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1.
J Neurosurg Pediatr ; 32(2): 173-183, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37119099

ABSTRACT

OBJECTIVE: Distinguishing tumor recurrence from therapy-induced imaging changes (TIIC) on brain MRI in children treated for primary malignant brain tumors may be challenging. The authors aimed to assess the diagnostic ability of multimodal MRI in differentiating TIIC from tumor recurrence. METHODS: The authors retrospectively included children with abnormal supratentorial brain MRI findings after treatment for primary malignant brain tumors (regardless of their localization) with complete resection and radiotherapy. A total of 18 patients with TIIC and 25 patients with tumor recurrence were compared, according to structural, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) imaging data accrued over time. TIIC were defined by a new MRI scan that was stable for at least 1 year or had regressed, or by histopathology findings in specimens obtained when the anomaly was surgically treated. RESULTS: The time interval between completion of radiotherapy and the appearance of abnormal brain MRI findings was significantly shorter in the TIIC group compared with the tumor recurrence group (median 6 vs 35 months; p < 0.001). TIIC appeared as foci of increased T2-weighted signal intensity, without nodule, associated with variable contrast enhancement. Tumor recurrence appeared as a well-defined nodule with intermediate signal intensity on T2-weighted images with nodular contrast enhancement. Relative ADC values were significantly higher in the TIIC group (median 1.43 vs 0.88; p < 0.001). Relative ASL-cerebral blood flow (CBF) values were significantly lower in the TIIC group (median 0.27 vs 0.43; p = 0.04). On follow-up MRI, TIIC could progress, regress, or remain stable. In most instances (72%), they decreased in size or remained stable at 4 years of follow-up. CONCLUSIONS: MRI features of TIIC include foci of increased signal intensity without a demonstrable nodule on T2-weighted images, high ADC values, and lower ASL-CBF values, whereas tumor recurrence appears as a well-defined nodule with low ADC values and higher ASL-CBF values.


Subject(s)
Brain Neoplasms , Supratentorial Neoplasms , Humans , Child , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/radiotherapy , Brain Neoplasms/surgery , Neoplasm Recurrence, Local/diagnostic imaging , Retrospective Studies , Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/methods , Supratentorial Neoplasms/diagnostic imaging , Supratentorial Neoplasms/radiotherapy , Supratentorial Neoplasms/surgery
2.
J Clin Neurosci ; 82(Pt A): 122-127, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33317719

ABSTRACT

Cerebellar glioblastoma (GB) is much rarer than its supratentorial counterpart, and potentially of different molecular origin. Prior database studies are of limited size and reported on patients who preceded the validation of temozolomide. Thus, we provide an updated population-based analysis of the treatment trends and outcomes since the standardization of GB adjuvant chemoradiation. Patients diagnosed with primary cerebellar and supratentorial GB were identified from the National Cancer Database spanning 2005-2015. Patients were characterized by demographics, extent of resection, and adjuvant chemotherapy or radiation status. Cohorts were primarily and secondarily assessed for overall survival by tumor site and treatment history, respectively. A total of 655 patients with cerebellar GB were identified (0.6%). Cerebellar GB patients, compared to supratentorial GB were more likely to undergo a biopsy or subtotal resection (13.4% vs 9.3% and 16.0% vs 13.4%, p-value < 0.001), and less likely to pursue adjuvant therapy (48.4% vs 52.7%, p-value < 0.001). Overall median survivals were 9.3 and 9.4 months, respectively. On multivariable analysis, gross total resection, radiation, and chemotherapy were found to be predictors of improved overall survival (HR 0.77, p = 0.038; HR 0.67, p < 0.001; and HR = 0.77, p = 0.030, respectively). While many management principles are currently shared between cerebellar and supratentorial GB, aggressive regimens appear less frequently prescribed. Survival continues to match supratentorial outcomes and may benefit from future, systemic guidance by distinguishing molecular features.


