Fractionated stereotactic radiotherapy for pediatric brain tumors: the Chicago children’s experience

Thirty-three children with a total of 35 benign/malignant brain and eye neoplasms were treated with fractionated stereotactic radiotherapy. In the first 11 children immobilization for treatment was achieved with plaster of Paris casts or aquaplast masks. In the remaining 22 children the Laitinen stereoadapter was used. Radiation was delivered with noncoplanar static or rotational beams. The dose fractionation used was 50.4–60 Gy in 28–30 fractions in patients receiving treatment with curative intent, and 10–32 Gy at 2–4 Gy/fraction for reirradiation. The accuracy of daily treatment was <2 mm. After a median follow-up of 27 months, 22 of the 25 children treated with curative intent achieved local control. One child had progressive brain necrosis following 54 Gy in 30 fractions for a pontine astrocytoma. The exact etiology of this complication is unknown. This series demonstrates that in children fractionated stereotactic radiotherapy using the Laitinen stereoadapter is well tolerated and accurate and results in good local control. Received: 26 July 1999     

Shall we treat hydrocephalus associated to brain stem glioma in children?

Purpose/method  

Brain stem glioma accounts for 6–9% of brain tumors in children. Tumor progression may lead to CSF pathway obstruction and development of hydrocephalus. We retrospectively reviewed charts of patients consecutively treated in our institution with diffuse intrinsic pontine glioma in order to assess incidence of hydrocephalus, its management, and its impact on overall survival. All patients had brain stem glioma not amenable to surgery. Cases with exophytic brain stem glioma were excluded.     

Decreased quality of life and depression as predictors for shorter survival among patients with low-grade gliomas: a follow-up from 1990 to 2003

Objectives To assess the long-term survival of brain tumor patients, and in particular to evaluate the relation of quality of life (QOL) to survival among low-grade glioma patients. Methods The postoperative survival of 101 brain tumor patients was followed from surgery (1990–1992) until the end of the year 2003. Depression was evaluated by the Beck Depression Inventory (BDI) and QOL with Sintonen’s 15D scale before operation and at one year as well as at five years after operation. Results The mean survival times in years (SD) were significantly related to tumor malignancy, being the shortest, 1.9 (0.6), for patients with high-grade gliomas, while patients with low-grade gliomas or a benign brain tumor had mean survival times of 9.1 (1.0) and 11.6 (0.5), respectively. At all follow-ups, depressed low-grade glioma patients had a significantly shorter survival time, 3.3–5.8 years, compared to non-depressed low-grade glioma patients, 10.0–11.7 years. A decreased level of QOL in low-grade glioma patients was significantly related to the shorter survival. Conclusions The results suggest that depression and decreased QOL among low-grade glioma patients is related to shorter survival at long-term follow-up. Decreased QOL may serve as an indicator for poor prognosis in low-grade glioma patients.     

恶性脑胶质瘤立体定向加常规放疗的疗效观察(附32例临床分析)

目的探讨病理高级别胶质瘤术后,常规外照射加立体定向照射放疗推量治疗模式的疗效。方法对病理诊断均为WHOⅢ～Ⅳ级胶质瘤治疗后患者,放射治疗前程常规照射和后程立体定向照射推量相结合的方式,外照射46～50Gy23～25f/4.6～5W后,紧接着用分次立体定向照射推量14～20Gy。结果治疗后近期效果满意,无严重神经功能障碍并发症。本组病例1、2、3年总体生存率分别为77.3%、52.5%、25.0%;1、2、3年无进展生存率分别为59.8%、36.7%、16.3%。急性放射反应多为1～2级,没有发现4级以上急性放射反应。结论采用分次立体定向加常规放疗治疗胶质瘤既发挥了放射物理剂量分布的优点,又符合放射生物学原则,是控制高分级胶质瘤生长及延迟复发的重要辅助治疗手段。     

