Quo vadis, academia? Can academic neurosurgery be resurrected?

Clinical neurosurgery is an endangered academic discipline. Neurosurgeons have competition from many directions: orthopedists, ear, nose and throat surgeons, plastic surgeons, radio-oncologists, and interventional radiologists, among others. Academic centers are no longer the only sites of neurosurgical education at the attending level, and neurosurgery is not felt to be an indispensible part of an undergraduate medical curriculum. There are insufficient data to determine if neurosurgical services for the general population are adequate or appropriate. The traditional strengths of academic neurosurgery are gathering data, analysis, research, innovation, and teaching within a context of understanding and tradition. Future healthy development of neurosurgery ideally requires multidisciplinary teams in specialized referral centers. When this consideration is combined with the existing shortage of neurosurgeons across the country, academic neurosurgery departments must logically focus on how best to allocate resources between "routine" clinical services and research objectives. We suggest here that new relationships may be required between university centers and community health care providers. Restructuring of the neurosurgical workforce may be necessary if academic neurosurgery is to develop as a specialty of comprehensive expertise in the challenging neurological disease entities that are its research objectives.

Long-term results of brachytherapy with temporary iodine-125 seeds in children with low-grade gliomas.

PURPOSE: To retrospectively review the results of temporary I-125 brachytherapy in 94 children and adolescents with low-grade glioma. METHODS AND MATERIALS: Treatment was performed in progressive tumors roughly spherical in shape with a diameter of up to 5 cm, including 79 astrocytomas, 5 oligodendrogliomas, 4 oligoastrocytomas, 1 ependymoma, and 5 other tumors. Location was suprasellar/chiasmal in 44, thalamic/basal ganglia in 18, hemispheric in 15, midbrain/pineal region in 13, and lower brainstem in 3. Initially, 8% of patients were free of symptoms, 47% were symptomatic but not disabled, and 30% were slightly, 6% moderately, and 3% severely disabled. RESULTS: 5- and 10-year survival was 97% and 92%. The response to I-125 brachytherapy over the long term was estimated after a median observation period of 38.4 (range, 6.4-171.0) months. At that time, 4 patients were in complete, 27 in partial, and 18 in objective remission; 15 showed stable and 30 progressive tumors. Treatment results did not correlate with age, sex, histology, tumor size, location, or demarcation of the tumor. Secondary treatment became necessary in 36 patients, including 19 who underwent repeated I-125 brachytherapy. At final follow-up, the number of symptom-free patients had risen to 21%. Thirty-eight percent showed symptoms without functional impairment, 19% were slightly and 11% moderately disabled, and only 4% were severely disabled. CONCLUSIONS: Response rates similar to those of conventional radiotherapy or chemotherapy can be anticipated with I-125 brachytherapy in tumors of the appropriate size and shape. We believe it to be a useful contribution to the treatment of low-grade gliomas in children.

Neurosurgical treatment strategies in childhood craniopharyngiomas: is less more?

OBJECTIVE: Craniopharyngiomas in children are typically present in combination with heterogeneous clinical and neuroradiological findings. It has remained highly challenging to choose the optimal treatment strategy with regard to local tumor control and clinical outcome. Here, we analyze different treatment methods and evaluate the results. METHODS: We performed a detailed retrospective evaluation of 32 children <18 years old treated for craniopharyngioma between 1990 and 2008 at the University Hospital Freiburg. Three patient groups could be identified: children treated with microsurgical resection (n=17), with stereotactic cyst drainage and radiotherapy (n=7), and with various combined approaches (n=8). RESULTS: Six of seven children treated with stereotactic cyst punction and radiation are still alive. All of them are in an age-appropriate neuropsychological condition. Two of seven patients in this group have tumor recurrences. Fourteen of the 17 children treated with microsurgical resection show tumor recurrences (p=0.02). Fifteen are alive, and ten out of 17 show an age-appropriate neuropsychological development. The 8.5 years freedom from progression differed from 24% in the resection group to 71% in the cohort treated with stereotactic cyst drainage and radiotherapy (p=0.05). In the third group treated with various approaches, three of eight patients were treated for cystic recurrence. The average follow-up is 5.5 years. CONCLUSIONS: Based on our nonrandomized retrospective monocentric analysis, patients treated with less invasive stereotactic and radiotherapeutical methods have a more favorable long-term clinical outcome compared to children treated with a more radical microsurgical approach. Due to the possible implications of these results, further prospective trials should be encouraged.