Subject(s)
Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Glioblastoma/drug therapy , Glioblastoma/radiotherapy , Adult , Aged , Brain Neoplasms/surgery , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Combined Modality Therapy , Databases, Factual , Female , Glioblastoma/pathology , Glioblastoma/surgery , Humans , Infratentorial Neoplasms/radiotherapy , Infratentorial Neoplasms/surgery , Male , Middle Aged , Neurosurgical Procedures , Supratentorial Neoplasms/radiotherapy , Supratentorial Neoplasms/surgery , Temozolomide/therapeutic use
3.
Zhonghua Wai Ke Za Zhi ; 57(5): 377-382, 2019 May 01.
Article in Chinese | MEDLINE | ID: mdl-31091594

ABSTRACT

Objective: To analyze the treatment effect of patients with glioblastoma (GBM) and explore prognostic factors. Methods: The clinical data of 635 patients diagnosed as GBM at Neurosurgical Oncology Department Ⅳ of Beijing Tiantan Hospital, Capital Medical University from January 2007 to March 2018 were retrospectively reviewed. There were 386 males and 249 females with an age of (48.7±11.8) years (range: 18-75 years). Patients were divided into three groups according to the time of admission: 2007-2010 group(n=174), 2011-2014 group (n=237) and 2015-2018 group (n=224). Kaplan-Meier plot was used to analyze the effects of different treatment periods, treatment schemes and clinical factors on the survival of patients with GBM. Cox proportion hazard regression analysis was used to identify independent prognostic factors. Results: The median progression-free survival (PFS) and overall survival (OS) of patients in 2007-2010 group, 2011-2014 group, 2015-2018 group was 9.0 months (95% CI: 7.5-10.5), 10.0 months (95% CI: 8.8-11.2), 12.0 months (95% CI: 10.7-13.3) and 17.0 months (95% CI: 13.2-20.8), 20.0 months (95% CI: 16.9-23.1), 23.0 months(95% CI: 17.5-28.5), respectively. The PFS and OS of patients improved significantly over the years (χ(2)=9.693, P=0.008 and χ(2)=8.616, P=0.013). Multivariate survival analysis showed that age, extent of resection, radiotherapy and tumor distant dissemination were independent prognostic factors (all P<0.05). Conclusions: With the continuous development of clinical treatment regimen, the therapeutic effect of Chinese GBM patients has improved remarkably. Age, extent of resection, radiotherapy and tumor distant dissemination are independent prognostic factors associated with survival time.


Subject(s)
Glioblastoma/mortality , Supratentorial Neoplasms/mortality , Adolescent , Adult , Aged , Female , Glioblastoma/pathology , Glioblastoma/radiotherapy , Glioblastoma/surgery , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Supratentorial Neoplasms/pathology , Supratentorial Neoplasms/radiotherapy , Supratentorial Neoplasms/surgery , Young Adult
4.
World Neurosurg ; 123: e549-e556, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30528526

ABSTRACT

OBJECTIVE: We investigated seizure outcomes of patients with supratentorial meningiomas (ST-MNGs) treated with stereotactic radiosurgery (SRS). METHODS: One hundred and thirty-three patients with a total of 144 ST-MNGs, who were treated with SRS between 2009 and 2016, were included in this study. The mean age was 59.0 ± 11.9 years (range, 13-87 years). The mean follow-up duration was 49.8 ± 24.5 months (range, 9-96 months). The median tumor volume was 2.60 cm3 (range, 0.06-32.40 cm3), and the median marginal dose was 14.0 Gy (range, 11.0-20.0 Gy). Postradiosurgery peritumoral edema (PRPTE) was developed in 43 lesions (29.9%). RESULTS: New seizure attacks developed in 16 patients (12.0%) after SRS (first seizure attack in 14 [87.5%]; seizure aggravation in 2 [12.5%]). In 15 patients with new seizure attacks (93.8%), PRPTE was proved on magnetic resonance imaging. The mean interval between SRS and new seizure attack was 6.6 ± 7.1 (range, 0.23-28.8) months. Simple partial seizure was the most common type of seizure (n = 9 [56.3%]). Five patients (31.3%) were seizure-free with antiepileptic drug (AED) medication (3 [18.8%] withdrew AEDs during the follow-up period); however, the remaining 11 patients (68.7%) did not achieve seizure-free outcomes even with AED medication. Moreover, seizures became intractable in 8 patients (50.0%). From multivariate analysis, the significant predictors of post-SRS seizure attack were PRPTE (odds ratio, 53.99; 95% confidence interval, 5.214-559.1; P = 0.001) and brain-tumor contact-surface index (odds ratio, 2.466; 95% confidence interval, 1.183-5.138; P = 0.016). CONCLUSIONS: The clinical outcomes of seizures after SRS for ST-MNGs fall short of our expectation, and seizures seem to be uncontrollable and even intractable.


