A Rare Case of Intracranial Growing Teratoma Syndrome in a Young Adult.

Intracranial growing teratoma syndrome (iGTS) is a rare phenomenon in patients with non-germinomatous germ cell tumor (NGGCT) after chemotherapy or radiotherapy. It manifests as paradoxical growth of teratomatous components, with multiple cystic lesions on cranial imaging despite normalized tumor markers. This paper presents a 22-year-old male with iGTS, diagnosed one month after chemotherapy against NGGCT. Initially diagnosed with presumptive pineal NGGCT causing obstructive hydrocephalus, the patient underwent endoscopic third ventriculostomy and extraventricular drainage with tumor biopsy followed by two chemotherapy cycles. Despite normalization of tumor markers, follow-up MRI showed increased tumor size with honeycomb-like cystic patterns. The patient underwent suboccipital craniotomy for tumor removal via combined telovelar and infratentorial supracerebellar approaches. The final pathology confirmed mature teratoma. However, postoperative bleeding and left thalamic infarction occurred, resulting in severe neurological deficits. Despite challenges, the patient eventually regained the ability to follow simple commands. To understand iGTS pathophysiology, several hypotheses, including the differentiation of immature components and the uninhibited growth of mature components induced by chemotherapy or radiotherapy, were explored. Surgical intervention remains as an ideal treatment, while clinical trials investigate chemotherapy options. Frequent imaging follow-ups are crucial for early detection in iGTS for NGGCT patients.

Temporal Analysis of Postoperative Outcomes With or Without Intraoperative Motor Evoked Potentials and Somatosensory Evoked Potentials Monitoring for Intracranial Meningioma Surgery.

BACKGROUND: This study aimed to retrospectively assess results of intracranial meningioma surgery with or without intraoperative neuromonitoring (IONM) in a single institution. METHODS: Two cohorts (a historical cohort and a monitoring cohort) were collected for the analysis. Before IONM was introduced, a total of 107 patients underwent intracranial meningioma operation without IONM from January 2000 to December 2008 by one neurosurgeon (historical cohort). After IONM was introduced, a total of 99 patients with intracranial meningioma were operated under IONM between November 2018 and February 2023 by two neurosurgeons (monitoring cohort). A retrospective comparison was made on the complications from meningioma surgery between the two groups. RESULTS: In the monitoring cohort, warning signals of motor evoked potential (MEPs) or somatosensory evoked potential (SSEPs) were alarmed in 10 patients. Two of these 10 patients aborted the operation and eight of these 10 patients with warning signals underwent tumor resection. Of these eight patients, five showed postoperative morbidity. Five of 89 patients without warning signals developed neurological deficits. In the historical cohort, 14 of 107 patients showed postoperative morbidity or mortality. CONCLUSION: Even after successful resection of intracranial meningiomas prior to the advent of IONM, integration of MEPs and SSEPs monitoring yielded valuable insights for surgical teams during operative procedures.

Noggin contributes to brain metastatic colonization of lung cancer cells.

BACKGROUND: Brain metastasis is a common complication among patients with lung cancer, yet the underlying mechanisms remain unclear. In this study, we aimed to investigate the pathogenesis of brain metastasis in lung cancer. METHODS: We established highly colonizing metastatic lung cancer cells, A549-M2, through multiple implantations of A549 human lung cancer cells in the carotid artery of athymic nude mice. RESULTS: Compared to parental cells (M0), M2 cells demonstrated slower growth in culture plates and soft agar, as well as lower motility and higher adhesion, key characteristics of mesenchymal-epithelial transition (MET). Further analysis revealed that M2 cells exhibited decreased expression of epithelial-mesenchymal transition markers, including ZEB1 and Vimentin. M2 cells also demonstrated reduced invasiveness in co-culture systems. RNA sequencing and gene set enrichment analysis confirmed that M2 cells underwent MET. Intriguingly, depletion of Noggin, a BMP antagonist, was observed in M2 cells, and replenishment of Noggin restored suppressed migration and invasion of M2 cells. In addition, Noggin knockdown in control M0 cells promoted cell attachment and suppressed cell migration, suggesting that Noggin reduction during brain colonization causes inhibition of migration and invasion of metastatic lung cancer cells. CONCLUSIONS: Our results suggest that lung cancer cells undergo MET and lose their motility and invasiveness during brain metastatic colonization, which is dependent on Noggin.

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study).

