Thalamic Glioblastoma Research Articles

INNV-15. OPTIMIZING THE ROLE OF THE ADVANCED PRACTICE PROVIDER IN THE MANAGEMENT OF A SINGLE PATIENT INVESTIGATIONAL NEW DRUG (IND)

Abstract BACKGROUND Single patient Investigational New Drug (IND) applications are a way through which experimental therapies may be accessed by patients with cancer especially if a clinical trial is not available. However, initiating and managing a single patient IND is complex. We will outline our approach used at an academic teaching center to leverage the skills and scope of practice of advanced practice providers (APPs) to facilitate successful initiation and monitoring of individual patients who may be receiving an investigational drug under a single patient IND. METHODS We describe a single case of a 52-year-old male with a left thalamic glioblastoma treated with standard of care and monitored off therapy from May 2021 until November 2022. Extended genomic profiling of his tumor at time of biopsy revealed a FGFR3-TACC3 fusion and MGMT promoter methylation, and the decision was made to pursue a single patient IND for anlotinib for use in combination with temozolomide. RESULTS Following permission from the US Food and Drug Administration (FDA) to proceed and IRB chair concurrence, the MD and APP conferred with the investigational and clinical pharmacists regarding procurement and dispensing of the drug, in addition to surveillance and associated toxicities. The APP obtained consent, collected data on monitoring parameters and adverse events, checked for drug interactions with the patient’s routine medications, ordered and reviewed all treatment related MRIs, labs, and EKGs, and coordinated with ophthalmology for baseline and monthly eye exams. Performance of initial and follow-up exams, ongoing toxicity review and management, and care coordination with the local oncology team were completed by the APP. CONCLUSION As first point of contact for the patient and family, the APP plays a key role in glioma research within the multidisciplinary team by providing ongoing symptom management, education, and monitoring for patients receiving investigational drugs.

The Equipoise Between the Treatment of Glioblastoma and the Risk of Secondary Acute Myelogenous Leukemia: An Illustrative Case Report.

We present a case report of a 56-year-old woman who was diagnosed with biopsy-proven left thalamic glioblastoma multiforme (GBM). She was treated with standard concurrent chemotherapy and radiation, as well as a 2-year period of adjuvant temozolomide. She relapsed 2 ½ years after starting her initial therapy and was treated with bevacizumab and lomustine, but she relapsed. She was then placed on a phase 1/2 clinical trial that included KHK2455 and mogamulizumab-kpkc individually and in combination for almost 4 years. She had a rapid demise due to the development of a neutropenic pneumonia and treatment-induced acute myeloid leukemia (AML) and elected for hospice care.

RADT-18. PARTICLE BEAM RADIATION THERAPY PLUS TUMOR TREATING FIELDS IN THE TREATMENT OF NEWLY DIAGNOSED WHO GRADE 4 GLIOMAS: AN EARLY RESULT OF PHASE 2 SINGLE-ARM TRIAL

Abstract OBJECTIVES Tumor Treating Fields (TTFields) is increasingly provided to patients with WHO grade 4 gliomas following radiotherapy. Particle beam radiotherapy (PBRT) represents a novel promising radiation approach with improved therapeutic ratio. This study was aimed to report an early result of TTFields in combination with PBRT for treating WHO grade 4 gliomas based on a prospective phase 2 trial from Shanghai Proton and Heavy Ion Center. METHODS This phase 2 trial was designed as a single-arm study to test the outcome of PBRT plus TTFields. Six patients with newly diagnosed WHO grade 4 gliomas receiving surgery, PBRT, temozolomide, and TTFields, from August 2021 to May 2022, were enrolled and analyzed. Tumor histologies based on the WHO CNS5 classification system were IDH-wild glioblastoma (n=4), IDH-mutant astrocytoma (n=1), and H3G34-mutant diffuse hemispheric glioma (n=1). For PBRT, all patients were irradiated with a baseline standard dose of 60GyE/30 utilizing proton. Carbon-ion boost of 15GyE/3 for tumor residual was performed for one patient prior to proton radiation. TTFields treatment was recommended to start soon after PBRT. RESULTS With a median follow-up of 5.5 months, all patients were alive at the time of this analysis; one patient with left thalamic glioblastoma had tumor progression of distant failure outside the radiation field at 4 months after partial tumor resection. The median interval between PBRT and TTFields was 2 days (range 1-22 days). No patient had dermatitis during PBRT. No severe TTField-related skin toxicity (Grade 3 or above) was observed. Five patients (83.3%, 5/6) developed mild skin toxicities (Grade 1) during TTField treatments. CONCLUSIONS Starting TTField early following PBRT is feasible for treating WHO grade 4 gliomas, the overall side effects are mild. Prospective studies with further follow-up are warranted to identify the outcomes of PBRT in combination with TTField in terms of survival and side effects.