Stereotactic interstitial radiosurgery with the Photon Radiosurgery System (PRS) for metastatic brain tumors: a prospective single-center clinical trial.

PURPOSE: To evaluate the efficacy and the treatment outcome of tumor patients being treated stereotactically with a miniature X-ray generator (Photon Radiosurgery System, PRS). METHODS AND MATERIALS: Thirty-five patients with histologically diagnosed cerebral metastases were treated with a single fraction of stereotactic interstitial irradiation (median, 18 Gy). Clinical and neuroimaging evaluation were assessed at 2-, 6-, and 12-week intervals postoperatively and every 3 months thereafter. Survival, local control, and distant and overall brain freedom from progression were obtained using the Kaplan-Meier method. RESULTS: Median survival was 7.37 months and the actuarial survival rates at 6 and 12 months were 60.0% and 34.3%, respectively. Acute complications on six patients were associated with shorter survival. Local tumor control at the initial stage and at the last follow-up were 82% and 50%. Eighteen patients (53%) developed distant brain metastases after treatment. At 1 year, the local control rate and distant and overall brain freedom from progression were 33.0%, 43.3%, and 14.7%, respectively. A shorter local tumor control was observed by PRS treatment of a recurrent tumor and by irregular tumor configuration. CONCLUSIONS: Interstitial radiosurgery with the PRS requires continued investigation. It allows for an immediate and potentially cost-efficient treatment for patients with singular, small (

Multiple intracranial melanoma metastases: case report and review of the literature.

Although intracerebral metastases of malignant melanoma are common, those located in the sellar region and within the pontocerebellar area are extremely rare. Furthermore, to our knowledge, there is no report about melanoma metastasis to the epiphysis published so far. We report here a 46-year-old patient who had metastatic lesions in the sellar region, cerebellopontine area and epiphysial gland, preceded by a primary melanoma at her left shoulder. The diagnosis of sellar metastasis was confirmed histopathologically following a stereotactic biopsy. The patient received whole-brain irradiation therapy combined with chemotherapy. After 10 months, she died from a severe hemorrhage in the cerebellopontine angle. Autopsy findings confirmed melanoma metastases both in the cerebellopontine angle and additionally in the epiphysial gland. To our knowledge, this is the first case of multiple intracranial melanoma metastases including the suprasellar region, the pontocerebellar and epiphysial area.

Radiosurgery followed by planned observation in patients with one to three brain metastases.

OBJECTIVE: To analyze the role of radiosurgery alone in patients with brain metastases. There were three specific study goals: 1) to determine whether survival of patients selected for this treatment approach can be predicted successfully by use of the recursive partitioning analysis classification defined by the Radiation Therapy Oncology Group; 2) to evaluate local control; and 3) to identify risk factors of cerebral failure. METHODS: A total of 101 patients with Karnofsky Performance Scale scores of at least 50 and up to three brain metastases, each 3 cm or less in maximum diameter, were treated with radiosurgery alone. Survival, local control, distant brain freedom from progression (FFP), and overall brain FFP were evaluated according the method of Kaplan and Meier. Risk factors for survival and overall brain FFP were analyzed using the Cox model. RESULTS: Median survival was 13.4 months, 9.3 months, and 1.5 months for patients in recursive partitioning analysis Classes 1, 2, and 3, respectively (P < 0.0001). At 1 year, local control, distant brain FFP, and overall brain FFP were 91, 53, and 51%, respectively. An interval greater than 2 years between diagnosis of the primary tumor and diagnosis of brain metastases and the presence of a single brain metastasis were associated with significantly higher overall brain FFP. CONCLUSION: Recursive partitioning analysis classification successfully predicted survival. Radiosurgery alone yielded high local control. Overall brain FFP was highest in patients with an interval greater than 2 years between primary diagnosis and diagnosis of a single brain metastasis.

Subthalamotomy in cervical dystonia: A case study of lesion location and clinical outcome.

