Sensory hypo- and hypersensitivity in patients with brain tumors.

OBJECTIVES: Hyper- and hyposensitivity in multiple modalities have been well-documented in subjects with autistic spectrum disorder (ASD) but not in subjects with acquired brain injury (ABI). The purpose of this study was to determine whether subjects with ABI experience altered sensory processing in multiple sensory modalities, and to examine the relationships between impaired sensory processing and the emotional state. METHODS AND PROCEDURES: Sixty-eight patients with brain or spinal cord tumors participated in the study. Cognitive ability and emotional function were tested, and subjective changes were evaluated in two directions (hyper- and hyposensitivity) and five modalities (visual, auditory, tactile, olfactory, and gustatory) at two time points (after disease onset and after surgery). RESULTS: One-fifth of the participants complained of hypersensitivity in the visual domain, and a similar proportion complained of hyposensitivity in the auditory and tactile domains. Additionally, one-third of participants complained of two or more sensory abnormalities after disease onset. A hierarchical regression analysis indicated that auditory and tactile sensory changes predicted a depressive state. CONCLUSION: In conclusion, multimodal sensory changes occurred in patients with brain tumors, manifesting as hyper- or hyposensitivity. Sensory changes might be related to depressive state, but the results were inconclusive.

Genetic analysis in patients with newly diagnosed glioblastomas treated with interferon-beta plus temozolomide in comparison with temozolomide alone.

PURPOSE: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonß (IFNß) plus temozolomide (TMZ) with that of TMZ alone. EXPERIMENTAL: DESIGN: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations. RESULTS: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30-0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21-0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22-2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNß + Radiotherapy (RT) group were found. CONCLUSION: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNß addition were identified.

JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonß plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma.

PURPOSE: This study explored the superiority of temozolomide (TMZ) + interferonß (IFNß) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. EXPERIMENTAL DESIGN: Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m2, daily) followed by TMZ maintenance (100-200 mg/m2/day, days 1-5, every 4 weeks) for 2 years. Patients in the TMZ + IFNß + RT arm intravenously received IFNß (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8). RESULTS: Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNß + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65-1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85-1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNß + RT (grade 3-4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%. CONCLUSIONS: TMZ + IFNß + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.

Preservation of hearing following awake surgery via the retrosigmoid approach for vestibular schwannomas in eight consecutive patients.

BACKGROUND: Hearing preservation in patients with vestibular schwannomas remains difficult by microsurgery or radiosurgery. METHOD: In this study, awake surgery via the retrosigmoid approach was performed for vestibular schwannomas (volume, 11.6 ± 11.2 ml; range, 1.3-26.4 ml) in eight consecutive patients with preoperative quartering of pure tone audiometry (PTA) of 53 ± 27 dB. RESULTS: After surgery, hearing was preserved in seven patients and improved in one patient. The postoperative quartering PTA was 51 ± 21 dB. Serviceable hearing (class A + B + C) using the American Association of Otolaryngology-Head and Neck Surgery (AAO-HNS) classification was preserved in all patients. Preoperative useful hearing (AAO-HNS class A + B) was observed in three patients, and useful hearing was preserved in all three of these patients after surgery. In addition, useful facial nerve function (House-Blackmann Grade 1) was preserved in all patients. CONCLUSIONS: These results suggest that awake surgery for vestibular schwannomas is associated with low patient morbidity, including with respect to hearing and facial nerve function.

Prognostic factors and treatment effects in patients with curatively resected brain metastasis from colorectal cancer.

BACKGROUND: Colorectal cancer infrequently causes brain metastasis, and the prognosis is poor. OBJECTIVE: The aim of this study was to identify the prognostic factors associated with survival and outcome of treatment for patients with brain metastasis from colorectal cancer. DESIGN: This is a retrospective study from a prospectively collected database. SETTINGS: The investigation took place in a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS: From 1979 to 2010, 113 consecutive patients who were treated for brain metastasis from colorectal cancer were identified. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival. RESULTS: Sixty-three patients had neurosurgical resection (including curative resection for 46 patients) followed by whole brain radiotherapy, 9 had stereotactic radiosurgery, 30 had whole brain radiotherapy, and 11 had steroid and palliative care. As a whole, the overall median survival time from diagnosis of brain metastasis was 5.4 months (95% CI, 4.3-7.6 months), and the 1-year survival rate was 29% (95% CI, 22%-38%). In the group of patients who underwent curative neurosurgical resection, the overall median survival time was 15.2 months (95% CI, 9.2-17.8 months), and the 1-year survival rate was 57% (95% CI, 43%-71%). On multivariate analysis, 1 or 2 brain metastatic lesions, no extracranial metastatic lesions, and neurosurgical resection were independent favorable prognostic factors overall (p = 0.0057, 0.0197, and <0.0001), and 1 or 2 brain metastatic lesions, no extracranial metastatic lesion, and no emergence of secondary brain metastatic lesions were independent favorable prognostic factors in the group of patients who underwent curative neurosurgical resection (p = 0.0137, 0.0081, and 0.0010). LIMITATIONS: This study was limited by its single-institute, retrospective, nonrandomized design and selection bias. CONCLUSIONS: Neurosurgical resection in select patients is a reasonable option for brain metastasis from colorectal cancer, although it is not associated with long-term (5-year) survival. (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A121 ).

