or post-treatment changes. RESULTS: We evaluated 29 lesions (5 low-grade gliomas and 24 high-grade gliomas); 14 were malignancies, and 15 were post-treatment changes. CBF ASL, nCBF ASL, rCBV DSC, and PET SUVmax were associated with tumor recurrence from post-treatment changes in patients with glioma through an univariable logistic regression. Whereas the multivariable logistic regression results showed only nCBF ASL (p = 0.008) was associated with tumor recurrence from post-treatment changes in patients with glioma with OR = 22.85, CI95%: (2.28-228.77). CONCLUSION: In our study, ASL was the best technique, among the other two MRI PWI and the 18F-DOPA PET/CT PET, in distinguishing disease recurrence from post-treatment changes in treated glioma.

Neural Functioning in Late-Life Depression: An Activation Likelihood Estimation Meta-Analysis.

Late-life depression (LLD) is a relatively common and debilitating mental disorder, also associated with cognitive dysfunctions and an increased risk of mortality. Considering the growing elderly population worldwide, LLD is increasingly emerging as a significant public health issue, also due to the rise in direct and indirect costs borne by healthcare systems. Understanding the neuroanatomical and neurofunctional correlates of LLD is crucial for developing more targeted and effective interventions, both from a preventive and therapeutic standpoint. This ALE meta-analysis aims to evaluate the involvement of specific neurofunctional changes in the neurophysiopathology of LLD by analysing functional neuroimaging studies conducted on patients with LLD compared to healthy subjects (HCs). We included 19 studies conducted on 844 subjects, divided into 439 patients with LLD and 405 HCs. Patients with LLD, compared to HCs, showed significant hypoactivation of the right superior and medial frontal gyri (Brodmann areas (Bas) 8, 9), left cingulate cortex (BA 24), left putamen, and left caudate body. The same patients exhibited significant hyperactivation of the left superior temporal gyrus (BA 42), left inferior frontal gyrus (BA 45), right anterior cingulate cortex (BA 24), right cerebellar culmen, and left cerebellar declive. In summary, we found significant changes in activation patterns and brain functioning in areas encompassed in the cortico-limbic-striatal network in LLD. Furthermore, our results suggest a potential role for areas within the cortico-striatal-cerebellar network in the neurophysiopathology of LLD.

"Vanishing" glioblastoma: A case report and review of the literature.

Contrast enhancement resolution induced by corticosteroids is a phenomenon primarily associated with primary central nervous system lymphoma, while malignant brain gliomas usually maintain a consistent radiological appearance during systemic steroid treatment. Although rare, a few primary and metastatic intracranial lesions have shown similar radiographic changes following corticosteroid therapy. In the case of glioblastomas, corticosteroid therapy is commonly used to alleviate pressure effects from peritumoral edema, but its impact on contrast enhancement is not well-established. A few reported cases in the literature describe reduced contrast enhancement in glioblastomas after corticosteroid treatment. We present a case of corticosteroid-induced regression on imaging of glioblastoma evaluated at our institutionwith the intention to explore the pathogenesis of this response and discuss the therapeutic and prognostic implications of this discovery.

Radioclinical Assessment of Posterior Tympanotomy Difficulties during Ordinary Cochlear Implantation: A Prospective Case-Series Study.

OBJECTIVES: This study proposes a preoperative radiologic scoring system for predicting posterior tympanotomy (PT) and mastoidectomy-associated difficulties during cochlear implantation (CI). STUDY DESIGN: It was a prospective case-series study. SETTINGS: The included CI surgeries were performed at tertiary referral institutions from October 2022 to April 2023. SUBJECTS: We included 73 CI candidates performed via the PT approach. INTERVENTION: The proposed radiologic score, composed of 13 items, was fulfilled and evaluated before each CI surgery. MAIN OUTCOME MEASURE: We correlated this score with the intraoperative difficulty and surgical duration. RESULTS: The operation was straightforward in 42 patients with a score of 3.87 ± 1.72 and challenging in 31 patients with a score of 10.66 ± 1.73. The radiologic score was strongly correlated with the surgical difficulty and duration (p < 0.0001). CONCLUSIONS: Our proposed radiologic score was a valid, reliable, and precise tool to predict intraoperative difficulty during cochlear implantation. Chorda-facial angle was the strongest predictor, significantly affecting the difficulty, surgical duration, and preoperative radiologic score. A score equal to or more than 7.5 was expected to be associated with surgical difficulty.

A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas.

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.

Extra-axial cranial nerve enhancement: a pattern-based approach.

