Contrast-enhancing Tumor Tissue Research Articles

EXTH-74. TUMOR PHARMACOKINETICS AND PHARMACODYNAMICS IN PATIENT-DERIVED XENOGRAFT MODELS OF GLIOBLASTOMA TREATED WITH THE PRMT5 INHIBITOR SKL27969

Abstract Epigenetic regulation plays a key role in the development of several cancers, including glioblastoma (GBM). Protein arginine methyltransferase 5 (PRMT5) has recently emerged as a promising therapeutic target for GBM. PRMT5 is the primary type II methyltransferase that catalyzes symmetric arginine dimethylation in multiple proteins. In this study, we evaluated the pharmacokinetics, pharmacodynamics, and radiation sensitization properties of SKL27969, a highly selective PRMT5 inhibitor, in orthotopic patient-derived xenograft (PDX) models of GBM. Mice with intracranial tumors were randomized to 50 mg/kg (oral) SKL27969 vs. placebo for two cycles either alone or in combination with radiation. SKL27969 levels in plasma and contrast-enhancing tumor tissue were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Unbound fractions were determined by equilibrium dialysis. Immunohistochemistry was performed to assess levels of SDMA, phospho-Histone H3, pH2AX, and cleaved caspase 3 (CC3). For survival studies, mice with intracranial tumors were randomized into four cohorts – vehicle, radiotherapy, SKL27969 monotherapy, and SKL27969 plus radiotherapy. The median brain-to-plasma and tumor-to-plasma partition coefficients of unbound SKL27969 were 1.8 and 2.9, respectively – indicating favorable brain and tumor penetration ability of SKL27969. A decrease in SDMA (+) cells (54% vs. 0.1%, p < 0.001) indicated PRMT5 inhibition and was accompanied by an increase in CC3 (+) cells (0.7% vs. 1.2%, p = 0.01). SKL27969 is well tolerated, achieves pharmacologically relevant unbound concentrations in GBM PDX models, and is associated with significant target modulation. Ongoing studies are evaluating in vivo survival benefit from combining PRMT5 inhibition with radiation therapy.

CTNI-28. FINAL RESULTS OF A PILOT STUDY TO EVALUATE INFUSION RATE ESCALATION TO MAXIMIZE VOLUME OF DISTRIBUTION DURING CONVECTION ENHANCED DELIVERY TO CONTRAST-ENHANCING GLIOBLASTOMA

Abstract BACKGROUND Volume of distribution (Vd) during convection enhanced delivery is impacted by the characteristics of the tissue being treated. For Glioblastoma (GBM), Vd is substantially higher in non-contrast enhancing tumor than in contrast enhancing tumor due to higher infusate efflux in enhancing tumor. We hypothesized that increasing the infusion rate could overcome the infusate efflux rate in enhancing tumor to improve the Vd to volume of infusion (Vi) ratio and provide better tumor coverage. METHODS A single center, IRB-approved pilot study was conducted under an IND (held by MAV) to perform rate escalated delivery of Topotecan with Gadolinium-DTPA to contrast-enhancing recurrent GBM (rGBM). A single Cleveland Multiport Catheter was surgically placed into enhancing tumor and then a 4-hour infusion was performed with real-time MRI visualization. Intra- and inter-patient rate escalation was performed. RESULTS 3 patients with rGBM were enrolled and treated. The initial infusion rate for patient 1 was 5 microliters/minute per microcatheter (4 total) and the final infusion rate for the third patient was 20 microliters/minute per microcatheter. We observed partial backflow at this rate and so did not escalate higher. There was coverage of both enhancing and non-enhancing tumor in all cases, and the Vd/Vi ratio ranged from 0.7 to 1.3. Patients tolerated the treatments well; there were no CTCAE Grade 3 or higher treatment related adverse events. CONCLUSIONS The higher efflux rate associate with contrast-enhancing tumor tissue can be overcome with sufficient infusion rate escalation.

