Efficacy and safety of tumor-treating fields in treatment of high-grade gliomas / 中华神经医学杂志

Objective:Tumor-treating fields (TTFields) is a kind of non-invasive anti-mitotic tumor therapy, which has been approved for patients with newly diagnosed and recurrent glioblastoma. This study aims to explore the efficacy and safety of TTFields in high-grade gliomas in clinical practice settings.Methods:The clinical data of 15 patients with recurrent glioma and 9 patients with newly diagnosed high-grade glioma admitted to our center from April 2019 to January 2021 were retrospectively analyzed. All patients accepted TTFields≥1 month. Follow-up was performed for 5.3 months (ranged from 2.3 to 10.7 months); Response Assessment in Neuro-Oncology Working Group (RANO) criteria was used to evaluate the glioma responses. The progression-free survival (PFS) and overall survival (OS) were calculated according to Kaplan-Meier method. Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Quality of life questionnaire-core 30 (QLQ-C30) and QLQ-brain cancer module (QLQ-BN20) questionnaires were used to evaluate the health-related quality of life (HRQoL). Treatment compliance was evaluated by data on the use of NovoTTF-200A devices, and calculated as a percentage of daily TTFields usage.Results:The median duration of TTFields was 4.2 months (ranged from 1.0 to 10.7 months), with a median compliance rate of 91.5% (67.0%-97.0%). TTFields was used alone in 2 patients and used with combination of chemotherapy in 22 patients. From follow-up to April 2021, 14 patients had stable symptoms and 10 had disease progression (8 died). The median PFS and OS of recurrent patients were 5.9 months ( 95%CI: 3.3-8.6 months) and 8.5 months ( 95%CI: 3.2-13.8 months), respectively; and the median PFS and OS of newly diagnosed patients were both 10.7 months (without 95%CI). The common adverse events included grading 1 dAE (58.3%) and grading 2 dAE (12.5%), without grading 3 or 4 dAE, manifested as contact or allergic dermatitis, erosion, folliculitis and ulcers. And 87.5% patients had stable HRQoL. Conclusions:The preliminary results showed that the survival of recurrent high-grade glioma patients treated by TTFields is similar to that reported in foreign literature; and the newly diagnosed patients need further survival follow-up. The patients' treatment compliance and safety are good. The dAE incidence (grading 1-2) is higher than that reported in the literature, and the toxicity was acceptable.

Long-term molecular changes in WHO grade II astrocytomas following radiotherapy / 癌症

Monitoring the long-term radiotherapy-associated molecular changes in low-grade gliomas (LGGs) facilitates the understanding of LGG response to radiotherapy. In this study, we used immunohistochemistry to analyze the expression of Ki-67, tumor protein P53 (TP53), P21, and P27 in 8 paired WHO grade II astrocytoma samples. The interval between radiotherapy (RT) and the second surgery was more than 3 months in all cases. The average Ki-67 labeling index (LI) was 5.3% in pre-RT samples and 11.54% in post-RT samples. Ki-67 LI was higher in the primary tumors that underwent malignant transformation observed at the second surgery after radiation. Post-RT Ki-67 LI decreased in 2 cases with an interval of less than 12 months between RT and the second surgery. TP53 expression was found in 3 out of 4 pre-RT samples with malignant transformation and in 1 out of 4 pre-RT samples without malignant transformation. Post-RT TP53 increased in 2 cases in which increased expression of P21 or P27 was also observed. Our study suggests that radiotherapy can inhibit WHO grade II astrocytoma proliferation as reflected by Ki-67 LI, but the effect attenuates with time. In addition, there is a tendency of malignant transformation for WHO grade II astrocytomas with a high Ki-67 level or TP53 expression in initial samples.

Nimotuzumab in combination with chemotherapy for patients with malignant gliomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Nimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas.</p><p><b>METHODS</b>The patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred. Individualized chemotherapy was administered based on O(6)-methylguanine-DNA methyltransferase (MGMT) expression and previous chemotherapy responses in combined with nimotuzumab.</p><p><b>RESULTS</b>Fourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 (median 7.5 times). Combined chemotherapy regimens included: continuous 21-day temozolomide (10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin (1 case), and teniposide plus nimustine (1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively. Disease control rate (PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI: 0.7 - 7.3) and PFS at 6 months was 30.6%. The most common toxicities include grade I-II neutropenia (2 cases), thrombocytopenia (2 cases), lymphopenia (1 case), nausea and vomitting (3 case) and asymptomatic transaminase increase (1 case). One patient developed grade IV neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash.</p><p><b>CONCLUSIONS</b>Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.</p>

Three-dimensional reconstruction of CT imaging in endoscopic surgery of patients with hypertensive intracerebral hemorrhage / 中华神经医学杂志