Cranial nerve enhancement is a common and challenging MRI finding that requires a meticulous and systematic evaluation to identify the correct diagnosis. Literature mainly describes the various pathologies with the associated clinic-radiological characteristics, while the radiologist often needs a reverse approach that starts from the radiological findings to reach the diagnosis. Therefore, our aim is to provide a new and practical pattern-based approach to cranial nerve enhancement, which starts from the radiological findings and follows pattern-driven pipelines to navigate through multiple differential diagnoses, guiding the radiologist to reach the proper diagnosis. Firstly, we reviewed the literature and identified four patterns to categorize the main pathologies presenting with cranial nerve enhancement: unilateral linear pattern, bilateral linear pattern, unilateral thickened pattern, and bilateral thickened pattern. For each pattern, we describe the underlying pathogenic origin, and the main radiological features are displayed through high-quality MRI images and illustrative panels. A suggested MRI protocol for studying cranial nerve enhancement is also provided. In conclusion, our approach for cranial nerve enhancement aims to be an easy tool immediately applicable to clinical practice for converting challenging findings into specific pathological patterns.

Interrater reliability of Brain Tumor Reporting and Data System (BT-RADS) in the follow up of adult primary brain tumors: a single institution experience in Italy.

Background: In 2018, a new system was proposed for classifying and reporting post-treatment adult brain tumor on magnetic resonance imaging, named as Brain Tumor Reporting and Data System (BT-RADS), that needs a validation by means of agreement studies. Methods: A retrospective study was designed with the aim of identifying contrast-enhanced magnetic resonance imaging (MRI) of adult patients on follow-up for primary brain tumor at Fondazione Policlinico Campus Bio-Medico. Four radiologists (2 radiology residents, 1 general radiologist, 1 neuroradiologist) read and scored each study using the BT-RADS scoring tool, blinded to the MRI original report. Interobserver agreement and Fleiss' k were calculated to assess the level of diagnostic agreement. It was assessed how many times the assignment of different scoring of BT-RADS would have led to a different patient management. Results: The total number of patients included in the study was 23 with 147 MRIs and a total of 588 BT-RADS scores retrospectively evaluated. The two most frequent tumor types were astrocytoma grade 4 (62%) and oligodendroglioma grade 3 (21%). The overall agreement rate for all 4 radiologists was 82% with a Fleiss' k of 0.70. The overall agreement rate between general radiologist and neuroradiologist was 91% with a Fleiss' k of 0.86. The overall agreement rate between 2 radiology residents and neuroradiologist was 80% with a Fleiss' k of 0.66. Astrocytoma grade 3 (k: 0.51) and oligodendroglioma grade 2 (k: 0.32) showed a poor agreement while higher values of agreement were found for astrocytoma grade 4 (k: 0.70), astrocytoma grade 2 (k: 0.78) and oligodendroglioma grade 3 (k: 0.78). All the radiologists agreed on BT-RADS assignment in 70% patients, three radiologists agreed in 17% and two radiologists agree in 13%. In no cases there was a complete disagreement among the readers. In 18% of cases the discrepancy in the estimated BT-RADS would have led to a different follow-up management. Conclusions: BT-RADS can be considered a valid tool for neuroradiologists and radiologists even with little experience in the interpretation of patients' images during follow-up for adult primary brain tumors supporting standardized interpretation, reporting and clinical management.

Radiosurgery for Brain Metastases: Challenges in Imaging Interpretation after Treatment.

Stereotactic radiosurgery (SRS) has transformed the management of brain metastases by achieving local tumor control, reducing toxicity, and minimizing the need for whole-brain radiation therapy (WBRT). This review specifically investigates radiation-induced changes in patients treated for metastasis, highlighting the crucial role of magnetic resonance imaging (MRI) in the evaluation of treatment response, both at very early and late stages. The primary objective of the review is to evaluate the most effective imaging techniques for assessing radiation-induced changes and distinguishing them from tumor growth. The limitations of conventional imaging methods, which rely on size measurements, dimensional criteria, and contrast enhancement patterns, are critically evaluated. In addition, it has been investigated the potential of advanced imaging modalities to offer a more precise and comprehensive evaluation of treatment response. Finally, an overview of the relevant literature concerning the interpretation of brain changes in patients undergoing immunotherapies is provided.

Giant serpentine aneurysm: Neuroradiological and neurosurgical management in a left-handed patient.