Abstract 2796: Tumor pharmacokinetics, pharmacodynamics and efficacy analysis of WEE1 inhibitor, zn-c3 in patient-derived xenograft models of glioblastoma

Abstract WEE1 kinase regulates G2/M checkpoint transition via phosphorylation of CDK1 and prevents entry into mitosis. WEE1 inhibition increases genomic instability due to G2/M checkpoint inactivation and can result in mitotic catastrophe as monotherapy or when combined with DNA damaging agents. In this study, we evaluated the efficacy as well as pharmacokinetic and pharmacodynamic properties of ZN-c3, a best-in-class WEE1 inhibitor, in orthotopic patient-derived xenograft (PDX) models of GBM. Mice with intracranial tumors were randomized to 80 mg/kg ZN-c3 PO QD x 2 weeks vs. placebo. ZN-c3 levels in plasma and contrast-enhancing tumor tissue were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Unbound fractions were determined by equilibrium dialysis. Immunohistochemistry was performed to assess levels of pCDK1, phospho-Histone H3 (pHH3), and cleaved caspase 3 (CC3). The median unbound concentrations of ZN-c3 were 315 nmol/L and 15 nmol/kg in plasma and tumor tissue, respectively - higher than the biochemical IC50 of ZN-c3 for inhibition of WEE1 (3.8nM). An increase in pHH3(+) cells (0.40% vs. 6.57%, p=0.03) indicated drug-induced mitotic entry upon ZN-c3 treatment. ZN-c3 was potently cytotoxic across multiple patient-derived xenograft (PDX)-derived cell lines (IC50- 150-10000nM). Time and dose-escalation experiments exhibited target engagement at concentrations lower than IC50 values within one hour of treatment. Basal levels of WEE1 and pCDK1 were correlated with cell viability in response to ZN-c3 across multiple PDX cell lines. Overall, ZN-c3 is well tolerated, achieves pharmacologically-relevant unbound concentrations in GBM PDX models, and is associated with significant checkpoint modulation. Preclinical evaluation of ZN-c3 in combination with radiation therapy and DNA damage response pathway inhibitors is currently underway, which will support future combinatorial strategy for glioblastoma treatment. Citation Format: Shwetal Mehta, An-Chi Tien, Sonam Patel, Tigran Margaryan, Anilkumar Thaghalli Shivanna, Leonel Elena, Jennifer Molloy, William Knight, Ruiheng Hon, Mackenna Elliott, Mariya Stavnichuk, Zorana Opachich, Yu-Wei Chang, Chelsea Montgomery, Sarah Himes, Barbara Hopkins, Artak Tovmasyan, Nader Sanai. Tumor pharmacokinetics, pharmacodynamics and efficacy analysis of WEE1 inhibitor, zn-c3 in patient-derived xenograft models of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2796.

EXTH-09. TUMOR PHARMACOKINETICS, PHARMACODYNAMICS AND RADIATION SENSITIZATION IN PATIENT-DERIVED XENOGRAFT MODELS OF GLIOBLASTOMA TREATED WITH THE AURORA KINASE A INHIBITOR LY3295668

Abstract Cell-cycle deregulation is at the crux of all malignancies, including glioblastoma (GBM). Aurora Kinase A (AURKA) plays a central role in G2/M transition and faithful chromosome segregation. In this study, we evaluated the pharmacokinetics, pharmacodynamics, and radiation sensitization properties of LY3295668, a highly specific AURKA inhibitor, in orthotopic patient-derived xenograft (PDX) models of GBM. Mice with intracranial tumors were randomized to 50 mg/kg LY3295668 PO BID x 4 days vs. placebo. LY3295668 levels in plasma and contrast-enhancing tumor tissue were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Unbound fractions were determined by equilibrium dialysis. Immunohistochemistry was performed to assess levels of pAURKA (T288), phospho-Histone H3 (pHH3), and cleaved caspase 3 (CC3). For survival studies, mice with intracranial tumors were randomized to four cohorts – vehicle, radiotherapy, LY3295668 monotherapy, and LY3295668 plus radiotherapy. The median unbound concentration of LY3295668 was 270.88 nmol/L and 22.33 nmol/kg in plasma and tumor tissue, respectively – significantly higher than the biochemical IC50 of LY3295668 for AURKA inhibition (0.8 nM). A decrease in pHH3(+) cells (0.8% vs. 6.4%, p=0.036) indicated drug-induced mitotic arrest and was accompanied by an increase in CC3(+) cells (6.4% vs. 8.0%, p=0.67). Combination of LY3295668 with radiotherapy prolonged survival compared to either therapy alone in orthotopic GBM PDX models. LY3295668 is well tolerated, achieves pharmacologically-relevant unbound concentrations in GBM PDX models, and is associated with significant target modulation. Preclinical combination of LY3295668 with radiation therapy leads to synergistic effects and supports future clinical study of this multimodal strategy in glioblastoma patients.