Risk Factors for Early Hydrocephalus on Post Unilateral Thalamic Tumor Resection.

ObjectiveThe outcome of surgical treatment for thalamic tumors is poor. Hydrocephalus is one of the most frequent postoperative complications after unilateral thalamic tumor resection. This study examined the relationship between surgical approaches, pathological grade, image characteristics, preoperative complications, extent of resection, and incidence of postoperative hydrocephalus.MethodsThe study retrospectively reviewed clinical data from 80 patients who underwent resection of thalamic tumors between 2015 and 2021. Data on patient survival and disease progression status were obtained retrospectively to calculate overall survival (OS) and progression free survival (PFS).ResultsNo patients died during the perioperative period and two patients suffered postoperative coma. Tumors were totally resected in 44 cases (55 %), subtotally resected in 21 cases (26.25 %), and partially resected in 15 cases (18.75 %). Thirty-five cases of hydrocephalus occurred within 1 month after operation(43.75%). Surgical approaches associated with hydrocephalus were as follows: hydrocephalus occurred in seven cases after trans-frontal lateral ventricle approach for tumor resection (62.9%), in 17 cases after through parieto-occipital transventricular approach tumor resection (43.58%), and in one case after trans-frontal lateral ventricle approach for tumor resection + third ventriculostomy (7.1%). Postoperative muscle strength decrease occurred in 41 patients (51.25%). Longer PFS and OS were correlated with degree of resection in patients with thalamic glioblastoma (P < 0.05) and had no relationship with hydrocephalus.ConclusionSurgical treatment of thalamic tumors is an effective therapeutic method. The incidence of postoperative hydrocephalus is not associated with tumor size, degree of tumor enhancement, peritumoral edema, tumor invasion, midline crossing, and pathological grade. The incidence of postoperative hydrocephalus was higher in patients with preoperative hydrocephalus and low resection degree, and lower in patients with endoscopic third ventriculostomy. The risk of early postoperative hydrocephalus in thalamic tumors is high. Intraoperative third ventriculostomy could reduce the incidence of early postoperative hydrocephalus. PFS and OS were longer in patients with thalamic glioblastoma with a high resection degree (P < 0.05) and were not associated with hydrocephalus.

STMO-19 Impact of aggressive resection for glioblastoma of the thalamus with histone H3-K27M mutation

Glioblastoma of the thalamus occurs predominantly in childhood and young adulthood, and cases with histone mutations are thought to have a particularly poor prognosis. We studied tumor resection rate, age, type of adjuvant therapy, and histone gene mutations on progression-free survival (PFS) and overall survival (OS) in patients who underwent aggressive removal. Eight cases of thalamic glioblastoma were included in the study. The mean age at surgery was 36.1 years (10–74 years, 3 cases under 18 years). Tumor removal was performed from the parieto-occipital lobe to the thalamus via the lateral ventricles in all cases. In all cases, more than 90% of the contrast-enhancing lesions were removed. Postoperatively, one patient had sensory disturbance of the left upper limb, and the other had incomplete paralysis of the left upper and lower limbs, but both were able to walk with a cane. In the case of the patient with postoperative complications, the tumor was located in the vicinity of the internal capsule. All patients were treated with radiation therapy and temozolomide, and bevacizumab and Novo-TTF were used in cases after approval. All patients were able to return home and return to school or work after initial treatment. The mean progression-free survival (PFS) was 0.87 years, and overall survival (OS) was 1.95 years. Five patients had histone H3-K27M mutations, and three patients had no mutations. PFS and OS were 1.02 years and 0.62 years, respectively, and 2.53 years and 1.20 years, respectively, both of which were longer in patients with mutations (PFS; p=0.16, OS; p=0.23).Aggressive removal of glioblastoma of the thalamus may improve prognosis, especially in patients with histone H3-K27M mutations. In patients with tumors extending to the vicinity of the internal capsule, total removal may cause paralysis and sensory disturbance.