Primary intracranial germinoma involving the midbrain

To our knowledge, this is the first reported case of a germinoma involving the midbrain without the demonstrable coexistence of any common midline tumors. A 27-year-old man was referred to our institution for evaluation and treatment of diplopia persisting for 5 years. Magnetic resonance imaging (MRI) showed the mass in the midbrain to be of iso intensity on T1-weighted images, and of high intensity on T2-weighted images with homogeneous enhancement. MRI-guided stereotactic biopsy was performed, and the histologic diagnosis was germinoma. Following biopsy, external beam radiotherapy of 50 Gy (whole brain 30 Gy; local 20 Gy) was performed. At the time of discharge, the patient's neurological symptoms had resolved. Follow-up MRI revealed disappearance of the tumor. These findings suggest the diagnostic value of magnetic resonance image-guided stereotactic biopsy in the differential diagnosis of adult brainstem lesions, which should now include germinoma.     

Second primary brain tumors following cranial irradiation for pediatric solid brain tumors

Purpose

We describe our institution’s experience with seven patients who developed second brain tumors following cranial irradiation.

Methods

The median age at first irradiation was 8 years (range, 3–20 years). Initial diagnoses were two cases of germinoma, one non-germinomatous germ cell tumor (NGGCT), three cases of medulloblastoma, and one pineal gland tumor (pathology undetermined). All patients received craniospinal irradiation followed by local boost and the median dose to the initial tumor area was 54.0 Gy (range, 49.8–60.6 Gy). Four patients (two medulloblastomas, one germinoma, and one NGGCT) received chemotherapy.

Results

Second brain tumors were diagnosed a median of 114 months (range, 64–203) after initial radiation. Pathologic diagnoses were one glioblastoma, two cases of anaplastic astrocytoma, one medulloblastoma, one low-grade glioma, one high-grade glial tumor, and one atypical meningioma. Five patients underwent surgical resection with subsequent radiotherapy. One anaplastic astrocytoma patient received chemotherapy only following stereotactic biopsy. The meningioma patient was alive 32 months after total resection and radiosurgery for subsequent recurrences. Six patients died within 18 months and most deaths were due to disease progression.

Conclusions

Most patients diagnosed with second brain tumors had received high-dose, large-volume radiotherapy with chemotherapy at a young age. Further studies are required to determine the relationship between radiotherapy/chemotherapy and the development of secondary brain tumors.     

The changes of cerebral blood flow and metabolism of normal brain tissue after surgery, radiation, and chemotherapy in brain tumor patients: evaluated by position emission tomography

The changes of cerebral blood flow (CBF) and metabolism of normal brain tissue after surgery, radiation, and chemotherapy in brain tumor patients were measured by positron emission tomography (PET). The subjects consisted of 6 men and 3 women, and were from 11 to 62 years old. Those were four patients with glioblastomas, one patient with malignant oligodendroglioma, one patient with astrocytoma grade II, one patient with astrocytoma grade III, one patient with pontine glioma, one patient with pineal germinoma. Seven patients were operated and pathohistologically diagnosed. Two patients with pineal germinoma and pontine glioma were not operated and radiologically diagnosed. Of 7 operated patients, first PET was performed before operation in 3 patients, and from 10 to 16 days after operation in 4 patients. Following first PET, the patients were treated with irradiation (1 case), or with both irradiation and chemotherapy (8 cases). The total radiation dose for tumor was from 59 to 61 Gy distributed in a period of 6-8 weeks. Whole brain irradiation was performed up to 30 or 40 Gy, with a remaining dosimetry (20-30 Gy focused on the tumor field. Chemotherapy consisted of intravenous administration of ACNU and oral administration of FT-207. Second PET was performed 1 month after therapy (9 cases), and third PET was performed from 4 to 24 months after therapy (6 cases). Fourth PET was performed in 2 patients (22 and 35 months after therapy), and fifth PET was performed in one patient (35 months after therapy).(ABSTRACT TRUNCATED AT 250 WORDS)     

