Carmustine wafer implantation for supratentorial glioblastomas, IDH-wildtype in "extreme" neurosurgical conditions.

We assessed the feasibility of Carmustine wafer implantation in "extreme" conditions (i.e. patients > 80 years and Karnofsky Performance Status score < 50) and of implantation ≥ 12 Carmustine wafers in adult patients harbouring a newly diagnosed supratentorial glioblastoma, IDH-wildtype. We performed an observational, retrospective single-centre cohort study at a tertiary surgical neuro-oncological centre between January 2006 and December 2021. Four hundred eighty patients who benefited from a surgical resection at first-line treatment were included. We showed that Carmustine wafer implantation in patients > 80 years, in patients with a Karnofsky performance status score < 50, and that implantation ≥ 12 Carmustine wafers (1) did not increase overall postoperative complication rates, (2) did not affect the completion of standard radiochemotherapy protocol, (3) did not worsen the postoperative Karnofsky Performance Status scores, and (4) did not significantly affect the time to oncological treatment. We showed that the implantation of ≥ 12 Carmustine wafers improved progression-free survival (31.0 versus 10.0 months, p = 0.025) and overall survival (39.0 versus 16.5 months, p = 0.041) without increasing postoperative complication rates. Carmustine wafer implantation during the surgical resection of a newly diagnosed supratentorial glioblastoma, IDH-wildtype is safe and efficient in patients > 80 years and in patients with preoperative Karnofsky Performance Status score < 50. The number of Carmustine wafers should be adapted (up to 16 in our experience) to the resection cavity to improve survival without increasing postoperative overall complication rates.

Effect of Systemic Lidocaine on Postoperative Early Recovery Quality in Patients Undergoing Supratentorial Tumor Resection.

Purpose: Lidocaine has been gradually used in general anesthesia. This study was designed to investigate the effect of systemic lidocaine on postoperative quality of recovery (QoR) in patients undergoing supratentorial tumor resection, and to explore its brain-injury alleviation effect in neurosurgical anesthesia. Patients and Methods: Sixty adult patients undergoing elective supratentorial tumor resection. Patients were randomly assigned either to receive lidocaine (Group L: 1.5 mg/kg bolus completed 10 min before anesthesia induction followed by an infusion at 2.0 mg/kg/h) or to receive normal saline (Group C: received volume-matched normal saline at the same infusion rate). Primary outcome measures were Quality of Recovery-40 (QoR-40) scores on postoperative day (POD) 1 and 2. Plasma concentrations of S100B protein (S100B), neuron specific enolase (NSE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) before anesthesia induction and at the end of surgery were assessed. Visual Analogue Scale (VAS) scores were assessed at 1, 2, 6, 12, 24 and 48 h after surgery. Perioperative parameters and adverse events were also recorded. Results: Patients between two groups had comparable baseline characteristics. Global QoR-40 scores on POD 1 and POD 2 were significantly higher (P <0.001) in group L (165.5±3.8 vs 173.7±4.7) than those in group C (155.6±4.0 vs 163.2±4.5); and scores of physical comfort, emotional state, and pain in group L were superior to those in group C (P <0.05). In group L, patients possessed lower plasma concentration of pro-inflammatory factors (IL-6, TNF-α) and brain injury-related factors (S100B, NSE) (P <0.05), consumed less remifentanil and propofol, and experienced lower pain intensity. Multiple linear regression analysis demonstrated age and pain were correlated with postperative recovery quality. Conclusion: Systemic lidocaine improved early recovery quality after supratentorial tumor resection with general anesthesia, and had certain brain-injury alleviation effects. These benefits may be attributed to the inflammation-alleviating and analgesic properties of lidocaine.

Small Cell Variant of Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma of the Dura Mimicking Tentorial Meningioma.

BACKGROUND: Primary central nervous system (CNS) anaplastic large cell lymphoma (ALCL) is an uncommon type of brain tumor, usually treated with a regimen that includes high-dose methotrexate (MTX). Only a few cases of primary CNS anaplastic lymphoma kinase (ALK)-positive ALCL have been reported so far, with no reported cases of a small cell variant. CASE DESCRIPTION: A 26-year-old man presenting with headache and visual field impairment was found to have a supratentorial mass mimicking meningioma. Craniotomy was performed for tumor resection, and postoperative histologic examination revealed atypical cells that were nonenlarged lymphocytes with irregularly shaped and enlarged nuclei; these cells were cluster of differentiation 30 and ALK-positive, leading to the diagnosis of a small cell variant of ALK-positive ALCL. In this case, the tumor exhibited an aggressive behavior with MTX resistance with metastases in the pelvis but responded well to cytarabine and etoposide (CYVE). CONCLUSIONS: In general, CNS ALK-positive ALCL responds well to MTX, but small cell variants show aggressive behavior and may be resistant to MTX. For small cell variants of ALCL that are resistant to MTX therapy, as in this case, CYVE therapy may be an effective treatment.

