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.     

Permanent I-125 brain stem implants in children

Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gy×4 fractions. After 4–6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7–9 months from diagnosis) and four patients remain alive (5–38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses. Received: 10 May 1998     

The first experience in interstitial brachytherapy for primary and metastatic tumors of the brain

In 2001-2002, the authors performed a course of brachytherapy in 15 patients with inoperable primary, recurrent, and metastatic brain tumors. The histostructural distribution was as follows: low-grade astrocytoma (grade II according to the WHO classification) in 2 patients, anaplastic astrocytoma (AA) in 3, glioblastoma multiforme (GBM) in 5. Five patients had solid tumor deposits in the brain. Computer tomographic (CT) and magnetic resonance imaging (MRI) data were used to define a path for forthcoming biopsy and implantation at a "Stryker" navigation station, by taking into account the anatomy of the brain, vessels, and functionally significant areas. After having histological findings, plastic intrastats whose number had been determined by the volume of a target were implanted into a tumor by the predetermined path. Dosimetric planning was accomplished by using CT and MRI images on an "Abacus" system. The final stage involved irradiation on a "GammaMed plus" with a source of 192Ir. Irradiation was given, by hyperfractionating its dose (3-4 Gy twice daily at an interval of 4-5 hours) to the total focal dose (TFD) of 36-44 Gy. Patients with gliomas untreated with radiation also underwent external radiation in a TFD of 54-56 Gy and patients with brain metastases received total external irradiation of the brain in a TFD of 36-40 Gy. The tolerance of a course of irradiation was fair. In patients with AA and GBM, one-year survival was observed in 66 and 60%, respectively; in those having metastasis, it was in 20%. Six patients died from progressive disease. All patients with low-grade astrocytoma and one patient with anaplastic astrocytoma were alive at month 24 after treatment termination. The mean lifespan of patients with malignant gliomas and solid tumor metastasis was 11.5 and 5.8 months, respectively. Brachytherapy is a noninvasive and tolerable mode of radiotherapy that increases survival in some groups of patients with inoperable brain tumors.     

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。     

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.     

Epilepsy and brain tumors in infancy and adolescence

Four boys and four girls with brain tumors who were admitted to our department in the last 8 years are herein described. They presented with epileptic fits, which began before the age of 14 years, with neither intracranial hypertension nor localizing signs during the first 6 months of the illness. The length of time between the first fit and the diagnosis of a tumor ranged from 2 months to 11 years (median of 3 years), during which period all patients but one received anticonvulsant therapy. The nontreated patient was under psychiatric treatment for 1 year. The electroencephalographic evolution was disconcerting, showing asymmetry of the recording with association of slow polymorphic waves and acute irregular waves, suggesting encephalitis. The neuroradiological diagnosis was made by cerebral arteriography in one patient and in the others by angiography and CT scans (which revealed hypodense cerebral areas in five cases and hyperdense areas in the other two). The histology of the tumor was that of a grade I astrocytoma in six cases; a grade III oligondendroglioma in one case, and a meningioma in the other. All patients underwent surgical treatment. Four also received radiation therapy, two for a partially excised astrocytoma and one each for an oligodendroglioma and a meningioma. Postoperatively, all patients were put on anticonvulsant drug therapy. There were no mortalities. To date, only one astrocytoma has recurred. The sequellae observed were hemiparesis in one case and marked psychomotor deficit in another. These two patients also still have epileptic fits. The others are all psychologically and neurologically normal, and two are now off antiepileptic drugs.     

