Unique image findings around "kissing" distal anterior cerebral artery aneurysms in addition to perianeurysmal edema: A case report.

Background: Some aneurysms cause edema formation in the surrounding brain parenchyma and are thought to reflect various phenomena occurring in the aneurysm. Some authors highlighted perianeurysmal edema (PAE) as a finding that indicates higher risk of rupture of the aneurysm. On the other hand, there are no reports of image changes in the surrounding brain parenchyma of aneurysm other than edema formation. Case Description: We describe a 63-year-old man with unique signal change in the surrounding brain parenchyma of "kissing" distal anterior cerebral artery aneurysms completely different from PAE. The large and partially thrombosed aneurysm presented well-defined signal change surrounding brain parenchyma in addition to PAE. Intraoperative findings revealed the signal change as a space of retaining serous fluid. Drain the fluid and clipping was made for the both anterior cerebral artery aneurysms. The postoperative course was uneventful and his headache was improved the day after the surgery. The perianeurysmal signal change was also disappeared immediately after the surgery except for the PAE. Conclusion: This case demonstrates a rare phenomenon of signal change around the aneurysm, and there is a possibility that the unique finding exists as an early manifestation of intracerebral hematoma associated with aneurysm rupture.

Acute neurological deterioration after surgical interruption of spinal dural arteriovenous fistulas: clinical characteristics, possible predictors, and treatment. Patient series.

BACKGROUND: Acute neurological deterioration develops paradoxically in some patients after obliteration of a spinal dural arteriovenous fistula (SDAVF), with thrombosis of the spinal cord veins as its primary cause. The authors aimed to clarify the clinical and radiological characteristics of acute deterioration to identify high-risk patients. They also discussed the optimal treatment for this complication. OBSERVATIONS: Ten patients with SDAVF presenting with congestive myelopathy who received microsurgical interruption were retrospectively reviewed. Severe myelopathy developed in three patients on postoperative days 1 to 3. Anticoagulation therapy was effective; however, discontinuing anticoagulants under residual spinal cord congestion caused redeterioration. These patients were characterized by significantly extended transit time on angiography and significant prolongation of spinal cord congestion. Acute deterioration exhibited a strong correlation with transit time (coefficient, 0.825; p = 0.006) and a strong correlation with spinal cord edema before surgery (coefficient, 0.656; p = 0.040). LESSONS: Acute deterioration after SDAVF treatment is likely to develop in patients with severe venous outflow impairment. Its pathology is prolonged spinal cord congestion caused by postoperative venous thrombosis and preexistent severe venous outflow impairment. Anticoagulation treatment should be continued for patients with acute deterioration until the resolution of spinal cord congestion is confirmed with magnetic resonance imaging.

Long-term survivors of primary central nervous system lymphoma.

Objective: In this study, we provide long-term outcome data of patients with primary central nervous system lymphoma. Methods: The long-term outcomes of PCNSL patients diagnosed between 1982 and 2006 were reviewed. Neurological late neurotoxicity symptoms, neuroradiological brain atrophy and leukoencephalopathy were evaluated. Surviving patients completed the Quality of Life Questionnaire-30 and Brain Cancer Module-20. The differences in overall survival were assessed using the Kaplan-Meier method and log-rank test. The differences between groups in terms of each investigated parameter were analyzed using the Wilcoxon signed-rank test. Results: Among 112 PCNSL patients, there were 33 (29.4%) long-term (> 5 years) survivors. The median survival of all long-term survivors was 105.7 months; of these, 8 (7.1%) were alive at the latest follow-up, with a mean survival time of 170.2 months (range, 121.8­286.4). Clinical assessment revealed severe neurotoxicity in 14 patients (42.4%), moderate neurotoxicity in 5 (15.1%), and normal status in 14 (42.4%). Correlations were seen between the neuroradiological imaging score changes and neurocognitive condition (P=0.0001), neurocognitive condition and the whole brain irradiation dose (P=0.0004), and atrophy and the whole brain irradiation dose (P=0.0035). Conclusions: A more severe clinical condition was found to be associated with increasing age and whole brain irradiation dose in long-term survivors with PCNSL.

Drainage patterns of the superficial middle cerebral vein: Effects on perioperative managements of petroclival meningioma.