Refined Temporal-to-Frontal Horn Shunt for Treatment of Trapped Temporal Horn After Surgery of Peri- or Intraventricular Tumor: A Case Series Study

BackgroundTrapped temporal horn (TTH) is a localized hydrocephalus that can be treated with cerebrospinal fluid diversion. Refined temporal-to-frontal horn shunt (RTFHS) through the parieto-occipital approach is rarely reported in the literature and its effectiveness remains unclear. The aim of the present study is to investigate the efficacy and outcome of RTFHS for treatment of TTH.Materials and MethodsWe consecutively enrolled 10 patients who underwent RTFHS for TTH after surgical resection of peri- or intraventricular tumors from February 2018 to March 2021. Clinical, radiological, and follow-up data were collected and analyzed. The most common underlying pathology was meningioma (n=4), followed by central neurocytoma (n=3), thalamic glioblastoma (n=2), and anaplastic ependymoma (n=1).ResultsThe mean Karnofsky performance scale (KPS) score and TTH volume at onset were 54.0 ± 15.1 (range 40-80) and 71.3 ± 33.2cm3 (range 31.7-118.6cm3), respectively. All patients (10/10, 100.0%) presented with periventricular brain edema (PVBE), while midline shift was observed in 9 patients (9/10, 90.0%). RTFHSs were implanted using valveless shunting catheters. No patients developed acute intracranial hemorrhage or new neurological deficit postoperatively. During the follow-up of 17.2 ± 13.7 months (range 3-39 months), all patients showed clinical and radiological improvement. The mean KPS score at the last follow-up was significantly increased to 88.0 ± 10.3 (range 70-100, p<0.0001). RTFHS resulted in significant complete remission in PVBE and midline shift in 8 (80.0%, p=0.0007) and 9 (100.0%, p=0.0001) patients, respectively. As the postoperative follow-up duration prolonged, the mean TTH volume decreased in a consistent, linear trend (p<0.0001). At last follow-up, the mean TTH volume was significantly reduced to 15.4 ± 11.5 cm3 (range 5.6-44.1 cm3, p=0.0003), resulting in a mean relative reduction of 77.2 ± 13.1% compared with the volume of TTH at onset. Over drainage was not observed during the follow-up. No patient suffered from proximal or distal shunt obstruction or shunt related infection, and the revision rate was 0%.ConclusionRTFHS seems to be safe and effective for the treatment of TTH with favorable outcomes. Advantages of this technique could be technically less complex and invasive, cost-effective, avoidance of various intraperitoneal complications, and maintaining a near-physiological CSF pathway.

Maximal surgical resection and adjuvant surgical technique to prolong the survival of adult patients with thalamic glioblastoma

The importance of maximal resection in the treatment of glioblastoma (GBM) has been reported in many studies, but maximal resection of thalamic GBM is rarely attempted due to high rate of morbidity and mortality. The purpose of this study was to investigate the role of surgical resection in adult thalamic glioblastoma (GBM) treatment and to identify the surgical technique of maximal safety resection. In case of suspected thalamic GBM, surgical resection is the treatment of choice in our hospital. Biopsy was considered when there was ventricle wall enhancement or multiple enhancement lesion in a distant location. Navigation magnetic resonance imaging, diffuse tensor tractography imaging, tailed bullets, and intraoperative computed tomography and neurophysiologic monitoring (transcranial motor evoked potential and direct subcortical stimulation) were used in all surgical resection cases. The surgical approach was selected on the basis of the location of the tumor epicenter and the adjacent corticospinal tract. Among the 42 patients, 19 and 23 patients underwent surgical resection and biopsy, respectively, according to treatment strategy criteria. As a result, the surgical resection group exhibited a good response with overall survival (OS) (median: 676 days, p < 0.001) and progression-free survival (PFS) (median: 328 days, p < 0.001) compared with each biopsy groups (doctor selecting biopsy group, median OS: 240 days and median PFS: 134 days; patient selecting biopsy group, median OS: 212 days and median PFS: 118 days). The surgical resection groups displayed a better prognosis compared to that of the biopsy groups for both the O6-methylguanine-DNA methyltransferase unmethylated (log-rank p = 0.0035) or methylated groups (log-rank p = 0.021). Surgical resection was significantly associated with better prognosis (hazard ratio: 0.214, p = 0.006). In case of thalamic GBM without ventricle wall-enhancing lesion or multiple lesions, maximal surgical resection above 80% showed good clinical outcomes with prolonged the overall survival compared to biopsy. It is helpful to use adjuvant surgical techniques of checking intraoperative changes and select the appropriate surgical approach for reducing the surgical morbidity.