Subject(s)
Meningeal Neoplasms/radiotherapy , Meningioma/radiotherapy , Radiosurgery , Seizures/etiology , Supratentorial Neoplasms/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Anticonvulsants/therapeutic use , Brain Edema/diagnostic imaging , Brain Edema/etiology , Female , Follow-Up Studies , Humans , Male , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/physiopathology , Meningioma/diagnostic imaging , Meningioma/physiopathology , Middle Aged , Radiotherapy Dosage , Retrospective Studies , Seizures/diagnostic imaging , Seizures/drug therapy , Supratentorial Neoplasms/diagnostic imaging , Supratentorial Neoplasms/physiopathology , Tumor Burden , Young Adult
5.
Int J Radiat Oncol Biol Phys ; 101(1): 217-225, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29502931

ABSTRACT

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.


Subject(s)
Chemoradiotherapy/adverse effects , Glioblastoma/radiotherapy , Lymphopenia/etiology , Lymphopenia/prevention & control , Supratentorial Neoplasms/radiotherapy , Acute Disease , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/therapeutic use , Bevacizumab/therapeutic use , Carmustine/therapeutic use , Chemoradiotherapy/methods , Chemoradiotherapy/mortality , Dasatinib/therapeutic use , Female , Glioblastoma/drug therapy , Glioblastoma/pathology , Humans , Kaplan-Meier Estimate , Lymphocyte Count , Lymphopenia/mortality , Male , Middle Aged , Photons/therapeutic use , Progression-Free Survival , Propensity Score , Quinazolines/therapeutic use , Radiotherapy Dosage , Radiotherapy, Conformal/methods , Snake Venoms/therapeutic use , Supratentorial Neoplasms/drug therapy , Supratentorial Neoplasms/mortality , Supratentorial Neoplasms/pathology , Temozolomide/therapeutic use , Young Adult
6.
PLoS One ; 13(2): e0192838, 2018.
Article in English | MEDLINE | ID: mdl-29444157

ABSTRACT

OBJECTIVE: This study evaluated the possibility of accelerated gadolinium accumulation in irradiated brain parenchyma where the blood-brain barrier was weakened. METHODS: From January 2010 to June 2015, 44 patients with supratentorial glioblastoma were retrospectively identified who underwent pre- and post-radiation brain MR imaging, including R1 mapping. The mean dose of administered gadobutrol (Gadovist, Bayer, Germany) was 5.1 vials. Regions of interest (ROIs) were drawn around tumors that were located within 50-100% iso-dose lines of maximum radiation dose. ROIs were also drawn at globus pallidus, thalamus, and cerebral white matter. Averages of R1 values (unit: s-1) before and after radiation and those of R1 ratio (post-radiation R1 / pre-radiation R1) were compared by t-test or rank sum test as appropriate. Multiple linear regression analysis was performed to evaluate independent association factors for R1 value increase at irradiated parenchyma. RESULTS: The mean R1 values in peri-tumoral areas were significantly increased after radiotherapy (0.7901±0.0977 [mean±SD] vs. 0.8146±0.1064; P <.01). The mean R1 ratio of high radiation dose areas was significantly higher than that of low dose areas (1.0055±0.0654 vs. 0.9882±0.0642; P <.01). The mean R1 ratio was lower in those who underwent hypofractionated radiotherapy (mean dose, 45.0 Gy) than those who underwent routine radiotherapy (mean dose, 61.1 Gy) (0.9913±0.0740 vs. 1.0463±0.0633; P = .08). Multiple linear regression analysis revealed that only radiotherapy type was significantly associated with increased R1 (P = .02) around tumors. CONCLUSIONS: Radiotherapy can induce R1 value increase in the brain parenchyma, which might suggest accelerated gadolinium accumulation due to damage to the blood-brain barrier.


