Tumor.

Gamma knife treatment is a clinically effective, safe, and cost-effective adjunctive therapy for primary malignant brain tumors. For most brain metastases, radiosurgery is the treatment of choice and will result in effective tumor control in more than 90% of treated tumors.

Malignant brain tumors (MBTs) encompass primary malignant brain tumors (PMBTs) and secondary brain tumors (SBTs). MBTs affect 5-10 out of 100,000 people annually and are responsible for 3% of all cancer deaths worldwide. These tumors are the second most common cause of cancer death in young people and the sixth most common cause of productive-years-loss in the community. MBTs carry very dismal prognosis and their diagnosis almost always means a death sentence deferred by merely 36 weeks or less (Obwegeser et al. 1995; Eljamel 2004). PMBT (intracranial gliomas) represent 38%–40% of primary brain tumors and glioblastoma multiforme (GBM) is the most common PMBT (Stupp 2007). GBMs are divided into two: primary and secondary GBMs. Primary GBMs arise de novo, represent 60% of GBMs, and are diagnosed mainly in people over 50 years of age. Secondary GBMs, on the other hand, represent 40% of GBMs and are most common in people under 45 years of age. Several researchers have studied GBMs extensively to assess their prognosis and factors associated with better survival. Three risk groups were identified (Lamborn, Chang, and Prados 2004): a low-risk group consisting of young patients (under 40 years of age) with tumors located in the frontal lobe; a moderaterisk group consisting of patients between 40 and 65 years of age and Karnofsky performance scores (KPSs) >70 who had surgical resection; and a high-risk group of patients >65 years of age and patients between 40 and 65 years who had KPS <80 or had tumor biopsy only. Several recent studies assessed the impact of genetic mutations on GBMs’ outcome (Rich et al. 2005; Kleihues, Burger, and Cavenee 1997). Loss of heterozygosity (LOH) on chromosome group 10q, the most frequent gene abnormality for both primaryand secondary GBMs, is associated with poor survival. It occurs in 60%–90% of GBMs. This mutation appears to be specific for GBMs and is found rarely in other tumor grades. Mutations of p53, a tumor suppressor gene, were among the first genetic alterations identified in astrocytic brain tumors and appear to be deleted or altered in approximately 25%–40% of all GBMs and particularly in secondary GBMs (Watanabe et al. 1997). Despite extensive clinical trials, the median survival remained about 12 months with fewer than 25% surviving for 2 years and fewer than 10% surviving for 5 years. In a series of 279 patients, only five (1.8%) survived for 3 years (Scott et al. 1998). Clearly, newer approaches for the management of GBMs are necessary and multimodality therapeutic approaches would be required to improve the outcome of these tumors. The joint tumor section of the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) in 2008 produced guidelines for the management of newly diagnosed GBMs (Olsen et al. 2008). The authors recommended maximum safe surgical resection of newly diagnosed GBMs (evidence level II), followed by 60 Gy of postoperative radiotherapy to the enhancing lesion (evidence level I) and for radiotherapy to include a 2 cm cuff around the enhancing lesion (evidence level II). The guidelines also recommended concurrent and postoperative temozolomide in newly diagnosed GBM (evidence level I) and BCNU (carmustine wafers) in those who undergo craniotomy (evidence level II). Temozolomide offers a mere 26% 2 year survival compared to 10% in placebo controls, a 14.6 month median survival compared to 12.1 months in placebo group, and a 7.2 month tumorprogression-free (TPF) survival compared to 5 months among placebo controls (Olsrn et al. 2008). Carmustine implants, on the other hand, prolong survival to 13.9 months compared to 11.942.1 Introduction ............................................................................................................................ 485 42.2 PD in MBT ............................................................................................................................... 486Fluorescence Image-Guided Surgery • Fluorescence Image-Guided Biopsy 42.3 PDT in MBT ............................................................................................................................ 48942.4 Specific Brain PD and PDT Equipment .............................................................................. 493 42.5 Conclusions.............................................................................................................................. 493 References ............................................................................................................................................ 493months in the placebo group (Vecht et al. 1990). The poor outcome of these tumors is due to local invasion and local relapse. The vast majority of these tumors recur locally within 2 cm of the resection margin and patients often succumb to and die from local recurrence, indicating that a more aggressive local therapy is required to eradicate these tumors. However, complete radical surgical excision is hindered by the elusive nature of these tumors: a significant amount of tumor cells are invisible to the naked eye even with the aid of the surgical microscope. The ability of these cancers to disguise themselves makes their identification at surgery almost impossible. Most of these tumors have invaded the brain widely by the time they manifest clinically, making wider excision margin out of the question in most cases par polar lesions in noneloquent brain.

