Frontal Tumor Research Articles

Extended endoscopic transplanum–transtuberculum approach for pituitary adenomas

Few pituitary adenomas require removal through a transcranial route. This may be associated with more significant morbidity and mortality, compared to the transsphenoidal approach. An endoscopic, extended, transplanum–transtuberculum approach (ETTA) in selected pituitary adenomas may offer an alternative to the transcranial route. We describe our technique and experience of ETTA in pituitary adenomas over 10 years. Between 2000 and 2010, we performed 700 endoscopic endonasal procedures for pituitary adenomas. Nineteen patients (13 men; mean age, 48 years; range, 22–76 years) underwent 22 ETTAs. Thirteen patients had non-functioning adenomas. Three tumor groups were identified: (1) tumors developing in or around the pituitary stalk; (2) tumours with sub- frontal extension and (3) tumours with a major extrasellar component. Mean follow-up was 37 months (range 6–72 months). Gross total resection was achieved in 11 procedures (no recurrences), with partial tumour resection in 11 procedures. Of the 12 patients with visual symptoms, ten improved. Of eight patients with hormonal hypersecretion four were cured. Complications included CSF leak (14%), haemorrhage (9%), hemiplegia (5%). There were no mortalities. Experience using the ETTA for pituitary adenomas is limited because it is indicated in highly selected cases (3.1% of our series). An absolute indication is represented by ectopic secreting pituitary stalk/peri-stalk adenomas. ETTA is a useful option in midline frontal adenomas and adenomas with a major extrasellar component, but has a higher morbidity than that seen in the standard transsphenoidal approach. A study comparing ETTA versus transcranial resection is highly desirable.

Teaching Neuro Images : Subacute intracerebral hemorrhage mimicking brain tumor

A 73-year-old man was referred to the outpatient clinic with a 2-week history of headache and apathy. Neurologic examination revealed mild left-sided facial, arm, and leg paresis. Head CT appeared to show a right frontal lobe tumor with finger-like vasogenic edema. Instead, MRI revealed a subacute lobar hemorrhage with perihematomal edema (figure). On follow-up imaging, no underlying cause was found.

Sarcomatous evolution of oligodendroglioma (“oligosarcoma”): Confirmatory report of an uncommon pattern of malignant progression in oligodendroglial tumors

By analogy to gliosarcoma, the neologism “oligosarcoma” is to describe an uncommon form of biphasic central nervous system tumor composed of contiguous neuroepithelial and mesenchymal elements, each of which individually meet the criteria of oligodendroglioma and sarcoma, respectively. By virtue of its distinctive genotype (codeletion 1p/19q), oligodendroglioma is a particularly inviting paradigm to test the assumption that such mixed tumors are clonally derived from a glial primary. We observed this constellation in a 41-year-old male who underwent two resection procedures for a recurring right frontal tumor at five years’ interval. On imaging, both lesions were contrast-enhancing, and measured 7cm×7cm×6.8cm and 7cm×6.5cm×4cm, respectively. Following the first operation, temozolomide monotherapy was administered. Whereas initial histology showed conventional anaplastic oligodendroglioma, the recurrence consisted mostly of a fibrosarcoma-like, fascicular neoplasm that was immunoreactive for vimentin, smooth muscle actin, S100 protein, and focally epithelial membrane antigen. In between, a subset of otherwise indistinguishable spindle cells expressed GFAP, and focally merged with residues of oligodendroglioma. Molecular testing for loss of heterozygosity confirmed codeletion of 1p/19q in both the primary tumor and the sarcomatous recurrence. Similarly, generalized immunoreactivity for the mutant R132H form of isocitrate dehydrogenase in both lesions indicated an identical mutation of the IDH1 gene. By the above standards, biologically consistent “oligosarcomas” are felt to be exceedingly rare, and possibly participate of a nosologically heterogeneous group of combined glial/mesenchymal lesions that may also include iatrogenically induced second malignancies as well as true collision tumors.

