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Introduction: Residual radiologically progressive masses following multimodality treatment of malignant mixed intracranial germ cell tumors are described. Often these enlarge, and this is called the growing teratoma syndrome. A similar phenomenon during radiotherapy alone has not been described., Subjects and Methods: A 5-year old boy presented with features of raised intracranial pressure. Imaging revealed a posterior third ventricular mass, which was biopsied endoscopically., Results: A review of the scanty tissue was suggestive of a pineal parenchymal tumor, and hence radiation was planned. After just ten fractions, he developed rapid neurological deterioration. Repeat imaging raised a possibility of a teratomatous tumor. He underwent emergency excision. However, he had a stormy postoperative course and succumbed to deep venous infarction. Histology revealed a purely mature teratoma., Conclusion: Though a growing teratoma syndrome has been described following chemotherapy, no such report while on radiation exists. Ours could be the first such reported case. We discuss the possible mechanisms with a review of the literature.

Metastatic Neuroendocrine Tumor (NET) to the pineal gland is a unique manifestation previously unreported in the literature. We describe an unusual case of metastatic bronchial NET to the pineal gland in a 71-year-old male patient. His primary NET had been resected six years previously and there was no indication of the presence of disseminated metastatic disease at that time. Due to increased uptake by the pituitary gland on the post-operative 111Indium-pentetreotide scintigraphy (Octreoscan), an intra-sellar mass was diagnosed and excised using a transsphenoidal approach; histology revealed an unrelated non-functional pituitary macroadenoma. Four years later, a new mass appeared on MRI, involving the pineal gland, and was diagnosed on biopsy as a metastatic lesion from the original bronchial NET. Since this lesion was not accessible to surgery, it was treated successfully with radiosurgery. The case suggests that NETs should be considered in the differential diagnosis of pineal gland metastases and that radiosurgery may be an effective alternative in the treatment of these patients.

We report a case of a mediastinal seminoma occurring 19 months after the resolution of a pineal germinoma. A 15-year-old boy with headaches and visual changes was diagnosed with a pineal germinoma by biopsy and mildly elevated beta-human chorionic gonadatropin (beta-HCG) in serum and cerebral spinal fluid. Radiation therapy leads to the resolution of his pineal germinoma and normalization of the beta-HCG. A mediastinal seminoma (germinoma) was diagnosed nearly 2 years later because of rising serum beta-HCG. There was no evidence of recurrent central nervous system disease. The patient underwent systemic chemotherapy with the complete resolution of the mediastinal seminoma.

This 18-year-old woman presented with headache and diplopia over several months and was found to have an enhancing pineal tumor with resultant obstructive hydrocephalus. Following standard preoperative diagnostic tests, including spinal axis imaging, the patient was taken to the operating room for an endoscopic third ventriculostomy to relieve hydrocephalus and then subsequently underwent a craniotomy for gross-total resection of the pineal mass. The patient was discharged after an uneventful hospital course and received standard adjuvant cranial-spinal radiation and chemotherapy as an outpatient. Follow-up imaging 1 year after surgery demonstrated a metabolically active, lytic lesion in the C-3 vertebral body and new lung lesions suggesting a metastatic pineoblastoma. The patient underwent a C-3 anterior corpectomy and reconstruction without complication as aggressive therapy for presumed metastatic disease. Final pathological results from the vertebral lesion were consistent with radiation-induced reactive changes, not metastatic pineoblastoma as originally suspected. The patient recovered well and remains symptom free. To the authors' knowledge this is the first reported case of reactive changes mimicking metastasis in a single vertebral body following standard therapy for resected primary pineoblastoma.

We report the case of an adult patient with pineoblastoma (PBL) who had a complete radiographic response following treatment with vorinostat and retinoic acid. This regimen was used to treat bulky residual tumor that persisted despite radiation therapy (RT) and two cycles of cytotoxic chemotherapy. Vorinostat and retinoic acid were chosen as an alternative to cytotoxic chemotherapy, which our patient was unable to tolerate, based on preclinical data suggesting efficacy of this combination. MRI demonstrated a complete response to this regimen, which continues to remain stable without evidence of recurrence.