Here we report a 63-year-old woman with primary cervical dystonia (CD) whose symptoms subsided for more than 30 years following a unilateral stereotactic subthalamotomy contralateral to the overactive left sternocleidomastoid muscle but then gradually recurred over a period of several months. The aim of the present study was to correlate the topography of the stereotactic lesion with the long lasting therapeutic effect. High-resolution magnetic resonance imaging and subsequent stereotactic analysis were performed to determine the anatomical localization of the lesion. The primary coagulation focus comprised the posterior subthalamic white matter in the prelemniscal radiation and field H of Forel. Neighboring structures were implicated to various extents. It is suggested that the posterior subthalamic area, with its abundance of interconnecting fibers and related nuclei, represents an effective target for the neurosurgical treatment of CD that may be explored further with deep brain stimulation.

High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system.

Thirteen patients (age 38-67 years) with primary lymphoma of the central nervous system (CNS) were treated with methotrexate and cytarabine/thiotepa induction-chemotherapy followed by high-dose carmustine/thiotepa and autologous stem-cell transplantation. Radiotherapy was restricted to patients who did not respond completely to chemotherapy. With a median follow up of 25 months, 3-year DFS and OS was 77%.

Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker?

PURPOSE: The combined loss of genetic material on chromosomes 1p and 19q is strongly associated with favorable outcome in patients with WHO grade 3 anaplastic oligodendroglial tumors. The prognostic value of 1p/19q loss in WHO grade 2 oligodendroglial tumors is less well defined. Importantly, the possible effect of combined 1p/19q loss has not been studied in patients who were not treated with radiotherapy or chemotherapy. EXPERIMENTAL DESIGN: Seventy-six patients with oligodendroglioma (n = 33), oligoastrocytoma (n = 30), anaplastic oligodendroglioma (n = 6), or anaplastic oligoastrocytoma (n = 7) were identified who had not received radiotherapy or chemotherapy after their first operation until the end of follow-up or until the first progression and had tissue for 1p/19q status available. 1p/19q status was assessed by multiplex ligation-dependent probe amplification. RESULTS: After a median follow-up of 3.8 years, progressive disease was documented in 34 patients. The estimated median progression-free survival was 4.6 years. Fifty-eight of the 76 patients had a combined loss of 1p and 19q. The absence or presence of combined 1p/19q loss was not prognostic for progression-free survival using multivariate adjustment for histology, extent of resection, and gender. CONCLUSIONS: Combined 1p/19q loss is not a sensitive prognostic biomarker in patients with oligodendroglial tumors who do not receive radiotherapy or chemotherapy. The gene products lost as a consequence of this codeletion may include mediators of resistance to genotoxic therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion promoting the formation of glial neoplasms, which retain high sensitivity to genotoxic stress.

Treatment options for gelastic epilepsy due to hypothalamic hamartoma: interstitial radiosurgery.

Surgical treatment of hypothalamic hamartomas (HHs) as the underlying etiology of gelastic epilepsy is associated with a high risk of complications because of the close vicinity of adjacent structures such as the optic tracts and mammillary bodies. Treatment with interstitial radiosurgery uses stereotactically implanted (125)I seeds emitting gamma radiation from the center of the lesion, with a steep spatial gradient, over a period of about 3 weeks. This form of HH therapy offers particular advantages regarding the risk for major side effects. In a series of 15 children and adolescents treated in Freiburg, Germany, 53% of patients achieved significant improvement in seizure frequency (Engel class I or II outcome). Transient side effects were related to the development of local edema, resulting in headache and mental slowing. A persistent weight gain was noted in 3 patients, which was severe in 1 (20 kg). There were no other neurologic, neuropsychologic, or neuropsychiatric side effects, which compares favorably with most surgical series.

Chronic high-frequency deep brain stimulation of the STN/SNr for progressive myoclonic epilepsy.

Chronic high-frequency deep brain stimulation (DBS) may also be effective in patients with refractory epilepsy. A possible benefit has been postulated because of the connections that exist between the subthalamic nucleus (STN) and the superior colliculus. Individual case reports and pilot studies of successful DBS in different types of epilepsy have already been presented. Here, the case of a 39-year-old male with progressive myoclonic epilepsy is reported who remained severely impaired despite VNS and combined antiepileptic drug therapy. Bilateral DBS electrodes were implanted into the STN, followed by implantation of a neurostimulation system under general anesthesia. Adjustment and testing of the remaining contacts was done over several months postoperatively. Bilateral monopolar DBS reduced the intensity and frequency of seizures by 50%. The patient has so far been followed for 12 months. This is the first report of positive effects of DBS in progressive myoclonic epilepsy in an adult patient. A subsequent prospective study will have to investigate whether the STN or other target nuclei are most suitable for DBS in these types of epilepsy and which long-term results can be obtained.