Subcortical surgical anatomy of the lateral frontal region: human white matter dissection and correlations with functional insights provided by intraoperative direct brain stimulation

Recent neuroimaging and surgical results support the crucial role of white matter in mediating motor and higher-level processing within the frontal lobe, while suggesting the limited compensatory capacity after damage to subcortical structures. Consequently, an accurate knowledge of the anatomofunctional organization of the pathways running within this region is mandatory for planning safe and effective surgical approaches to different diseases. The aim of this dissection study was to improve the neurosurgeon's awareness of the subcortical anatomofunctional architecture for a lateral approach to the frontal region, to optimize both resection and postoperative outcome. Ten human hemispheres (5 left, 5 right) were dissected according to the Klingler technique. Proceeding lateromedially, the main association and projection tracts as well as the deeper basal structures were identified. The authors describe the anatomy and the relationships among the exposed structures in both a systematic and topographical surgical perspective. Structural results were also correlated to the functional responses obtained during resections of infiltrative frontal tumors guided by direct cortico-subcortical electrostimulation with patients in the awake condition. The eloquent boundaries crucial for a safe frontal lobectomy or an extensive lesionectomy are as follows: 1) the motor cortex; 2) the pyramidal tract and premotor fibers in the posterior and posteromedial part of the surgical field; 3) the inferior frontooccipital fascicle and the superior longitudinal fascicle posterolaterally; and 4) underneath the inferior frontal gyrus, the head of the caudate nucleus, and the tip of the frontal horn of the lateral ventricle in the depth. Optimization of results following brain surgery, especially within the frontal lobe, requires a perfect knowledge of functional anatomy, not only at the cortical level but also with regard to subcortical white matter connectivity.

410O - Conditional Probability of Survival in Patients with Glioblastoma Multiforme in the Temozolomide Treatment Era

ABSTRACT Introduction Glioblastoma multiforme (GBM) is the most aggressive of gliomas. With standard treatment consisting of surgery followed by radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ), median survival is approximately 14.6 mo. These estimates are not as informative to patients (pts) who have survived for some time after diagnosis. Aim: To retrospectively review outcomes and report conditional probability estimates in the TMZ treatment era of pts who presented to a multidisciplinary team at the tertiary referral center PrincessMargaretHospital, Toronto, with a diagnosis of GBM. Methods 892 pts were followed from 01/04 – 08/10. Complete demographics, performance status (PS), GBM localization, extent of surgery, percent receiving RT +/- TMZ, overall survival (OS) and conditional probability were analyzed. Results The cohort includes 548 (61%) males with median age 62 (5-93). Baseline PS was 0-1 in 600 (67%), 2-3 in 251 (28%) pts. 205 (23%) had frontal lobe tumors. Extent of surgery; 26% biopsy, 68% partial/subtotal resection, 6% unknown. 516 (58%) received concurrent RT/TMZ +/- adjuvant TMZ. Survival was similar for those with frontal lobe tumors vs other locations (10.2 vs 9.7 mo, Logrank test p = 0.28). OS for biopsy pts was 4.5 mo (3.5 – 6.2), and partial/subtotal resection pts; 11.6 mo (10.3 – 12.5) (p Time Overall Survival (%) 95% CI Conditional Probability of Survival (%) 95% CI 1 Year 43.1 39.8 – 46.4 41.4 35.9 – 47.0 2 Year 17.9 15.2 – 20.7 57.4 47.5 – 67.4 3 Year 10.3 8.0 – 12.8 80.6 68.4 – 92.8 4 Year 8.3 6.1 – 10.9 85.6 71.1 – 100 5 Year 7.1 5.0 – 9.7 81.5 60.9 – 100 Conclusion The conditional probability of surviving an additional yr after survival to 2 yrs post diagnosis exceeds the 1 yr survival rate, indicating that the future prognosis of a pt who has survived for 2 yrs may be as good as those recently diagnosed. Conditional probabilities of survival in this general disease population in the era of TMZ therapy may provide more accurate life expectancy predictions for survivors of GBM. Disclosure All authors have declared no conflicts of interest.