Objective: The objective of this study is to report our initial experience treating pediatric patients with central nervous system tumors using a frameless, optically guided linear accelerator., Materials and Methods: Pediatric patients were selected for treatment after evaluation by a multidisciplinary neuro-oncology team including neurosurgery, neurology, pathology, oncology, and radiation oncology. Prior to treatment, all patients underwent treatment planning using magnetic resonance imaging (MRI) and treatment simulation on a standard computed tomography scanner (CT). For CT simulation, patients were fitted with a customized plastic face mask with a bite block attached to an optical array with four reflective markers. After ensuring adequate reproducibility, these markers were tracked during treatment by an infra-red camera. All treatments were delivered on a Varian Trilogy linear accelerator. The follow-up period ranges from 1-18 months, with a median follow-up of 6 months., Results: Nine patients, ages ranging from 12 to 19 years old (median age 15 years old), with a variety of tumors have been treated. Patients were treated for juvenile pilocytic astrocytoma (JPA; n = 2), pontine low-grade astrocytoma (n = 1), pituitary adenoma (n = 3), metastatic medulloblastoma (n = 1), acoustic neuroma (n = 1), and pineocytoma (n = 1). We followed patients for a median of 12 months (range 3-18 months) with no in-field failures and were able to obtain encouraging toxicity profiles., Conclusion: Frameless stereotactic optically guided radiosurgery and radiotherapy provides a feasible and accurate tool to treat a number of benign and malignant tumors in children with minimal treatment-related morbidity.

With the development of diagnostic, radiologic, and therapeutic modalities, strategies for management of central nervous system (CNS) germinoma are changing gradually. The author advocates that typical germinomas can be diagnosed based on their typical clinical and radiological findings, together with slight elevation of beta-human chorionic gonadotropin levels in the serum and/or cerebrospinal fluid (CSF) and quick response to radiation or chemotherapy. Radiation therapy has been the standard treatment for CNS germinoma until recently. Germinomas 4 cm or less in diameter can be cured with radiation doses of 40-45 Gy. Regarding the treatment volume, an individualized approach is recommended and a focal radiation field covering at least major parts of the ventricular system is recommended if no CSF dissemination is present and CSF cytology is negative. Such irradiation is best given by intensity-modulated radiation therapy. Systemic chemotherapy with reduced doses (24-30 Gy) of radiation has to some extent been successful, but longer follow-up periods are necessary to draw conclusions regarding the superiority of this treatment over standard-dose radiation therapy. CNS germinoma patients should be completely cured with minimum morbidity, probably by employing appropriate doses of chemotherapy and intensity-modulated radiation therapy in the future., (Copyright (c) 2009 S. Karger AG, Basel.)

The histopathological entity 'germ cell tumor' (GCT) encompasses a number of histological subtypes. Pineal GCTs can be grossly divided into three categories: those with a good, intermediate, and poor prognostic. Germinoma and mature teratoma are curable and classified into the good prognostic group, whereas embryonal carcinoma, yolk sac tumor, and other highly malignant neoplasms leave patients with a dismal prognosis. There are other types of GCT that have an intermediate prognosis, such as immature teratoma. Only mature teratomas are curable by surgical resection alone; the other types require adjuvant therapy. To plan a surgical strategy, then eurosurgeon has to acquire enough knowledge of the effect of adjuvant therapies and biological behavior of the GCTs. Germinoma can be cured by low-dose radiotherapy in combination with chemotherapy, and nowadays needs only to be biopsied. Other tumors, such as highly malignant tumors need a sophisticated combination therapy that includes surgery, craniospinal radiation therapy, and intensive chemotherapy. An appropriate neoadjuvant therapy prior toradical surgical removal will remarkably reduce the surgical risk. The goal of treatment should be tightly focused on the reduction of posttreatment sequelae, including surgical morbidity, and not on a complete microsurgical resection., (Copyright (c) 2009 S. Karger AG, Basel.)

Purpose: To assess the quality of life (QOL) of extremely long-time survivors with germinoma mainly treated with radiotherapy., Patients and Methods: We enrolled 52 of 68 patients who received radiotherapy between 1968 and 1995 at our hospital. They were 41 males and 11 females; the tumor location was pineal in 20, neurohypophyseal in 15, pineal and neurohypophyseal in 11 patients; in 6 it was located in another region. All underwent radiotherapy; the median dose was 48.2 (range 40.0-60.2) Gy. The median follow-up period was 226 (range 0-448) months. The clinical outcome and QOL were evaluated retrospectively., Results: In 6 patients, the tumor recurred; 6 other patients developed second tumors while in complete remission from the first tumor. The main cause of 12 deaths was complications due to primary tumor invasion, the initial treatment, or tumor recurrence rather than tumor progression. The 10-, 20-, and 30-year actuarial survival rate was 83.6, 77.5, and 64.2%, respectively. Of 44 patients, 6 were married and 3 males with solitary pineal tumors were fathers. Among 32 patients, 14 had, or had not, graduated from high school; the other 18 went on to higher education. Twenty-one patients had no occupation; 7 of 11 formerly employed patients had left their jobs., Conclusion: Radiotherapy delivered between 1968 and 1995 to patients with germinoma yielded satisfactory outcomes but a decline in the QOL., (Copyright (c) 2009 S. Karger AG, Basel.)