Low perfusion compartments in glioblastoma quantified by advanced magnetic resonance imaging and correlated with patient survival.

BACKGROUND AND PURPOSE: Glioblastoma exhibits profound intratumoral heterogeneity in perfusion. Particularly, low perfusion may induce treatment resistance. Thus, imaging approaches that define low perfusion compartments are crucial for clinical management. MATERIALS AND METHODS: A total of 112 newly diagnosed glioblastoma patients were prospectively recruited for maximal safe resection. The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were calculated from diffusion and perfusion imaging, respectively. Based on the overlapping regions of lowest rCBV quartile (rCBVL) with the lowest ADC quartile (ADCL) and highest ADC quartile (ADCH) in each tumor, two low perfusion compartments (ADCH-rCBVL and ADCL-rCBVL) were identified for volumetric analysis. Lactate and macromolecule/lipid levels were determined from multivoxel MR spectroscopic imaging. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier's and multivariate Cox regression analyses, to evaluate the effects of compartment volume and lactate level on survival. RESULTS: Two compartments displayed higher lactate and macromolecule/lipid levels compared to contralateral normal-appearing white matter (each P < 0.001). The proportion of the ADCL-rCBVL compartment in the contrast-enhancing tumor was associated with a larger infiltration on FLAIR (P < 0.001, rho = 0.42). The minimally invasive phenotype displayed a lower proportion of the ADCL-rCBVL compartment than the localized (P = 0.031) and diffuse phenotypes (not significant). Multivariate Cox regression showed higher lactate level in the ADCL-rCBVL compartment was associated with worsened survival (PFS: HR 2.995, P = 0.047; OS: HR 4.974, P = 0.005). CONCLUSIONS: Our results suggest that the ADCL-rCBVL compartment may potentially indicate a clinically measurable resistant compartment.

Convection-Enhanced Delivery of Polymeric Nanoparticles Encapsulating Chemotherapy in Canines with Spontaneous Supratentorial Tumors.

BACKGROUND: Despite aggressive multimodal treatment, survival for patients with glioblastoma remains dismal. One obstacle to improving patient outcomes is the difficulty in delivering adequate therapeutic to the central nervous system due to the presence of the blood-brain barrier. Although direct drug infusion by convection-enhanced delivery (CED) can bypass the blood-brain barrier and facilitate delivery to intracranial tumors, determining the distribution of delivered therapeutic remains problematic. Image guidance is a strategy that can optimize the accuracy of therapeutic delivery. METHODS: Here we performed an open-label clinical trial in 10 pet dogs with spontaneous intracranial tumors to examine the target coverage accuracy of delivering polymeric magnetite nanoparticles (PMNPs) encapsulating temozolomide (TMZ). A modified small animal frame was applied to the head of each subject, and PMNPs were delivered stereotactically to the center of the tumor. Magnetic resonance imaging (MRI) was performed immediately postoperatively to examine PMNP distribution, and the animals were followed until death. RESULTS: Nine of the 10 dogs underwent PMNP infusion without complications. No infusate backflow was observed during any procedure. In 70% of the cases, the infusion accurately targeted the tumor mass, as determined by the presence of PMNP signal in the tumor on immediate postoperative MRI. CONCLUSIONS: These data suggest that CED of PMNPs carrying TMZ is safe in dogs with intracranial tumors and can lead to nanoparticle distribution in the region of the target. Image guidance is an important adjunct to CED, because distribution is unpredictable, with the potential for missed target delivery.

Effect of Radiation Treatment Volume Reduction on Lymphopenia in Patients Receiving Chemoradiotherapy for Glioblastoma.