Abstract A09: Cerebrospinal fluid (CSF) as a source of ctDNA for diagnosis and monitoring of pediatric patients with midline diffuse gliomas

Abstract Background: Midline diffuse gliomas are aggressive pediatric tumors, characterized molecularly by the presence of H3K27 mutation. These tumors are extremely malignant, with median overall survival of less than a year. Localized mainly in the pons or thalamic regions, they are not amenable to a gross total resection; however, a biopsy is needed for pathologic and molecular diagnosis. In this scenario, liquid biopsy is of utmost importance and has the potential to spare the risk of morbidity with surgical procedures, determine diagnosis and prognosis, as well as serve as a tool to identify potential targetable alterations. The objective of this pilot feasibility study is to explore the use of CSF ctDNA using ddPCR and next-generation sequencing tools to diagnose and monitor patients with midline diffuse gliomas. Methods: We extracted CSF ct DNA collected from external ventricular drain in two patients diagnosed with midline diffuse glioma (one thalamic glioblastoma, one DIPG). ctDNA was extracted from 2 mL of CSF, quantification was done by quibit, and samples were processed first with ddPCR for detection of H3K27M point mutation followed by comprehensive profiling by whole-exome sequencing using Illumina HiSeq2500 sequencer. We assessed the feasibility of identifying diagnostic point mutations, as well as potential evolution of the tumor molecular landscape at disease progression. Results: The first case, a thalamic GBM, had tissue available for molecular analysis; targeted RNA sequencing was performed on a clinical basis detecting H3K27M mutation (VAF=43%) and a PDGFRA N659K mutation (VAF=43%). ddPCR analysis of the CSF ctDNA identified the H3K27M mutation with VAF of 14%. Whole-exome sequencing (WES) confirmed the presence of H3K27M point mutation at VAF 11% and PDGFRA mutation at VAF 13%. This patient received radiation and chemotherapy but progressed rapidly and passed 7 months after the diagnosis. The second case, a DIPG diagnosed upon radiologicl and clinical criteria, was previously treated with conventional focal radiation and needed an EVD upon massive leptomeningeal progression with associated meningitis. CSF was then processed for ctDNA analysis. ddPCR confirmed the presence of H3K27M mutation with VAF of 48%. WES confirmed the presence of H3K27M mutation (VAF 14%) and additional TP53 R273C point mutation with VAF of 87%. This patient passed roughly 11 months post diagnosis. Conclusion: We have demonstrated the feasibility of detection of molecular markers in CSF through ddPCR and NGS platform to not only to assist in diagnosis of pediatric midline diffuse gliomas, but also to monitor these patients for additional/new molecular events that may be targetable. Building on these results, we are currently implementing a targeted sequencing panel to establish the specificity of this method in a large pediatric brain tumor cohort. Citation Format: Liana Nobre, Robert Siddaway, Monique Johnson, Scott Ryall, Michal Zapotocky, Julie Bennet, Uri Tabori, Cynthia Hawkins. Cerebrospinal fluid (CSF) as a source of ctDNA for diagnosis and monitoring of pediatric patients with midline diffuse gliomas [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A09.

Awake Surgical Management of Third Ventricular Tumors: A Preliminary Safety, Feasibility, and Clinical Applications Study.