Giant serpentine aneurysms are rare huge and partially thrombosed aneurysms, with an eccentric tortuous intra-aneurysmal vascular channel. Surgical treatment is often necessary due to the great mass effect. We describe a case of a left-handed woman with a giant serpentine aneurysm of the left middle cerebral artery whose management was complex. The challenge was to exclude the aneurysm from circulation, reduce the mass effect, and, mostly, preserve the language function. Since the patient was left-handed the language dominance needed to be assessed; functional MRI (fMRI) and Wada test (WT) showed a right dominance. Surgical treatment was performed, as a complication, the patient developed left fronto-basal ischemia with a slight paresis of the right hand but without any language deficit. Our case shows the importance of a multidisciplinary team in patient management, with a pivotal role of neuroradiological functional tests in presurgical planning.

Long-term treatment outcomes of temozolomide-based chemoradiation in patients with adult-type diffuse IDH-mutant grade 2 astrocytoma.

PURPOSE: To report the long-term outcomes in adult patients with grade 2 IDH-mutant astrocytoma treated with temozolomide (TMZ)-based chemoradiation. METHODS: One hundred and three patients with histologically proven grade 2 astrocytoma received radiation therapy (RT), 50.4-54 Gy in 1.8 Gy fractions, and adjuvant TMZ up to 12 cycles. Fifty-two patients received RT at the time of tumor progression and 51 in the early postoperative period for the presence of at least one high-risk feature (age > 40 years, preoperative tumor size > 5 cm, large postoperative residual tumor, tumor crossing the midline, or presence of neurological symptoms). Overall survival (OS) and progression-free survival (PFS) were calculated from the time of diagnosis. RESULTS: With a median follow-up time of 9.0 years (range, 1.3-15 years), median PFS and OS times were 9 years (95%CI, 6.6-10.3) and 11.8 years (95%CI, 9.3-13.4), respectively. Median PFS was 10.6 years in the early treatment group and 6 years in delayed treatment group (hazard ratio (HR) 0.30; 95%CI 0.16-0.59; p = 0.0005); however, OS was not significantly different between groups (12.8 vs. 10.4 years; HR 0.64; 95%CI 0.33-1.25; p = 0.23). Extent of resection, KPS, and small residual disease were associated with OS, with postoperative tumor ≤ 1 cc that emerged as the strongest independent predictor (HR: 0.27; 95%CI 0.08-0.87; p = 0.01). CONCLUSIONS: TMZ-based chemoradiation is associated with survival benefit in patients with grade 2 IDH-mutant astrocytoma. For this group of patients, chemoradiation can be deferred until time of progression in younger patients receiving extensive resection, while early treatment should be recommended in high-risk patients.

Intradural abscess: A challenging diagnosis. Case series and review of the literature.

Spinal intradural abscesses are extremely rare. To our knowledge, only a few cases have been described in the literature. We report 2 cases of spinal intradural abscesses in patients presenting to our institution with different symptomatology. Both cases involved the lumbar spine, with different etiologies: Case 1 was presumptively related to spondylitis phenomena, with surgery confirming the intradural localization of the abscess; case 2 was of probable iatrogenic nature (secondary to lumbar drain positioning). The aim of this report is to briefly discuss the clinical significance and pathogenesis of these cases.

European Cancer Organisation Essential Requirements for Quality Cancer Care: Adult glioma.

European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCCs) are explanations of the organisation and actions necessary to provide high-quality care to patients with a specific cancer type. They are compiled by a working group of European experts representing disciplines involved in cancer care, and provide oncology teams, patients, policymakers and managers with an overview of the essential requirements in any healthcare system. The focus here is on adult glioma. Gliomas make up approximately 80% of all primary malignant brain tumours. They are highly diverse and patients can face a unique cognitive, physical and psychosocial burden, so personalised treatments and support are essential. However, management of gliomas is currently very heterogeneous across Europe and there are only few formally-designated comprehensive cancer centres with brain tumour programmes. To address this, the ERQCC glioma expert group proposes frameworks and recommendations for high quality care, from diagnosis to treatment and survivorship. Wherever possible, glioma patients should be treated from diagnosis onwards in high volume neurosurgical or neuro-oncology centres. Multidisciplinary team working and collaboration is essential if patients' length and quality of life are to be optimised.

The Role of Advanced MRI Sequences in the Diagnosis and Follow-Up of Adult Brainstem Gliomas: A Neuroradiological Review.