Subject(s)
Contrast Media/pharmacokinetics , Gadolinium/pharmacokinetics , Glioblastoma/diagnostic imaging , Glioblastoma/radiotherapy , Magnetic Resonance Imaging/methods , Supratentorial Neoplasms/diagnostic imaging , Supratentorial Neoplasms/radiotherapy , Adult , Aged , Blood-Brain Barrier/radiation effects , Female , Glioblastoma/metabolism , Humans , Magnetic Resonance Imaging/statistics & numerical data , Male , Middle Aged , Neuroimaging/methods , Neuroimaging/statistics & numerical data , Supratentorial Neoplasms/metabolism
7.
Oper Neurosurg (Hagerstown) ; 14(6): E66-E69, 2018 06 01.
Article in English | MEDLINE | ID: mdl-28961956

ABSTRACT

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.


Subject(s)
Astrocytoma/complications , Supratentorial Neoplasms/complications , Tremor/etiology , Antineoplastic Agents/therapeutic use , Astrocytoma/diagnostic imaging , Astrocytoma/drug therapy , Astrocytoma/radiotherapy , Biopsy/methods , Chemotherapy, Adjuvant , Combined Modality Therapy , Cranial Irradiation , Hand , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuroimaging , Radiotherapy, Adjuvant , Severity of Illness Index , Supratentorial Neoplasms/diagnostic imaging , Supratentorial Neoplasms/drug therapy , Supratentorial Neoplasms/radiotherapy , Temozolomide/therapeutic use
8.
J Neurooncol ; 135(1): 83-92, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28669011

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Alkylating/administration & dosage , Carmustine/administration & dosage , Glioblastoma/drug therapy , Glioblastoma/surgery , Supratentorial Neoplasms/drug therapy , Supratentorial Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/adverse effects , Carmustine/adverse effects , Combined Modality Therapy , Drug Implants , Female , Glioblastoma/radiotherapy , Humans , Karnofsky Performance Status , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Supratentorial Neoplasms/radiotherapy , Survival Analysis , Treatment Outcome , Young Adult
9.
Hum Gene Ther Clin Dev ; 28(1): 7-16, 2017 03.
Article in English | MEDLINE | ID: mdl-28319448

ABSTRACT

Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors. G207 is a genetically engineered HSV-1 lacking genes essential for replication in normal brain cells. Safety has been established in preclinical investigations involving intracranial inoculation in the highly HSV-sensitive owl monkey (Aotus nancymai), and in three adult phase 1 trials in recurrent/progressive high-grade gliomas. No dose-limiting toxicities were seen in the adult studies and a maximum tolerated dose was not reached. Approximately half of the 35 treated adults had radiographic or neuropathologic evidence of response at a minimum of one time point. Preclinical studies in pediatric brain tumor models indicate that a variety of pediatric tumor types are highly sensitive to killing by G207. This clinical protocol outlines a first in human children study of intratumoral inoculation of an oncolytic virus via catheters placed directly into recurrent or progressive supratentorial malignant tumors.


Subject(s)
Genetic Vectors/administration & dosage , Herpesvirus 1, Human/genetics , Oncolytic Virotherapy , Research Design , Supratentorial Neoplasms/genetics , Supratentorial Neoplasms/radiotherapy , Adolescent , Adult , Brain Neoplasms/genetics , Brain Neoplasms/radiotherapy , Brain Neoplasms/virology , Child , Child, Preschool , Female , Genetic Therapy , Humans , Male , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/virology , Oncolytic Viruses/genetics , Safety , Supratentorial Neoplasms/virology
10.
J Pediatr Hematol Oncol ; 39(1): e39-e42, 2017 01.
Article in English | MEDLINE | ID: mdl-27879538

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Down Syndrome/complications , Germinoma/drug therapy , Supratentorial Neoplasms/drug therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Basal Ganglia/diagnostic imaging , Basal Ganglia/pathology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cranial Irradiation , Etoposide/administration & dosage , Etoposide/adverse effects , Germinoma/complications , Germinoma/diagnostic imaging , Germinoma/radiotherapy , Humans , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Magnetic Resonance Imaging , Male , Neutropenia/chemically induced , Paresis/etiology , Remission Induction , Supratentorial Neoplasms/complications , Supratentorial Neoplasms/diagnostic imaging , Supratentorial Neoplasms/radiotherapy
11.
Stereotact Funct Neurosurg ; 94(4): 273-278, 2016.
Article in English | MEDLINE | ID: mdl-27721314