BACKGROUND: Although the superficial middle cerebral vein (SMCV) usually connects with the cavernous sinus, there are several anatomical variations. We determined whether differences in SMCV drainages patterns affected the perioperative management of petroclival meningioma. METHODS: The subjects included 17 patients (4 men; 13 women) who underwent resection of a petroclival meningioma. SMCV drainage patterns were classified into four groups according to angiographic findings: (1) The SMCV connected with the cavernous sinus (Group A); (2) The SMCV was either absent or connected directly with the superior sagittal or transverse sinus through the cortical veins (Group B); (3) The SMCV turned downward and connected with the pterygoid plexus through the sphenobasal vein (SpBV, Group C); and (4) The SMCV ran across the bottom of the middle fossa and connected with transverse sinus via the sphenopetrosal sinus (SpPS, Group D). RESULTS: In all 9 patients in Group A, the SMCV drainage pattern did not affect any aspect of perioperative management. In contrast, SMCV drainage patterns in 3 of 4 patients in Group B and both patients in Groups C and D had an effect on perioperative management, indicating a significant impact of variations in SMCV drainage patterns (P < 0.005). In 2 patients in Group C and 1 in Group D, the operating corridor provided by a transpetrosal approach was small in order to preserve the SpBV or SpPS. In the other patient in Group D, an anterior transpetrosal approach was not selected preoperatively because the SpPS would likely be injured during surgery. CONCLUSIONS: In cases, where the SMCV directly connects with superior sagittal or transverse sinus, SpBV or SpPS, surgeons have to meticulously select a safe and effective approach and take measures to preserve the SpBV or SpPS during surgery.

[Long-term Results Regarding the Instability of Decompressive Surgery without Fusion for Degenerative Spondylolisthesis].

PURPOSE: The long-term results of decompressive surgery for degenerative spondylolisthesis (DS) were evaluated with reference to instability. MATERIALS AND METHODS: Patients (n=48) undergoing decompressive surgery without fusion were studied. The diagnosis of spondylolisthesis was made based on the presence of sagittal vertebral slippage greater than 3mm. Instability was defined as translation more than 2mm on lateral functional radiography. Surgical interventions were divided into two groups: bilateral laminotomy (n=25)and laminectomy (n=23). Clinical results were evaluated according to the McCulloch's classification and Japanese Orthopedic Association(JOA)score. RESULTS: Of 48 patients, 25 showed preoperative instability. Eleven patients showed both pre-and postoperative instability. The mean pre-and postoperative slippages were 7.5 and 7.6mm, respectively. Of 23 patients without preoperative instability, nine developed postoperative instability. In this group, slippage changed from 6.2 to 6.1mm. Instability was not related to slippage progression. Surgical results of patients undergoing laminotomy were superior to those undergoing laminectomy. The mean pre-and postoperative JOA scores and recovery rate were 14.5, 20.9, and 63.1 in instability group patients with laminotomy and 15.6, 23.2, and 59.0 in the non-instability group, respectively. Surgical results were similar and not related to preoperative instability. Low back pain (LBP) showed no correlation to the degree of slippage, instability, and surgery type. LBP improved in each group. CONCLUSIONS: Instability, defined by vertebral translation on lateral functional radiography, did not affect the surgical results of patients with DS treated with laminotomy.

Pharyngeal Motor Evoked Potential Monitoring During Skull Base Surgery Predicts Postoperative Recovery from Swallowing Dysfunction.

OBJECTIVE: Monitoring pharyngeal motor evoked potential (PhMEP) with a modified endotracheal tube is useful for predicting postoperative swallowing dysfunction. However, the relationship between intraoperative PhMEP findings and recovery from postoperative swallowing dysfunction has not been clarified. The aim of this study was to determine whether PhMEP monitoring predicts swallowing dysfunction not only immediately after surgery but also in the postoperative recovery period. METHODS: We analyzed PhMEPs in 36 patients during treatment for skull base tumors. Recovery from postoperative swallowing dysfunction was evaluated when oral intake was started postsurgery and drip or tube feeding was discontinued. The correlation between the final to baseline PhMEP ratio and postoperative recovery times from swallowing dysfunction was examined. RESULTS: The PhMEP ratio significantly correlated with postoperative swallowing function immediately after surgery (P < 0.001). The period before starting oral intake in patients with a PhMEP ratio >50% (mean ± standard deviation [SD], 3.8 ± 4.3 days) was shorter than those with a PhMEP ratio ≤50% (mean ± SD, 14.7 ± 11.8 days; P < 0.01). Drip or tube feeding was removed from patients with a PhMEP ratio >50% significantly earlier (mean ± SD, 13.7 ± 19.2 days) than those with a PhMEP ratio ≤50% (mean ± SD, 38.3 ± 27.3 days; P < 0.05). Both univariate and multivariate analysis showed that only the PhMEP ratio was predictive of early recovery from swallowing dysfunction. CONCLUSIONS: PhMEP monitoring allowed us to predict not only immediate swallowing dysfunction but also recovery from the dysfunction in the postsurgery period.