Although radiation therapy (RT) is essential to the management of intracranial germ cell tumors, the ideal radiation dose and field remain controversial. For the treatment of germinoma, whole central nervous system radiation, which was once the standard RT field, is being replaced by whole ventricle (WV) field radiation for localized disease. The use of induction chemotherapy has been expected to further reduce the RT field and dose; however, use of a localized field smaller than the WV field has resulted in a higher recurrence rate. Therefore, the WV field should be considered appropriate even after induction chemotherapy. With regard to the radiation dose to the primary tumor site, it can be reduced to 40-45 Gy in RT alone. The further reduction of the radiation dose when using a combination of chemotherapy and RT is yet to be determined. Unlike germinomas, nongerminomatous germ cell tumors, with the exception of mature teratomas, are refractory to conventional RT. The whole central nervous system field should thus be used for all but immature teratomas. Given that local progression is the primary pattern of recurrence even after effective induction chemotherapy, RT dose increase through the use of modern techniques, including stereotactic irradiation and intensity-modulated RT, should be investigated., (Copyright (c) 2009 S. Karger AG, Basel.)

Background and Purpose: Whole craniospinal irradiation cannot be achieved in one field at a normal treatment distance for adults. The aim of this newly developed technique is to minimize problems of matching fields and to maximize precision of craniospinal radiotherapy., Patients and Methods: Twelve patients (3-59 years) had craniospinal irradiation in supine position. The head was treated with lateral opposed isocentric fields with collimator rotation and isocentric table rotation. Using an extended source-skin distance of 160 cm only one dorsal field is necessary to cover the whole spinal axis. To avoid systematic under- or overdosage, junction field edges were moved twice by 1.5 cm. Treatment planning was performed based on CT scans. For visual verification of field matching an additional line laser was first adjusted to the caudal edge of one lateral light field and then checked against the light field of the spinal field under the table., Results: Control films show good homogeneity in the junction between lateral and vertical fields. Reproducibility of table movements is acceptable. Total time needed for one fraction is about 15-20 min., Conclusion: The described technique is now well established, feasible and leads to less risk of dose uncertainties.

Introduction: Pineoblastomas are a category of supratentorial primitive neuroectodermal tumors (sPNETs) occurring in the pineal gland; some studies support the impression that patients with pineoblastomas have a worse prognosis than those with other sPNETs., Methods: We reviewed the medical records and tissue sections of all patients with the diagnosis of pineoblastoma that were treated at the Dana-Farber Cancer Institute/Children's Hospital Boston Pediatric Brain Tumor Program between 1986 and 2005., Results: Thirteen patients with the pathologic diagnosis of pineoblastoma were treated at our Hospital; 11 of these cases had complete records suitable for study. The median age was 8 years 8 months (5 F, 6 M). Surgical, radiation and chemotherapeutic regimens varied from case to case. Three patients had gross total resection and are alive and free of disease, versus four of eight with subtotal resection or biopsy only. Patients who received CSI and multi-agent chemotherapy had improved overall survival., Conclusions: Seven of eleven patients with pineoblastoma are currently alive and free of disease, reflecting an improved outcome and longer survival than previously appreciated. Gross total surgical resection appeared to correlate with improved survival, as did treatment with craniospinal irradiation and multi-agent chemotherapy. Further study of this group of patients as a distinct diagnostic entity will be necessary to determine optimal therapy.

Secondary brain tumors rarely arise after cranial irradiation; among them, meningiomas and glioblastomas are the most common and secondary oligodendroglial tumors the most rare. We present a 48-year-old man who developed an oligodendroglial tumor 38 years after receiving 50 Gy of cranial irradiation to a pineal tumor. He underwent gross total removal of a calcified, ring-enhanced mass in the right temporal lobe. The tumor was histologically diagnosed as anaplastic oligodendroglioma. Our review of previously reported secondary oligodendroglial tumors that developed after cranial irradiation revealed that these rare tumors arose after low-dose cranial irradiation or at the margin of a field irradiated with a high dose. We suggest that secondary oligodendroglial tumors arising after cranial irradiation are more aggressive than primary oligodendrogliomas.