CTNI-07. ABTC-1701: PILOT SURGICAL PK STUDY OF BGB324 (BEMCENTINIB) IN RECURRENT GLIOBLASTOMA PATIENTS – RESULTS FROM INTERIM FUTILITY ANALYSIS

Abstract BACKGROUND Glioblastoma often can relapse as mesenchymal (MES) tumors, indicating a phenotypic shift during clinical progression. Glioma spheres, when they gain MES phenotypes, develop dependence on AXL for their growth both in vitro and in vivo. The first-in-class orally bioavailable AXL kinase inhibitor bemcentinib has IC50 of 14 nM and is > 100-fold selective for AXL over other kinases. Bemcentinib is currently under evaluation as a monotherapy and in combination with other treatments across various PhII trials in several oncology indications. METHODS This is an open-label, multicenter, intratumoral pharmacokinetic study of bemcentinib in patients with recurrent glioblastoma for whom a surgical resection is medically indicated. All subjects must have had histological confirmation of glioblastoma by either biopsy or resection that is progressive or recurrent following radiation therapy ± chemotherapy. Intratumoral drug levels were analyzed by LC/MS. RESULTS A planned analysis after the first 5 patients were enrolled with glioblastoma (4 IDH WT and 1 IDH-mutant), (3m, 2f, median age 57, KPS 80). Bemcentinib concentration in contrast enhancing brain tissue ranged from 3.1 to 43.0 uM with a geometric mean concentration of 11.1 uM (% CV, 132.1). The drug concentration in contrast enhancing tumor tissue exceeded the 1.0 uM threshold in all 5 patients, satisfying the criteria of the protocol to enroll an additional 15 patients into the surgical study. Total drug levels were approximately 2-fold greater in contrast enhancing tissue as compared to tissue from a non-enhancing region of the tumor (geometric mean, 5.8 uM; % CV, 187.7). The mean ratio of the drug concentration in brain tissue to plasma was 25.9 (% CV, 92.7) for contrast enhancing tissue and 13.4 (% CV, 126.8) for non-enhancing tissue. CONCLUSIONS Bemcentinib readily distributes in brain tumor tissue following oral administration. The study continues to complete accrual for the remaining 15 patients.

Endoscope-assisted fluorescence-guided resection allowing supratotal removal in glioblastoma surgery.

Several studies have proven the benefits of a wide extent of resection (EOR) of contrast-enhancing tumor in terms of progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma (GBM). Thus, gross-total resection (GTR) is the main surgical goal in noneloquently located GBMs. Complete tumor removal can be almost doubled by microscopic fluorescence guidance. Recently, a study has shown that an endoscope with a light source capable of inducing fluorescence allows visualization of remnant fluorescent tumor tissue even after complete microscopic fluorescence-guided (FG) resection, thereby increasing the rate of GTR. Since tumor infiltration spreads beyond the borders of contrast enhancement on MRI, the aim of this study was to determine via volumetric analyses of the EOR whether endoscope-assisted FG resection enables supratotal resection beyond the borders of contrast enhancement. The authors conducted a retrospective single-center analysis of a consecutive series of patients with primary GBM presumed to be noneloquently located and routinely operated on at their institution between January 2015 and February 2018 using a combined microscopic and endoscopic FG resection. A 20-mg/kg dose of 5-aminolevulinic acid (5-ALA) was administered 4 hours before surgery. After complete microscopic FG resection, the resection cavity was scanned using the endoscope. Detected residual fluorescent tissue was resected and embedded separately for histopathological examination. Nonenhanced and contrast-enhanced 3D T1-weighted MR images acquired before and within 48 hours after tumor resection were analyzed using 3D Slicer. Bias field-corrected data were used to segment brain parenchyma, contrast-enhancing tumor, and the resection cavity for volume definition. The difference between the pre- and postoperative brain parenchyma volume was considered to be equivalent to the resected nonenhancing but fluorescent tumor tissue. The volume of resected tumor tissue was calculated from the sum of resected contrast-enhancing tumor tissue and resected nonenhancing tumor tissue. Twelve patients with GBM were operated on using endoscopic after complete microscopic FG resection. In all cases, residual fluorescent tissue not visualized with the microscope was detected. Histopathological examination confirmed residual tumor tissue in all specimens. The mean preoperative volume of brain parenchyma without contrast-enhancing tumor was 1213.2 cm3. The mean postoperative volume of brain parenchyma without the resection cavity was 1151.2 cm3, accounting for a mean volume of nonenhancing but fluorescent tumor tissue of 62.0 cm3. The mean relative rate of the overall resected volume compared to the contrast-enhancing tumor volume was 244.7% (p < 0.001). Combined microscopic and endoscopic FG resection of GBM significantly increases the EOR and allows the surgeon to achieve a supratotal resection beyond the borders of contrast enhancement in noneloquently located GBM.