A case report of chronic myelocytic leukemia with multiple brain metastases, which responded to the gamma-knife therapy]

We report a 78-year-old woman who had multiple leukemic cell tumors in the brain in the course of chronic myelocytic leukemia (CML). As far as we could survey, such brain tumors were extremely rare. She had been followed because of chronic phase of CML until October, 1998, when she noticed muscle weakness in her left upper and lower extremity. A head MRI revealed multiple masses in the brain, a biopsy of which revealed a tumor of CML cells. Although 40 Gy gamma-knife therapy had reduced the size and numbers of brain tumors, we found recurrence of left hemiparesis and tumors three months after the gamma-knife therapy. Whole brain irradiation therapy (total 30 Gy) was somewhat effective to the tumor and hemiparesis transiently subsided. Thereafter her general condition worsened again, and she died in June, 1999, eight months after the diagnosis of the brain tumors of leukemic cells. We had not seen any other clinical evidence of generalized blastic crisis in this patient. In our case, MRI of the brain showed two patterns of metastases, tumor forming and cortical invasive type. We thought that these two patterns of brain involvement might show different responses to the radiation therapy, and it was characteristic in this patient.     

经胼胝体-穹窿间切除第三脑室松果体区肿瘤

目的 探讨经胼胝体-透明隔-穹窿间入路显微手术切除第三脑室松果体区肿瘤的方法及疗效,并对相应的显微解剖学基础加以讨论.方法 经胼胝体-透明隔-穹窿间入路显微手术切除第三脑室松果体区肿瘤16例.结果 术前1例先行脑室-腹腔分流术、1例行神经内镜第三脑室底终板造瘘术.16例在手术显微镜下肿瘤全切除9例,次全切除4例,大部切除3例.5例在处理完肿瘤后做终板造瘘术.结论 经胼胝体-透明隔-穹窿间入路手术切除第三脑室松果体区肿瘤系通过胚胎组织残留的透明隔间隙进入第三脑室,损伤少,肿瘤全切除、次全切除率高,术后并发症少.     

丘脑及脑干占位病变的显微与激光手术

本文总结１８例丘脑及脑干占位性病变的显微与激光手术治疗体会。其中４例位于丘脑，中脑者２例，桥脑者６例，延髓者６例。除１例桥脑胶质瘤术后第三个月死于肿瘤复发呼吸衰竭，１例丘脑肿瘤于术后１年死于再手术后感染外，其他皆有良好的神经功能恢复．１２例于术中后２～３周作ＣＴ／ＭＲ检查，显示有明显改善．随访５个月～２年无症状复发表现．本文就丘脑及脑干占位病变的手术适应证、手术入路及激光应用作重点讨论．     

Stereotactic biopsy for multifocal, diffuse, and deep-seated brain tumors using Leksell's system.

Using the Leksell stereotactic system, we selectively performed 91 biopsies for surgically inaccessible brain lesions. There were 25 multiple (27.5%), 15 diffuse (16.5%), and 51 (56.0%) deep-seated lesions. However, we avoided subjecting the patients with lesions adjacent to major vascular trunks or complex vascular structures such as the cavernous sinus, peri-insular regions and the pineal regions to stereotactic biopsy. The diagnosis was histologically confirmed in 84 cases (92.3%). Sixty-nine (75.8%) lesions were primary tumors; 44 (48.4%) were malignant gliomas, 18 (19.8%) malignant lymphomas, and five (5.5%) low-grade gliomas. Thirteen (14.3%) cases had previously undergone radiation and/or chemotherapy for brain tumors, seven had recurrent glioma (five with malignant transformation) and six manifested radiation necrosis. None of the patients died due to the stereotactic procedure; one (1.1%) exhibited morbidity due to complicated hemorrhage. We found asymptomatic minor bleeding occurred in nine (9.9%) patients; the rate of hemorrhage was significantly higher in patients with preoperative angiographic evidence of tumor stain. Two patients (2.2%) suffered seizures, in one case seizure was induced by electric stimulation test at the target site. All five patients younger than 15 years underwent the procedure without complications. The Leksell stereotactic system is useful for diagnostic tissue sampling and contributes effectively to the selection of appropriate therapy in patients with malignant brain tumors. While it carries a low morbidity rate without mortality in our series, care must be taken for selected target sites in highly vascularized lesions exhibiting positive tumor stains.     