Subthalamic nucleus deep brain stimulation in elderly patients--analysis of outcome and complications.

BACKGROUND: There is an ongoing discussion about age limits for deep brain stimulation (DBS). Current indications for DBS are tremor-dominant disorders, Parkinson's disease, and dystonia. Electrode implantation for DBS with analgesia and sedation makes surgery more comfortable, especially for elderly patients. However, the value of DBS in terms of benefit-risk ratio in this patient population is still uncertain. METHODS: Bilateral electrode implantation into the subthalamic nucleus (STN) was performed in a total of 73 patients suffering from Parkinson's disease. Patients were analyzed retrospectively. For this study they were divided into two age groups: group I (age <65 years, n = 37) and group II (age > or = 65 years, n = 36). Examinations were performed preoperatively and at 6-month follow-up intervals for 24 months postoperatively. Age, UPDRS motor score (part III) on/off, Hoehn & Yahr score, Activity of Daily Living (ADL), L-dopa medication, and complications were determined. RESULTS: Significant differences were found in overall performance determined as ADL scores (group I: 48/71 points, group II: 41/62 points [preoperatively/6-month postoperatively]) and in the rate of complications (group I: 4 transient psychosis, 4 infections in a total of 8 patients, group II: 2 deaths [unrelated to surgery], 1 intracerebral hemorrhage, 7 transient psychosis, 3 infections, 2 pneumonia in a total of 13 patients), (p < 0.05). Interestingly, changes in UPDRS scores, Hoehn & Yahr scores, and L-dopa medication were not statistically different between the two groups. CONCLUSION: DBS of the STN is clinically as effective in elderly patients as it is in younger ones. However, a more careful selection and follow-up of the elderly patients are required because elderly patients have a higher risk of surgery-related complications and a higher morbidity rate.

Stent placement for intracranial cysts by combined stereotactic/endoscopic surgery.

OBJECTIVE: The treatment of space-occupying cystic lesions includes percutaneous cyst aspiration, marsupialization, percutaneous ventriculocystotomy, or Rickham catheter implantation. In some patients, the cysts tend to recur and repeated evacuations are necessary. The authors present a new treatment method with internal drainage of cysts into the ventricular system using a balloon-mounted vascular stent. METHODS: Six patients with cysts of low-grade gliomas, one with monocystic craniopharyngioma, and one with suprasellar arachnoid cyst were treated between September 2003 and May 2005. All patients were symptomatic after multiple previous treatments. Stent implantations were performed under local anesthesia in adults and under general anesthesia in children. In all patients, the stereotactic frame and computed tomographic and magnetic resonance fusion were used for an optimized approach. The treatment was performed in a compassionate manner and the patients were informed about the off-label use of the device. RESULTS: Stent placement was successful in all eight patients without procedure-related complications. Improvement of clinical symptoms was seen in seven out of eight patients. Seven out of eight cysts decreased in size within a follow-up period of up to 23 months (mean, 17 mo; median, 18 mo; range, 6-23 mo). The first patient showed recurrence of the tumor cyst 3 months after initial treatment with a Herkulink stent (5 x 18 mm), followed by retreatment with an Omnilink stent (6 x 28 mm; Guidant Corp., Santa Clara, CA). Stenting was ineffective in one patient. CONCLUSION: Treatment of intracranial cystic lesions by internal drainage is possible with the use of stent-assisted ventriculocystostomy.

Capillary physiology of human medulloblastoma: impact on chemotherapy.