Consistency of normalized cerebral blood volume values in glioblastoma using different leakage correction algorithms on dynamic susceptibility contrast magnetic resonance imaging data without and with preload

Background and purposeSeveral leakage correction algorithms for dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI)-based cerebral blood volume (CBV) measurement have been proposed, and combination with a preload of contrast agent is generally recommended. A single bolus application scheme would largely simplify and facilitate standardized clinical applications, while reducing contrast agent (CA) dose. The aim of this study was, therefore, to investigate whether appropriate leakage correction redundantizes prebolus application by comparing normalized DSC-based CBV (nCBV) measures of two consecutive CA boli. Materials and methodsTwenty-seven patients with suspected glioblastoma (WHO-grade-IV) underwent DSC-MRI during two consecutive boli of Gd-based CA. Four variants of two post-processing leakage correction techniques were compared with respect to nCBV in contrast enhancing tumor tissue. First, a reference curve approach with first pass and full integration of corrected ΔR2*(t), and second, a deconvolution-based approach using singular value decomposition (SVD) with a standard noise-dependent cutoff or Tikhonov regularization. ResultsCompared to respective uncorrected values, all leakage correction techniques increased nCBV for data acquired without prebolus, while there was no consistent trend for data acquired with prebolus. The best agreement between corrected nCBV values in contrast enhancing tumor, obtained in the same patients without and with prebolus, respectively, was obtained for the reference curve-based correction approach with either first pass or full integration. ConclusionThe reference curve-based leakage correction approach with integration-based nCBV calculation yielded a high accordance between nCBV values without and with prebolus, respectively. Thus, it appears possible to obtain valid nCBV in glioblastoma with a single CA injection.

The Treatment of Gliomas in Adulthood.

Gliomas are the most common intrinsic tumors of the brain, with an incidence of 6 per 100 000 persons per year. Recent years have seen marked changes in the diagnosis and treatment of gliomas, with molecular parameters now being an integral part of the diagnostic evaluation. This review is based on pertinent articles retrieved by a selective search in PubMed, with special attention to the new WHO glioma classification. The classification of gliomas on the basis of additional molecular parameters enables more accurate prognostication and serves as a basis for therapeutic decision-making and treatment according to precisely specified algorithms. PET scanning with 18F-fluoroethyl tyrosine and 11C-methionine for the measurement of metabolic activity in gliomas has further refined the diagnostic evaluation. The median overall survival of patients with glioblastoma who have undergone resection of all tumor tissue with a disrupted blood-brain barrier (i.e., all contrast-enhancing tumor tissue) has been prolonged to up to 20 months. The 5-year survival of patients with WHO grade II gliomas is now as high as 97% after near-total resection. The surgical resection of all contrast-enhancing tumor tissue and subsequent radiotherapy and chemotherapy remain the key elements of treatment. New surgical strategies and new methods of planning radiotherapy have made these techniques safer and more effective. The percutaneous application of tumor-treating fields is a new therapeutic option that has gained a degree of acceptance. Accompanying measures such as psycho-oncology and palliative care are very important for patients and should be considered mandatory. The consistent application of the existing multimodal treatment options for glioma has led in recent years to improved survival. Areas of important current and future scientific activity include immunotherapy and targeted and combined chemotherapy, as well as altered neurocognition, modern approaches to palliative care, and complementary therapies.