[Long-term results of decompressive surgery without fusion for degenerative spondylolisthesis].

PURPOSE: The long-term results of decompressive surgery for degenerative spondylolisthesis with symptomatic lumbar spinal stenosis were evaluated retrospectively with regard to the postoperative progression of slippage and clinical symptoms. MATERIALS AND METHODS: The study included 53 patients who underwent surgery, and for whom follow-up of at least 5 years was conducted. Spondylolisthesis was diagnosed based on the presence of sagittal vertebral translation greater than 3mm on lateral radiographs. The patients were divided into two groups:Group I:37 patients undergoing bilateral laminotomy, and Group II:16 patients undergoing laminectomy. The clinical results were evaluated according to McCulloch's classification and the Japanese Orthopaedic Association(JOA)score. RESULTS: The mean pre-and postoperative JOA scores were 14.6 and 22.9 in Group I and 14.7 and 21.0 in Group II, respectively. The JOA scores improved soon after surgery, after which the scores declined gradually in both groups. The recovery rate was 63.0% in Group I and 43.7% in Group II. The average amount of pre- and postoperative slippage was 7.3mm and 6.9mm in Group I and 6.2mm and 6.9mm in Group II, respectively. In Group I, the slippage progressed within the first year, after which the degree of slippage slowly decreased to lower values than those observed preoperatively, whereas slippage progressed for 5 years before declining in Group II. No correlations were observed between progression of slippage and clinical outcomes in either group. CONCLUSIONS: Laminotomy produces satisfactory long-term results both clinically and radiographically in patients with degenerative spondylolisthesis.

Clinical factors predicting outcomes after surgical resection for sporadic cerebellar hemangioblastomas.

OBJECTIVE: To determine whether various clinical factors are related to long-term outcomes of patients with sporadic cerebellar hemangioblastomas. METHODS: Subjects included 36 patients (19 men and 17 women) who underwent resection of sporadic hemangioblastoma in the cerebellum. Age at surgery ranged from 17-79 years (mean, 49.7 years). The tumor size, which was defined as the largest diameter of the lesion including the extratumoral cyst, ranged from 10-67 mm (mean, 36.4 mm). Obstructive hydrocephalus secondary to mass effect on the fourth ventricle was present in 21 (58.3%) patients preoperatively. RESULTS: Total tumor removal was achieved in 31 of 36 patients (86%). In 4 (11%) patients with solid tumors, postoperative hematoma occurred in the removal cavity, and hematoma removal was required immediately after surgery. We followed 30 patients for >12 months after the initial surgery (mean, 72.9 months; range, 12-274 months). Recurrence of hemangioblastoma developed in 4 of 30 patients (13%) at 6 months, 17 months, 6 years, and 22 years after surgery. At the final follow-up examination, 9 (30%) of 30 patients showed some residual neurologic symptoms (poor group), whereas the remaining 21 patients showed no deficits (good group). Using univariate analysis, both age at surgery and tumor characteristics (cystic or solid) were significantly related to long-term patient outcomes (P < 0.05). However, in a multiple logistic regression analysis, only tumor characteristics were correlated with outcomes (P = 0.017). At the final follow-up examination, patients with solid tumors more frequently showed poor outcomes than patients with cystic tumors. CONCLUSIONS: The solid configuration observed on preoperative images of sporadic cerebellar hemangioblastomas is one of the most important clinical factors related to both immediate and long-term outcomes after surgery.

Novel devices for intraoperative monitoring of glossopharyngeal and vagus nerves during skull base surgery.