Own experience in surgical treatment of the pineal region and midbrain tumors via the infratentorial approach

Nine cases of tumours located in the pineal and midbrain region in adults operated on between November 1998 and July 2002 in Dept. of Neurosurgery, Central Military Hospital in Warsaw are reported. The patients (2 men and 7 women) were aged from 27 and 69 years (mean age 43.6 years). Their main initial symptoms were caused by hydrocephalus. The histopathological examination revealed anaplastic pinealoma in 2 cases, and pineocytoma, pineal cyst, mesencephalic glial cyst, protoplasmatic astrocytoma, epidermoid cyst, unclear glial scar, and papillary ependymoma in single cases. Five patients had been treated, usually elsewhere, with shunt implantation prior to the surgery. Occipito-suboccipital osteoplastic craniotomy was performed in each case and tumours were totally removed microsurgically via the infratentorial epicerebellar approach. In one case a part of the glial periaqueductal tumour was resected additionally via the fourth ventricle and aqueduct in one stage. Postoperative haematomas in the third and fourth ventricle were found in 2 cases. Main complaints after the surgery included transient diplopia. All the patients improved significantly and resumed their previous life activities. Follow-up ranged from 3 to 44 months. Three patients with pineal tumours and one with a small postoperative ependymoma recurrence were irradiated after the surgery. One patient had been irradiated prior to surgery. Very good results of the surgical treatment of tumours in this area suggest that such patients should be referred earlier to one stage surgical management, as the procedure is easier to perform and shunt implantation may be avoided.     

Intracranial hemorrhage from an aneurysm encased in a pilocytic astrocytoma – case report and review of the literature

The authors present an unusual complication of a recurrent chiasmal/hypothalamic pilocytic astrocytoma. From his second year of lifeonwards, the patient was repeatedly operated on and also underwent external radiation therapy (54 Gy total dose) 1 month after the first subtotal tumor resection. Nine years after irradiation, the patient was referred to our center with a sudden onset of severe headache, vomiting and neck stiffness. Computed tomography, magnetic resonance imaging, and cerebral angiography demonstrated an intratumoral, intraventricular, and subarachnoidal hemorrhage from an anterior communicating artery aneurysm encased in the pilocytic astrocytoma. The aneurysm was clipped and the patient recovered nicely from the hemorrhage. Three years later, the patient suddenly died of cardiac failure. Autopsy disclosed vessel wall changes compatible with radiation-induced vasculopathy. In light of this finding, the importance of radiation therapy and intracranial neoplasms for aneurysm formation is discussed. Received: 7 February 2000     

Pineal tumors: experience with 48 cases over 10 years

The authors retrospectively reviewed 48 patients treated at Seoul National University Hospital (SNUH) between 1986 and 1995. There were 35 children and 13 adults, accounting for 10.1% of 345 pediatric and 0.68% of 1914 adult brain tumors in SNUH during the same period. The 48 cases consisted of 33 cases of germ cell tumor (69%, GCT); 6 of pineoblastoma (PB, 12.5%); 3 of pineocytoma (PC, 6.3%); 3 of anaplastic astrocytoma (6.3%); 1 of astrocytoma; 1 of glioblastoma; and 1 of ependymoma. The median age was 13 years (range 1–59) and the male-to-female ratio was 3.36:1. The most frequent presenting symptom was due to increased intracranial pressure (90%), followed by Parinaud syndrome or diplopia (50%). Patients with a benign tumor, such as teratoma (TE), astrocytoma, or ependymoma, underwent surgery by the occipital transtentorial approach (OTT) for attempted radical resection without adjuvant therapy, while patients with immature teratoma (imTE), PC, and anaplastic astrocytoma underwent regional radiotherapy (RT) after debulking via OTT. Seven patients with nongerminomatous malignant GCT (NG-MGCT) and 3 with germinoma (GE) underwent craniospinal radiation only, 6 with GE, a NG-MGCT, and 2 with GE+TE received craniospinal radiotherapy (CSRT) after debulking via OTT. Three patients with GE, 4 with NG-MGCT, and 3 with PB underwent radiochemotherapy after debulking via OTT. Forty-four patients were followed up after treatment. The median follow-up period was 36 months. All patients with GE were alive after RT at 36 months (median) of follow-up (range 7–70 months). All with GE+TE and TE were alive. Three patients with PC or astrocytoma were also alive with stable or no evidence of disease. In 1 of the 3 cases of imTE there was a recurrence. However, 4 patients with NG-MGCT died, all of whom had undergone CSRT only; 2 PB patients were alive (12, 19 months), 1 in a moribund status (36 months), and 2 were dead (6, 60 months). The overall mean survival time with pineal tumors was 66 months and the 3-year survival rate was 84% with minimal posttreatment complications. It is concluded that pineal region tumors have male and childhood predominances, and the most common tumor is GCT. The majority of pineal region tumors are malignant. Pineal region tumors can be approached safely and effectively and the surgical complications are mostly transient. Their prognosis is dependent on the pathologies and treatment modalities.     