ABSTRACT

BACKGROUND: Supratentorial primitive neuroectodermal tumors (PNETs) are highly malignant and rare tumors of the central nervous system. OBJECTIVES: The aim of this study was to determine the role of Gamma Knife surgery (GKS) as a salvage treatment option for patients with recurrent or residual supratentorial PNETs. METHODS: Between 1998 and 2014, 11 patients with supratentorial PNETs were retrospectively analyzed. This series consisted of 7 male and 4 female patients. The median age was 17 years. All patients received surgical resection followed by adjuvant therapy. The median time from operation to the first GKS treatment was 72.5 months. The median tumor volume was 17.5 cm3, and the median marginal dose was 11.5 Gy. RESULTS: 15 (65%) of the 23 tumors had been controlled. The actuarial local tumor control rate was 91% at 3 months, 73% at 6 months, and 44% at 12 months. At the time of analysis, 9 (82%) of the patients had died. The median survival time after the first GKS session was 17 months. The median survival time from the initial diagnosis was 65 months. No adverse radiation effect after GKS treatment occurred in any patient. CONCLUSIONS: GKS treatment might be an effective salvage treatment option for recurrent or residual supratentorial PNETs after multimodal treatment.


Subject(s)
Neoplasm Recurrence, Local/radiotherapy , Neoplasm, Residual/radiotherapy , Neuroectodermal Tumors, Primitive/radiotherapy , Radiosurgery , Supratentorial Neoplasms/radiotherapy , Adolescent , Adult , Child , Child, Preschool , Combined Modality Therapy , Female , Humans , Male , Neoplasm Recurrence, Local/surgery , Neoplasm, Residual/surgery , Neuroectodermal Tumors, Primitive/surgery , Neurosurgical Procedures , Retrospective Studies , Salvage Therapy , Supratentorial Neoplasms/surgery , Young Adult
12.
J Neurooncol ; 128(1): 137-145, 2016 05.
Article in English | MEDLINE | ID: mdl-26945580

ABSTRACT

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.


Subject(s)
Ependymoma/radiotherapy , Infratentorial Neoplasms/radiotherapy , Proton Therapy , Supratentorial Neoplasms/radiotherapy , Adolescent , Chemotherapy, Adjuvant , Child , Child, Preschool , Dose-Response Relationship, Radiation , Ependymoma/drug therapy , Ependymoma/surgery , Female , Follow-Up Studies , Humans , Infant , Infratentorial Neoplasms/drug therapy , Infratentorial Neoplasms/surgery , Male , Proton Therapy/adverse effects , Proton Therapy/methods , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Supratentorial Neoplasms/drug therapy , Supratentorial Neoplasms/surgery , Treatment Outcome
13.
Neuro Endocrinol Lett ; 36(2): 127-32, 2015.
Article in English | MEDLINE | ID: mdl-26071580

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Glioblastoma/drug therapy , Supratentorial Neoplasms/drug therapy , Adult , Drug Administration Schedule , Glioblastoma/radiotherapy , Glioblastoma/surgery , Humans , Male , Neoplasm Grading , Neoplasm Recurrence, Local , Supratentorial Neoplasms/radiotherapy , Supratentorial Neoplasms/surgery
14.
Eur J Neurol ; 22(9): 1304-9, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26053493

ABSTRACT

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.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Glioblastoma/drug therapy , Outcome Assessment, Health Care , Supratentorial Neoplasms/drug therapy , Aged , Angiotensin II Type 1 Receptor Blockers/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Antineoplastic Agents, Alkylating/therapeutic use , Dacarbazine/analogs & derivatives , Dacarbazine/therapeutic use , Disease-Free Survival , Female , Glioblastoma/mortality , Glioblastoma/radiotherapy , Humans , Hypertension/drug therapy , Male , Middle Aged , Supratentorial Neoplasms/mortality , Supratentorial Neoplasms/radiotherapy , Temozolomide
15.
Cancer Radiother ; 19(3): 187-91, 2015 May.
Article in English | MEDLINE | ID: mdl-25835374

ABSTRACT

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.