PURPOSE: To evaluate whether reduction in glioblastoma radiation treatment volume can reduce risk of acute severe lymphopenia (ASL). METHODS AND MATERIALS: A total of 210 patients with supratentorial/nonmetastatic glioblastoma were treated with radiation therapy (RT) plus temozolomide from 2007 to 2016 and had laboratory data on total lymphocyte counts. Before 2015, 164 patients were treated with standard-field RT (SFRT), and limited-field RT (LFRT) was implemented thereafter for 46 patients to reduce treatment volume. Total lymphocyte counts were evaluated at baseline, during RT, and at approximately week 12 from initiating RT. Acute severe lymphopenia was defined as any total lymphocyte count < 500 cells/µL within 3 months (by week 12) of initiating RT. Multivariate analysis for overall survival (OS) was performed with Cox regression and with logistic regression for ASL. Propensity score matching was performed to adjust for variability between cohorts. Acute severe lymphopenia, progression-free survival (PFS), and OS were compared using the Kaplan-Meier method. RESULTS: Limited-field RT patients had higher gross tumor volume than SFRT patients yet lower brain dose-volume parameters, including volume receiving 25 Gy (V25 Gy: 41% vs 53%, respectively, P < .01). Total lymphocyte count at week 12 was significantly higher for LFRT than for SFRT (median: 1100 cells/µL vs 900 cells/µL, respectively, P = .02). On multivariate analysis, ASL was an independent predictor of OS, and brain V25 Gy was an independent predictor of ASL. The ASL rate at 3 months was 15.5% for LFRT and 33.8% for SFRT (P = .12). In a propensity-matched comparison of 45 pairs of LFRT and SFRT patients, PFS (median: 5.9 vs 6.2 months, respectively, P = .58) and OS (median: 16.2 vs 13.9 months, respectively, P = .69) were not significantly different. CONCLUSIONS: Limited-field RT is associated with less lymphopenia after RT plus temozolomide and does not adversely affect PFS or OS. Brain V25 Gy is confirmed as an important dosimetric predictor for ASL.

Tremor Secondary to a Thalamic Glioma: A Case Report.

BACKGROUND AND IMPORTANCE: Tremor is the most prevalent movement disorder. While the exact pathophysiology remains to be elucidated, the importance of the thalamus in tremor circuitry is well recognized. Thalamic lesions from demyelination, trauma, ischemia, or neoplasm rarely cause isolated tremor. We report the case of a patient presenting with a tremor secondary to a thalamic grade II astrocytoma that improved with treatment. CLINICAL PRESENTATION: A 50-yr-old male presented with a 1-yr history of right-hand tremor. The presence of long tract signs prompted imaging that revealed a lesion within the left thalamus. Stereotactic biopsy revealed a World Health Organization grade II astrocytoma. Prior to biopsy, the patient's tremor was graded using the Clinical Rating Scale for Tremor. Immediately postoperatively the patient remained at his neurological baseline without improvement in his tremor. Subsequent fractionated radiotherapy with concomitant temozolomide followed by adjuvant temozolomide led to radiographic response as well as clinical improvement. The patient reported less tremor, which was confirmed objectively with improved Clinical Rating Scale for Tremor scores at 6 and 12 mo postoperatively. CONCLUSION: This case of a thalamic glioma presenting with isolated contralateral tremor highlights the role of the thalamus in the development of tremor. Moreover, this particular case contrasts with other published reports on the lack of additional symptoms and tremor response to chemoradiation.

Extent of resection and Carmustine wafer implantation safely improve survival in patients with a newly diagnosed glioblastoma: a single center experience of the current practice.

For newly diagnosed glioblastomas treated with resection in association with the standard combined chemoradiotherapy, the impact of Carmustine wafer implantation remains debated regarding postoperative infections, quality of life, and feasibility of adjuvant oncological treatments. To assess together safety, tolerance and efficacy of Carmustine wafer implantation and of extent of resection for glioblastoma patients in real-life experience. Observational retrospective monocentric study including 340 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent surgical resection with (n = 123) or without (n = 217) Carmustine wafer implantation as first-line oncological treatment. Carmustine wafer implantation and extent of resection did not significantly increase postoperative complications, including postoperative infections (p = 0.269, and p = 0.446, respectively). Carmustine wafer implantation and extent of resection did not significantly increase adverse events during adjuvant oncological therapies (p = 0.968, and p = 0.571, respectively). Carmustine wafer implantation did not significantly alter the early postoperative Karnofsky performance status (p = 0.402) or the Karnofsky performance status after oncological treatment (p = 0.636) but a subtotal or total surgical resection significantly improved those scores (p < 0.001, and p < 0.001, respectively). Carmustine wafer implantation, subtotal and total resection, and standard combined chemoradiotherapy were independently associated with longer event-free survival (adjusted Hazard Ratio (aHR), 0.74 [95% CI 0.55-0.99], p = 0.043; aHR, 0.70 [95% CI 0.54-0.91], p = 0.009; aHR, 0.40 [95% CI 0.29-0.55], p < 0.001, respectively) and with longer overall survival (aHR, 0.69 [95% CI 0.49-0.96], p = 0.029; aHR, 0.52 [95% CI 0.38-0.70], p < 0.001; aHR, 0.58 [95% CI 0.42-0.81], p = 0.002, respectively). Carmustine wafer implantation in combination with maximal resection, followed by standard combined chemoradiotherapy is safe, efficient, and well-tolerated in newly diagnosed supratentorial glioblastomas in adults.