Value of quantitative magnetic resonance imaging T1-relaxometry in predicting contrast-enhancement in glioblastoma patients.

SUMMARIZING THE IMPORTANCE OF THE STUDYThe repetitive usage of gadolinium-based contrast agents (GBCA) is critical for magnetic resonance imaging (MRI) evaluation of tumor burden in glioblastoma patients. It is also a crucial tool for determination of radiographical response to treatment. GBCA injection, however, comes with a 2.4% rate of adverse events including life-threatening conditions such as nephrogenic systemic fibrosis (NSF). Moreover, GBCA have been shown to be deposited in brain tissue of patients even with an intact blood-brain barrier (BBB). The present study explores quantitative T1 relaxometry as an alternative non-invasive imaging technique detection of tumor burden and determination of radiographical response. This technique exploits specific properties of brain tissue with impaired BBB. With a sensitivity and specificity as high as 86% and 80%, respectively, quantitative T1-relaxometry allows for detecting contrast-enhancing areas without the use of GBCA. This method could make it unnecessary to subject patients to the risk of adverse events associated with the use of GBCA. Nonetheless, a large-scale analysis is needed to confirm our findings.BackgroundGadolinium-based contrast agents (GBCA) are crucial for magnetic resonance imaging (MRI)-based evaluation of tumor burden in glioblastoma (GBM). Serious adverse events of GBCA, even though uncommon, and gadolinium deposition in brain tissue could be avoided by novel imaging techniques not requiring GBCA. Altered tissue composition in areas with impaired blood-brain-barrier also alters the quantified T1 relaxation time (qT1), so that qT1 analysis could replace GBCA-based MRI for the analysis of tumor burden and response.MethodsAs a part of a prospective pilot MRI-relaxometry trial, patients with newly-diagnosed GBM who relapsed under standard radiochemotherapy were selected for this study. At recurrence, subtraction of qT1 maps pre and post-GBCA application (ΔqT1 maps) was used to determine areas of contrast-enhancement. With the contrast-enhancement on ΔqT1 maps as reference, ROC analysis served to detect an optimal qT1 cut-off on qT1 maps prior to GBCA to distinguish between contrast-enhancing tissue and its surroundings.ResultsTen patients were included. A qT1 value >2051ms predicted contrast-enhancing tumor tissue with a sensitivity of 86% and specificity of 80% (AUC, 0.92; p<0.0001). Interestingly, qT1 prolongation >2051 ms that did not overlap with contrast-enhancing area transformed into contrast-enhancement later on (n=4).ConclusionT1-relaxometry may be a useful technique to assess tissue properties equivalent to contrast-enhancement without the need for GBCA application. It may also provide information on sites with future tumor progression. Nonetheless, large-scale studies are needed to confirm these findings.

Towards a Genomic Definition of Completeness of Resection?

Towards a Genomic Definition of Completeness of Resection?

Abstract B152: MR-based assessment and quantification of cerebral edema in an orthotopic mouse glioma model.