Damage to the left ventral, arcuate fasciculus and superior longitudinal fasciculus-related pathways induces deficits in object naming, phonological language function and writing, respectively.

The anatomic localization of brain functions can be characterized via diffusion tensor imaging in patients with brain tumors and neurological symptoms. The goal of the present study was to evaluate the function of the ventral, arcuate fasciculus (AF) and the superior longitudinal fasciculus (SLF)-related language pathways using these techniques by analyzing 9 patients treated in our hospital between 2007 and 2011. In cases 1-3, the left ventral pathways, namely, the inferior longitudinal fasciculus, uncinate fasciculus or inferior fronto-occipital fasciculus, were mainly damaged, and the common dysfunction experienced by these patients was a deficit in object naming. In cases 4-6, the left SLF was mainly damaged, and the common deficit was dysgraphia. In cases 7-9, the left AF was mainly damaged, and almost all language functions related to phonology were abnormal. These results suggest that the left ventral, AF and SLF-related pathways are closely related to visual, auditory and hand-related language function, respectively.

Phase II study of single-agent bevacizumab in Japanese patients with recurrent malignant glioma.

OBJECTIVE: This single-arm, open-label, Phase II study evaluated the efficacy and safety of single-agent bevacizumab, a monoclonal antibody against vascular endothelial growth factor, in Japanese patients with recurrent malignant glioma. METHODS: Patients with histologically confirmed, measurable glioblastoma or World Health Organization Grade III glioma, previously treated with temozolomide plus radiotherapy, received 10 mg/kg bevacizumab intravenous infusion every 2 weeks. The primary endpoint was 6-month progression-free survival in the patients with recurrent glioblastoma. RESULTS: Of the 31 patients enrolled, 29 (93.5%) had glioblastoma and 2 (6.5%) had Grade III glioma. Eleven (35.5%) patients were receiving corticosteroids at baseline; 17 (54.8%) and 14 (45.2%) patients had experienced one or two relapses, respectively. The 6-month progression-free survival rate in the 29 patients with recurrent glioblastoma was 33.9% (90% confidence interval, 19.2-48.5) and the median progression-free survival was 3.3 months. The 1-year survival rate was 34.5% with a median overall survival of 10.5 months. There were eight responders (all partial responses) giving an objective response rate of 27.6%. The disease control rate was 79.3%. Eight of the 11 patients taking corticosteroids at baseline reduced their dose or discontinued corticosteroids during the study. Bevacizumab was well-tolerated and Grade ≥3 adverse events of special interest to bevacizumab were as follows: hypertension [3 (9.7%) patients], congestive heart failure [1 (3.2%) patient] and venous thromboembolism [1 (3.2%) patient]. One asymptomatic Grade 1 cerebral hemorrhage was observed, which resolved without treatment. CONCLUSION: Single-agent bevacizumab provides clinical benefit for Japanese patients with recurrent glioblastoma.

Advantages and disadvantages of awake surgery for brain tumours in the primary motor cortex: institutional experience and review of literature.

Patients undergoing awake surgery for resection of brain tumours in the primary motor cortex (M1) are at high risk of developing new motor deficits. Thus, use of this procedure requires consideration of several important points, including the optimal modality to localise M1 on the affected side and the overall advantages and disadvantages of the procedure. In our experience with awake surgery for 21 brain tumours located in the M1 from January 2004 through October 2008, we found that functional magnetic resonance imaging was the most reliable modality in terms of localising the M1 and that the anatomic relationship between motor tracts and brain tumours is a critical determinant of postoperative motor function. Other considerations, including potential complications of this procedure and relative efficacy and safety versus surgery under general anaesthesia for patients with brain tumours in the M1, are discussed.

Utility of monitoring the serum levetiracetam concentration for intraoperative seizure control during awake craniotomy.