PURPOSE: Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide. METHODS: Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m2, daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety. RESULTS: Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19-21.68 months) in the experimental group and 7.69 months (95% CI 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively. CONCLUSIONS: Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017.

What is the optimal prolactin cutoff for predicting the presence of a pituitary adenoma in patients with polycystic ovary syndrome?

Objective: Hyperprolactinemia (HPRL) and polycystic ovary syndrome (PCOS) are common causes of infertility in women of reproductive age. A pituitary adenoma (PA) is the most common type of brain tumor that causes HPRL. In the neurosurgical field, the co-existence of PA and PCOS is not common. However, neurosurgeons often treat patients who are referred from gynecology. Because most of these patients are young and reproductive-aged, it is difficult for a neurosurgeon to come up with a treatment plan alone. In this study, we investigated the prevalence of PAs in PCOS patients, the cutoff prolactin (PRL) level to detect PAs, and the treatment strategy, then assessed the relationship between these diseases via a literature review. Methods: Medical records from November 2009 to March 2020 were reviewed at our institute. A total of 657 PCOS patients were enrolled. Initial prolactin levels were investigated and hyperprolactinemic patients were selected. As a result of sella magnetic resonance imaging (MRI), patients were divided into 2 groups of those with hyperprolactinemia but without PAs (group A) and those with both hyperprolactinemia and PAs (group B), respectively. We then compared and analyzed each group to find the characteristics and statistical differences. Receiver operating characteristic (ROC) curve analysis was performed to determine a cutoff value of the serum PRL level that could detect PAs in hyperprolactinemic PCOS patients. Results: Of 657 patients diagnosed with PCOS, 76 patients had hyperprolactinemia (76/657, 11.6%). Sella MRI was performed in 56 patients, excluding 20 patients for various reasons. Patients in groups A and B numbered 43 and 13, respectively, and the mean serum prolactin level significantly differed between the groups (39.89 ± 41.64 vs. 108.59 ± 60.70 ng/mL, P < 0.001). Based on the ROC curve analysis of the prolactin threshold level for predicting PAs in PCOS patients, the area under the ROC curve was 0.853 (95% confidence interval, 0.733-0.934; P < 0.001), and the sensitivity and specificity were 76.9% and 86.1%, respectively. Ultimately, the cutoff value for prolactin level was 52.9 ng/mL. Conclusion: PCOS and hyperprolactinemia are common causes of infertility in reproductive-age women. PCOS patients with a PRL level of ≥ 52.9 ng/mL may need to undergo sella MRI for detecting PAs. To help ensure a favorable clinical course for these patients, systematic diagnosis, treatment, and follow-up plan should be established. Therefore, a multidisciplinary approach involving both neurosurgery and gynecology is essential.

Advances in Brain Metastasis Models.

To obtain achievements in addressing the clinical challenges of brain metastasis, we need a clear understanding of its biological mechanisms. Brain metastasis research is challenged by many practical scientific barriers. Depending on the purpose of the study, experimental brain metastasis models in vivo can be used. It is now possible to re-create the architecture and physiology of human organs. Human organoids provide unique opportunities for the study of human disease and complement animal models. The translation of experimental findings to clinical application has several barriers in the development of treatment for brain metastasis. A variety of models have provided significant contributions to the knowledge of brain metastasis pathology and remain pivotal tools for examining novel therapeutic strategies.

Lipid Accumulation Product Index Predicts New-Onset Type 2 Diabetes Among Non-Obese Koreans: A 12-Year Longitudinal Study.

Purpose: The lipid accumulation product (LAP) has been a potential indicator of central lipid accumulation status. This study aimed to assess the longitudinal association between LAP index and incident type 2 diabetes among non-obese Korean adults using a large, community-based Korean cohort observed over 12 years. Patients and Methods: This study included 4281 non-diabetic adults without generalized obesity and abdominal obesity and aged 40-69 years from the Korean Genome and Epidemiology Study. The participants were divided into four groups according to LAP index quartiles, calculated as (waist circumference [cm] - 65) x (triglycerides [mmol/L]) in men and (waist circumference [cm] - 58) x (triglycerides [mmol/L]) in women. We prospectively assessed hazard ratios (HRs) with 95% confidential intervals (CIs) for incident type 2 diabetes using multivariate Cox proportional hazard regression models. Results: Overall, 608 (14.2%) participants developed type 2 diabetes during the follow-up period. HRs for incident type 2 diabetes in the second, third, and fourth LAP quartile were 1.32 (95% CI: 0.97-1.79), 1.51 (95% CI: 1.11-2.06), and 2.14 (95% CI: 1.56-2.94), respectively, after adjusting for age, sex, body mass index, smoking status, alcohol intake, physical activity, mean arterial blood pressure, family history of diabetes, and impaired glucose tolerance. Conclusion: A high LAP index can be an additional indicator for new-onset T2DM among middle-aged and elderly non-obese Koreans.