Purpose: To describe our preliminary experience with supine craniospinal irradiation. The advantages of the supine position for craniospinal irradiation include patient comfort, easier access to maintain an airway for anesthesia, and reduced variability of the head tilt in the face mask., Methods and Materials: The cranial fields were treated with near lateral fields and a table angle to match their divergence to the superior edge of the spinal field. The collimator was rotated to match the divergence from the superior spinal field. The spinal fields were treated using a source to surface distance (SSD) technique with the couch top at 100 cm. When a second spinal field was required, the table and collimator were rotated 90 degrees to allow for the use of the multileaf collimator and so the gantry could be rotated to match the divergence of the superior spinal field. The multileaf collimator was used for daily dynamic featherings and field-in-field dose control., Results: With a median follow-up of 20.2 months, five documented failures and no cases of radiation myelitis occurred in 23 consecutive patients. No failures occurred in the junctions of the spine-spine or brain-spine fields. Two failures occurred in the primary site alone, two in the spinal axis alone, and one primary site failure plus distant metastasis. The median time to recurrence was 17 months., Conclusion: The results of our study have shown that supine approach for delivering craniospinal irradiation is not associated with increased relapses at the field junctions. To date, no cases of radiation myelitis have developed.

The authors report a case of a recurrent intracranial germinoma along the site of an endoscopic third ventriculostomy (ETV) after complete local tumor control using 3D conformal radiation therapy. A 13-year-old girl presented with sudden left upward gaze limitation for 4 days. A pineal region tumor and obstructive hydrocephalus were noted on magnetic resonance (MR) images. An ETV and tumor biopsy procedure were performed, which revealed the lesion to be a germinoma. The patient's visual symptoms and hydrocephalus disappeared postoperatively. Chemotherapy using cisplatin, etoposide, vincristine, and cyclophosphamide was initiated on postoperative Day 10. An MR image obtained 10 weeks after surgery and 2 weeks after chemotherapy revealed a significant (> 50%) reduction of the lesion. Radiation therapy was administered at 50.4 Gy to the target and 36 Gy to the periphery. Ten months after surgery, an MR image revealed further shrinkage of the tumor mass. One year after surgery, follow-up MR imaging demonstrated a small mass lesion at the entry site of the ETV, measuring 1.0 x 1.4 x 1.5 cm. An operation was performed to remove the small lesion, and pathological findings revealed it to be of the same histology as the primary tumor.

Extraneural metastases of intracranial germinoma are rarely reported. The authors describe the first case of metastatic lung germinoma of the thoracic spine. A 27-year-old man presented with right shoulder pain and right upper limb weakness. He had a history of repetitive radiation therapy - nine (whole-abdomen; 15Gy), 12 (whole brain; 30Gy, whole spine 42Gy) and 14 years ago (local; 32Gy) - for abdominal metastasis, temporal and fourth ventricle metastasis and spinal dissemination and metastatic pineal germinoma, respectively. Magnetic resonance imaging revealed a lung mass invading the thoracic spine that was diagnosed as a germinoma by tumor biopsy. He was treated by irradiation with 54Gy and two cycles of chemotherapy with cisplatin and etoposide. He did not have any sign of tumor eight years later.

Background: Trilateral retinoblastoma (TRB) is a syndrome consisting of unilateral or bilateral hereditary retinoblastoma (Rb) associated with an intracranial neuroblastic tumor. Although its incidence is low, the prognosis is very poor. This article reports four cases of TRB and discusses the role of neuroimaging screening for early detection., Procedure: From January 1986 to December 2003, 470 children with Rb were admitted to the Pediatrics and Ophthalmology Departments, A C Camargo Hospital, São Paulo, Brazil., Results: There were four patients with pineoblastoma, two of whom had a positive familial history. The age at diagnosis of Rb was 4, 6, 10, and 24 months while the age of diagnosis of TRB was 10, 25, 57, and 72 months. One patient presented TRB at initial diagnosis of Rb. Three patients had bilateral disease and all of them had one eye enucleated, followed by chemotherapy and/or external beam radiation therapy (EBRT). One child with unilateral disease was only submitted to enucleation. In spite of intensive treatment, all patients died with progressive disease within 7, 8, 12, and 12 months after diagnosis of TRB., Conclusions: Early diagnosis as well as new therapeutic approaches are needed to achieve better results., ((c) 2006 Wiley-Liss, Inc.)