Stereotactic neurosurgery in children and adolescents

Between March 1992 and January 1998, 100 stereotactic procedures were carried out in our Stereotactic Department. Of these, 24 were performed on patients under 18 years of age, 22 of them under a local anaesthetic and sedation. The ages of these patients ranged between 4 months and 18 years. The stereotactic procedures carried out were: 15 cerebral biopsies, 5 iodine-125 implants, 4 implantations of Rickham reservoirs with ventricular catheter, with additional holes to establish a connection between the cyst content and the ventricular system (internal drainage): 2 of these patients had arachnoidal cysts in the pineal region, 1 a thalamic neuroepithelial cyst and 1 a cystic craniopharyngioma, with excellent control of hydrocephalus. All cerebral biopsies were positive, including 3 in which brain stem tumours were detected. Of the 5 patients treated by brachytherapy, 4 had pilocytic astrocytomas and 1 an anaplastic astrocytoma. The sites of the tumours for which implants were used were the thalamus in 4 cases, and the basal ganglia (corpus striatum) in 1. In only 2 cases was there some transistory morbidity, and mortality was nil. The stereotactic procedures in this varied group were well tolerated, with low morbidity and mortality rates, which proves that this method is effective and safe for patients. It can also be used for the diagnosis of brain stem tumours. Midline cysts can also be treated by means of internal drainage with catheters (a minimally invasive form of surgery). Received: 6 November 1998     

Biopsy of pediatric brain stem tumors.

26 patients, average age of 7.3 years, has biopsies of a brain stem tumor. 62% of the patients presented with hydrocephalus, and ventriculoperitoneal shunts were placed 7-10 days prior to biopsy. The midbrain was biopsied 13 times, the pons 3 and the medulla 12 times. Tissue for histopathologic examination was obtained at each operation and demonstrated astrocytoma in 13 patients, glioblastoma in 6, 'no tumor seen' in 5 and ependymoma in 2. Astrocytomas were usually located in the upper brain stem, and all of the glioblastomas were located in the medulla. The operative mortality was zero, and the morbidity was largely related to increased cranial nerve deficit. All the astrocytoma patients were treated with radiation only; whereas, 4 patients with glioblastoma were treated with vincristine, CCNU and methylprednisone in addition to radiation as described by the Children's Cancer Study Group (CCG-944). 3 patients with 'no tumor' were not treated and are alive and well 15-41 months following operation. 2 patients with no tumor were treated, one as a glioblastoma multiforme, subsequently verified at postmortem examination, and one as a midbrain astrocytoma. 1 patient with astrocytoma died 3 months following operation, all the remainder are living and well 4-51 months following operation. Irrespective of the treatment, all 7 patients with glioblastoma expired within 9 months of diagnosis. The prognosis for survival for patients with brain stem astrocytoma is superior to those with glioblastoma multiforme. Specific histopathologic correlation with clinical management may lead to improved and prolonged survival for patients with brain stem glioma.     

Establishment of experimental glioma models at the intrinsic brainstem region of the rats

OBJECTIVES: As the treatment of human intrinsic brainstem gliomas remains challenging, experimental glioma models are needed. METHODS: We developed a rat model of intrinsic brain stem glioma that uses a stereotactic frame to fix the head for the delivery of C6 glioma cells to target sites via a permanently implanted cannula. We inoculated the rat midbrain, pons or cerebral cortex with 5 x 10(4) cells suspended in 1 microl culture medium over the course of 2 minutes. RESULTS: Three days post-implantation, tumor formation was visible in the periaqueductal gray matter in the midbrain and the tegmentum of the pons. On the tenth day, the tumor diameter exceeded over 2 mm; there was no tumor cell seeding into the cerebrospinal fluid space. The tumor manifested the histological features typical of glioblastoma; Ki-67 labeling index was 32%. DISCUSSION: Because in our model the cannula is permanently implanted, additional inocula can be delivered. Here we detail our rat brainstem glioma model and discuss its usefulness for the investigation of these tumor in humans.     