Awake craniotomy is an established procedure for resecting brain tumors in eloquent lesions, and intraoperative seizure is one of the most important complications. Phenytoin is normally used to control intraoperative seizures. Recently, phenytoin was replaced with levetiracetam at our institution because the latter has fewer side effects. While the phenytoin dose is calibrated in accordance with the serum concentration, there is currently no consensus on a method of monitoring the serum concentration of levetiracetam or the effective concentration range needed to control intraoperative seizures during awake craniotomy. The present study therefore aimed to determine whether monitoring the serum levetiracetam concentration is useful for controlling intraoperative seizures during awake craniotomy. The intraoperative serum concentration of levetiracetam during awake craniotomy was measured in 34 patients and compared with that of phenytoin in 33 patients undergoing the same procedure. The levetiracetam concentration inversely correlated with body surface area (BSA) and estimated glomerular filtration rate (eGFR). Levetiracetam was superior to phenytoin in terms of the correlation between the serum concentration and the dose adjusted for BSA and eGFR (correlation coefficient, 0.49 vs 0.21). Furthermore, the serum levetiracetam concentration in patients with intraoperative seizures was below the 95% confidence interval (CI) of the regression line whereas the serum phenytoin concentration of two patients with seizures was within the 95% CI, indicating that evaluating the serum levetiracetam concentration against the BSA and eGFR-adjusted dosage may be useful in preventing intraoperative seizures during awake craniotomy by allowing prediction of the seizure risk and enabling more accurate dosage calibration.

Genetic Characteristics of Mismatch Repair-deficient Glioblastoma.

Mismatch repair (MMR) gene deficiency is rarely observed in gliomas, a constitutional defect is associated with tumorigenesis in Lynch syndrome, and an acquired defect is associated with hypermutation after temozolomide treatment. However, the meaning of MMR gene deficiency in gliomas is unclear. Two cases of MMR-deficient glioblastomas are reported, and mutational status of oncogenes was compared between primary and recurrent tumor samples in a glioblastoma patient with Lynch syndrome. Additionally, the characteristics of MMR-deficient glioblastomas were analyzed using public glioma datasets to determine the meaning of MMR deficiency in gliomas. Case 1 was a glioblastoma patient with Lynch syndrome, and treatment with pembrolizumab for the recurrent tumor was temporarily effective for a short period. Comparison of mutational changes between primary and recurrent tumor samples showed many additional mutated genes associated with multiple signaling pathways in the recurrent tumor. Tumor recurrence and chemoresistance could be associated with intratumoral heterogeneity and accelerated tumor progression due to defects of multiple signaling pathways. Case 2 was a glioblastoma patient with acquired MMR gene deficiency, and she died of rapid progression of bone marrow metastases. This rare clinical course was considered to be associated with gene expression changes and heterogeneity that resulted from MMR gene deficiency. Two cases of MMR gene-deficient glioblastomas were presented, and their genetic characteristics suggested that their clinical courses could be associated with MMR gene deficiency.

Combined movement of multi-joint muscles activates a smaller area compared to the sum of areas activated by respective single-joint muscles after restoration of paresis.

Awake surgery provides accurate localization of brain function based on rapid reversible neurological changes during surgical manipulation. In this study, hand clenching rapidly deteriorated due to surgical manipulation during awake surgery and instantly recovered not by hand clenching alone but by combined movement of hand clenching and elbow flexion. Postoperative fMRI (functional MRI) showed a smaller area activated by combined movement of hand clenching and elbow flexion than the sum of areas activated by hand clenching alone and elbow flexion alone. Conversely, the activated area by combined movement of hand clenching and elbow flexion was almost the same as the sum of areas by hand clenching alone and elbow flexion alone in fMRI of normal volunteers. These findings indicate reorganization of the motor area by combined movement including the motor function of previous transient weakness, and might suggest the effectiveness of combined movement to improve motor paresis in rehabilitation.

Damage of left temporal lobe resulting in conversion of speech to Sutra, a Buddhist prayer stored in the right hemisphere.

The present study describes a case of a right-handed 74-year-old woman with a brain tumor who showed conversion of speech to Sutra, a Buddhist prayer, which was stored in the right hemisphere according to the Wada test. After surgery, relative improvement in the speech disorder was observed, and frequency of speech production of simple normal words with normal phonology increased. These observations indicate that damage to left temporal lobe resulted in conversion of speech to Sutra, and that Sutra was stored in this patient's right hemisphere.

Deficits in the left inferior longitudinal fasciculus results in impairments in object naming.