Glioblastoma multiforme and pregnancy: case report

This is a case report of a 27-year-old female patient, G2P1, diagnosed at 20 weeks of gestation with a left frontal supratentorial tumor of a glioblastoma multiforme type, which manifested in the form of ictal absence. The patient was taken to surgery on week 28 and underwent a craniotomy under general anesthesia and fetal monitoring, with a successful outcome for both the mother and the fetus. We consider it important to report this case given this rare association.

Malignant pediatric brain tumor of primitive small round cell proliferation with bland-looking mesenchymal spindle cell elements

It is often difficult to classify rare malignant pediatric mixed brain tumors composed of mesenchymal elements. A 6-year-old boy presented to our hospital with a left frontal massive tumor manifesting as complaints of rapidly progressive right hemiparesis and motor aphasia over 2weeks. Computed tomography showed a left frontal mass with thick calcification. Magnetic resonance imaging revealed an enhanced lesion with perifocal edema and mass effect. Total removal of the tumor was performed. Histological examination of the resected tumor revealed an anaplastic malignant small round cell component with a bland-looking mesenchymal spindle cell component. The patient was treated with irradiation to the whole craniospinal axis and a boost to the tumor bed, followed by chemotherapy consisting of ifosfamide, cisplatin, and etoposide, resulting in good control without local recurrence or metastasis at 2years. A combined malignant tumor composed of ectodermal and mesenchymal components is generally named malignant ectomesenchymoma (MEM). The more malignant part of MEM is the mesenchymal component in most cases. In the present case, the more malignant component was not the mesenchymal component, but the small round cells.

Unexpected behaviour of the bispectral index (BIS) after brain injury

As Grocott pointed out in his editorial, processed electroencephalography (EEG) monitors such as the bispectral index (BIS) are increasingly being used [1]. In response to this editorial we present two cases with BIS values that contradict the equation ‘low BIS = less brain activity’, highlighting that certain patients’ characteristics may result in misleading BIS values, especially in the presence of low brain activity [2, 3]. The first case was a 60-year-old male, three months after frontal tumour resection, who presented for a ventricular peritoneal shunt. Pre-operatively he was cognitively impaired but clearly responsive. We did not prescribe any premedication. Because of miscommunication about the site of surgery, we applied the BIS to the left forehead, directly over a large fluid collection. The initial BIS reading before induction was 44. We then induced and maintained anaesthesia with propofol and fentanyl. As the patient lost consciousness the BIS readings did not decrease, but actually increased to above 60. Postoperatively and with the patient conscious, the BIS readings were again in the low 40s, confirming BIS’s completely inverse behaviour: according to the BIS, the patient was deeply unconscious while he was alert, and apparently susceptible to awareness while he was deeply unconscious. The second case was a 44-year-old male scheduled for a ventricular peritoneal shunt two months after traumatic brain injury and left frontal parietal craniectomy. He had been unresponsive since the day of the accident. Two BIS monitors were applied, one over each side of the forehead, showing similar, adequately high values before induction. After induction, both BIS values dropped, but interestingly, the BIS placed over the pathologic left side showed consistently higher values than the right side. According to the values obtained, the severely damaged brain tissue of the patient’s left side was less affected by anaesthesia than the right side. Or, in other words, only the intact right side was able to produce the EEG pattern identified by BIS as indicating adequate anaesthesia and lack of susceptibility to awareness. The exact BIS algorithm has not been published, and therefore explanations for this phenomenon remain speculative. Both patients suffered from extensive left frontal/parietal brain tissue loss, significantly reducing electrical output from neurons on one side of BIS placement. Therefore, the BIS could have relied more on electric signals from the face and eye muscles, which were unmasked on the pathologic side. Discrepancies of a lesser degree between simultaneously recorded BIS values on each side have been reported [4]. But further studies are needed in patients suffering from frontal lobe injuries to verify our observations of higher BIS values over damaged brain tissue and of inverse BIS values over damaged brain tissue after anaesthesia induction. Depth of anaesthesia remains a complex, and in some patients, probably an impossible assessment with our present monitors.