BACKGROUND: Swallowing disturbance is among the most burdensome complications suffered by patients with glossopharyngeal and vagus nerve involvement in lesions adjacent the jugular foramen. For monitoring these nerves, we have developed new devices that comprised four contacts adhering to the surface of the cuff of an endotracheal tube, with attachment the posterior pharyngeal wall. To determine whether these devices are useful for monitoring the glossopharyngeal and vagus nerves and predicting postoperative swallowing dysfunction in patients undergoing removal of skull base tumors involving these nerves. METHODS: We studied 10 patients. Compound muscle action potentials (CMAPs) were recorded from the posterior pharyngeal wall by stimulating the glossopharyngeal or vagus nerve in order to identify the nerve course, especially in patients showing severe nerve distortion due to the tumor. Pharyngeal motor evoked potential (PhMEP) elicited by transcranial electrical stimulation were recorded in all patients. The correlation between the final to baseline PhMEP ratio and postoperative swallowing function was examined. RESULTS: Responses were obtained in six of the seven patients in whom CMAP monitoring was performed. Deterioration of swallowing function postoperatively was demonstrated in six of seven (86%) patients with intraoperative PhMEP ratios <50%. None of the three patients with intraoperative PhMEP ratios >50% showed deterioration of swallowing function after surgery, although the one patient already had severe swallowing dysfunction requiring preoperative tracheostomy. CONCLUSIONS: Our novel devices were useful for monitoring the glossopharyngeal and vagus nerves in patients undergoing removal of skull base tumors involving these nerves.

Gene expression signature-based prognostic risk score in patients with glioblastoma.

The present study aimed to identify genes associated with patient survival to improve our understanding of the underlying biology of gliomas. We investigated whether the expression of genes selected using random survival forests models could be used to define glioma subgroups more objectively than standard pathology. The RNA from 32 non-treated grade 4 gliomas were analyzed using the GeneChip Human Genome U133 Plus 2.0 Expression array (which contains approximately 47 000 genes). Twenty-five genes whose expressions were strongly and consistently related to patient survival were identified. The prognosis prediction score of these genes was most significant among several variables and survival analyses. The prognosis prediction score of three genes and age classifiers also revealed a strong prognostic value among grade 4 gliomas. These results were validated in an independent samples set (n = 488). Our method was effective for objectively classifying grade 4 gliomas and was a more accurate prognosis predictor than histological grading.

Interactive presurgical simulation applying advanced 3D imaging and modeling techniques for skull base and deep tumors.

OBJECT: In this paper, the authors' goal was to report their novel presurgical simulation method applying interactive virtual simulation (IVS) using 3D computer graphics (CG) data and microscopic observation of color-printed plaster models based on these CG data in surgery for skull base and deep tumors. METHODS: For 25 operations in 23 patients with skull base or deep intracranial tumors (meningiomas, schwannomas, epidermoid tumors, chordomas, and others), the authors carried out presurgical simulation based on 3D CG data created by image analysis for radiological data. Interactive virtual simulation was performed by modifying the 3D CG data to imitate various surgical procedures, such as bone drilling, brain retraction, and tumor removal, with manipulation of a haptic device. The authors also produced color-printed plaster models of modified 3D CG data by a selective laser sintering method and observed them under the operative microscope. RESULTS: In all patients, IVS provided detailed and realistic surgical perspectives of sufficient quality, thereby allowing surgeons to determine an appropriate and feasible surgical approach. Surgeons agreed that in 44% of the 25 operations IVS showed high utility (as indicated by a rating of "prominent") in comprehending 3D microsurgical anatomies for which reconstruction using only 2D images was complicated. Microscopic observation of color-printed plaster models in 12 patients provided further utility in confirming realistic surgical anatomies. CONCLUSIONS: The authors' presurgical simulation method applying advanced 3D imaging and modeling techniques provided a realistic environment for practicing microsurgical procedures virtually and enabled the authors to ascertain complex microsurgical anatomy, to determine the optimal surgical strategies, and also to efficiently educate neurosurgical trainees, especially during surgery for skull base and deep tumors.

Gene expression signature-based prognostic risk score in patients with primary central nervous system lymphoma.