立体定向植入125I籽粒治疗脑深部肿瘤

目的探讨局部植入125I籽粒治疗脑肿瘤的方法与疗效。方法采用机器人辅助立体定位技术施行脑肿瘤内植入125I籽粒手术66例,其中星形细胞瘤56例(Ⅰ～Ⅱ级39例,Ⅲ～Ⅳ级17例),室管膜瘤3例,恶性脑膜瘤2例,脑转移癌4例,恶性黏液瘤1例。结果本组手术操作顺利,肿瘤边缘放射总剂量设计为200Gy,平均每例手术用时26min,无严重并发症。术后随访1个月,有效率90.9%,无变化9.1%,无死亡病例;随访6～24个月,有效率87.9%,无变化6.1%,死亡6.1%。结论脑肿瘤内放疗的病例选择主要为开颅手术难以切除的原发和复发肿瘤。本方法手术创伤小,对脑深部肿瘤的治疗具有较好的临床效果。     

Conventional external radiotherapy in the management of clivus chordomas with overt residual disease

Cranial chordomas are uncommon tumors accounting for less than 1% of all intracranial neoplasms. Although they are slowly growing, rarely metastasising tumors, cranial chordomas are challenging to treat due to their critical location, invasive nature and aggressive recurrence. The aim of this retrospective study was to evaluate the role of conventional irradiation in the treatment of clival chordomas with overt residual disease after incomplete surgery. Between January 1979 and December 1997, 18 patients with histologically confirmed clival chordoma were treated with radiotherapy. Median age at the time of diagnosis was 32 years. The mean duration of the symptoms before diagnosis was 33.9 months. Median tumor diameter at initial presentation was 5 cm (range, 3–7 cm). The type of surgical procedure was subtotal excision in 11 patients and biopsy in 7. Radiation treatment was delivered with megavoltage units, and total doses between 50 Gy and 64 Gy (median, 60 Gy) were administered with conventional daily fractions. One patient received additional 12.50 Gy with linear accelerator-based stereotactic radiosurgery after subtotal excision and external irradiation. The mean follow-up time was 43.2 months. Overall survival at 5 years was 35%. Eleven patients showed progression after radiotherapy. The median time to progression after radiotherapy was 40.8 months (38.4–43.2) with a 5-year progression-free survival of 23%. Five patients (29.4%) showed symptomatic relief after radiotherapy while persistent symptoms were recorded for 6 patients. Incomplete surgery and conventional external radiotherapy with a dose of around 60 Gy seem to be inadequate in the treatment of clival chordomas. Received: 31 March 2000 / Accepted in revised form: 11 July 2000     

Efficacy of anti-epileptic drugs in patients with gliomas and seizures

Although seizures in brain tumor patients are common, the knowledge on optimal anti-seizure therapy in this patient group is limited. An observational study was carried out using a database of all patients from the neuro-oncology service during the period 2000–2005, with data on seizure characteristics, therapy with AEDs, the underlying brain tumor and its treatment. A total of 140 brain tumor patients were studied of whom 23.6% had a low-grade glioma, 53.6% a high-grade glioma, and 22.8% belonged to a mixed group existing of ependymoma, meningioma, and brain metastasis. Epilepsy as the presenting sign was more frequent in low-grade vs. high-grade gliomas (69.7 vs. 52%, P = 0.087), and a total of 75.8% of patients developed seizures with low-grade and of 80.0% with high-grade gliomas. Of all 99 patients with seizures, 80.1% received valproic acid (VPA) as first choice, and either levetiracetam (LEV), carbamazepine (CBZ) or lamotrigine (LMT) as the most frequent next choice. Patients treated with a combination of VPA and LEV showed the highest percentage of responders (81.5%), with a decline in seizure frequency of more than two categories in 55.6% and seizure freedom in 59%. No correlation was found between the use of VPA and survival. A combination of VPA and LEV seems effective, if seizure control cannot be achieved by VPA alone. This indicates that adding levetiracetam may be preferable over sequential trials of AED monotherapy in treatment-resistant seizures in patients with brain tumors.     