Picture-naming in patients with left frontal lobe tumor – a functional neuroimaging study

The objective of this study was to investigate behavioral performance as well as cortical activation patterns while picture-naming, in patients with left frontal lobe tumor prior to surgery. Functional magnetic resonance imaging was used to compare behavior and brain activations while 10 patients with a tumor in the left frontal lobe and 9 controls, named aloud simple pictures presented in a block design inside a 3T Philips Achieva scanner. Evaluations of task performance included naming accuracy and articulation time. Behaviorally, patients took significantly longer to articulate picture names but naming accuracy was preserved. Analysis of brain activations showed differences only in the frontal regions of the cortical network. In particular, while the frontal activations in the control population were focused and localized in the left inferior orbito-frontal gyrus, in patients the frontal network was distributed and included a significantly greater number of clusters that were distributed in homologous or near homologous areas of the (orbito-frontal gyrus) left and/or right hemisphere of the frontal lobe. Our results suggest that in patients with a left frontal lobe tumor the process of naming simple pictures is preserved but the cortical network of activation in the frontal region is altered and is distributed in the frontal regions of both hemispheres.

Extended Endoscopic Transplanum-Transtuberculum Approach for Pituitary Adenomas

Few pituitary adenomas require removal through a transcranial route. This may be associated with more significant morbidity and mortality, compared to the transsphenoidal approach. An endoscopic, extended, transplanum-transtuberculum approach (ETTA) in selected pituitary adenomas may offer an alternative to the transcranial route. We describe our technique and experience of ETTA in pituitary adenomas over 10 years. Between 2000 and 2010, we performed 700 endoscopic endonasal procedures for pituitary adenomas. Nineteen patients (13 men; mean age, 48 years; range, 22-76 years) underwent 22 ETTAs. Thirteen patients had non-functioning adenomas. Three tumor groups were identified: (1) tumors developing in or around the pituitary stalk; (2) tumours with sub- frontal extension and (3) tumours with a major extrasellar component. Mean follow-up was 37 months (range 6-72 months). Gross total resection was achieved in 11 procedures (no recurrences), with partial tumour resection in 11 procedures. Of the 12 patients with visual symptoms, ten improved. Of eight patients with hormonal hypersecretion four were cured. Complications included CSF leak (14%), haemorrhage (9%), hemiplegia (5%). There were no mortalities. Experience using the ETTA for pituitary adenomas is limited because it is indicated in highly selected cases (3.1% of our series). An absolute indication is represented by ectopic secreting pituitary stalk/peri-stalk adenomas. ETTA is a useful option in midline frontal adenomas and adenomas with a major extrasellar component, but has a higher morbidity than that seen in the standard transsphenoidal approach. A study comparing ETTA versus transcranial resection is highly desirable.

Anarchic hand syndrome following resection of a frontal lobe tumor

Anarchic hand syndrome (AHS) is a rare disorder characterized by unwilled, but seemingly purposeful movements of the affected upper limb which are perceived by the patients not to be under their control. It often interferes with goal-directed movements and bimanual tasks. At present there is no effective method of treatment of AHS. We report here a case of AHS following resection of a frontal lobe tumor and describe its effects on the patient's functional activities. The patient used avoidance behavior and mental concentration to overcome the disabling effect of AHS. These strategies appear to be useful in the management of AHS.