64-Year-Old Woman With Aphasia and Troponin Elevation

Reasons for worldwide variability in the burden of primary malignant brain and central nervous system (CNS) tumors remain unclear. This study compares the incidence and survival of malignant brain and CNS tumors by selected histologic types between the United States (US) and Taiwan. Data from 2002 to 2010 were selected from two population-based cancer registries for primary malignant brain and CNS tumors: the Central Brain Tumor Registry of the United States and the Taiwan Cancer Registry. Two registries had similar process of collecting patients with malignant brain tumor, and the quality of two registries was comparative. The age-adjusted incidence rate (IR), IR ratio, and survival by histological types, age, and gender were used to study regional differences. The overall age-adjusted IRs were 5.91 per 100,000 in the US and 2.68 per 100,000 in Taiwan. The most common histologic type for both countries was glioblastoma (GBM) with a 12.9% higher proportion in the US than in Taiwan. GBM had the lowest survival rate of any histology in both countries (US 1-year survival rate = 37.5%; Taiwan 1-year survival rate = 50.3%). The second largest group was astrocytoma, excluding GBM and anaplastic astrocytoma, with the distribution being slightly higher in Taiwan than in the US. Our findings revealed differences by histological type and grade of primary malignant brain and CNS tumors between two sites.

Malignant primary and metastatic brain tumors are group of malignancies radiologically difficult to distinguish between one another. Meanwhile, the treatment regimens between the two entities are very different. The right regimen can maintain patient’s survival. MRI is the modality of choice for diagnosing brain tumors; although, malignant primary brain tumors and solitary metastases appear similar on conventional MRI. The difference in the pathophysiology of peritumoral edema in malignant primary and metastatic brain tumors has the potential for differentiation of the two entities. In malignant primary brain tumors, tumor cell infiltration occurs in the edema area, meaning that the peritumoral edema is narrower than that of the metastases. This study analyzed the ratio of peritumoral edema volume to tumor (EP/T volume ratio) in malignant primary and metastatic brain tumors by means of MRI examination with a cross-sectional design, using MRI data on FLAIR and T1WI sequences with contrast in malignant brain tumor of patients that have been pathologically proven. Then, volume contouring was performed on peritumoral edema (EP) and tumor (T), and comparation was done to obtain the EP/T volume ratio. The ratio of EP/T volume data in both groups was analyzed using the Mann–Whitney test with the SPSS 22 software. The results of statistical analysis revealed that the EP/T volume ratio of the malignant primary brain tumor group was smaller with a median value (max-min) of 1.1 (5.65-0.17) and in the metastatic group, 2.3 (64.03-0.09). There was a significant difference in the EP/T volume ratio between the two groups, which the brain metastatic tumor group have a double ratio of EP/T with a value of p=0.008 (p<0.05).

Introduction. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adults. Recent whole-genome studies revealed novel GBM prognostic biomarkers such as mutations in metabolic enzyme IDH—isocitrate dehydrogenases (IDH1 and IDH2). The distinctive mutation IDH1 R132H was uncovered to be a strong prognostic biomarker for glioma patients. We investigated the prognostic role of IDH1 R132H mutation in GBM patients in West Bohemia. Methods. The IDH1 R132H mutation was assessed by the RT-PCR in the tumor samples from 45 GBM patients treated in the Faculty Hospital in Pilsen and was correlated with the progression free and overall survival. Results. The IDH1 R132H mutation was identified in 20 from 44 GBM tumor samples (45.4%). The majority of mutated tumors were secondary GBMs (16 in 18, 89.9%). Low frequency of IDH1 mutations was observed in primary GBMs (4 in 26, 15.3%). Patients with IDH R132H mutation had longer PFS, 136 versus 51 days (P < 0.021, Wilcoxon), and OS, 270 versus 130 days (P < 0.024, Wilcoxon test). Summary. The prognostic value of IDH1 R132H mutation in GBM patients was verified. Patients with mutation had significantly longer PFS and OS than patients with wild-type IDH1 and suffered more likely from secondary GBMs.