Association between Temporal Muscle Thickness and Overall Survival in Non-Small Cell Lung Cancer Patients with Brain Metastasis.

Temporal muscle thickness (TMT) has recently been suggested as a novel biomarker of sarcopenia in head and neck malignancies. However, few studies have evaluated TMT as a prognostic marker in patients with brain metastasis. This study investigated the association of TMT with overall survival (OS) in non-small cell lung cancer (NSCLC) patients with brain metastasis. The records of all NSCLC patients with brain metastasis between 2009 and 2018 at St. Vincent's Hospital were reviewed retrospectively. A total of 221 patients met our eligibility criteria. In the group with TMT thicker than the median, OS was longer than the group with TMT thinner than the median (240 days versus 139 days, p = 0.014). In multivariate analysis, the thicker TMT group had longer survival (HR 0.73 CI 0.56−0.96, p = 0.024). Male (HR 1.58 CI 1.19−2.09, p = 0.002) and older age (≥65 years) (HR 2.05 CI 1.53−2.74, p < 0.001) also showed statistical significance. We also performed subgroup analysis in older patients (≥65 years). In this subgroup of 107 patients, the thicker TMT group also showed longer OS than the thinner TMT group (209 days versus 82 days, p = 0.009). Our findings suggest that TMT can be a useful biomarker for OS in NSCLC patients with brain metastasis.

[Corrigendum] Effect of duty cycles of tumor­treating fields on glioblastoma cells and normal brain organoids.

Subsequently to the publication of the above article, the authors have realized that Fig. 3 on p. 6, showing the results of bioluminescence imaging of U87 and U373 cells after applying tumor­treating fields for 72 h, was published containing an erroneous image. Essentially, the data analysis panel for the U87 / U87TTF experiment was inadvertently copied across for the U373 / U373TTF experiment for the '75% Duty' experimental condition. The revised version of Fig. 3, now showing the correct data analysis panel for the '75% Duty' U373 / U373TTF experiment, is shown below. The authors confirm that the error made in the presentation of Fig. 3 did not adversely affect the conclusions reported in this paper, and they are grateful to the Editor of International Journal of Oncology for granting them this opportunity to publish a Corrigendum. All the authors agree to the publication of this Corrigendum; they also apologize to the readership for any inconvenience caused. [International Journal of Oncology 60: 8, 2022; DOI: 10.3892/ijo.2021.5298].

Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-ß Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer's Disease.

The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer's disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electrophysiological features, and then evaluated the protective effect of hNTSCs against amyloid-ß peptide (Aß1-42) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aß1-42 induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aß1-42 exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aß1-42. Silencing OPN via siRNA suppressed Aß-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD.

Clinical feasibility of modified procarbazine and lomustine chemotherapy without vincristine as a salvage treatment for recurrent adult glioma.

Procarbazine, lomustine and vincristine (PCV) chemotherapy is considered a salvage option for adult glioma; however, its significant toxicities frequently lead to dose reduction or discontinuation in patients with recurrent glioma. The current study evaluated the safety and efficacy of modified procarbazine and lomustine (PC) chemotherapy that omits vincristine and reduces the lomustine dose compared with those of conventional PCV chemotherapy. Using electronic medical records, all patients with adult recurrent glioma who received PC or PCV chemotherapy between 2009 and 2020 at Seoul St. Mary's Hospital or St. Vincent's Hospital were examined retrospectively. A total of 59 patients met the eligibility criteria. Among them, 15 patients received modified PC chemotherapy (PC group) and 44 patients received PCV chemotherapy (PCV group). The PC group presented a significantly lower hematology toxicity (anemia, 6.7 vs. 45.5%, P=0.02; thrombocytopenia 20.0 vs. 70.4%, P<0.001). Additionally, the clinical impacts of PC chemotherapy, including delay of a cycle, dose reduction, discontinuation of drug(s) or total cessation of chemotherapy, were significantly less frequent compared with the PCV group (26.7 vs. 68.2%, P=0.012). The overall survival of the PC group was also significantly longer than that of PCV group (396 vs. 232 days, P=0.042), while there was no significant difference in progression-free survival between the two groups (284.5 vs. 131 days, P=0.077). The results suggested that modified PC chemotherapy may be an alternative chemotherapeutic regimen with tolerable toxicity and without loss of clinical efficacy in patients with recurrent adult glioma. Further prospective and larger studies are required to validate our findings.