Background: This Phase II study was designed to determine response to chemotherapy and survival after response-based radiation (RT) in children with CNS germ cell tumors., Procedure: Children with germinomas and normal markers received cisplatin 100 mg/m(2) + etoposide, alternating with vincristine + cyclophosphamide (CPM) 2 g/m(2)/d, for four cycles. Children with nongerminomatous tumors or with abnormal markers received doubled doses of cisplatin and CPM. For germinoma patients in complete response (CR), RT was decreased from 50.4 to 30.6 Gy. High-risk patients received neuraxis RT: 50.4 Gy local + 30.6 Gy neuraxis in CR; 54 Gy local + 36 Gy if less than CR., Results: Of 12 germinoma patients, 4 had cerebrospinal fluid (CSF) human chorionic gonadotropin (HCG) 6.9-21 mIU/ml. Of 14 nongerminomatous patients, HCG in serum or CSF was >50 mIU/ml in 9, alpha-fetoprotein (AFP) abnormal in 9. Four germinoma patients attained CR, six PR, one SD, one not evaluable after resection. Two nongerminomatous patients had CR, three PR, three SD, one PD, four not evaluable after resection; one inadequately treated patient had progressive disease (PD). Both PD patients died; one SD patient died during a seizure. Eleven germinoma patients are PF at median 66 months; one patient in CR refused RT, had PD at 10 months, received RT, and was PF at 56 months. Eleven of 14 nongerminomatous patients were PF at median 58 months., Conclusion: Response (germinoma, 91%; nongerminomatous, 55%) and survival are encouraging after this regimen plus response-based RT., ((c) 2006 Wiley-Liss, Inc.)

Object: Increasingly, radiosurgery is used to treat pineal region tumors, either as a primary treatment or as an adjunct to conventional radiation therapy. The authors report their experience with Gamma Knife surgery (GKS) for the treatment of pineal region tumors., Methods: The authors retrospectively reviewed the charts of all patients undergoing GKS at their institution between 1997 and 2005. Seventeen patients underwent GKS for nonmetastatic tumors of the pineal region. All patients were treated using Leksell Gamma Plan treatment planning software (versions 4.12::5.34). The mean treatment volume was 7.42 cm(3) (range 1.2-32.5 cm(3)). Prescribed doses ranged from 12 to 18 Gy. All doses were prescribed to the 50% isodose line. Independent neuroradiologists reviewed all follow-up imaging studies for evidence of progression of disease., Results: One patient (Case 10) died 6 days after GKS. Mean clinical and imaging follow-up in the remaining 16 cases was 31 months. Local control was established during a mean neuroimaging follow-up period of 31 months (range 1-95) in 16 patients (100%). In 2 of these 16 patients (one with an anaplastic astrocytoma, the other with a primitive neuroectodermal tumor), leptomeningeal and spinal spread of tumor developed despite control of the pineal lesions. There were no new neurological deficits attributable to GKS. Three patients died (including the one who died 6 days after GKS) during the follow-up period. Conclusions Excellent control of pineal region brain tumors can be obtained with GKS when it is used in conjunction with surgery, conventional radiation therapy, or both. Patient survival and quality of life can be optimized through the use of multimodal treatment, including surgery, conventional radiation therapy and/or radiosurgery, and chemotherapy, when applicable.

Objective: To analyze the outcome of children with pineoblastoma (PB), treated within the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91 of German-speaking countries., Patients: We report on 11 children suffering from PB. Five children younger than 3 years of age received chemotherapy after surgery until eligible for radiotherapy (HIT-SKK87 and HIT-SKK92). Five of six children older than 3 years were treated after surgery with immediate chemotherapy and craniospinal irradiation, and one child received maintenance chemotherapy after postoperative radiotherapy (HIT91)., Results: Five of the six older children are still alive in continuous complete remission (CCR) with a median overall survival (OS) and progression free survival (PFS) of 7.9 years. Five of these six HIT91 patients responded to postoperative chemotherapy and radiotherapy. The only patient with tumor progression during initial chemotherapy achieved complete remission with radiotherapy and is alive. In contrast, all five young children died of tumor progression after a median OS of 0.9 years (PFS 0.6 years). They had either metastatic disease (M1) and/or postoperative residual tumor. Response to postoperative chemotherapy was lower than in the older age group, and only one of these children received radiotherapy., Conclusions: Combined chemotherapy and radiotherapy were feasible and effective in the older age group, leading to prolonged remissions in five of six children. Tumor biology may be more aggressive in younger children with PB, who presented more frequently with high-risk features at diagnosis and had poorer response rates to neoadjuvant postoperative chemotherapy. More intensified treatment regimens may be needed for young children with PB.