Effective and safe mannitol administration in patients undergoing supratentorial tumor surgery: A prospective, randomized and double blind study.

OBJECTIVES: Although osmotic diuresis with mannitol is commonly used to provide brain relaxation, there is no consensus regarding its optimal dose and combination with loop diuretics. The aim of the present study is to evaluate the effects of mannitol and combination of furosemide with different doses of mannitol on brain relaxation and on blood electrolytes, lactate level, urine output, fluid balance and blood osmolarity in patients undergoing supratentorial tumor surgery. PATIENTS AND METHODS: This prospective, randomized, double blind, placebo-controlled study included 51 patients (ASA I-III) scheduled for elective supratentorial craniotomy. Different doses and combinations of diuretics were administered after the bone flap removal. The Group 1 received mannitol at 0.5gkg-1 and furosemide at 0.5mgkg-1, the Group 2 received mannitol at 1gkg-1 and furosemide at 0.5mgkg-1, and the Group 3 received mannitol at 0.5gkg-1 and placebo. The primary end-point of the present study is to evaluate the effects of mannitol and combination of furosemide with different doses of mannitol on brain relaxation and the secondary end-points are to evaluate their effects on blood electrolytes, lactate level, urine output, fluid balance and blood osmolarity. RESULTS: This study shows that mannitol alone (0.5gkg-1), and the combinations of furosemide (0.5mgkg-1) with different doses of mannitol (0.5gkg-1-1gkg-1) provides adequate brain relaxation. However, administration of furosemide with low or high doses of mannitol may cause reduction in the sodium and chloride levels as well as rise in the lactate level. Moreover it may cause high urine output and negative intra-operative fluid balance. CONCLUSION: Administration of 0.5gkg-1 mannitol provides adequate brain relaxation without causing systemic side effects in patients undergoing supratentorial tumor surgery. This study is registered to clinical trials (Clinical Trials.gov identifier NCT02712476).

Efficacy of Ifosfamide-Cisplatin-Etoposide (ICE) Chemotherapy for a CNS Germinoma in a Child With Down Syndrome.

Intracranial germ cell tumor is sometimes associated with Down syndrome; however, no optimal treatment has been developed due to the high risk of recurrence and treatment-related mortality. Here, we report on a patient with an intracranial germinoma in the bilateral basal ganglia. The patient received 3 courses of ifosfamide-cisplatin-etoposide in combination with whole-brain irradiation (24 Gy), with no serious complications. The patient is alive and disease free 16 months after the initial diagnosis. This regimen is a feasible treatment for intracranial germ cell tumor associated with Down syndrome, although careful attention must be paid to the increased risk for severe infection.

Epilepsy in Adults with Supratentorial Glioblastoma: Incidence and Influence Factors and Prophylaxis in 184 Patients.

AIM: To analyze the incidence of epilepsy in adult patients with supratentorial glioblastoma, assess the factors influencing the development of epilepsy in these cases, and evaluate patients' response to antiepileptic drugs (AEDs) in a series of 184 patients. METHODS: We retrospectively analyzed the 184 adult patients diagnosed with supratentorial glioblastoma. All subjects were treated within our hospital and subsequently died between 2003 and 2013. The incidence of epilepsy was assessed before and after initial resection and reexamined every 2 months thereafter. We evaluated the efficacy of prophylactic AEDs in this patient population based on the gathered incidence data. RESULTS: Of 184 patients, 43 (23.37%) were diagnosed with epilepsy before their initial resection. The total incidence of epilepsy (both pre- and postoperative) was 68.48%. The prevalence of active epilepsy reached over 80% in patients with epilepsy and survival of greater than 13 months postoperatively. Patients with glioblastoma in the frontal and/or temporal lobes had a higher prevalence of epilepsy. In the 43 patients with preoperative epilepsy, total resection of glioblastoma resulted in significantly lower seizure frequency. Patients who received epilepsy prophylaxis with AEDs for at least 6 months had significantly fewer seizures and higher Karnofsky scores than those receiving AEDs for less than one month or not at all. CONCLUSION: The incidence of epilepsy in adult patients with glioblastoma was high and responded poorly to AEDs in the short term. However, when taken for longer periods, AEDs can reduce the frequency of seizures in patients with glioblastoma.