Effect of duty cycles of tumor­treating fields on glioblastoma cells and normal brain organoids.

Tumor­treating fields (TTFields) are emerging cancer therapies based on alternating low­intensity electric fields that interfere with dividing cells and induce cancer cell apoptosis. However, to date, there is limited knowledge of their effects on normal cells, as well as the effects of different duty cycles on outcomes. The present study evaluated the effects of TTFields with different duty cycles on glioma spheroid cells and normal brain organoids. A customized TTFields system was developed to perform in vitro experiments with varying duty cycles. Three duty cycles were applied to three types of glioma spheroid cells and brain organoids. The efficacy and safety of the TTFields were evaluated by analyzing the cell cycle of glioma cells, and markers of neural stem cells (NSCs) and astrocytes in brain organoids. The application of the TTFields at the 75 and 100% duty cycle markedly inhibited the proliferation of the U87 and U373 compared with the control. FACS analysis revealed that the higher the duty cycle of the applied fields, the greater the increase in apoptosis detected. Exposure to a higher duty cycle resulted in a greater decrease in NSC markers and a greater increase in glial fibrillary acidic protein expression in normal brain organoids. These results suggest that TTFields at the 75 and 100% duty cycle induced cancer cell death, and that the neurotoxicity of the TTFields at 75% was less prominent than that at 100%. Although clinical studies with endpoints related to safety and efficacy need to be performed before this strategy may be adopted clinically, the findings of the present study provide meaningful evidence for the further advancement of TTFields in the treatment of various types of cancer.

Association between height and the risk of primary brain malignancy in adults: a nationwide population-based cohort study.

BACKGROUND: The association between height and the risk of developing primary brain malignancy remains unclear. We evaluated the association between height and risk of primary brain malignancy based on a nationwide population-based database of Koreans. METHODS: Using data from the Korean National Health Insurance System cohort, 6 833 744 people over 20 years of age that underwent regular national health examination were followed from January 2009 until the end of 2017. We documented 4771 cases of primary brain malignancy based on an ICD-10 code of C71 during the median follow-up period of 7.30 years and 49 877 983 person-years. RESULTS: When dividing the population into quartiles of height for each age group and sex, people within the highest height quartile had a significantly higher risk of brain malignancy, compared to those within the lowest height quartile (HR 1.21 CI 1.18-1.32) after adjusting for potential confounders. We also found that the risk of primary brain malignancy increased in proportion with the quartile increase in height. After analyzing subgroups based on older age (≥ 65) and sex, we found positive relationships between height and primary brain malignancy in all subgroups. CONCLUSIONS: This study is the first to suggest that height is associated with an increased risk of primary brain malignancy in the East-Asian population. Further prospective and larger studies with precise designs are needed to validate our findings.

Modified Orbitozygomatic Approach for Resecting a Parasellar Tumor in a Single Institution.

BACKGROUND: Modified orbitozygomatic craniotomy is characterized by simplicity and wide exposure. The purpose of the present study was to describe a modified orbitozygomatic approach without resecting the zygomatic arch for large parasellar tumor surgeries. METHODS: Between April 2016 and December 2019, seven patients with parasellar tumor underwent surgiest with a modified orbitozygomatic approach. Surgical procedures, clinical outcomes, and complications were analyzed. RESULTS: This study included 3 meningiomas, 2 pituitary adenomas, 1 chondrosarcoma, and 1 schwannoma. Modified orbitozygomatic craniotomy provides a wider surgical freedom in the opticocarotid and prechiasmatic cistern than frontotemporal craniotomy without orbitotomy, Total, subtotal, and partial resections were achieved for 3, 2, and 2 patients, respectively. Reasons for partial resections were tight adhesion to the carotid artery and encasing of the carotid artery. Permanent morbidities developed in one patient with 3rd nerve palsy and one patient with hemiparesis. CONCLUSION: Modified orbitozygomatic approach can provide the shortest access to the interpeduncular cistern with a minimum brain retraction. Surgeons who experience surgical challenge during the conventional approach for parasellar tumor resection are recommended to learn the modified orbitozygomatic approach.

Associations of General and Abdominal Obesity with the Risk of Glioma Development.