Fifteen patients with progressive primary malignant or metastatic brain tumors were treated on a clinical and pharmacokinetic study with intracarotid cisplatin and bleomycin. Toxicity was tolerable and consisted mainly of nausea and vomiting. Neurologic toxicity included focal seizures (1), leukoencephalopathy (1), and motor weakness (1). Five patients had improvement in CT scans and four patients had stabilization of disease. Recommended dosage for future clinical trials are cisplatin 60 mg/m2 and bleomycin 100 units. Pharmacokinetics of intracarotid cisplatin revealed the jugular vein concentration was twice the peripheral vein level at the end of infusion. Cisplatin is a drug which has demonstrated in vitro activity against malignant gliomas (1). Clinical trials with intravenous administration of cisplatin has shown definite, although limited antitumor activity against primary brain tumors (2,3,4) and metastatic brain tumors (5,6). To enhance its antitumor effect, cisplatin has been administered by the intracarotid route (7,8,9). The results appear encouraging, but neurological and ophthalmological toxicity may occur (8). In our initial study with intracarotid cisplatin, 35 patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation +/- chemotherapy were treated. Of 20 evaluable patients with primary tumors, 6 responded to therapy and 5 had stable disease. Five of 10 evaluable patients with brain metastases responded and 2 had stable disease. For responding primary brain tumor patients the median time to progression was 33 weeks. The recommended dose for intracarotid cisplatin was 60-75 mg/m2 administered every 3-4 weeks (7,8). Higher cisplatin doses produced more central neurological toxicity. There is limited data on the central nervous system pharmacology of cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Survival of adults with primary malignant brain tumours in Europe; Results of the EUROCARE-5 study

INTRODUCTION The effectiveness of palliative care for cancer patients has already been widely recognized. However, in Japan, palliative care for brain tumor patients remains in its early stages, and related information is limited. This is because the treatment culture for brain tumors in Japan is unique, with primary brain tumors being treated by neurosurgeons and metastatic brain tumors being treated by the department of the primary tumor, making it difficult to collect comprehensive information on end-of-life care for patients with malignant brain tumors. This study investigated end-of-life care for patients with malignant brain tumors from the perspective of a palliative care unit at a single hospital in Japan. PATIENTS AND METHODS This study included 606 cancer patients who were admitted to the palliative care unit at Tsurumaki Onsen Hospital between January 2020 and December 2024 and received end-of-life care. Information was extracted from medical records and imaging tests, and a retrospective analysis was conducted. RESULTS Of the 606 patients, 71 (11.7%) had malignant brain tumors (primary malignant brain tumors and metastatic brain tumors), of which 16 (2.6%) were primary and 55 (9.1%) were metastatic. Among the 71 cases,21 patients (29.6%) presented with impaired consciousness, and 29 patients (40.8%) were unable to take oral intake. Additionally, 15 patients (2.4%) experienced seizures during hospitalization, and 12 of these were patients with malignant brain tumors. DISCUSSION The incidence of metastatic brain tumors was consistent with previous reports; however, based on the incidence rate, primary brain tumors are also frequently treated. Palliative care for common symptoms such as impaired consciousness and seizures in brain tumor patients is considered an important challenge for all of physicians treat brain tumors. CONCLUSION A Japanese palliative care unit treats more brain tumor patients than anticipated. Smoothening collaboration between neurosurgeons and palliative physicians is essential for optimizing end-of-life care.