Pencil beam scanning proton therapy for pediatric intracranial ependymoma.

To assess the clinical outcome and late side effect profile of pencil beam scanning proton therapy (PT) delivered to children with intracranial ependymoma. Between July-2004 and March-2013, 50 patients with intracranial ependymoma (n = 46, grade 3) received involved-field PT at Paul Scherrer Institute (PSI). Median age at time of PT was 2.6 years (range 1.1-15.2). Thirty-six patients had infratentorial and 14 supratentorial ependymomas. Seventeen patients presented with macroscopic residual disease after subtotal resection before starting PT (8 with ≤1.5 cc and 9 with >1.5 cc residual tumor respectively). Forty-three (86 %) patients received post-operative chemotherapy before PT according to protocols; 44 (88 %) patients younger than 5 years required general anesthesia. Median prescribed dose was 59.4 Gy (RBE) (range 54-60) delivered in 1.8-2 Gy (RBE) per fraction. Late toxicity was assessed according to CTCAE v4.0. With a mean follow-up time of 43.4 months (range 8.5-113.7) seven patients experienced local failure (6 with infratentorial tumors and 1 with supratentorial tumor); four of the local failures were in patients with residual disease ≥1.5 cc at the time of PT and 3 without residual macroscopic disease. Five patients died from tumor progression. Actuarial 5-year Local Control rates were 78 ± 7.5 % and 5-year OS rates were 84 ± 6.8 %. Three patients developed grade ≥3 toxicity: 2 developed unilateral deafness (infratentorial tumors infiltrating into the internal acoustic canal), one patient developed a fatal brainstem necrosis. Repeated general anesthesia in children younger than 5 years was delivered without complications. Our data indicate the safety and the effectiveness of PT for pediatric ependymomas. Local control and survival rates are encouraging considering the high grade histology in 92 % of the patients and the number of patients with residual tumor ≥1.5 cc. The rates of late effects compare favorably with published photon-treated cohorts.

Recurrent Glioblastoma Multiforme (grade IV - WHO 2007): a case of complete objective response - concomitant administration of Somatostatin / Octreotide, Retinoids, Vit E, Vit D3, Vit C, Melatonin, D2 R agonists (Di Bella Method.

In a 41 year old man, with Glioblastoma Multiforme (Grade IV - WHO 2007) and loco-regional recurrence, treated conventionally with surgery, radio-therapy and Temolozomide, a complete objective response was subsequently achieved by means of the well-tolerated concomitant administration of Somatostatin + slow-release Octreotide, Melatonin, Retinoids solubilized in Vitamin E, Vit D3, Vit C, D2 R agonists, and Temolozomide. In addition to the positive and previously unreported therapeutic finding, this result allowed the patient to avoid further surgical trauma and the correlated risks, achieving an excellent quality of life and working capacity.

Impact of renin-angiotensin system blockade on clinical outcome in glioblastoma.

BACKGROUND AND PURPOSE: Despite surgery, radiotherapy (RT) and temozolomide (TMZ), the prognosis of glioblastoma (GBM) patients remains dismal. Normally prescribed with the aim to lower blood pressure, angiotensin-II (Ang-II) inhibitors were reported to reduce angiogenesis and tumour growth in several tumour models including one glioma. Thus whether treatment with Ang-II inhibitors could be associated with a better clinical outcome in GBM patients was investigated. METHODS: A series of 81 consecutive patients, homogeneously treated with RT and TMZ for a newly diagnosed, supratentorial GBM, were analysed. The objective of this retrospective study was to assess the impact of angiotensin-converting enzyme inhibitors (ACEIs) and Ang-II receptor 1 blockers (ARBs) on functional independence, progression-free survival (PFS) and overall survival (OS). RESULTS: Amongst the 81 GBM patients analysed, 26 were already treated for high blood pressure (seven with ACEIs and 19 with ARBs). The number of patients who remained functionally independent at 6 months after RT was higher in the group of patients treated with Ang-II inhibitors compared to the other patients (85% vs. 56%, P = 0.01). In patients treated with Ang-II inhibitors, PFS was 8.7 months (vs. 7.2 months in the other patients) and OS was 16.7 months (vs. 12.9 months). The use of Ang-II inhibitors was a significant prognostic factor for both PFS (P = 0.04) and OS (P = 0.04) in multivariate analysis. CONCLUSION: Treatment with Ang-II inhibitors in combination with RT and TMZ might improve clinical outcome in GBMs. Prospective trials are needed to test this hypothesis.