Subject(s)
Cranial Irradiation/methods , Glioma/radiotherapy , Hippocampus/radiation effects , Neoplasm Recurrence, Local/radiotherapy , Organ Sparing Treatments/methods , Radiotherapy, Adjuvant/methods , Radiotherapy, Intensity-Modulated/methods , Supratentorial Neoplasms/radiotherapy , Antineoplastic Agents, Alkylating/therapeutic use , Astrocytoma/pathology , Brain Damage, Chronic/prevention & control , Cell Dedifferentiation , Combined Modality Therapy , Cranial Irradiation/adverse effects , Dacarbazine/analogs & derivatives , Dacarbazine/therapeutic use , Disease Progression , Female , Frontal Lobe/pathology , Glioma/drug therapy , Glioma/surgery , Humans , Neoplasm Recurrence, Local/drug therapy , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated/adverse effects , Supratentorial Neoplasms/drug therapy , Supratentorial Neoplasms/surgery , Temozolomide , Tumor Burden , Young Adult
16.
Br J Neurosurg ; 29(4): 524-31, 2015.
Article in English | MEDLINE | ID: mdl-25724425

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Alkylating , Carmustine , Glioblastoma , Intraoperative Care/methods , Outcome Assessment, Health Care , Supratentorial Neoplasms , Adult , Aged , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/pharmacology , Antineoplastic Protocols , Carmustine/administration & dosage , Carmustine/pharmacology , Chemoradiotherapy , Combined Modality Therapy , Female , Glioblastoma/drug therapy , Glioblastoma/radiotherapy , Glioblastoma/surgery , Humans , Male , Middle Aged , Supratentorial Neoplasms/drug therapy , Supratentorial Neoplasms/radiotherapy , Supratentorial Neoplasms/surgery , Young Adult
17.
Stereotact Funct Neurosurg ; 93(1): 38-41, 2015.
Article in English | MEDLINE | ID: mdl-25662091

ABSTRACT

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.


Subject(s)
Cerebral Peduncle/surgery , Glioma/surgery , Infratentorial Neoplasms/surgery , Laser Therapy/instrumentation , Neurofibromatosis 1/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Astrocytoma/drug therapy , Astrocytoma/radiotherapy , Bevacizumab/administration & dosage , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Child , Combined Modality Therapy , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Glioma/genetics , Humans , Infratentorial Neoplasms/genetics , Irinotecan , Laser Therapy/methods , Male , Neoplasms, Multiple Primary/radiotherapy , Neoplasms, Multiple Primary/surgery , Neuroimaging , Optic Nerve Glioma/radiotherapy , Supratentorial Neoplasms/drug therapy , Supratentorial Neoplasms/radiotherapy , Temozolomide
18.
Clin Neurol Neurosurg ; 128: 60-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25462098

ABSTRACT

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.


Subject(s)
Glioblastoma/mortality , Glioblastoma/surgery , Supratentorial Neoplasms/mortality , Supratentorial Neoplasms/surgery , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/therapeutic use , Combined Modality Therapy , Dacarbazine/analogs & derivatives , Dacarbazine/therapeutic use , Female , Glioblastoma/drug therapy , Glioblastoma/radiotherapy , Humans , Karnofsky Performance Status , Male , Neoplasm Grading , Retrospective Studies , Supratentorial Neoplasms/drug therapy , Supratentorial Neoplasms/radiotherapy , Temozolomide , Treatment Outcome
19.
Childs Nerv Syst ; 31(1): 67-75, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25374270

ABSTRACT

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.


Subject(s)
Neurosurgery/methods , Supratentorial Neoplasms/surgery , Treatment Outcome , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Intracranial Hypertension/etiology , Kaplan-Meier Estimate , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Male , Radiotherapy, Adjuvant , Retrospective Studies , Supratentorial Neoplasms/drug therapy , Supratentorial Neoplasms/radiotherapy
20.
Pan Afr Med J ; 18: 204, 2014.
Article in French | MEDLINE | ID: mdl-25419331
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