BACKGROUND Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults, but in contrast to many other malignancies they rarely metastasize. Metastasizing GBMs cause both diagnostic and therapeutic challenges and are generally poorly investigated. Therefore, our aim was to characterize these tumors clinically and molecularly. MATERIAL AND METHODS We collected and examined the largest cohort to date of tissue from 16 glioma patients (14 GBMs and 2 lower-grade gliomas) with extracranial metastases, including metastases to scalp (7) lymph nodes (5), bone (2), liver (1), and upper neck (1). After histopathological re-evaluation of the tumors, we assessed the associated magnetic resonance imaging (MRI) scans. Paired samples from the primary tumors, recurrences and metastases were investigated by next-generation sequencing (NGS) analysis with the TSO500 panel, genome-wide 850 K methylation profiling and immunohistochemistry followed by artificial intelligence-based quantification of markers of stemness and immune cells in the tumor microenvironment (TME). RESULTS Clinically, the patients were comparable to other GBM patients (gender, age, treatment, and survival). 12/16 patients developed one or more intracranial recurrence(s). MRI scans revealed proximity of the brain tumors to dura, large vessels, and ventricles in a high proportion of the patients. Moreover, we found that (6/7) scalp lesions were in fact extracranial extensions of the brain tumors. NGS data showed that the metastases were clonally derived from the primary tumors and not from the brain recurrences. Methylation- and copy number analysis overall confirmed the initial diagnoses and revealed a patient-specific signature across paired samples in a majority of the patients. Additionally, we observed methylation subclass switch during tumor progression and identified differentially methylated regions enriched in the olfactory transduction pathway when comparing metastases to primary tumors. Levels of tumor stemness were generally preserved according to methylation-based stemness index and OLIG2 and SOX2 protein expression. Similarly, the composition of immune cells in the TME did not change significantly, as shown by cell-type deconvolution and immune cell quantification. CONCLUSION Extracranial metastases occurred as early events and overall preserved the tumor- and TME characteristics of the primary brain tumors. Factor such as brain tumor location, neurosurgery and epigenetic regulation of genes associated with olfactory transduction could be involved in glioblastoma metastasis.

Brain tumors are a large and heterogeneous group of neoplasms affecting the central nervous system that, despite the progress of the modern medicine, still represent a great challenge for physicians all over the world. The annual global age-standardized incidence of primary malignant brain tumors is ~3.7 per 100,000 for males and 2.6 per 100,000 for females. Rates appear to be higher in more developed countries (males 5.8, and females 4.1 per 100,000) than in less developed countries (males 3.0 and females 2.1 per 100,000). Conversely, the incidence of both primary malignant and non-malignant brain tumors is about 10 14 cases per 100,000/ year all over the world, with white males having the highest rate. Males also generally have higher rates of primary malignant brain tumors while females have higher rates of nonmalignant tumors, primarily meningiomas. Worldwide age-standardized mortality for primary malignant brain tumors is ~2.8 for male and 2.0 for females per 100,000. Mortality rates differ significantly by histology and age. For example, glioblastoma multiforme (GBM) has a 5-year survival rate of 3.3%, low grade gliomas, such as pilocytic astrocytomas, oligo‐ dendrogliomas, and ependymomas have 5-year survival rates of over 70%, while anaplastic astrocytoma, malignant gliomas and lymphomas have 5-year survival rates less than 40% [1].

Thirty-five patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation +/- chemotherapy received cisplatin, 60 to 120 mg/m2, into the internal carotid artery by a transfemoral approach. Courses of therapy were repeated every 4 weeks. Therapeutic evaluation was performed monthly using the CT scan of the brain and clinical neurologic examination. Thirty patients were evaluable for response. Of 20 evaluable patients with primary malignant brain tumors, 6 responded to therapy and 5 had stable disease. The median time to tumor progression for responding patients was 33 weeks, for stable patients 16 weeks, and 13 weeks for all patients. Five of 10 evaluable patients with brain metastases responded to intracarotid cisplatin, and 2 patients had stable disease. The estimated median time to progression for responding patients was 30+ weeks and 12+ weeks for patients with stable disease. Side effects included seizures in 5 courses, mental agitation and motor restlessness in 1, and transient hemiparesis in 7. One patient may have had a drug-related death, and one patient appeared to develop encephalopathy after treatment. Five patients had clinical deterioration in vision; in two patients it was bilateral. Intracarotid cisplatin has definite activity in patients with malignant primary brain tumors and in patients with brain metastases. The recommended starting dose for intracarotid cisplatin is 60 to 75 mg/m2. At this dose level side effects are uncommon, but includes the risk of neurologic and retinal toxicity.