Abstract Introduction: Brain edema is a prominent feature of brain cancer and contributes to neurologic dysfunction and impaired quality of life. While corticosteroids are the standard of care, improved treatments that are more efficacious and reduce side effects are sought after. In discovery of novel therapies for edema, animal brain tumor models that show relevant, reproducible and high incidence of tumor and cerebral edema are needed. Additionally, quantitative, non-invasive methods for detecting and measuring brain tumor associated edema are needed to facilitate therapeutic discovery efforts. In this work, an intracranial U251-luc human glioma model was characterized for edema incidence and progression. MRI-based relaxivity and contrast-enhancement protocols for edema detection and delineation from tumor tissue, were tested and characterized in the model. Methods: Female nude mice were implanted intracranially with 1×10∧6 U251-luc (Luc-mCherry) glioma cells. Tumor volume assessment was performed by manual segmentation of T1-weighted, gadolinium-enhanced anatomical brain images based on the assumption of tumor enhancement due to leaky vessels or compromised blood-brain barrier. Edema assessment was performed by manual segmentation of T2-weighted anatomical brain images based on the assumption that enhancing regions include tumor tissue in addition to regions of brain edema. The difference in T2-weighted and T1-weighted volumes was assumed to be edema. T2 maps were also generated over the whole brain to measure T2 values over the respective regions of interest, and confirm the differentiation between tumor tissue and edema. Results: Edema volume was successfully distinguished from contrast enhancing tumor tissue and quantified in orthotopically implanted U251-luc (Luc-mCherry) glioma. Incidence was 100%. Edema progression occurred with increasing tumor volume over time. Regions of edema exhibited greater T2 values compared to tumor tissue regions (that also had greater T2 than normal tissue). This is consistent with edematous tissue water content, compared with tumor tissue and normal brain. These results support the use of intracranial U251-luc (Luc-mCherry) as a reliable model for studying the effects of therapies targeting tumor-related cerebral edema, and the application of MR imaging for quantifying those effects real-time in vivo. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B152. Citation Format: Deanne R. Lister, Deepa Balagurunathan, Meridith Baugher, Erin Trachet, Patrick McConville, Scott Wise, W.R. Leopold. MR-based assessment and quantification of cerebral edema in an orthotopic mouse glioma model. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B152.

Magnetic resonance imaging volumetric assessment of the extent of contrast enhancement and resection in oligodendroglial tumors

Oligodendrogliomas that enhance on MR images are associated with poor prognosis. However, the importance of the volume of enhancing tumor tissue, and the extent of its resection, is uncertain. The authors examined the prognostic significance of preoperative and residual postoperative enhancing tissue volumes in a large single-center series of patients with oligodendroglioma. They also examined the relationship between enhancement and characteristic genetic signatures in oligodendroglial tumors, specifically deletion of 1p and 19q (del 1p/19q). The authors retrospectively analyzed 100 consecutive cases of oligodendroglioma involving patients who had undergone T1-weighted gadolinium-enhanced MRI at diagnosis and immediately after initial surgical intervention. The presence of preoperative enhancement was determined by consensus. Preoperative and residual postoperative volumes were measured using a quantitative, semiautomated method by a single blinded observer. Intrarater reliability for preoperative volumes was confirmed by remeasurement in a subset of patients 3 months later. Intrarater and interrater reliability for residual postoperative volumes was confirmed by remeasurement of these volumes by both the original and a second blinded observer. Multivariate analysis was used to assess the influence of contrast enhancement at diagnosis and the volume of pre- and postoperative contrast-enhancing tumor tissue on time to relapse (TTR) and overall survival (OS), while controlling for confounding clinical, pathological, and genetic factors. Sixty-three of 100 patients had enhancing tumors at initial presentation. Presence of contrast enhancement at diagnosis was related to reduced TTR and OS on univariate analysis but was not significantly related on multivariate analysis. In enhancing tumors, however, greater initial volume of enhancing tissue correlated with shortened TTR (p = 0.00070). Reduced postoperative residual enhancing volume and a relatively greater resection of enhancing tissue correlated with longer OS (p = 0.0012 and 0.0041, respectively). Interestingly, patients in whom 100% of enhancing tumor was resected had significantly longer TTR (174 vs 64 weeks) and OS (392 vs 135 weeks) than those with any residual enhancing tumor postoperatively. This prognostic benefit was not consistently maintained with greater than 90% or even greater than 95% resection of enhancing tissue. There was no relationship between presence or volume of enhancement and del 1p/19q. In enhancing oligodendrogliomas, completely resecting enhancing tissue independently improves outcome, irrespective of histological grade or genetic status. This finding supports aggressive resection and may impact treatment planning for patients with these tumors.