Results of hyperfractionated radiation therapy used in combination with lomustin in malignant gliomas of the brain

The postoperative use of lomustin, a nitrosourea agent, was investigated for its impact on the efficiency of hyperfractionated radiation therapy performed in patients with glioblastoma and anaplastic astrocytoma of the brain. A total of 35 patients (26 and 9 patients with glioblastoma and anaplastic astrocytoma, respectively) were followed up. Radiation therapy was performed, by using a total focal dose of 65 Gy in 2 steps or a single dose of 1.25 Gy twice daily every 4-6 hours. The patients received lomustin in a single oral dose of 160-200 mg at each of 2 stages of a hyperfractionated course of radiation therapy. The interval between two successive administrations was 5 weeks. Lomustin in combination with hyperfractionated radiation therapy was found to have no effect on the survival of patients with glioblastoma and anaplastic astrocytoma.     

The efficacy of a biopsy of intrinsic brainstem lesions for decision making of the treatments

Object

The diagnosis of diffuse intrinsic pontine gliomas (DIPGs) has been generally made mainly by magnetic resonance imaging (MRI) and clinical course. However, the accuracy of MRI-based diagnosis has not been fully confirmed yet. Our aim was to review efficacy of biopsy for decision making of the treatments.

Methods

We retrospectively analyzed pediatric patients undergoing biopsy for intrinsic brainstem lesions which were considered atypical for DIPGs by MRI findings. The lesion was evaluated atypical when it extended beyond the pons or it had a well-margined localized enhancing portion.

Results

Seven patients underwent biopsy. Preoperative MRI revealed a lesion extending beyond the pons in five patients and a focal enhancing lesion in four. Two patients had both of these. Open biopsy was performed via midline suboccipital approach in six patients and retrosigmoid approach in one. No intraoperative complications were observed. Histopathological examination revealed diffuse brainstem glioma in five patients, primitive neuroectodermal tumor (PNET) in one, and pilocytic astrocytoma in one. In the case with PNET, chemotherapy and radiotherapy were effective and the patient had been stable for 12 months without recurrence. The patient with pilocytic astrocytoma did not undergo radiotherapy and has been stable without regrowth of the tumor for 9 months.

Conclusions

Open biopsy of intrinsic brainstem lesions is considered to be safe and effective for selecting an appropriate course of therapy. Patients with intrinsic pontine lesions which extend beyond the pons or with localized enhancing portion seem to be benefited from the biopsy.     