The association between obesity and the risk of glioma remains unclear. We sought to evaluate the potential association between general and abdominal obesity and the risk of glioma based on a nationwide population-based cohort study of Koreans. Using data from the Korean National Health Insurance System cohort, 6,833,744 people older than 20 years who underwent regular national health examination in both 2009 and 2011 were followed until the end of 2017. We documented 4771 glioma cases based on an ICD-10 code of C71 during the median follow-up period of 7.30 years. Individuals with a body mass index (BMI) ≥ 25.0 kg/m2 were at significantly higher risk of developing glioma than those with a BMI < 25.0 kg/m2 (HR 1.08 CI 1.02-1.15). Individuals with a waist circumference (WC) ≥ 90 cm (males)/85 cm (females) also had a significantly higher risk of glioma than those with a WC < 90 cm (males)/85 cm (females) (HR 1.16 CI 1.09-1.24). In the group with a BMI ≥ 25.0 kg/m2, individuals with abdominal obesity were at significantly higher risk of developing glioma (HR 1.18 CI 1.09-1.27) than those without abdominal obesity. The role of abdominal obesity in this association was stronger in women than in men. To the best of our knowledge, this is the first demonstration that obese people may be at higher risk of glioma, especially centrally obese people from an Asian population with a BMI ≥ 25.0 kg/m2. Loss of visceral fat in people with abdominal obesity may reduce their risk of developing glioma.

Estimation of the occurrence rates of IDH1 and IDH2 mutations in gliomas and the reconsideration of IDH-wildtype anaplastic astrocytomas: an institutional experience.

OBJECTIVES: Most diffuse gliomas are reported to harbor isocitrate dehydrogenase (IDH) mutations. However, when these mutations are tested in clinical practice, the results are often negative. METHODS: This study examined the frequency of IDH1 and IDH2 mutations in gliomas classified according to the revised 2016 World Health Organization classification, and investigated their prognostic relevance. We tested 87 gliomas for IDH1 and IDH2 mutations using the peptide nucleic acid clamp method. RESULTS: IDH1 mutations were observed in 42% of diffuse astrocytomas, 23% of anaplastic astrocytomas, all oligodendrogliomas and anaplastic oligodendrogliomas, and 17% of glioblastomas. An IDH2 mutation was identified in one case of diffuse astrocytoma. In the survival analysis of diffuse astrocytic tumors, patients with IDH1/2-wildtype anaplastic astrocytomas tended to have a poor prognosis, similar to that of glioblastomas. CONCLUSIONS: IDH2 mutations were infrequent in gliomas. In anaplastic astrocytomas, the frequency of IDH1/2-wildtype was relatively high, and the prognosis of patients with this type of tumor was very similar to that of those with glioblastomas. It may therefore be necessary to reconsider the classification and treatment strategies for IDH1/2-wildtype anaplastic astrocytomas.

Epidemiological Study of Malignant Gliomas in Korea Using Nationwide Dataset from 2007 to 2017.

BACKGROUND: The purpose of the study was to investigate the incidence, prevalence, and survival of malignant gliomas (MGs) using population-based Korean National Health Insurance Database (NHID) data. METHODS: Using the Korean NHID, we identified patients with MG as C71 codes in KCD 5-7 according to ICD-10 from January 1, 2007 to December 31, 2017. Epidemiological characteristics of MG, including annual incidence, prevalence, mortality rates, and survival rates, were collected and analyzed according to socioeconomic state (SES) and treatments received. RESULTS: We identified 45,066 newly diagnosed-MG patients from 2007 to 2017, for an age-adjusted incidence of 7.47 per 100,000 people. The mean age at diagnosis was 54 years. The male to female ratio was 1.11. Mortality and survival probability were analyzed among total subjects and in subgroups. The mortality rates were lower in female than that of male patients (hazard ratio, 0.69; 95% confidence interval, 0.67-0.71), and in younger age population and in higher income group. Patients operated had a slightly higher survival rate. The 1-, 3-, 5-, and 10-year survival rates were estimated at 63.4%, 46.2%, 39.4%, and 34.8%, respectively. This is the first population-based study to determine the incidence and prevalence of MG according to epidemiological characteristics in Korea using NHID. CONCLUSION: Our study found that female sex and high SES were factors that significantly lowered the mortality rate in MG, and younger groups and operated patients showed significantly higher survival rates.

High-dose methotrexate monotherapy for newly diagnosed primary central nervous system lymphoma: 15-year multicenter experience.