The 2021 WHO (World Health Organization) classification of brain tumors incorporated the rapid advances in the molecular, genetic, and pathogenesis understanding of brain tumor pathogenesis, behavior, and treatment response. It revolutionized brain tumor classification by placing great emphasis on molecular types and completely splitting adult-type and pediatric-type diffuse gliomas. Brainstem gliomas (BSGs) are the leading primary tumors of the brainstem, although they are quite uncommon in adults compared with the pediatric population, representing less than 2% of adult gliomas. Surgery is not always the treatment of choice since resection is rarely feasible and does not improve overall survival, and biopsies are not generally performed since the location is treacherous. Therefore, MRI (Magnetic Resonance Imaging) without and with gadolinium administration represents the optimal noninvasive radiological technique to suggest brainstem gliomas diagnosis, plan a multidisciplinary treatment and for follow-up evaluations. The MRI protocol encompasses morphological sequences as well as functional and advanced sequences, such as DWI/ADC (Diffusion-Weighted Imaging/Apparent Diffusion Coefficient), DTI (Diffusion Tensor Imaging), PWI (Perfusion-Weighted Imaging), and MRS (Magnetic Resonance Spectroscopy), which improve the accuracy of the diagnosis of BSGs by adding substantial information regarding the cellularity, the infiltrative behavior toward the v fiber tracts, the vascularity, and the molecular changes. Brainstem gliomas have been divided into four categories on the basis of their MRI radiological appearance, including diffuse intrinsic low-grade gliomas, enhancing malignant gliomas, localized tectal gliomas, and other forms. The aim of our review is to provide insight into the role of advanced MRI sequences in the diagnosis and follow-up of adult brainstem gliomas.

The impact of labyrinthine magnetic resonance signal alterations on the treatment of sudden sensory-neural hearing loss.

BACKGROUND: Sudden sensory-neural hearing loss (SSNHL), with positive findings on magnetic resonance imaging (MRI), possibly related to labyrinthine hemorrhage, is a rare condition and difficult to be diagnosed. OBJECTIVES: We evaluated the role of MRI in detecting labyrinthine signal changes and the impact of these changes on the prognosis of SSNHL after the intratympanic corticosteroid injection. METHODS: A prospective study was held between January and June 2022. We included patients who complained of SSNHL, either idiopathic (30 patients) or labyrinthine signal alterations (14 patients), as diagnosed by MRI performed 15 days after the SSNHL onset. In addition, all patients underwent a course of intratympanic prednisolone injections. RESULTS: 83.3% of the idiopathic group showed a complete or marked improvement after the intratympanic injection. Conversely, most cases of positive MR signal alterations (92.8%) had slight or poor improvement after the therapeutic course. CONCLUSIONS: Our study revealed that MRI imaging is essential for assessing any SSNHL case. It can diagnose labyrinthine hemorrhage, whose course and prognosis differ significantly from idiopathic SSNHL. SIGNIFICANCE: Intratympanic prednisolone injection was effective in managing idiopathic SSNHL. On the other hand, this therapeutic modality was ineffective in improving SSNHL associated with labyrinthine hemorrhage.

Italian Guidelines for the Management of Prolactinomas.

INTRODUCTION: This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" have been considered in the systematic review of evidence and only those classified as "critical" have been considered in the formulation of recommendations. RESULTS: The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the firstchoice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide. CONCLUSION: The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.

Dural Tail Sign and Middle Meningeal Artery Hypertrophy in Glioblastoma: A Rarity?

BACKGROUND: Dural tail sign and increased caliber of branches of the external carotid artery (ECA) are common findings in meningioma and they have been rarely reported in intra-axial lesions. Anyway, some cases of glioblastoma (GBM) are reported in the literature, mostly superficially localized, characterized by these 2 findings and therefore, misdiagnosed with meningioma. The aim of this study is to verify the prevalence of dural tail sign and hypertrophy of middle meningeal artery (MMA) in a large cohort of GBMs. METHODS: 180 GBM patients were retrospectively evaluated. Deep or superficial localization of GBM was established and the presence of dural tail sign and hypertrophy of the ipsilateral MMA were assessed. The rate of tumor necrosis and the incidence of dural metastases during the radiological follow-up were also evaluated. Inter-rater reliability was calculated using Cohen's K-test. RESULTS: Dural tail sign and enlarged MMA were evident in 30% and 19% of 96 superficial GBM, respectively. Deep GBM did not present those signs. Only one patient developed dural metastasis at follow-up and no differences in terms of tumor necrosis and hypoxic biomarkers expression were evident among GBMs with and without dural and vessel signs. CONCLUSIONS: Dural tail sign and hypertrophy of the MMA in superficial GBM are more common than expected. They probably represent reactive rather than a neoplastic infiltration. Knowing these radiological signs may be important in terms of neurosurgery planning and avoiding excessive bleeding. Anyway, this hypothesis should be confirmed by a prospective neurosurgery studio.