Endoscopic and microneurosurgical approaches to third ventricular lesions are commonly performed under general anesthesia. To report our initial experience with awake transsulcal parafascicular corridor surgery (TPCS) of the third ventricle and its safety, feasibility, and limitations. A total of 12 cases are reviewed: 6 colloid cysts, 2 central neurocytomas, 1 papillary craniopharyngioma, 1 basal ganglia glioblastoma, 1 thalamic glioblastoma, and 1 ependymal cyst. Lesions were approached using TPCS through the superior frontal sulcus. Pre-, intra-, and postoperative neurocognitive (NC) testing were performed on all patients. No cases required conversion to general anesthesia. Awake anesthesia changed intraoperative management in 4/12 cases with intraoperative cognitive changes that required port re-positioning; 3/4 recovered. Average length of stay (LOS) was 6.1 d±6.6. Excluding 3 outliers who had preoperative NC impairment, the average LOS was 2.5 d±1.2. Average operative time was 3.00 h±0.44. Average awake anesthesia time was 5.05 h±0.54. There were no mortalities. This report demonstrated the feasibility and safety of awake third ventricular surgery, and was not limited by pathology, size, or vascularity. The most significant factor impacting LOS was preoperative NC deficit. The most significant risk factor predicting a permanent NC deficit was preoperative 2/3 domain impairment combined with radiologic evidence of invasion of limbic structures - defined as a "NC resilience/reserve" in our surgical algorithm. Larger efficacy studies will be required to demonstrate the validity of the algorithm and impact on long-term cognitive outcomes, as well as generalizability of awake TPCS for third ventricular surgery.

Letter: Thalamic Glioblastoma: Clinical Presentation, Management Strategies, and Outcomes

Letter: Thalamic Glioblastoma: Clinical Presentation, Management Strategies, and Outcomes

In Reply: Thalamic Glioblastoma: Clinical Presentation, Management Strategies, and Outcomes.

In Reply: Thalamic Glioblastoma: Clinical Presentation, Management Strategies, and Outcomes.

High frequency of H3K27M immunopositivity in adult thalamic glioblastoma.

Adult thalamic glioblastomas (GBM) are uncommon tumors with limited available molecular data. One of the reported molecular alterations in these tumors is the H3K27M mutation. It has been documented that H3K27M mutation is found in a high proportion of pediatric thalamic gliomas. In this study, we have analyzed the molecular alterations exclusive to adult thalamic GBM. This is a 6 years retrospective study of adult thalamic GBM patients who underwent surgical decompression of the tumor. Clinical data were obtained from the case records. Immunohistochemistry (IHC) was performed on the tumors using antibodies directed against the gene products of R132H mutant isocitrate dehydrogenase 1 (IDH1), alpha-thalassemia/mental retardation X-linked (ATRX), p53, H3K27M, H3K27me3, and V600E mutant BRAF. Molecular analyses were carried out to detect other IDH1 and IDH2 mutations, O6 -methylguanine-DNA-methyltransferase gene (MGMT) promoter methylation, and epidermal growth factor gene (EGFR) and telomerase reverse transcriptase gene (TERT) promoter mutations. A total of 42 cases of adult thalamic GBM were studied. The mean age of presentation was 42 years with age range of 19-58 years. Male predominance was noted. All the tumors were IDH wild-type, BRAF (V600E)-immunonegative and unmethylated for MGMT promoter. H3K27M immunopositivity was noted in 60% of tumors. Of these 33.3% were from older adults above the age of 50 years. Of the H3K27M-immunopositive cases, ATRX loss of expression was seen in 32%, p53 immunopositivity in 24% and EGFR amplification in 12%. Higher frequency of TERT promoter mutations was noted in H3K27M-immunonegative cases (58.8%) compared to immunopositive cases (20%). Ours is one of the few studies elucidating the molecular alterations exclusive to adult thalamic GBM. We show a high frequency of H3K27M immunopositivity, suggestive of its mutational status in these tumors, including in older adults.

Thalamic Glioblastoma: Clinical Presentation, Management Strategies, and Outcomes.