Background: Germinomas represent the most frequent tumour type in the pineal region and the synchronous involvement of the suprasellar region, frequently termed bifocal disease, is increasingly recognised. The incidence, pathogenesis, histomorphological, radiological, clinical features, and management strategies are discussed., Case Report: A 6-year-old girl presented with clinical features of hypothalamic-pituitary axis dysfunction. MRI showed two distinct lesions in the pineal and suprasellar regions. Tumour markers for germ cell tumours from blood and cerebrospinal fluid were within the normal range. The suprasellar lesion was biopsied and the histology revealed a germinoma. She received a radical course of radiotherapy covering the entire craniospinal axis (24 Gy/15#) followed by focal boost to the sites of primary disease (16 Gy/10#). Three months after the completion of treatment, the patient achieved a complete clinical and radiological response, which was maintained during the 13-month follow-up period., Conclusions: The optimum management of primary intracranial pineal and suprasellar (bifocal) germinomas still remains controversial. The definition as either localised or disseminated disease has major implications on required treatment and its associated late morbidity. Prospective studies with large cooperative groups worldwide and consensus meetings may reduce uncertainties regarding available management options.

Objective: Tumors of the hypothalamic-pineal region may present with a wide variety of symptoms, including disturbed eating. We present a case where such a tumor was misdiagnosed as anorexia nervosa., Method: We describe a case of pineal germinoma invading the hypothalamus, which was initially diagnosed as anorexia nervosa., Results: Clinical features included weight loss, vomiting, pyrexia, hypernatraemia, and visual disturbance and the typical psychopathology of anorexia nervosa was absent., Conclusion: Organic disorder should always be considered before making a diagnosis of anorexia nervosa, particularly if the presentation is atypical., ((c) 2006 by Wiley Periodicals, Inc.)

Pineal parenchymal tumour of intermediate differentiation (PPTID) in adults is rare and a treatment strategy for this condition has not yet been established. We present a case of an elderly patient treated with postoperative adjuvant therapy using radio- and chemotherapy. This 60-year-old man presented with a 3-month history of memory disturbance, gait instability and double vision. Computed tomography and magnetic resonance imaging demonstrated a mass in the pineal region that suggested a malignant tumour. Partial removal of the tumour was undertaken via the right occipital transtentorial approach. The histological diagnosis was PPTID. Postoperative radio- and chemotherapy were administered, with a good response. Little is known about the clinical behaviour of PPTID in adults. Our treatment plan indicates one effective option for the management of such tumours.

Objective: The aim of the present work is to report the volumetric changes of tumor in two pineoblastoma patients treated with stereotactic interstitial irradiation and to present a review on radiosurgery of pineal parenchymal tumors., Methods: Two of our patients with pineoblastoma were treated with CT and image-fusion guided 125-iodine brachytherapy. The tumor volumes were determined with outlined contours on planning and control CT/MRI images and were compared., Results: Until January 2006, there were 61- and 58-month follow-up periods in the two cases. 56 and 53 months after irradiation the MRI images showed significant tumor shrinkage. In case 1 tumor volume was 0.76 cm (3) on the last control MRI image, compared to the 2.87 cm (3) at the time of interstitial irradiation, which means 73% shrinkage. In case 2, tumor volume measured with the last control MRI examination was 0.29 cm (3), which represents 77% shrinkage of the original tumor volume. In both Cases 1 and 2, PET examinations using (11)C-methionine showed no active tumor mass 56 and 53 months following brachytherapy., Conclusion: Two successful treatments of pineoblastoma are reported. The interstitial irradiation of the tumors decreased their volumes significantly. The CT and image fusion-guided 125-iodine stereotactic brachytherapy can be planned well dosimetrically and is surgically precise.