The objective of the present study was to perform a prospective evaluation of the potential efficacy and safety of intraoperative photodynamic therapy (PDT) using talaporfin sodium and irradiation using a 664-nm semiconductor laser in patients with primary malignant parenchymal brain tumors. In 27 patients with suspected newly diagnosed or recurrent primary malignant parenchymal brain tumors, a single intravenous injection of talaporfin sodium (40 mg/m(2)) was administered 1 day before resection of the neoplasm. The next day after completion of the tumor removal, the residual lesion and/or resection cavity were irradiated using a 664-nm semiconductor laser with a radiation power density of 150 mW/cm(2) and a radiation energy density of 27 J/cm(2). The procedure was performed 22-27 hours after drug administration. The study cohort included 22 patients with a histopathologically confirmed diagnosis of primary malignant parenchymal brain tumor. Thirteen of these neoplasms (59.1%) were newly diagnosed glioblastomas multiforme (GBM). Among all 22 patients included in the study cohort, the 12-month overall survival (OS), 6-month progression-free survival (PFS), and 6-month local PFS rates after surgery and PDT were 95.5%, 91%, and 91%, respectively. Among patients with newly diagnosed GBMs, all these parameters were 100%. Side effects on the skin, which could be attributable to the administration of talaporfin sodium, were noted in 7.4% of patients and included rash (2 cases), blister (1 case), and erythema (1 case). Skin photosensitivity test results were relatively mild and fully disappeared within 15 days after administration of photosensitizer in all patients. Intraoperative PDT using talaporfin sodium and a semiconductor laser may be considered as a potentially effective and sufficiently safe option for adjuvant management of primary malignant parenchymal brain tumors. The inclusion of intraoperative PDT in a combined treatment strategy may have a positive impact on OS and local tumor control, particularly in patients with newly diagnosed GBMs. Clinical trial registration no.: JMA-IIA00026 (https://dbcentre3.jmacct.med.or.jp/jmactr/App/JMACTRS06/JMACTRS06.aspx?seqno=862).

Intracranial Glioblastomas: New Hope for an Effective Treatment

e14000 Background: The purpose of the study was to analyze changes in the total activity of trypsin-like proteinases (TLPs) in the blood plasma in patients with brain tumors for the preoperative differential diagnosis of benign, primary and secondary malignant brain tumors. Methods: TLPs were measured in 164 patients with brain tumors. The blood had been collected from the patients in a standard plastic tube with 3.8% sodium citrate (9:1) 3 days prior to the surgery. Citrate blood was centrifuged; citrated plasma was obtained and used to determine the total TLP activity by the unified kinetic method. Results were compared with the data in donors. Results: TLP activity in 37 (22.6%) of 164 patients was within the normal range (258–402 IU/mL, on the average 333.0±27.1 IU/mL). Benign brain tumors (meningioma) were diagnosed in all 37 patients after the tumor removal and histological analysis. In 74 (45.1%) of 164 patients, TLP activity was within 1158–1626 IU/mL (on the average 1331.0±102.4 IU/mL, p &lt; 0.05), i.e. 3.8-5.3 times higher than the norm in donors (malignancy coefficient on average 4.4±0.3 times). Primary malignant brain tumors (glioblastoma) were diagnosed in all 74 patients after the tumor removal and histological analysis. In 53 (32.3%) of 164 patients, TLP activity was within 1794–2868 IU/mL (on the average 2227.0±174.1 IU/mL, p &lt; 0.05), i.e. 5.9-9.4 times higher than the norm in donors (malignancy coefficient on average 7.3±0.5 times). Secondary malignant brain tumors (metastases) were diagnosed in all 53 patients after the tumor removal and histological analysis. Conclusions: The specificity of the proposed method for the differential diagnosis of brain tumors was very high: for benign tumors - 97.2%, for primary malignant tumors - 98.6% and for secondary malignant tumors - 98.1%. So, TLP activity indices in the blood plasma are an informative auxiliary laboratory test that will help in clarifying and/or confirming the differential diagnosis of brain tumors.