Volumetric modulated arc therapy for hippocampal-sparing radiotherapy in transformed low-grade glioma: A treatment planning case report.

Timing of radiotherapy for low-grade gliomas is still controversial due to concerns of possible adverse late effects. Prevention of possible late cognitive sequelae by hippocampal avoidance has shown promise in phase II trials. A patient with progressive low-grade glioma with gradual dedifferentiation into anaplastic astrocytoma is presented along with description of radiotherapy planning process attempting to spare the hippocampus. To our knowledge, this is the first described case using volumetric modulated arc technique to spare hippocampus during transformed low-grade glioma radiotherapy. Using modern intensity-modulated radiotherapy systems it is possible to selectively spare hippocampus together with other standard organs at risk. For selected patients, an attempt to spare hippocampus can be considered as long as other dose characteristics are not significantly compromised compared to standard treatment plan created without any effort to avoid hippocampus.

Combining intraoperative carmustine wafers and Stupp regimen in multimodal first-line treatment of primary glioblastomas.

BACKGROUND: The study investigated if intraoperative use of carmustine wafers, particularly in combination with Stupp regimen, is a viable and safe first-line treatment option of glioblastomas. METHODS: Eighty-three consecutive adult patients (50 men; mean age 60 years) with newly diagnosed supratentorial primary glioblastomas that underwent surgical resection with intraoperative carmustine wafers implantation (n = 7.1 ± 1.7) were retrospectively studied. RESULTS: The median overall survival (OS) was 15.8 months with 56 patients dying over the course of the study. There was no significant association between the number of implanted carmustine wafers and complication rates (four surgical site infections, one death). The OS was significantly longer in Stupp regimen patients (19.5 months) as compared with patients with other postoperative treatments (13 months; p = 0.002). In addition patients with eight or more implanted carmustine wafers survived longer (24.5 months) than patients with seven or less implanted wafers (13 months; p = 0.021). Finally, regardless of the number of carmustine wafers, median OS was significantly longer in patients with a subtotal or total resection (21.5 months) than in patients with a partial resection (13 months; p = 0.011). CONCLUSIONS: The intraoperative use of carmustine wafers in combination with Stupp regimen is a viable first-line treatment option of glioblastomas. The prognostic value of this treatment association should be evaluated in a multicenter trial, ideally in a randomized and placebo-controlled one.

Cerebral peduncle tumor ablated by novel 3-mm laser tip.

BACKGROUND/OBJECTIVE: Decisions to use open surgery or radiotherapy in pediatric patients with familial neoplastic syndromes must consider not only the symptomatic benefits of treatment, but also future limitations these treatments may impose. Specifically, open surgical resection of noncurable tumors may preclude or encumber future lesion resections, while radiotherapy has detrimental effects on pediatric cognitive development and increases the risk of future malignancy development. We provide the first report of using a novel 3.0-mm diffusing laser tip with laser-induced thermal therapy (LiTT) to treat a pediatric patient with neurofibromatosis type 1 (NF-1). METHODS: A 12-year-old boy with NF-1 presented with a progressively enlarging lesion in the right midbrain. A stereotactic biopsy was performed, followed by LiTT with a novel 3.0-mm laser applicator. RESULTS: MRI 1 week after LiTT showed stable gross total ablation of the lesion with reduction in fluid-attenuated inversion recovery signal. The patient remained neurologically intact 6 months after his procedure, and follow-up MRI showed no evidence of recurrence. CONCLUSION: LiTT is a powerful adjunct to conventional open surgical and radiotherapy modalities in the treatment of patients with familial neoplastic syndromes or incurable lesions. The novel laser applicator tip described expands the treatment scope of this technique.