An unusual case of myopic shift post acquired brain injury

Background Ocular and visual problems are frequent consequences of an acquired brain injury (ABI). The literature suggests that many patients demonstrate a myopic shift in refractive error after a traumatic brain injury (TBI), a form of an ABI. Three reported courses are suggested. Most commonly the myopia resolves under cycloplegic conditions, secondly the shift is transient, and least commonly the myopia increases over time. This case report, although not due to a TBI, is an example of the least common subgroup.
 Case Report The patient, a 63 year-old male, presented with a history (15 months prior to initial evaluation) of an excised right frontal temporal lobe tumour. The history included dexamethasone 4mg QD pre- and post-surgery which caused blood glucose levels to fluctuate between 5.72-22.2 mmol/l; a stroke occured postsurgery causing hemiparesis on his left side; and shunt surgery to decrease swelling to the area of excision and the optic nerves. Medications included: Cartia, lisinopril, Toprol XL, prednisone, Reglan, and Temodar. The patient was receiving chemotherapy to treat remnants of the tumour. His last eye exam in 2004 indicated a refractive error of -2.50-1.25X080 in his right eye and -3.000.75X080 in his left eye with visual acuity of 6/7.5 in both the right and left eye. He presented to our clinic with an aided visual acuity of 8/100 (6/110) in both the right and left eye and a left homonymous hemianopsia on finger counting fields. Cycloplegic retinoscopy revealed -6.003.00X090 in his right eye and -6.002.00X090 in his left eye. Dilated fundus exam showed mild swelling of both optic nerves. The patient reported blood glucose levels of 103-140. At a one-month follow-up, his best corrected visual acuity at a distance improved to 6/60 in both the right and left eye through the new prescription. His cycloplegic retinoscopy did not show any change in myopia or astigmatism and the disk edema was resolved. 
 Conclusion This case illustrates an unusual presentation of myopic shift post ABI. The patient’s condition continued to deteriorate eventually taking his life. It remains unclear whether the myopia and astigmatism continued to increase or remained stable. Although, the cause of this change is not fully understood and needs further investigation, providing appropriate optical correction did improve the patient’s quality-of-life.

The Supraorbital Approach for Removal of Intra-Axial Frontal Brain Tumors: A Technical Note

The Supraorbital Approach for Removal of Intra-Axial Frontal Brain Tumors: A Technical Note

Intracranial dural metastasis from uterine leiomyosarcoma with orbital extension

Intracranial metastases from uterine leiomyosarcoma are very rare and have been found mainly in the brain (17 cases); on the other hand, metastases to the skull, dura and orbit are really exceptional. The authors report the case of a 57-year-old woman who presented with a 6-week history of right proptosis, left hemiparesis, intracranial hypertension and torpor 8 months after surgery for uterine leiomyosarcoma. CT scan showed a very large right frontal tumor with both intracranial and intraorbital extension. At operation the tumor was found to arise from the dura of the right anterior cranial fossa; complete removal of the intracranial tumor mass and partial removal of the intraorbital component were performed. However, early tumor regrowth was observed 45 days after operation and death occurred 2 months later. Pathologic examination showed a high-grade sarcoma with smooth muscle differentiation and high mitotic activity. Immunohistochemical staining revealed positivity for actin and vimentin and negativity for S-100 protein, cytocheratin and desmin. This is the first reported case of uterine leiomyosarcoma metastatic to the dura of the anterior cranial fossa with intracranial and intraorbital extension. An aggressive surgical resection is the best treatment of intracranial metastatic leiomyosarcoma, because of the scarce response to radiotherapy and chemotherapy. However, the outcome is poor, with early recurrence.

IDH1/2 mutations in WHO grade II astrocytomas associated with localization and seizure as the initial symptom

IntroductionSeizures are the most common initial symptom in patients with low-grade glioma and their occurrence strongly depends on the tumor location. The majority of low-grade gliomas reveal mutations in the genes encoding isocitrate-dehydrogenase 1 (IDH1) or 2 (IDH2). These mutations are associated with metabolic changes that are potentially epileptogenic. We investigated the correlation between IDH1/2 mutations and tumor localization and seizure as the initial symptom. Materials and methodsThis retrospective study included patients with a diagnosis of WHO grade II astrocytoma and cortical infiltration and in whom initial symptoms were documented and biopsy tissue was available for IDH1/2 analysis. IDH1/2 mutation analysis was performed by direct sequencing or by immunohistochemistry with an antibody which detects mutated protein IDH1 R132H. Sequencing was carried out if immunohistochemistry was negative. IDH1/2 status was defined as mutated if either of these investigations were positive. ResultsSeventy-nine patients were included. IDH1 or IDH2 mutation was present in 63 (80%) patients who on average were younger than patients without IDH1/2 mutation (40 vs. 47 years, p=0.0331, t-test). IDH1/2 mutations were associated with frontal tumor location (p=0.0202). All 12 tumors in the insula revealed IDH1/2 mutations. Seizure as the initial symptom was recorded in 57 (72%) patients and was associated with IDH1 or IDH2 mutation by multivariate analysis (OR 22.563, p=0.0019). ConclusionIn WHO grade II astrocytomas, IDH1/2 mutations mostly occur in tumors infiltrating the frontal lobe. Seizure as the initial symptom is associated with IDH1 or IDH2 mutation.