Thalamic glioblastomas (GBMs) represent a significant neurosurgical challenge. In view of the low incidence of these tumors, outcome data and management strategies are not well defined. To identify the natural history and factors associated with survival in patients with thalamic glioblastoma. A retrospective review of all patients with thalamic glioblastoma over a 10-yr period was performed. Presenting clinical, radiological, and outcome data were collected. Chi-squared and Fisher's exact tests were used to compare clinical characteristics across tumor groups. Cox proportional hazard models were utilized to investigate variables of interest with regard to overall survival. Fifty-seven patients met inclusion criteria, with a median age of 53 and median Karnofsky Performance Scale (KPS) score of 80. The most common presenting symptoms were weakness, confusion, and headache. Hydrocephalus was present in 47% of patients preoperatively. Stereotactic biopsy was performed in 47 cases, and 10 patients underwent craniotomy. The median overall survival was 12.2 mo. Higher KPS, younger age, and cerebrospinal fluid (CSF) diversion were correlated with better overall survival univariately, respectively, while the presence of language deficits at initial presentation was associated with poorer survival. In multivariate analysis, the only significant predictor of survival was presenting KPS. The overall survival of patients with thalamic glioblastoma is comparable to unresectable lobar supratentorial GBMs. Younger patients and those with good presenting functional status had improved survival. Midbrain involvement by the tumor is not a negative prognostic factor. Improved therapies are needed, and patients should be considered for early trial involvement and aggressive upfront therapy.

Abstract 3271: Novel orthotopic pediatric high grade glioma xenografts evaluated with magnetic resonance imaging mimic human disease

Abstract Pediatric high grade gliomas (pHGG) may arise supratentorially in the cerebral hemispheres, or in midline structures such as the thalamus or the pons (diffuse intrinsic pontine glioma, DIPG). Tumors have distinct underlying biology compared with adult disease, with genetic subtypes corresponding to anatomical location. Differential mutations in genes encoding histone H3.3/H3.1 variants occur in supratentorial and midline tumors, while mutations in the gene encoding the BMP type I receptor ACVR1 are restricted to the pons and occur in a quarter of DIPGs. Co-option of existing brain vasculature in areas of infiltrative tumor growth leaves the blood brain barrier (BBB) intact. It is imperative to accurately model these tumors in vivo for the evaluation of emerging targeted therapeutics. Assessment of such models in situ is vital and requires sensitive functional imaging. T2-weighted (T2-w) MRI of orthotopically implanted PBT7 cells (supratentorial glioblastoma (GBM), 9yr old, H3F3A wt) showed heterogeneous tumors with relatively well defined borders. Hypointensity on T2-w and fluid-attenuated inversion recovery (FLAIR) images suggests the presence of necrosis and edema. Minimal heterogenous enhancement following Gd-DTPA administration demonstrated some loss of BBB integrity. FLAIR hyperintensity is used clinically to identify infiltrative tumor. Serially xenografted D-212 MG cells (supratentorial giant-cell GBM, 11yr old, H3F3A wt) formed tumors with FLAIR hyperintensity principally at the rim and Gd-DTPA enhancement prevalent at the tumor core. Histopathological assessment of H&amp;E staining confirmed the presence of masses with focal invasion at the periphery. Tumors established following pontine injection of HSJD-DIPG-007 cells (6yr old, H3F3A K27M, ACVR1 R206H) were identifiable by T2-w MRI hyperintensity in the pons and cerebellum. Histology confirmed a highly infiltrative tumor throughout the pons, cerebellum and leptomeninges, including the fissures of the cerebellum, which was validated by human nuclear antigen immunohistochemical staining. No extravasation of Gd-DTPA was observed indicating that the BBB remained intact. SU-DIPG-VI cells (6yr old, H3F3A K27M) grew diffusely in the pons with evidence of edema detected by T2-w MRI hyperintensity and FLAIR hypointensity. Diffusely hyperintense T2-w lesions with indistinct boundaries and limited Gd-DTPA extravasation were observed when imaging the diffusely infiltrative tumors resulting from thalamic implantation of QCTB-R059 primary thalamic GBM cells (10yr old, H3F3A K27M). In vivo propagation of primary and serially xenografted pHGG cells results in tumors that possess features of clinical disease, including infiltrative growth and necrosis. There is substantial potential for the use of these models to evaluate preclinical efficacy of novel therapeutics in a range of anatomical and biological subgroups of GBM and DIPG. Citation Format: Jessica K.R. Boult, Kathryn R. Taylor, Maria Vinci, Sergey Popov, Alexa Jury, Valeria Molinari, Marta M. Alonso, Wendy Ingram, Angel M. Caraboso, Michelle Monje, Suzanne A. Eccles, Chris Jones, Simon P. Robinson. Novel orthotopic pediatric high grade glioma xenografts evaluated with magnetic resonance imaging mimic human disease. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3271. doi:10.1158/1538-7445.AM2015-3271