Neuronavigation in Solitary Intracerebral Tumors

Object. The goal of this study was to assess the impact of neuronavigation on the cytoreductive treatment of solitary contrast-enhancing intracerebral tumors and outcomes of this treatment in cases in which neuronavigation was preoperatively judged to be redundant. Methods. The authors conducted a prospective randomized study in which 45 patients, each harboring a solitary contrast-enhancing intracerebral tumor, were randomized for surgery with or without neuronavigation. Peri- and postoperative parameters under investigation included the following: duration of the procedure; surgeon's estimate of the usefulness of neuronavigation; quantification of the extent of resection, determined using magnetic resonance imaging; and the postoperative course, as evaluated by neurological examinations, the patient's quality-of-life self-assessment, application of the Barthel index and the Karnofsky Performance Scale score, and the patient's time of death. The mean amount of residual tumor tissue was 28.9% for standard surgery (SS) and 13.8% for surgery involving neuronavigation (SN). The corresponding mean amounts of residual contrast-enhancing tumor tissue were 29.2 and 24.4%, respectively. These differences were not significant. Gross-total removal (GTR) was achieved in five patients who underwent SS and in three who underwent SN. Median survival was significantly shorter in the SN group (5.6 months compared with 9 months, unadjusted hazard ratio = 1.6); however, this difference may be attributable to the coincidental early death of three patients in the SN group. No discernible important effect on the patients' 3-month postoperative course was identified. Conclusions. There is no rationale for the routine use of neuro-navigation to improve the extent of tumor resection and prognosis in patients harboring a solitary enhancing intracerebral lesion when neuronavigation is not already deemed advantageous because of the size or location of the lesion.

Effectiveness of neuronavigation in resecting solitary intracerebral contrast-enhancing tumors: a randomized controlled trial

The goal of this study was to assess the impact of neuronavigation on the cytoreductive treatment of solitary contrast-enhancing intracerebral tumors and outcomes of this treatment in cases in which neuronavigation was preoperatively judged to be redundant. The authors conducted a prospective randomized study in which 45 patients, each harboring a solitary contrast-enhancing intracerebral tumor, were randomized for surgery with or without neuronavigation. Peri- and postoperative parameters under investigation included the following: duration of the procedure; surgeon's estimate of the usefulness of neuronavigation; quantification of the extent of resection, determined using magnetic resonance imaging; and the postoperative course, as evaluated by neurological examinations, the patient's quality-of-life self-assessment, application of the Barthel index and the Karnofsky Performance Scale score, and the patient's time of death. The mean amount of residual tumor tissue was 28.9% for standard surgery (SS) and 13.8% for surgery involving neuronavigation (SN). The corresponding mean amounts of residual contrast-enhancing tumor tissue were 29.2 and 24.4%, respectively. These differences were not significant. Gross-total removal (GTR) was achieved in five patients who underwent SS and in three who underwent SN. Median survival was significantly shorter in the SN group (5.6 months compared with 9 months, unadjusted hazard ratio = 1.6); however, this difference may be attributable to the coincidental early death of three patients in the SN group. No discernible important effect on the patients' 3-month postoperative course was identified. There is no rationale for the routine use of neuronavigation to improve the extent of tumor resection and prognosis in patients harboring a solitary enhancing intracerebral lesion when neuronavigation is not already deemed advantageous because of the size or location of the lesion.

Radiological modalities in the staging of colorectal tumors: new perspectives for increasing accuracy.

The purpose of this study was to evaluate the diagnostic accuracy of contrast-enhanced endorectal MRI for the staging of rectal adenoma versus rectal carcinoma in correlation to findings from biopsy and histopathology. Ten volunteers and 20 patients underwent body-coil and endorectal MRI (1.5T supraconducting unit) using plain, T1-weighted (w) T2-w SE and TSE-w sequences, a dynamic Gd-DTPA enhanced protocol (turboFLASH), and postcontrast T1-w-SE sequences. Histopathological correlation via biopsy (n = 10) and surgical resection (n = 19) were conducted for all patients. An independent, two-observer, reader evaluation was performed and qualitative and quantitative data calculated. In volunteers and all patients endorectal MRI reliably delineated normal wall layers. Rectal adenomas (n = 7) were identified by a visualization of an intact muscularis mucosae, a homogeneous inner structure, and a significant contrast enhancement. T1 carcinomas (n = 4) were best identified in dynamic turboFLASH sequences by delineation of an intact muscularis propria. The visualization of contrast-enhancing tumor tissue was indicative of a T2 carcinoma (n = 4). All T3 (n = 3) and T4 (n = 2) carcinomas were correctly staged on dynamic and static MRI. The endorectal MRI stage agreed with the staging results from pathological study in 16 of 20 (80%) patients. Endorectal surface coil MRI provides reliable data for the preoperative staging and evaluation of rectal lesions.