Leptomeninges as a site of relapse in locally controlled,diffuse pontine glioma with review of literature

Case report Leptomeningeal involvement in diffuse intrinsic brain stem gliomas is rarely diagnosed clinically and in majority of the instances diagnosed only on postmortem examination. We report two cases of diffuse pontine glioma diagnosed clinicoradiologically and treated with conventional radiotherapy.Observations On follow-up, both patients showed clinical features suggestive of meningeal spread although imaging for pontine tumor showed stable disease. Leptomeningeal disease in the spine was confirmed on imaging and in one case by cerebrospinal fluid examination also. During the follow-up of patients with pontine glioma, the possibility of leptomeningeal involvement must be borne in mind.     

手术切除联合放射性粒子永久性植入治疗复发性胶质瘤

目的探讨外科手术切除联合放射性粒子永久性植入治疗复发性胶质瘤的疗效。方法117例复发性胶质瘤完全随机分组，65例为间质放疗组，52例为普通放疗对照组，均行电磁导航辅助下显微神经外科手术全切除或次全切除。间质放疗组术中根据术前计算机三维治疗计划系统（TPS）在瘤床永久性植入125^I放射性粒子进行组织间近距离连续照射，总量为50～60Gy。对照组术后行常规外照射，50～60Gy/25～30次。随访3～36个月，观察肿瘤再次复发率、中位生存期。结果间质化疗组第2次手术后12个月复发31例（47.7%）；24个月复发46例（70.8%），较对照组（71.2%、86.5%）有显著差异；中位生存时间18.2月，较对照组13.5月显著延长；对照组并发症发生率53.8%，间质化疗组无显著的放疗并发症。结论力争手术全切除联合放射性粒子永久性植入对复发性恶性胶质瘤细胞近距离持续照射，疗效明显提高，安全且并发症少。     

显微手术切除加125I粒子置入治疗复发性脑胶质瘤12例分析

目的研究12例复发性脑胶质瘤显微手术切除加125I粒子置入治疗复发性脑胶质瘤的近期治疗效果。方法对12例复发性恶性脑胶质瘤患者行开颅显微手术全切除,术中在瘤床植入125I粒子,每颗粒子活度0.3~0.4mCi,病灶周边剂量50~80Gy。随访6~18个月,观察肿瘤再次复发率和患者病死率。结果全组12例获得6~18个月的随访。12例中有2例复发病例,复发的时间分别是在治疗后9个月和15个月。有2例死亡病例,1例在术后15月复发放弃治疗后死亡,另1例在术后4月死于并发症,其余9例粒子聚集病灶无扩大化表现,CT增强也未见肿瘤复发。无1例发生急性放射性反应。有2例出现粒子游走,但无功能损害的表现。有4例粒子周围出现的水肿持续达4~7月,给以脱水治疗后好转。有2例病人术后肿瘤残腔出血,保守治疗好转。全组病人抗癫治疗,无癫病例发生。结论显微手术切除加125I粒子置入,可提高复发性脑胶质瘤的疗效。     

Accuracy of frameless and frame-based image-guided stereotactic brain biopsy in the diagnosis of glioma: comparison of biopsy and open resection specimen

OBJECTIVES: Tissue heterogeneity and rapid tumor progression may decrease the accuracy a prognostic value of stereotactic brain biopsy in the diagnosis of gliomas. Correct tumor grading is therefore dependent on the accuracy of biopsy needle placement. There has been a dramatic increase in the utilization of frameless image-guided stereotactic brain biopsy; however, its accuracy in the diagnosis of glioma remains unstudied. METHODS: The diagnoses of 21 astrocytic brain tumors were derived using image-guided stereotactic biopsy (12 frame-based, nine frameless) and followed by open resection of the lesion 1.5 (0.5-4) months later. The histologic diagnoses yielded by the biopsy were compared with subsequent histologic diagnosis from open tumor resection. RESULTS: Histology of 21 stereotactic biopsies accurately represented the greater lesion at open resection a median of 45 days later in 16 (76%) cases and correctly guided therapy in 19 (91%) cases. Biopsy accuracy of frameless versus frame-based stereotaxis was similar (89 versus 66%, p=0.21). In three (14%) cases, biopsy specimens were adequate to diagnose glioma; however, histology was insufficient for definitive tumor grading. Anaplastic oligodendroglioma (ODG) was under-graded as low-grade ODG in one (5%) case. Biopsy of new onset glioblastoma multiforme (GBM) yielded necrosis/gliosis and was termed non-diagnostic in one patient. Tumors <50 cm(3) were 8-fold less likely to accurately represent the grade of the entire lesion at resection compared with lesions <50 cm(3) (OR, 8.8; 95% CI, 0.9-100, p=0.05). DISCUSSION: Both frameless and frame-based MRI-guided stereotactic brain biopsy are safe and accurately represent the larger glioma mass sufficiently to guide subsequent therapy. Large tumor volume had a higher incidence of non-concordance. Increasing the number of specimens taken through the long dimension of large tumors may improve diagnostic accuracy.     