Objective To develop a simple, fast and accurate preoperative planning method for endoscopic surgery of patients with hypertensive intracerebral hemorrhage (HICH).Methods Eighteen patients with HICH, admitted to our hospital from June 2008 to August 2010, were performed endoscopic minimally invasive surgery; CT three-dimensional reconstruction was employed to locate the intracerebral hematoma and select the appropriate endoscopic approach before the endoscopic surgery.The clinical data and treatmem efficacy were analyzed.Results According to the results of CT three-dimensional reconstruction, our neurosurgeons could design the best endoscopic approach; the three-dimensional relationship between intracerebral hematoma and scalp markers was shown directly and accurate positioning of the location of drilling was achieved; therefore, the time for preoperative preparation, anesthesia and operation was shortened. The mean operating time of these 18 patients was about 1.5 h; the volume of blood loss was only 30-40 mL; and the evacuation ratio was about 89.2%.After the elimination of hematoma, the brain tissues were flabby, so decompressive craniectomy was not needed. Conclusion CT three-dimensional reconstruction is a simple, fast and accurate preoperative planning method for endoscopic surgery of patients with HICH.

Treatment of nonsmall cell lung cancer patients with synchronous brain metastasis: an analysis of 19 cases / 中华神经医学杂志

Objective To explore whether aggressive treatment of primary focus can benefit nonsmall cell lung cancer(NSCLC)patients with synchronous brain metastasis,and search the appropriate treatment protocols.Methods The clinical data of 19 NSCLC patients with synchronous brain metastasis,received treatment at our Cancer Center from January 2000 to January 2009,were reviewed; their treatments and survival statuses were analyzed.Results Median survival time of these patients was 14.5 months; the 1-year survival rate was 52.6％,and 2-year survival rate was 17.5％.Patients had different survival rates when different treatments were given to the primary focus,and significant difference was noted(x2=10.532,P=0.005); after neurosurgical intervention,patients underwent thoracic operation and chemotherapy(24.9 months)had a significantly longer survival time than those underwent chemotherapy(14.5 months)or palliative therapy(5.4 months,P＜0.05).The survival time of patients with single metastases was 16.3 months,and that of those with multiple metastases was 5.4 months; and significant difference was noted between them(P＜0.05).Conclusion Aggressive therapy including neurosurgical intervention,pulmonary resection and chemotherapy should be recommended for NSCLC patients with synchronous brain metastasis,especially those with single brain metastasis.

Neuroendoscope-assisted micro-invasive surgical treatment of hypertensive thalamic hemorrhage / 中华神经医学杂志

Objective To develop a minimally invasive operating technique for the treatment of hypertensive thalamic hemorrhage. Methods The clinical data of 15 patients with hypertensive thalamic hemorrhage performed neuroendoscope-assisted micro-invasive surgical treatment in our hospitals from July 2007 to June 2010 were retrospectively analyzed; their treatment efficacy were also concluded. Results The mean operation time of these patients was (1.5±0.4) h and the amount of blood loss was 30-40 mL; the mean clearance rate of hematoma in the thalamus was (86.2 ±7.9)percentage. Patients were followed up and evaluated by Glasgow outcome scale for at least 3 months.Three patients (21.4%) showed good recovery, 4 (28.6%) moderate disability, 4(28.6%) severe disability and 2 (14.3%) vegetative survival; 1 patient (7.1%) died. Conclusion Neuroendoscope-assisted micro-invasive surgical treatment is a fast and minimally invasive operating technique with little blood loss in the treatment of hypertensive thalamic hemorrhage.

Detection of T lymphocyte subsets in patient with glioma / 中华神经医学杂志

Objective To explore the relationship between T lymphocyte subsets and both glioma malignancy and its prognosis, and determine a clinical immunologic index for evaluating preoperative glioma malignancy and its prognosis. Methods The data of 117 inpatients with primary intracranial tumors, including glioma (n=85) and meningioma (n=32), were retrospectively analyzed. Fluorescence-activated cell sorting (FACS) analysis was performed to detect the preoperative contents of T lymphocyte subsets on 32 patients with meningioma and patients with glioma, including 45 high-grade glioma (WHO, grade Ⅲ-Ⅳ) and 40 low-grade glioma (WHO, grade Ⅰ -Ⅱ); and then the differences of their immunologic indexes were analyzed. Based on the detection result of T lymphocyte subsets, patients with glioma were divided into two groups: CD4~+CD8~+<1 and CD4~+CD8~+>1. Follow-up for 3-5 years was performed and the survival difference of these two groups was analyzed. Results Patients with high-grade glioma showed a decreased ratio of CD4~+CD8~+ and an increased value of CD8~+ with significant difference as compared with patients with low-grade glioma (P<0.05); patients with high-grade glioma showed a decreased ratio of CD4~+CD8~+, and an increased value of CD8~+ with statistical significance compared with patients with meningioma (P <0.05); patients with low-grade glioma showed a decreased ratio of CD4~+CD8~+ with statistical significance compared with the patients with meningioma (P<0.05). Patients with glioma showed a decreased ratio of CD4~+CD8~+ and CD4~+, and an increased CD8~+ with statistical significance compared with patients with meningioma (P<0.05). After follow-up for 3-5 years, 48 patients with glioma was found in the CD4~+CD8~+>1 group with 21 death (43.8%) and 31 months as a median survival time; 37 patients with glioma was found in the CD4~+CD8~+<1 group with 23 death (62.2%) and 16 months as a median survival time. The Kaplan-Meier survival curves were analyzed with statistical significance (P<0.05). Conclusion The prognosis is poor in patients with low ratio of CD4~+CD8~+. The preoperative level of T lymphocyte subsets in peripheral blood, correlated to the glioma malignancy, can be considered as an index to evaluate the glioma malignancy and the prognosis in patients with glioma.