The functional characteristics of the left inferior longitudinal fasciculus (ILF) remain unclear. The present study describes a case of a right-handed 74-year-old woman with a brain tumor who showed marked deterioration in object naming ability after invasion of the tumor into the medial region of the left posterior (middle and inferior) temporal lobe just beside the atrium of the lateral ventricle. Diffusion tensor imaging showed possible interruption of the left ILF after invasion of tumor at this site. By contrast, the left superior longitudinal fasciculus (SLF) remained intact after invasion of tumor, and the inferior fronto-occipital fasciculus (IFOF) was already disrupted prior to tumor invasion. These observations indicate that intact ILF function may be required for object naming ability.

Damage to the upper portion of area 19 and the deep white matter in the left inferior parietal lobe, including the superior longitudinal fasciculus, results in alexia with agraphia.

Analysis of lesions and symptoms in patients with brain tumors combined with information from diffusion tensor imaging provides direct evidence of the anatomical localization of brain function. Using these methods, we evaluated 8 patients who underwent surgery for metastatic brain tumors located in the left occipital lobes between 2007 and 2009. Preoperatively, 4 patients (cases 1-4) had alexia with agraphia while the other 4 patients (cases 5-8) did not. Tractography for the superior longitudinal fasciculus (SLF) was performed before surgery in case 1. The common brain tumors in cases 1-4 were located in the upper portion of area 19, and peritumor edema in that area resulted in compromise of the deep white matter of the inferior parietal lobe (IPL). The SLF was compressed and disrupted in the white matter of the IPL near the upper portion of area 19 in case 1. In cases 5-8, the brain tumors were not located in the upper portion of area 19. These results suggest that damage to the upper portion of area 19 and to the white matter in the left IPL, including the SLF, resulted in alexia with agraphia.

Relationships between brain tumor and optic tract or calcarine fissure are involved in visual field deficits after surgery for brain tumor.

PURPOSE: Diffusion tensor tractography provides useful information regarding the surgical strategy for brain tumors. The goal of the present study was to analyze relationships between visual field deficits and the locations of brain tumors compared with optic tracts as visualized by tractography, and compared with the calcarine fissure. METHODS: Subjects comprised 11 patients with brain tumor in the occipital lobe or atrium of the lateral ventricle who underwent surgery between October 2006 and February 2009. Tumors were categorized as Type A, with almost all the optic tract in the occipital lobe or atrium of the lateral ventricle running close to and stretched by the brain tumor; and Type B, with the optic tract running at least partially distant to the brain tumor and remaining unstretched. RESULTS: Those type A optic tracts that were laterally compressed by brain tumors (Cases 1-3) displayed hemianopsia after surgery. When the brain tumor was located rostro-medial to the calcarine fissure and optic tracts were compressed caudally by the tumor, lower quadrant hemianopsia remained after surgery (Cases 4, 5). In other cases, the visual field remained or improved to normal after surgery. CONCLUSION: The relationship between optic tracts or the calcarine fissure, and brain tumors in the occipital lobe or atrium of the lateral ventricle is related to visual field deficits after surgery. In particular, those Type A optic tracts that are compressed laterally show hemianopsia of the visual field after surgery.

Dissociation of the subjective and objective bodies: Out-of-body experiences following the development of a posterior cingulate lesion.

An out-of-body experience (OBE) is a phenomenon whereby an individual views his/her body and the world from a location outside the physical body. Previous studies have suggested that the temporoparietal junction (TPJ), the brain region responsible for integrating multisensory signals, is responsible for OBE development. Here, however, we first present a case of OBE after brain tumour development in the posterior cingulate cortex (PCC). The patient was a 46-year-old right-handed female; she underwent brain surgery. She reported that she had experienced OBEs several times monthly (during daily life) before surgery but never after surgery. She defined her OBEs explicitly; she drew pictures. Her OBEs exhibited phenomenological, overt dissociation of the subjective and objective bodies. We discuss the mechanisms underlying this phenomenon and the relationship between OBEs and the PCC in terms of anatomical and functional brain connectivity. Our case sheds some light on the mechanism involved in creating spatial (dis)unity between the self and the body.

Bone marrow metastasis of glioblastoma multiforme mimicking acute myeloid leukemia.

A 46-year-old female patient with glioblastoma multiforme (GBM), IDH wild type developed severe pancytopenia 5 months after postoperative chemoradiotherapy. Bone marrow aspirate showed normocellular marrow with 70.0% abnormal cells, which suggested the possibility of acute myeloid leukemia. Immunophenotypic analysis did not show any hematological lineage markers, except for cluster of differentiation 56. The results of immunohistochemical staining of glial fibrillary acidic protein and oligodendrocyte transcription Factor 2 were positive. Based on these findings, the patient was diagnosed with bone marrow metastasis from GBM. Bone marrow metastasis from GBM is rare and little is known about the morphological characteristics of bone marrow aspiration smear findings. We experienced a rare case with marrow metastasis from GBM mimicking acute myeloid leukemia.