PURPOSE: Better understanding of the underlying biology of primary central nervous system lymphomas (PCNSL) is critical for the development of early detection strategies, molecular markers, and new therapeutics. This study aimed to define genes associated with survival of patients with PCNSL. EXPERIMENTAL DESIGN: Expression profiling was conducted on 32 PCNSLs. A gene classifier was developed using the random survival forests model. On the basis of this, prognosis prediction score (PPS) using immunohistochemical analysis is also developed and validated in another data set with 43 PCNSLs. RESULTS: We identified 23 genes in which expressions were strongly and consistently related to patient survival. A PPS was developed for overall survival (OS) using a univariate Cox model. Survival analyses using the selected 23-gene classifiers revealed a prognostic value for high-dose methotrexate (HD-MTX) and HD-MTX-containing polychemotherapy regimen-treated patients. Patients predicted to have good outcomes by the PPS showed significantly longer survival than those with poor predicted outcomes (P < 0.0001). PPS using immunohistochemical analysis is also significant in test (P = 0.0004) and validation data set (P = 0.0281). The gene-based predictor was an independent prognostic factor in a multivariate model that included clinical risk stratification (P < 0.0001). Among the genes, BRCA1 protein expressions were most strongly associated with patient survival. CONCLUSION: We have identified gene expression signatures that can accurately predict survival in patients with PCNSL. These predictive genes should be useful as molecular biomarkers and they could provide novel targets for therapeutic interventions.

Deterioration after surgical treatment of spinal dural arteriovenous fistula associated with spinal perimedullary fistula.

Spinal dural arteriovenous fistulas (SDAVFs) are the most common type of vascular malformations of the spine and are defined as abnormal arteriovenous shunts within the dura. SDAVFs are considered to be acquired and should be distinguished from congenital intradural perimedullary arteriovenous fistulas (PMAVFs). A 32-year-old female presented with both SDAVF and PMAVF, manifesting as a slowly progressive paraparesis over a 6-month period. Initial spinal angiography demonstrated an SDAVF in the sacral region and was terminated with incomplete demonstration of all segmental arteries. The fistula was obliterated by surgery and the patient showed transient postoperative improvement followed by delayed deterioration 2 months later. Magnetic resonance (MR) imaging showed many hypointense flow voids around the cord. The second angiography verified a PMAVF in the lumbar region and complete obliteration of the SDAVF. The fistula was closed by surgery and the patient improved slightly. Surgical results of SDAVFs are generally good. Therefore, if a patient fails to improve or deteriorates further after surgery with persistent perimedullary vessel abnormalities on MR imaging, the possibility of reopening of the fistula or the presence of another fistula should be considered and repeat angiography must be performed, especially if the initial angiography was incomplete.

Interactive virtual simulation using a 3D computer graphics model for microvascular decompression surgery.

OBJECT: The purpose of this paper is to report on the authors' advanced presurgical interactive virtual simulation technique using a 3D computer graphics model for microvascular decompression (MVD) surgery. METHODS: The authors performed interactive virtual simulation prior to surgery in 26 patients with trigeminal neuralgia or hemifacial spasm. The 3D computer graphics models for interactive virtual simulation were composed of the brainstem, cerebellum, cranial nerves, vessels, and skull individually created by the image analysis, including segmentation, surface rendering, and data fusion for data collected by 3-T MRI and 64-row multidetector CT systems. Interactive virtual simulation was performed by employing novel computer-aided design software with manipulation of a haptic device to imitate the surgical procedures of bone drilling and retraction of the cerebellum. The findings were compared with intraoperative findings. RESULTS: In all patients, interactive virtual simulation provided detailed and realistic surgical perspectives, of sufficient quality, representing the lateral suboccipital route. The causes of trigeminal neuralgia or hemifacial spasm determined by observing 3D computer graphics models were concordant with those identified intraoperatively in 25 (96%) of 26 patients, which was a significantly higher rate than the 73% concordance rate (concordance in 19 of 26 patients) obtained by review of 2D images only (p < 0.05). Surgeons evaluated interactive virtual simulation as having "prominent" utility for carrying out the entire surgical procedure in 50% of cases. It was evaluated as moderately useful or "supportive" in the other 50% of cases. There were no cases in which it was evaluated as having no utility. The utilities of interactive virtual simulation were associated with atypical or complex forms of neurovascular compression and structural restrictions in the surgical window. Finally, MVD procedures were performed as simulated in 23 (88%) of the 26 patients . CONCLUSIONS: Our interactive virtual simulation using a 3D computer graphics model provided a realistic environment for performing virtual simulations prior to MVD surgery and enabled us to ascertain complex microsurgical anatomy.

Identification and validation of a gene expression signature that predicts outcome in malignant glioma patients.

Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes selected using random survival forests model could be used to define subgroups of gliomas objectively. RNAs from 50 non-treated gliomas were analyzed using the GeneChip Human Genome U133 Plus 2.0 Expression array. We identified 82 genes whose expression was strongly and consistently related to patient survival. For practical purposes, a 15-gene set was also selected. Both the complete 82 gene signature and the 15 gene set subgroup indicated their significant predictivity in the 3 out of 4 independent external dataset. Our method was effective for objectively classifying gliomas, and provided a more accurate predictor of prognosis. We assessed the relationship between gene expressions and survival time by using the random survival forests model and this performance was a better classifier compared to significance analysis of microarrays.

Induction of autophagy in temozolomide treated malignant gliomas.

Autophagy is a dynamic process of protein degradation. Induction of autophagy by temozolomide (TMZ) has been noted in glioma cell lines. Twenty-eight specimens, obtained from 14 patients before and after TMZ treatment, were analyzed to investigate whether induction of autophagy could be detected in surgical specimens by immunohistochemical analysis. Macroautophagy was monitored by immunohistochemical analysis employing anti-light chain 3 isoform B (LC3B) and anti-lysosome-associated membrane protein 1 (LAMP1) antibodies; chaperone-mediated autophagy was monitored by anti-LAMP2A antibody immunostaining. Furthermore, detection of LC3B protein by Western blotting was performed on six specimens obtained from the preserved frozen tissues of three patients. All specimens showed dot-like staining for each immunostain in the cytoplasm of glioma cells, indicating induction of autophagy. LC3B, LAMP1 and LAMP2A immunostains were semiquantitatively scored from 1 to 3 points. Combination of the three scores after TMZ treatment (6.4 ± 1.2) showed a significant increase (P = 0.020) compared to pre-treatment scores (5.2 ± 1.5). Western blotting for LC3B showed increased LC3B-I and LC3B-II expression after TMZ treatment. The present study proved that autophagy monitoring by immunohistochemical staining of surgical specimens was feasible. These results suggest that autophagy is induced by TMZ.

Hematoma in the splenium of the corpus callosum in the subacute stage of subarachnoid hemorrhage--three case reports.

Three patients developed hemorrhage in the splenium of the corpus callosum 2 weeks after the onset of subarachnoid hemorrhage (SAH) associated with acute hydrocephalus. Computed tomography performed a few days after the onset showed a low density area in the splenium of corpus callosum in all three patients, and preventive measures against symptomatic vasospasm were begun, including vasodilator administration. Computed tomography showed hemorrhage in the splenium of the corpus callosum 17 to 22 days after onset of SAH, manifesting as mental deterioration or headache. Antivasospasm agents were immediately discontinued, and strict blood control measures were instituted. Splenial hematoma is another potential cause of neurological deterioration after surgery for SAH, in addition to vasospasm, hydrocephalus, and rebleeding.

Results of treatment of 112 cases of primary CNS lymphoma.

BACKGROUND: Chemotherapy with or without radiotherapy is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, either as a single agent or in combination with other drugs. Due to the lack of well-conducted randomized trials, the optimal treatment remains controversial. Available retrospective studies are difficult to discuss, however, some common themes can be found. METHODS: One hundred and twelve patients with PCNSL were treated with four different regimens over a period of 24 years. Treatment regimens were: whole-brain irradiation (WBI) alone, MVP (MTX, vincristine, and predonisolone), ProMACE-MOPP hybrid (cyclophosphamide, pirarubicin, etoposide, vincristine, procarbazine, prednisone, and MTX) and R-MTX (rituximab, MTX, pirarubicin, procarbazine, and prednisone) combined-modality therapy. RESULTS: The median failure-free survival was 16 months, and the median overall survival (OS) was 24 months. The 2- and 5-year actuarial probability of survival was 52.4 +/- 4.8% [95% confidence intervals (CI)] and 30.2 +/- 4.8% (95% CI), respectively. The ProMACE-MOPP protocol, Karnofsky performance status (KPS), MTX dose and WBI were associated with good OS by univariate models. By multivariate analysis, MTX dose, WBI dose, and its square dose were significantly associated with good OS. 20-30 Gy WB, and 500 mg/m(2) of MTX dose appeared important determinants of OS. CONCLUSIONS: A modest dose of MTX (500 mg/m(2)) followed by reduced-dose WBI for patients who respond appears a feasible treatment approach that minimizes serious toxicity.