Clinical features and differential diagnosis in 18 cases of lepromatous type brain abscess / 中华神经医学杂志

Objective To investigate the clinical features and differential diagnosis of lepromatous type brain abscess. Methods A total of 18 cases with brain abscess admitted to Department of Neurosurgery, Cancer Center, Sun Yat-sen University during October 2000 to February 2007 were retrospectively analyzed with regard to their clinical data and prognosis during follow-up.Results 11 cases had been diagnosed with gliomas and 7 cases had been diagnosed with metastatic tumors in other hospitals. Among the 18 cases, 16 patients took the onset in winter and spring. All of the 18 cases had not found the primary focus of infection. Two cases among them had got a fever 1 month prior to hospitalization. Among the 18 cases, 7 cases had higher total white blood cells (10.1×109/L-13.7×109/L), and 6 cases had higher neutrophil rate (80.8%-90.5%). And the other 11 cases had normal blood routine. After hospitalization, all of the patients received MRI. 14 cases of them were diagnosed with brain abscess, 2 cases with metastatic tumor, 1 case with glioma, and 1 case with parasite. All of the patients got bacterial culture, and showed asepsis in 9 cases, Gram-positive bacteria in 4 cases, streptococci in 3 cases,Staphylococcus epidermidis in 1 case, and Klebsiella pneumoniae in 1 case. Twelve cases underwent resection, and 6 cases received puncture and drainage. During the follow-up ranging 1-6 years, 17 cases healed well, and 1 case get better. Conclusion Lepromatous type brain abscess commonly occurs in winter and spring. The clinical manifestations are untypical. MRI is the most valuable auxiliary examination, and the magnetic resonance spectroscopy and diffusion weighted imaging takes an important role in differential diagnosis between brain abscess and cystic brain tumor with necroses.

Neuroprotective effect of a peptide inhibitor of c-Jun N-terminal kinase on global cerebral ischemia in gerbils / 中华神经医学杂志

Objective To assess the effect of D-JNKI1, an inhibitor of c-Jun N-terminal kinase (JNK), on delayed neuronal death (DND) in a gerbil model of transient global cerebral ischemia, so as to further study the roles of JNK activation in mediating neuronal cell death in brain ischemia. Methods Fifty-five Mongolian gerbils were randomly divided into 11 groups. Animals (n=35) assigned into 7 groups (n=5 per group) were subjected to 5-min occlusion of bilateral common carotid arteries (BCCAO);among the 7 groups, different doses of D-JNKI1 (0.00012, 0.0012, 0.012, 0.12, 1.2 μmol/L in 2 μL PBS,n=5 each) were administered stereotaxically into right lateral ventricles 3 h after reperfusion; the control group (n=5) received 2 μL PBS; and another group (n=5) received 1.2 μmol/L of D-JNKI1 in 0.5 mL PBS intraperitoneally. Sham-operated animals (n=5) only received the exposure of bilateral common carotid arteries without occlusion. Three groups (n=5 in each) were pretreated with D-JNKI1 (0.00012,0.0012 μmol/L in 2 μL PBS) or only 2 μL PBS 30 min before 2-min BCCAO, and subjected to 5-min BCCAO 48 h after the first ischemic insult. All animals were sacrificed 4 d after 5-min BCCAO and prepared for frozen section and Nissl staining. Results The treatment with D-JNKI 3 h after 5-min ischemia was neuroprotective with a maximum effect at a dose of 0.0012 μmol/L. Pretreatment with D-JNKI augmented ischemic tolerance induced by 2-min ischemia. Conclusion D-JNKI1 has a potential neuroprotective effect on DND in CA1 of hippocampus in gerbils with global cerebral ischemia-reperfusion injury.