AIM: Primary central nervous system lymphoma (PCNSL) is rare disease and shows poor prognosis although methotrexate-based chemotherapy is used. Here, we present our experiences with high-dose methotrexate (HD-MTX) monotherapy for immunocompetent patients with PCNSL at three institutions and investigate factors related to survival. METHODS: PCNSL patients, who were histologically confirmed with diffuse large B cells and treated with HD-MTX monotherapy from 2001 to 2016, were retrospectively reviewed. Patients underwent induction chemotherapy with 8 g/m2 of MTX every 10 days (maximum three cycles). Maintenance chemotherapy of 3.5 g/m2 of MTX (maximum six cycles) was selectively performed depending on the response to induction chemotherapy. RESULTS: A total of 67 patients were included. Although seven patients discontinued induction chemotherapy because of MTX toxicity, 40 (59.7%) patients showed a complete response (CR) to induction chemotherapy. Twenty-six (38.8%) and three (4.5%) patients showed a CR and partial response, respectively, after maintenance chemotherapy. Forty-one patients with recurrence or progression following HD-MTX underwent second-line treatment. Progression-free survival rates were 43% and 24% at 1 and 2 years, respectively. The median overall survival was 40.3 months. In a multivariate analysis, a radiological CR to induction chemotherapy was a significant factor related to prolonged progression-free survival and overall survival (P < 0.05). CONCLUSION: MTX-monotherapy is tolerable in terms of adverse effects and still considered as a treatment option in patients with PCNSL. However, an additional therapeutic option should be prepared for non-CR responders to induction chemotherapy.

Cigarette Smoking Is Associated with Increased Risk of Malignant Gliomas: A Nationwide Population-Based Cohort Study.

The association between cigarette smoking and the risk of developing malignant glioma (MG) remains unclear. We aimed to evaluate this potential association in a large general population, using a well-established and validated longitudinal nationwide database. Using data from the Korean National Health Insurance System cohort, 9,811,768 people over 20 years old without any cancer history in 2009 were followed until the end of 2017. We documented 6100 MG cases (ICD-10 code C71) during the median follow-up period of 7.31 years. Current smokers had a higher risk of developing MG (HR = 1.22, CI: 1.13-1.32) compared with never-smokers, after adjusting for confounders. This association was stronger for those who smoked ≥ 20 cigarettes daily (HR = 1.50, CI: 1.36-1.64). Furthermore, having 30 or more pack-years of smoking over the course of one's lifetime was associated with an increased risk of developing MG in a dose-dependent manner, compared with never-smokers (HR = 1.31, CI: 1.16-1.48 for 30-39 pack-years of smoking; HR = 1.36, CI: 1.17-1.59 for 40-49 pack-years of smoking; HR = 1.68; CI: 1.44-1.95 for ≥ 50 pack-years of smoking). These results suggest that cigarette smoking may be associated with developing MG. Further prospective studies could help elucidate this association.

The association between total lymphocyte count after concomitant chemoradiation and overall survival in patients with newly diagnosed glioblastoma.

Several studies have been conducted to determine the relationship between post-treatment total lymphocyte count (TLC) and overall survival (OS) in patients with malignant tumors including glioblastomas (GBMs). In this retrospective study, whether patients with newly diagnosed GBM experience significant lymphopenia after concomitant chemoradiation (CCRT) was evaluated, and whether TLC after this treatment is associated with OS in the treated population was examined. Using electronic medical records, all patients newly diagnosed with GBM between 2008 and 2016 at Seoul St. Mary's Hospital were retrospectively examined. The eligible criteria included the following: 1) craniotomy with surgical resection or biopsy, 2) completion of CCRT, 3) accessible baseline and/or follow-up complete blood count (CBC). Median TLC significantly decreased after completion of CCRT, compared to TLC at baseline (1742 versus 1319 cells/mm3, P-value < 0.001). Patients with TLC < 1200 cells/mm3 at 4 weeks after the completion of CCRT showed shorter survival than those with TLC ≥ 1200 cells/mm3 with median OS of 14.5 versus 21.0 months (P-value = 0.017). Also, in multivariate analysis for OS, TLC < 1200 cells/mm3 at 4 weeks after the completion of CCRT (HR 1.97, 95% CI 1.61 - 2.25, P-value = 0.004) were significantly associated with shorter survival. The results from the present study indicate that treatment-related total lymphocyte counts after CCRT is associated with worse survival in patients with newly diagnosed GBM.