Magnetic Resonance Spectroscopy of Adult Thalamic Glioblastoma Multiforme

Thalamic glioblastoma multiforme (GBM) is a rare malignant primary central nervous system (CNS) tumor. Here we report a case of adult unilateral GBM involving the right thalamus. The diagnosis of GBM was first indicated by a region of irregular enhancement with central necrosis in the thalamus, visualized with traditional magnetic resonance imaging (MRI) with contrast. Magnetic resonance spectroscopy (MRS), showing elevated lipid and lactate peaks, provided further evidence of GBM while rendering primary CNS lymphoma (PCNSL), anaplastic glioma, or metastasis less likely. The final diagnosis of GBM was confirmed by pathological examination of the tumor specimen. This report highlights the utility of combining MRS with other imaging modalities to facilitate the diagnosis of CNS lesions. [N A J Med Sci. 2012;5(1):51-54.]

Image-guided frameless stereotactic biopsy without intraoperative neuropathological examination

Stereotactic biopsy is a safe and effective technique for the diagnosis of brain tumors. The use of intraoperative neuropathological examination has been routinely advocated to increase diagnostic yield, but the procedure lengthens surgical time, may produce false-negative and -positive results, and current biopsy techniques have a very low nondiagnostic rate. Therefore, the authors questioned the need for intraoperative histological evaluation. The authors prospectively studied all patients undergoing image-guided biopsy under the care of a single surgeon (P.L.G.) between July 2005 and October 2007. A Stryker neuronavigation system with a trajectory guide was used to plan a single trajectory, and, using a side-cutting biopsy cannula, multiple biopsy samples were taken from between 1 and 4 sites within the tumor. Tissue was inspected macroscopically by the surgeon and was only submitted for neuropathological assessment postoperatively. One hundred thirty-four biopsies were performed during the study. A positive diagnosis was established in 133 cases (99.3%). One biopsy was negative (0.7%) and postoperative imaging (performed because the tissue was macroscopically normal) demonstrated inaccurate targeting of the lesion. Significant complications were seen in 3 patients (2.2%) who all had preoperative WHO performance scores of III or IV. Two patients suffered delayed deterioration and died due to probable surgical complications--one with thalamic glioblastoma multiforme (GBM) and one with gliomatosis cerebri. One patient with GBM suffered an intracerebral hematoma that was managed conservatively. Postoperative seizures were seen in 4 patients (3%), and 2 patients (1.5%) experienced a transient neurological deficit. Histological diagnosis showed a GBM in 64 cases, Grade III glioma in 19, Grade I or II in 23, metastasis in 10, lymphoma in 13, and other disease in 4. There were 32 patients discharged to home on the same day as surgery. Compared with the authors' previous retrospective audit into 127 biopsies, this technique showed improved diagnostic yield (99.3 vs 94.5%, p = 0.032) with fewer complications (2.2 vs 4.7% [not statistically significant]). This technique of image-guided biopsy has high diagnostic yield with acceptably low morbidity and may be performed as a day case. Intraoperative neuropathological examination would not have increased the diagnostic yield further in this study, and its routine use may not be necessary. In the authors' department pounds sterling 70,350 (UK)/$114,522 (US) would have been saved by not using intraoperative neuropathology in this series. Therefore, intraoperative neuropathology should no longer be routinely recommended.