Awake surgery with continuous motor testing for resection of brain tumors in the primary motor area.

Resection of brain tumors in the primary motor area (M1) is difficult to achieve without adversely affecting motor function. Between November 2003 and November 2006, 16 patients with 18 brain tumors involving the M1 (11 metastatic, 6 gliomas, 1 cavernous angioma) underwent craniotomy and awake surgery with continuous motor testing at our hospital. Patients were classified as either type A (9 patients), indicating that motor tracts ran in close proximity to the brain tumors, or type B (7 patients), indicating that motor tracts ran distant to the tumor. The relationship between the extent of resection and post-operative motor function was subsequently evaluated. In 17 out of 18 cases, final post-operative motor function was either preserved or improved relative to pre-operative levels, although transient deterioration of motor function and partial removal of the tumor were observed in 7 and 8 cases, respectively. The remaining patients experienced slight deterioration in motor function of the upper extremities. All type A patients experienced suboptimal outcomes, involving transient or permanent deterioration of motor function after surgery or only partial removal of the tumor. By contrast, most type B patients experienced good outcomes (no deterioration of motor function and gross total removal of the tumor). In conclusion, awake surgery with continuous motor testing allowed for resection of brain tumors in the M1 and preservation of motor function, although the patients in whom motor tracts ran in close proximity to the tumors experienced suboptimal outcomes.

Corticospinal tract extraction combining diffusion tensor tractography with FMRI in patients with brain diseases.

PURPOSE: Our goal was to visualize diffusion tensor tractography (DTT) of the corticospinal tract (CST) with areas of activation on functional magnetic resonance imaging (fMRI) to acquire useful, highly accurate preoperative information. We investigated the usefulness of the technique and our method of precisely evaluating the depicted DTT in patients with brain disease. MATERIALS AND METHODS: Nineteen subjects underwent 3-dimensional T(1)-weighted imaging for anatomical reference; gradient-echo, echo-planar imaging (EPI) for fMRI; and single-shot, diffusion-weighted EPI for DTT. The target point for DTT was placed within activated areas in the primary motor area on fMRI, and the seed point was placed in the cerebral peduncle. DTT was depicted with the seed and target points. We examined the precision of DTT using this method by assessing the anteroposterior relationship of depicted DTTs of the upper and lower extremities in the posterior limb of the internal capsule. RESULTS: DTT was depicted in 18 of 19 cases of the upper extremity and in 12 of 19 cases of the lower extremity. In the evaluation of precision, DTT reflected the posterior limb of the internal capsule in all cases. In terms of the anteroposterior relationship of DTTs, nine of 12 cases showed that fibers in the upper extremities passed in front of fibers in the lower extremities. CONCLUSION: This technique allows depiction of DTT associated with a local brain function in the CST in patients with brain disease and may be useful for operative planning. Our method of evaluating precision is also likely to prove useful.

Continuous intrathecal injection therapy of methotrexate is a therapeutic option in primary CNS lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin's lymphoma, and its prognosis is still very poor despite the conventional therapy of high-dose methotrexate (HD-MTX) followed by whole-brain radiation therapy (WBRT). The purpose of the present study was to evaluate the survival benefit of continuous intrathecal injection therapy of methotrexate (CIT-MTX) combined with the conventional therapy. A total of 26 PCNSL patients treated with CIT-MTX were analyzed. Ten mg of methotrexate were continuously injected into the lateral ventricle via a subcutaneous port over 5 days biweekly for 5 cycles. CIT-MTX was performed with WBRT in addition to HD-MTX in 15 cases, and 11 cases with high risk for HD-MTX were treated with CIT-MTX and WBRT. The response rate of all patients was 92.3%, and median progression-free survival and median overall survival (mOS) were 59.4 months and 93.8 months, respectively. Median OS of patients treated with CIT-MTX in addition to HD-MTX and WBRT was longer than the previously reported mOS with HD-MTX and WBRT (95 vs 33 months). In cases that could not tolerate HD-MTX, mOS of patients treated with CIT-MTX and WBRT was longer than the previously reported mOS with WBRT alone (36.7 vs 18 months). There was no difference in OS between patients with cerebrospinal fluid dissemination and patients without (p = 0.83). Better prognosis in patients treated with CIT-MTX may be derived from stable concentration of methotrexate in the cerebrospinal fluid. CIT-MTX was an effective additional therapeutic option for PCNSL.