Interstitial brachytherapy with iodine-125 seeds for low grade brain stem gliomas in adults: Diagnostic and therapeutic intervention in a one-step procedure

Purpose

To report on iodine-125 (I125) interstitial irradiation in the treatment of low grade brain stem gliomas in adults.

Patients and methods

Ten patients with well-circumscribed lesions of the brainstem and histological confirmation of low grade glioma treated with stereotactically implanted I-125 seed in our department between 1995 and 2012 were retrospectively analyzed.

Results

In 9 patients the lesion was treated with one I-125 seed and in one patient, 2 spatial separated lesions were implanted, therefore a total of 11 I-125 seeds were implanted. The mean volume of the 11 lesions was 2.76 ml (range: 0.5–7.2 ml), mean activity of the seeds was 6.23 mCi (range: 1.5–11.1 mCi), mean duration of irradiation was 28.5 days (range: 21–41 days) and mean effective dose rate was 9.16 cGy/h (range: 6.2–12 cGy/h). The 30 days perioperative morbidity and mortality rate was 0%. Median follow up was 72.5 month (range 5–168 months). Six of ten patients were free of progression until last follow up.

Conclusion

In our experience at the University Clinic in Freiburg Germany, interstitial radiosurgery based on MRI is a safe and effective method to diagnose and treat low grade gliomas of the brain stem. Furthermore randomized studies are needed to confirm the therapeutic impact of this method in comparison to external beam radiation of brain stem gliomas.     

Diffuse brain stem gliomas Are we improving outcome?

We reviewed our experience with diffuse brain stem glioma (dBSG) to evaluate whether any improvement of outcome had occurred in our patients over the years. Of the 24 children referred to our department with suspected dBSG from 1981 to 1997, 5 had a different final diagnosis based on the clinical course. Mean survival in the remainder was 16±9.8 months from diagnosis. Survival increased with a longer interval from onset of symptoms to diagnosis (12.9±9.0 months with an interval of 1–4 weeks; 19.50±10.8 months with a longer interval). Visual symptoms at presentation were associated with a poorer prognosis. Survival was better in the 3- to 5-year age group (at diagnosis). Overall, a trend toward a slight improvement in survival was seen over the years, which we presumptively attribute to the introduction of intensive chemotherapy for these patients. We suggest that chemotherapy may be important in the management of dBSG until a better modality is found. Received: 10 May 1998     

脑干胶质瘤磁共振波谱分析

目的探讨磁共振波谱(Magnetic resonance spectroscopy,MRS)在脑干胶质瘤诊断中的意义。方法回顾性分析10例脑干胶质瘤的临床资料,肿瘤位于中脑1例,中脑脑桥1例,脑桥7例,延髓1例。均行MRS检查,对肿瘤区、肿瘤边缘区和正常对照区进行对照研究。结果MRS均显示肿瘤区N-乙酰天门冬氨酸(N-acetylaspartate,NAA)峰值下降,胆碱(Choline,Cho)峰上升。与肿瘤边缘区和正常对照区比较,肿瘤区NAA/Cr明显减低,Cho/Cr和Cho/NAA明显升高。星形细胞瘤4例,间变性星形细胞瘤1例,胶质母细胞瘤2例;另3例根据临床特点和影像学表现诊断为脑干胶质瘤。结论MRS可检测到脑干胶质瘤的代谢改变,具有无创、敏感、诊断准确的特点。