An 11-year-old boy first presented with a pineal tumor identified by neuroimaging but without positive serum or cerebrospinal fluid markers. The tumor disappeared after the craniotomy and following cranial irradiation. The pathologic diagnosis of the tumor was of a pure germinoma. Eight years later he returned to the hospital with spinal epidural metastasis from the pineal germinoma and required surgery. Intraoperative findings showed that the spinal tumor was solitarily located in the epidural space. Pathologically the tumor was a pure germinoma metastasis. He was treated by a combination of whole spinal irradiation and chemotherapy. The tumor disappeared after the therapy. A pineal germinoma occasionally disseminates through the ventricular system and spinal subarachnoid region. However, a solitary spinal epidural metastasis from pineal germinoma has rarely been reported. Regarding the route of this metastasis, we speculate that the CSF dissemination of the germinoma cells occurred first and some of those cells were trapped in the spinal nerve sleeve and extended into the epidural space.

Papillary tumor of the pineal region has recently been proposed as a new, distinct clinicopathological entity. On the basis of the immunophenotypic and ultrastructural properties of these lesions, origin from specialized ependymocytes of the subcommissural organ was postulated. We present the third publication on a papillary pineal tumor and describe the morphological, immunohistochemical and ultrastructural features of this neoplasm. The patient was a young woman who presented with signs of raised intracranial pressure and Parinaud syndrome. Magnetic resonance imaging revealed a neoplastic lesion in the pineal region. She underwent surgical resection of the tumor through a midline infratentorial-supracerebellar approach. Papillary tumor of the pineal region represents a new, distinct clinicopathological entity. The differential diagnosis, possible histogenesis and management of these lesions are discussed.

Microsurgical resection remains the mainstay of treatment for truly benign brain tumors that can be safely resected because of the potential for permanent cure with most histologic findings, including most of the histologic findings discussed in this article. Physicians must keep in mind the indolent nature of many of the benign brain tumors and realize that many patients are likely to live out normal life spans if tumor control is achieved. Therefore, it is not sufficient simply to consider local tumor control rates and short-term toxicity risks when choosing between surgery, stereotactic radiosurgery, and fractionated radiotherapy. Patients need to be apprised of all therapeutic options and to make their decisions with all information required to evaluate the risks and benefits. For benign brain tumors, these decisions may have consequences that last for decades.

This retrospective study was conducted to evaluate local control and overall survival after radiotherapy for patients with intracranial germ cell tumors and to investigate the influence of irradiated field on treatment outcome. Thirty-two patients with surgically confirmed or suspected primary intracranial germ cell tumors (GCT) treated at the Division of Therapeutic Radiology and Oncology, Chiang Mai University, Chiang Mai, Thailand between January 1988 and December 1999 were reviewed Seven patients were not included in the analysis of treatment outcome and survival due to incompleteness of radiation treatment or death before the end of treatment. The median follow up time of 39.5 months (range from 2.3 months to 136.1 months). Median age at diagnosis was 16.5 years with 23 males and 9 females. Patients were irradiated to the primary tumor with an adequate margin in 7 patients, to the whole brain with a cone down boost in 8 patients. Craniospinal irradiation (CSI) was performed in 10 patients. For the 25 evaluable patients, 5 year overall survival was 86.4%. Five-year disease free survival was 72.9%. Five year overall survival rates were 83.1% and 90.0% for the germinoma and nonbiopsied group. (p-value = 0. 6052). Routine prophylactic CSI was not given with a spinal only failure rate of 33.3%. Five-year overall survival were 85.7%, 87.5%, 85.7% for CSI, whole brain irradiation with boost and local field irradiation (p-value = 0.9037). Five-year disease free survival were 85.7%, 72.9%, 85.7% for CSI, WBRT, and local field (p-value = 0. 6403). This retrospective study suggests that definitive radiation therapy is effective in controlling germinoma, and cure rates are excellent with irradiation alone. Craniospinal irradiation can eliminate the risk of relapse especially in patients who had incomplete diagnostic craniospinal evaluation.

Introduction: Pineal parenchymal tumours make up 0.3% of all brain tumours. Stereotactic biopsy has by now become an indispensable method to detect these tumours and it can be safely performed., Patients and Method: Two patients with pineoblastoma were treated with 125I brachytherapy. The MRI and CT images taken 15 and 18 months after irradiation showed significant tumour shrinkage., Results: Tumour volume was 0.76 cm3 in the control CT image in Case 1, a shrinkage by 73% compared to 2.87 cm3 measured at the time of planning the interstitial irradiation. In Case 2, tumour volume measured on the control MRI examination was 0.29 cm3 as opposed to 1.27 cm3 of original tumour volume, which represents a 77% shrinkage., Conclusion: The insertion of isotope seeds was performed at the same time as the biopsy, because thus the knowledge of the histological diagnosis could spare the patients from a second stereotactic intervention. The CT- and image fusion guided 125I stereotactic brachytherapy is a procedure that can be dosimetrically precisely planned and surgically accurately and safely performed.