The impact of fusion imaging technique on middle ear cholesteatoma surgery: a prospective comparative study.

BACKGROUND: The fusion of computed tomography images with non-echo planner diffusion-weighted magnetic resonance images may overcome the limitations of each individual modality. OBJECTIVES: This study aimed to assess the ability of the 'fusion' technique to predict the location of middle ear cholesteatoma by evaluating Its impact on preoperative surgical planning and postoperative results. METHODOLOGY: Eighty-three adults with cholesteatoma underwent preoperative CT scans and non-EPI-DW-MRI with or without the 'fusion' technique. We evaluated cholesteatoma localization in both groups, selecting the most appropriate surgical technique, and correlating it with the intraoperative findings. Both groups were compared in terms of residual/recurrent cholesteatoma at one, six and twelve months after surgery. RESULTS: The 'fusion' technique's sensitivity, specificity, and accuracy in predicting the location of cholesteatoma were 97.5. 97.4, and 97.5%, respectively, versus 97.59, 57.69, and 73.21% of CT alone. There was a total operators agreement after the evaluation of the 'fusion' images with the adopted surgical technique. A statistically significant decrease in residual and recurrence cholesteatoma rates was found in group A. CONCLUSIONS: The 'fusion' technique provides the surgeon with the precise cholesteatoma location, guiding him in making the correct surgical decision, contributing to the decrease in postoperative residual and recurrence rates.

Diffusion Weighted Imaging in Neuro-Oncology: Diagnosis, Post-Treatment Changes, and Advanced Sequences-An Updated Review.

DWI is an imaging technique commonly used for the assessment of acute ischemia, inflammatory disorders, and CNS neoplasia. It has several benefits since it is a quick, easily replicable sequence that is widely used on many standard scanners. In addition to its normal clinical purpose, DWI offers crucial functional and physiological information regarding brain neoplasia and the surrounding milieu. A narrative review of the literature was conducted based on the PubMed database with the purpose of investigating the potential role of DWI in the neuro-oncology field. A total of 179 articles were included in the study.

Epidural bleeding secondary to a synovial cyst rupture: a case report and review of literature.

Hemorrhage into a juxtafacet cyst is rare and cyst rupture with hemorrhagic extension into the epidural space is even less commonly seen. We describe the case of a patient with a hemorrhagic synovial cyst with rupture associated to abundant bleeding in the epidural space. A 61-year-old man had a 5-month history of worsening low back pain radiating into the right leg with associated weakness and numbness. A magnetic resonance imaging scan showed the presence of a mild anterior spondylolisthesis of L5 on S1 with increased synovial fluid into both facet joints. A suspected synovial cyst of the right facet joint at level L5-S1, with signal characteristics consistent with hemorrhage was seen. Caudally, epidural blood was evident from S1 to S2 that involved spinal canal and right S1 and S2 foramens. These findings were confirmed at surgery.

Feasibility of clinical target volume reduction for glioblastoma treated with standard chemoradiation based on patterns of failure analysis.

PURPOSE: To analyze recurrence patterns in patients with glioblastoma (GBM) after standard chemoradiation according to different target volume delineation strategies. METHODS AND MATERIALS: Two hundred seven patients with GBM who recurred after standard chemoradiation were evaluated. According to ESTRO target volume delineation guideline, the CTV was generated by adding a 2-cm margin to the GTV, defined as the resection cavity plus residual tumor. Patterns of failure were analyzed using dose-volume histogram. Recurrent lesions were defined as in-field, marginal, or distant if > 80 %, 20-80 %, or < 20 % of the intersecting volume was included in the 95 % isodose line.For each patient, a theoretical plan consisting of reduced 1-cm GTV-to-CTV margin was created to compare patterns of failure and radiation doses to normal brain. RESULTS: Median overall survival and progression-free survival times were 15.3 months and 7.8 months, respectively, from the date of surgery. Recurrences were in-field in 180, marginal in 5, and distant in 22 patients. According to MGMT promoter methylation, distant recurrences occurred in 18.6 % of methylated and 6 % of unmethylated tumors (p = 0.0046). Following replanning with 1-cm reduced margin, dosimetric analysis showed similar patterns of failure. Recurrences were in-field, marginal, and distant in 177, 3, and 27 plans, respectively, although radiation doses to the healthy brain and hippocampi were significantly lower compared with standard target delineation (p = 0.0001). CONCLUSION: Current provide the rationale for evaluating GTV-to-CTV margin reduction in future clinical trials with the aim of limiting the cognitive sequelae of GBM irradiation while maintaining survival benefits of standard chemoradiation.