A Case of Extra-abdominal Desmoid Neck Tumor

Desmoid tumor, a benign fibrous tumor of the connective tissue of the skeletal muscles, fascia, and tendon membranes, tends to recur locally despite being pathologically benign tumor so-called “clinically malignant”. We report a case of frontal neck desmoid tumor. A 37-year-old man reporting frontal cervical pain was seen based on a cervical tumor diagnosis. Cervical ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography showed a clear round, relatively benign tumor necessitating resection based on a preoperative diagnosis of cervical schwannoma. The tumor consisted histologically of uniform, spindle cells and collagen growth with no noticeable division. Cellular atypia was scarce. Cells and collagen fibers immunostained negative for S-100 and CD34 and positive for α-SMA, β-catenin staining, confirmed extra-abdominal desmoid tumor. Postoperative treatment was not done due to complete tumor resection without apparent recurrence.

Radiation-Induced World Health Organization Grade II Meningiomas in Young Patients Following Prophylactic Cranial Irradiation for Acute Lymphoblastic Leukemia in Childhood

Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation. We treated 3 young patients with World Health Organization grade II meningiomas who had previously received cranial irradiation for the treatment of childhood ALL: a cerebellopontine angle tumor in a 19-year-old woman, a petroclival tumor in a 28-year-old man, and a frontal parasagittal tumor in a 19-year-old woman. These cases were difficult to treat due to the aggressive and invasive biology of the tumors. Therefore, we recommend systematic cranial imaging and long follow-up periods for leukemia survivors to detect brain tumors before progression.

P-1492 - Late onset obsessive compulsive disorder after resection of a right frontal meningioma

Introduction Obsessive-comxulsive disorder (OCD) is relatively common and frequentlydisabling psychiatrix disoxder. Xxx onset of OCD is usually in adxlesence and earlyadulthood.Expxcially in cases with onset after age 40, the possibility of an underlyingmxdical causeshould be investigated (1). Case report We report a casx whx developed late onset obsessive-compulsxve disorderaxtex resection of a frontal meningioma. Discussion Some studies have investigated the devolopment of symptoms of OCD afterbrain injury.The majority of structural and functional imaging studies have demostrateddifferences in the frontal cortex- xspecially prefrontal coxxex- between patients with OCD andhealthy subjecxs (2); however in literature there are limited case reports which wereinvestigating the association between frontal brain tumors and OCD. In our case, patient hadno psychiatric history and interestingly the onset of OCD was after neurosuxgical treatmentand patient had not any cognitive disorder accompanxing to OCD. Conclusion We argue that our case is important for demonstrating the direct associationbetween frxntal lobe and OCD and also it might have an xmporxance to give a viewpoint forxeuxosurgeons to screen patients for OCD after frontal brain surgery and for psychiatrixts toscreen caxefullx organic causes in patients xith late onset OCD. Download : Download full-size image [mri]

Deformable Anatomic Templates Embed Knowledge Into Brain Images

This study evaluated the concordance between the Deformable Anatomic Template (DAT)-identified origin of motor hand fibers and localization of the motor cortex of the hand by functional magnetic resonance imaging (fMRI). Preoperative fMRI during hand motor tasks was performed on 36 hemispheres in 26 patients with gliomas in or near eloquent areas. Reformatted volume-rendered surface images were labeled with the DAT's hand motor fibers and fMRI data. Five reviewers assessed the data for concordance. Available fMRI data were diagnostically usable in 92% (33/36 analyzed hemispheres), with DAT anatomic accuracy in the remaining cases. The DAT prediction and fMRI findings were concordant in all 9 normal hemispheres and in 20 (83%) of 24 glioma-bearing hemispheres. The 4 discordant cases resulted from substantial mass effect by large frontal tumors. This study validated DAT's anatomic atlas and alignment process for the expected position of the motor cortex of the hand.

Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study may help to stratify patients at risk for late effects to develop strategies to reduce frequency and severity of radiation sequelae.