BACKGROUND: Advances in the treatment of medulloblastoma have largely been attributed to the introduction of chemotherapy, although Phase III trials have shown advantages for chemotherapy only in subgroups. Because the efficacy of chemotherapy depends on tumor vascularization, the vascular physiology of human medulloblastomas was evaluated. METHODS: Seven patients with histologically proven medulloblastomas underwent measurements of capillary permeability and vascular plasma volume using contrast-enhanced dynamic computer tomography. Regional blood flow was measured in 5 patients using xenon computed tomography (CT). RESULTS: The capillary permeability-surface product for water-soluble compounds ranged from 1.7 +/- 5.5 to 17.6 +/- 12.3 muL/g/min with a mean of 10.5 +/- 6.3 microL/g/min. The vascular plasma volume ranged from 0.02 +/- 0.021 to 0.045 +/- 0.049 mL/g with a mean of 0.03 +/- 0.01 mL/g. The efflux rate ranged from 0.012 +/- 0.007 to 0.065 +/- 0.064 1/min with a mean of 0.039 +/- 0.020 1/min. Regional tumoral blood flow showed a mean of 19.86 +/- 6.8 mL/100g/min as compared with normal cerebellum with 45.4 +/- 12.03 mL/100g/min (P < .005). CONCLUSIONS: The current study demonstrated a low capillary permeability and blood flow in medulloblastomas that could explain the limited response rates of partially resected tumors even after aggressive high-dose chemotherapy, as recently reported.

High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma.

PURPOSE: To improve survival and reduce toxicity in primary CNS lymphoma (PCNSL) treatment, we conducted a multicenter phase II study with early high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) followed by hyperfractionated whole-brain radiotherapy (WBRT) for newly diagnosed PCNSL patients younger than 65 years of age. PATIENTS AND METHODS: Chemotherapy included three steps: three cycles of methotrexate (8 g/m2); cytarabine (AraC; two doses of 3 g/m2) and thiotepa (40 mg/m2) followed by stem-cell harvest; HDT with carmustine (400 mg/m2) and thiotepa (two doses of 5 mg/kg body weight) followed by ASCT. WBRT (45 Gy, two doses of 1 Gy/d) was administered for consolidation. RESULTS: Thirty patients with PCNSL younger than 65 years of age (median, 54 years; range, 27 years to 64 years) were enrolled (nine pilot-phase; 21 phase II). Twenty-eight patients responded to methotrexate: six patients with complete remission (CR), 15 patients with partial remission (PR), and seven patients with stable disease (SD) with clinical improvement. Of 26 patients proceeding to AraC and thiotepa, 10 patients achieved CR, 14 patients achieved PR, one patient experienced SD with clinical improvement, and one patient suffered disease progression. Twenty-three patients received HDT plus ASCT, resulting in 15 patients with CRs and eight patients with PRs. After WBRT, 21 of 21 patients had CRs. One patient died from liver failure after methotrexate. HDT was well tolerated apart from WHO grade 3/4 cytopenia. With a median follow-up of 63 months (range, 4 months to 84 months), 5-year overall survival probability is 69% for all patients and 87% for the 23 patients receiving HDT plus ASCT. The 5-year probability of relapse-related death is 21% for all patients (n = 30) and 8.7% for patients treated with HDT plus ASCT (n = 23). CONCLUSION: Sequential systemic methotrexate and AraC and thiotepa followed by HDT plus ASCT and hyperfractionated WBRT is very effective with little toxicity as initial therapy for PCNSL.

Interstitial 125I radiosurgery of supratentorial de novo WHO Grade 2 astrocytoma and oligoastrocytoma in adults: long-term results and prognostic factors.

BACKGROUND: Detailed long-term outcome data are not available for adult patients with World Health Organization (WHO) Grade 2 astrocytoma or oligoastrocytoma. METHODS: A previously published short-term data set of 239 adult patients with circumscribed de novo supratentorial astrocytoma (187 patients) and oligoastrocytoma (52 patients) treated with interstitial iodine-125 ((125)I) radiosurgery as primary treatment (1979-1992) was revisited. Survival, progression-free survival, functionally independent survival, postrecurrence survival, and time to malignant transformation were estimated with the Kaplan-Meier method. Prognostic factors were obtained from the Cox multivariate proportional hazards model. RESULTS: Five-, 10-, and 15-year survival was 56%, 37%, and 26%, respectively (median follow-up, 10.3 yrs). Progression-free survival was 45%, 21%, and 14%, respectively. The corresponding malignant transformation rates were 33%, 54%, and 67%. No leveling off of the Kaplan-Meier curves could be observed for any of the chosen endpoints. Age > 50 years, a tumor volume > 20 mL, and/or a Karnofsky score < or = 80 were associated with decreased survival or progression-free survival. Age > 35 years and/or a tumor volume > 20 mL increased risk of malignant transformation. Prognostic factors determined subsets of patients with 10-year survival ranging from as low as 6% to as high as 55% and progression-free survival ranging 1-31%. CONCLUSIONS: Long-term tumor stabilization is rare. As outcome is mainly determined by treatment-independent factors, minimization of any treatment-related risk must be considered essential.