立体定向治疗颅脑病变

目的：探讨立体定向技术治疗脑深部病变的疗效。方法：利用ASA－601S和Fischer脑立体定向仪治疗82例脑深部病变患者,行定向活检治疗22例,血肿清除治疗5例,脑脓肿抽吸术2例,囊性颅咽管瘤置入Ommaya管治疗53例。结果：活检确诊为胶质瘤10例,生殖细胞瘤4例,脑寄生虫3例,肺癌脑转移4例,1例第三脑室后部病变活检为胶质细胞增生。4例胶质瘤行手术治疗后病情好转,其余肿瘤行放射治疗,有6例痊愈（4例生殖细胞瘤,2例转移性肿瘤）。3例寄生虫经过症治疗后痊愈;2例脑脓肿经抽吸、抗炎治疗后痊愈;脑血肿5例经治疗痊愈;53例颅咽管瘤置放Ommaya管后3例痊愈（行囊内放疗）,50例好转。结论：立体定向治疗脑深部病变定位精确、损伤小、操作简便、安全可靠、值得提倡。     

Case management of hydrocephalus associated with the progression of childhood brain stem gliomas

OBJECT: Most patients diagnosed with brain stem glioma become bedridden because of deteriorating brain stem function. Many brain stem glioma patients develop hydrocephalus. Both of these outcomes greatly detract from the quality of life of these patients. We have analyzed the occurrence of hydrocephalus in diffuse brain stem gliomas in children, and we discuss the management of advanced cases. METHODS: Eighteen patients diagnosed with brain stem glioma while under 15 years of age, including 1 with dissemination, were studied retrospectively. The average overall survival was 11.8 +/- 6.5 months (mean +/- SD). Hydrocephalus occurred in 16 (88.9%) of the 18 cases. The patients diagnosed with hydrocephalus all exhibited a rapid decline in consciousness. The average time to onset of hydrocephalus after tumor diagnosis was 5.1 +/- 3.3 months. Twelve of the 16 patients with hydrocephalus were treated with cerebrospinal fluid (CSF) diversion, by means of a Torkildsen shunt, a ventriculoperitoneal shunt, or third ventriculostomy. The level of consciousness and patient performance status improved after CSF diversion except in 2 patients who had received Torkildsen shunts. The patients treated for hydrocephalus survived significantly longer than those patients who did not undergo any intervention for hydrocephalus. CSF diversion may be a therapeutic intervention that significantly improves the quality of life and survival of patients. CONCLUSION: Our results suggest that patients diagnosed with brain stem glioma should be closely monitored for signs of hydrocephalus and be examined by neuroimaging rapidly when indicated. Our results also suggest that once hydrocephalus is diagnosed CSF diversion should be performed promptly.     

Delayed brain hemorrhage associated with prophylactic whole brain irradiation for pediatric malignant brain tumor: a case report

Intraparenchymal hemorrhage in the left frontal lobe suddenly occurred in a 7-year-old girl who had undergone partial removal of an undifferentiated brain stem glioma and received craniospinal (30 Gy) and posterior fossa booster (20 Gy) irradiation at the age of 20 months. The brain hemorrhage was thought to be delayed irradiation effect. Follow-up neuro-imaging at age 9 years showed two more small occult chronic and subacute hemorrhages in the brain. The possibility of repeated hemorrhage as a delayed reaction to brain irradiation is emphasized.     

Therapy and survival of adult patients with intracranial glioma in a defined population

During the 3 years 1978-1980 146 adult patients with intracranial glioma were diagnosed in the Province of Uusimaa in southern Finland. The median survival of all patients was 15 months, of glioblastoma (n = 41) 5.1 months, of anaplastic astrocytoma (n = 29) 12.4 months, of benign grade I-II astrocytoma (n = 30) 93.5 months, of other glioma 82.9 months (n = 27), and of probable glioma 9.8 months (n = 19); 22 patients are still alive 8.9-11.9 years after diagnosis. The patients who were 15-44 years of age at the time of diagnosis survived 75.4 months in the median (n = 58), 45-64 years 10.5 months (n = 61) and 65 years or older 4.8 months (n = 27); 96 patients were operated, 89 received radiotherapy and 34 chemotherapy. According to the proportional hazards' model, follow-up time, age and histological type of tumor were statistically highly significant in explaining differences in survival.