Pediatric thalamic glioblastoma associated with Ollier disease (multiple enchondromatosis): a rare case of concurrence

Ollier disease and Maffucci syndrome are rare syndromes in which there is deforming dysplasia of cartilage, primarily but not exclusively involving the metaphyses and diaphyses of long bones. In a minority of patients, dysplasia can lead to sarcomatous degeneration, producing chondrosarcomas. There also appears to be an association with other neoplasms. Little has been written about the association between Ollier disease and intracranial tumors, and these papers have largely consisted of case reports in adults. The authors present the case of a 6-year-old girl with left arm osseous changes consistent with Ollier disease and a biopsy-proven thalamic glioblastoma multiforme. They then examine the co-occurrence of brain tumors in conjunction with a dyschondroplasia syndrome in children and adolescents to assess the presentation, treatment offered, and disease course of similar cases. Eight other such cases were identified, 6 in patients with Ollier disease (ranging in age from 7 to 18 years), and 2 with Maffucci syndrome (both in late adolescence). Including our own patient, 7 of the 9 cases of comorbid dyschondroplasia and intracranial malignancy occurred in girls. Some patients presented soon after the acute onset of symptoms, and others had a more subtle, protracted course over as many as 2 years. Some tumors were deemed resectable and others not. In only 1 instance was follow-up beyond 1 year reported.

Transcortical mixed aphasia in a case of thalamic glioblastoma

Abstract We report a case of transcortical mixed aphasia associated with left thalamic glioblastoma. A 60-year-old right-handed woman was admitted to our hospital with speech disturbance and right hemiparesis. She was alert and well oriented. However, spontaneous speech was remarkably reduced, and object naming, word fluency, verbal comprehension, reading and writing were all severely disturbed. However, repetition of phonemes and sentences was fully preserved. CT scan revealed a huge tumour in the left thalamus. The rCBF (regional cerebral blood flow) study and 99mTc-HM-PAO SPECT (single-photon emission CT) showed a low-flow area in the entire left hemisphere. It is possible that rCBF does not necessarily reflect cerebral function, so that function in the tumour area may be retained even in the presence of reduced rCBF caused by a brain tumour. In this case, reduced linguistic ability might have reflected compensation by the contralateral hemisphere.

Immunological fluctuations during intrathecal immunotherapy in three patients affected by CNS tumours disseminating via CSF.

The immunological therapy of cancer has been proposed in a number of neoplasms (Borden, Sondel, 1989; Foon, 1989; Rosenberg, 1992) and has recently been adopted in the treatment of Central Nervous System (CNS) tumors in combination with conventional surgical and radiotherapeutical approach. In this context, loco-regional administration of immunomodulating agents (for instance in post-surgical cavity) allows to achieve much higher in situ concentrations than by systemic route. Since these treatments have potential adverse effects, careful assessment of clinical and immunological parameters in phase I trials is needed. CNS tumors disseminating via Cerebrospinal Fluid (CSF) pathways offer a stimulating opportunity for intrathecal immunotherapy. In this context, alpha-IFN and IL2 (alone or in combination with LAK cells) have been employed either loco-regionally or intrathecally (Merchant, Mc Vicar, Merchant & Young, 1992; Schiller, Hank, Storer, Borchert, Moore, Albertini, Bechhofer, Wesley, Brown, Bastin & Sondel, 1993). The rationale for the use of both these substances includes the known anti-tumor action of alpha-IFN (Mahaley, Urso, Whaley, Blue, Williams, Guaspari & Selker, 1985; Nagai, 1988) and the ability of r-IL2 to generate activated cells effective in lysing tumor cell targets (Hayes, Moore, Pierz, Chen, Da Rosso, Nirenberg & Allen, 1993). We treated 3 patients (2 affected by disseminating cerebellar medulloblastoma, 1 by disseminating thalamic glioblastoma) by intrathecal r-IL2 via recervoir. In the first 2 patients, this treatment was preceded by alpha-IFN (also intrathecally). Monitoring of immunological effects of the treatment schedule involved kinetics of CSF and serum TNF-alpha, IL2s and IL2R during the first day of r-IL2 treatment, as well as on day +2 and +4 of both r-IL2 cycles, and assessment of CSF cells, protein and CSF and PB NK cell activity and CD3-CD56+ cells during the course of all treatment cycles. We also assessed clinical and neuroradiological effects of immunotherapy.