Validation of intraoperative diagnoses using smear preparations from stereotactic brain biopsies: intraoperative versus final diagnosis--influence of clinical factors.

OBJECTIVE: Despite improvements in imaging techniques, histopathological diagnosis is still an important tool in neuro-oncology. At Freiburg University Hospital in Germany, approximately 450 patients per year undergo a serial stereotactic biopsy to obtain a diagnosis. We analyzed the accuracy of intraoperative diagnosis for rapid establishment of treatment options. Furthermore, we wanted to find out whether the location and histopathology of the tumors as well as the age and sex of the patients affected accuracy. Because of the large number of biopsies performed per year, parameters could also be evaluated for rare cerebral lesions. METHODS: We retrospectively analyzed 5000 consecutive stereotactic brain biopsies from 4589 patients. The digital database comprises the intraoperative and final diagnoses, the location of the tumors, and the sex and age of the patients. Regression analysis was performed to identify parameters that had a significant impact on the results. RESULTS: Intraoperative diagnosis was correct in 90.3% of biopsies. This included complete correlation in 81.3% of the biopsies and partial correlation in 9% of the biopsies. In 5.1% of the biopsies, no correlation between the intraoperative and final diagnosis was obtained. In 4.6% of the biopsies, no diagnosis could be made during or after surgery. A high correlation was found for World Health Organization Type II astrocytomas and, with regression analysis, for World Health Organization Type I astrocytomas, glioblastomas, and metastases. CONCLUSION: Intraoperative diagnosis with stereotactic biopsy has high validity. Immediate treatment based on the intraoperative diagnosis can be justified (e.g., for metastases or glioblastomas). Stereotactic biopsy with an exact histopathological diagnosis is strongly recommended for planning adequate therapy for patients with unidentified brain lesions.

Is older age associated with a worse prognosis due to different patterns of care? A long-term study of 1346 patients with glioblastomas or brain metastases.

BACKGROUND: The objective of this study was to find out whether the worse prognosis of older patients with primary or metastatic brain tumors can be explained by different patterns of care compared with younger patients. METHODS: A data base that included 430 patients with glioblastomas and 916 patients with brain metastases who underwent radiotherapy at the author's hospital between 1980 and 2000 was analyzed. Patterns of care were compared for different age groups using the chi-square test. RESULTS: In both patient groups, age turned out to be an independent risk factor. Older age was associated with worse overall survival. Independent of the cut-off age (< 50 years vs. > or = 50 years, < 60 years vs. > or = 60 years, < 65 years vs. > or = 65 years, and < 70 years vs. > or = 70 years), there were no statistically significant differences between the age groups concerning the use of different imaging modalities (computed tomography scans vs. magnetic resonance imaging), type of surgery (none vs. biopsy vs. resection), waiting time for radiotherapy (< median vs. > or = median), radiotherapy treatment planning (simulator-based vs. computer-based), use of radiation sources (cobalt unit vs. linear accelerator), and fractionation protocols (conventional vs. modified). When the recruitment period of 21 years was divided into 3 intervals, impressive changes with regard to the patterns of care became apparent. However, the changes were seen similarly throughout the different age groups. CONCLUSIONS: Older age did not limit access to state-of-the-art patterns of care in neurooncology. Patients participated in medical progress irrespective of their age. The worse prognosis of older patients with glioblastomas or brain metastases was not determined by age-related differences in access to health care.

Capillary physiology and drug delivery in central nervous system lymphomas.

To evaluate whether the chemosensitivity of primary central nervous system lymphomas to water-soluble drugs could result from improved drug delivery, we quantitatively assessed pharmacokinetic factors in seven patients. The capillary permeability surface product was found to be significantly increased in central nervous system lymphomas compared with glioblastoma multiforme, medulloblastomas, and metastases. Tumoral blood flow was significantly greater than in normal white matter. Our results suggest favorable pharmacokinetics to water- and lipid-soluble drugs in primary central nervous system lymphomas.