The impact of surgical resection of giant supratentorial brain tumor in pediatric patients: safety and neurological outcome evaluated in 23 consecutive cases.

OBJECTIVE: This study aims to evaluate the impact of gross total resection of giant supratentorial brain tumors (GSBT) on survival and neurological outcome in a consecutive single-center pediatric series. METHODS: Clinical data of 23 patients under 18 years of age operated with GSBT (≥5 cm in diameter) were reviewed to determine epidemiological aspects, clinical presentation, associated factors, histopathological features, and outcome. Volumetric measurements were performed on magnetic resonance imaging or computed tomography scans obtained at the time of the initial surgical procedure. RESULTS: The group included 23 patients (mean age 4.5 years). Signs and symptoms of raised intracranial pressure were present in 19 patients (82.6%). The most frequent tumor location was the parietal lobe in 19 patients (82.6%), and the mean tumor volume was 208 cm(3). Gross total or radical resection was achieved in all patients. Histopathological analysis revealed malignant brain tumors in 18 cases (78.2%). The most common neoplasm was choroid plexus carcinoma in seven (30.4 %). Mean intraoperative blood transfusion volume was 51.2 ml/kg. Chemotherapy and/or radiotherapy were performed as adjuvant treatment in 16 patients (69.5%). Mean length of follow-up was 36.7 months. Tumor malignancy grade significantly correlated with recurrence of the disease (P = 0.03) and death (P = 0.01), as opposed to tumor location, size, and extension to the ventricles. CONCLUSIONS: Our clinical experience suggests that tumor mass reduction by en bloc surgery seems to be an effective approach in pediatric patients with GSBT, relieving symptoms related to raised intracranial pressure and providing a better response to adjuvant treatment.

Treatment results and outcome in elderly patients with glioblastoma multiforme--a retrospective single institution analysis.

OBJECTIVE: Although glioblastoma multiforme is more common in patients older than 65 years, the elderly population is often excluded from clinical studies. Decision making in this subgroup can be challenging due to the lack of evidence for different neurosurgical and adjuvant treatment strategies. METHODS: In this retrospective study, we evaluated clinical, treatment and survival data of 124 consecutive patients over 65 years of age with supratentorial glioblastoma multiforme. RESULTS: Median OS was 6.0 months (std. error 0.783, 95% CI 4.456-7.535). Mean OS was 9.7 months (std. error 0.830, 95% CI 8.073-11.327). In univariate regression analysis, low KPS was of negative prognostic value (p < 0.006 for KPS ≤ 80), while greater advanced age did not have any impact on survival (p = 0.591 for differences between groups). Gross total resection and subtotal resection led to significantly improved overall survival (median 15.0 and 11.0 months; p < 0.02) compared to partial resection or biopsy (both 4.0 months), but complications were more common in subtotal and partial resections. The last observation did not reach statistical significance (p = 0.06). Combinations of irradiation and Temozolomide chemotherapy proved to be more effective than other adjuvant therapies. Extent of resection (gross total resection vs. all others) and form of adjuvant treatment were the only factors of independent prognostic value in multivariate analysis (p = 0.031 and p < 0.001, respectively). CONCLUSIONS: It appears that more aggressive treatment regimens can lead to longer overall survival in elderly glioblastoma multiforme patients. Gross total resection should be offered whenever safely possible; otherwise, biopsy may be preferred. Non-surgical treatment should consist of postoperative radiotherapy and concomitant and/or adjuvant chemotherapy. Possibly higher rates of hematological side effects in concomitant chemotherapy need to be further investigated.

Supratentorial low-grade diffuse astrocytoma: medical management.

Diffuse astrocytomas (DAs) represent less than 10% of all gliomas. They are diffusely infiltrating World Health Organization (WHO) grade II neoplasms that have a median survival in the range of 5-7 years, generally with a terminal phase in which they undergo malignant transformation to glioblastoma (GBM). The goals of treatment in addition to prolonging survival are therefore to prevent progression and malignant transformation, as well as optimally managing symptoms, primarily tumor-associated epilepsy. Available data suggest that the course of this disease is only minimally impacted by adjuvant therapies and that there does not seem to be much difference in terms of outcome of whether patients are treated in the adjuvant setting with irradiation or chemotherapy. We review the experience with chemotherapy as a treatment modality and offer some guidelines for its usage and discuss medical management of arising symptoms.