Unlabelled: Malignant non-germinomatous intracranial germ cell tumors (MNGGCTs) are a heterogenous group of neoplastic lesions. Their treatment concept follows a multimodal concept that may include tumor resection for local tumor control, craniospinal irradiation to cover leptomenigeal tumor spread and chemotherapy to eliminate systemic tumor dissemination. A Platinum-based chemotherapy proven to be highly effective in testicular and non-testicular malignant germ cell tumors in adults as well as in children has also been chosen for intracranial sites. While therapeutic concepts have been thoroughly evaluated for children and adolescents with extracranial nongonadal GCTs, no such detailed long term follow-up data are available for intracranial MNGGCTs. This paper reports on the long-term outcome of 41 patients with intracranial malignant non-germinomatous GCTs enrolled into the German prospective protocol MAKEI 89. The analysis focuses on the impact of surgery, radio- and chemotherapy., Patients and Methods: Between January 1989 and January 1994, 41 patients with malignant intracranial non-germinomatous GCTs were registered. Patients were compared in respect to protocol (n = 27) and non-protocol treatment (n = 14). Estimated were with chi (2) and Fisher exact test the impact of surgery, chemotherapy and irradiation on outcome., Results: The estimated (Kaplan-Meier) 5-year event free survival (EFS) of patients treated according to protocol recommendations was 0.59 +/- 0.06 (n = 27), compared to an EFS of 0.37 +/- 0.33 for patients with different treatments (n = 14) (p = 0.70, log-rank). The 5-year relapse-free survival rate (RFS) was 0.74 +/- 0.06 in protocol patients and 0.38 +/- 0.33 in non-protocol patients (median observation time of 112 months after diagnosis for surviving patients) (p = 0.14, log-rank). Surgery, complete or incomplete had no significant impact on survival (p = 0.12). Radiotherapy, in terms of craniospinal irradiation had a significant influence on survival (p = 0.035) as well as a cumulative cisplatin dose >/= 400 mg/m (2) (p = 0.002)., Conclusion: Cisplatin chemotherapy and craniospinal irradiation with tumor boost are of significant influence on long term survival in patients with MNGGCTs. The exclusion of major surgery at diagnosis using modern advances in neurosurgery or related tumor resection after neoadjuvant chemotherapy will allow a further reduction of treatment related mortality and long lasting morbidity. The analysis reveals that, given effective treatment, intracranial malignant non-germinomatous GCTs should not longer carry a poor prognosis.

Treatment strategies for CNS germinoma are currently evolving. Current approaches include reducing the volume and dose of radiation by adding pre-irradiation chemotherapy. Very accurate staging is necessary with such an approach to prevent failures. Eight consecutive patients with pineal germinoma at one institution underwent endoscopic surgery for tumor biopsy, direct visualization of the third ventricular region, and third ventriculostomy for those with hydrocephalus. All patients were treated with 4 cycles of chemotherapy. Conformal field radiation therapy followed, with the dose to the tumor bed dependent on the response to chemotherapy. Patients who had MRI, endoscopic, or cerebrospinal fluid evidence of multicentric or disseminated disease also received craniospinal radiation. Six patients had diabetes insipidus (DI) at presentation. All 6 had tumor studding the floor of the third ventricle on endoscopic visualization, while only 4 of those patients had MRI evidence of disease in that region. All patients have completed therapy and are alive, with no evidence of disease at median follow-up of 31.5 months from diagnosis. Direct endoscopic visualization of the third ventricular region may be more sensitive than MRI for evaluating the presence of suprasellar disease and appears to add important information. This parameter should be added to the staging evaluation when feasible. In this series, the presence of DI was 100% predictive of suprasellar disease, even when the MRI was negative for involvement of that region. Patients should be evaluated for DI as part of the initial staging, and if it is present, the patients should be treated for suprasellar disease regardless of MRI findings.

We describe functional imaging findings using MRI, 1H-Magnetic resonance spectroscopy and positron emission tomography in a case of radiation-induced medulloblastoma following radiotherapy for pineal gland tumor. MRS showed a prominent choline peak; FDG, 11C-Met and 11C-Choline PET showed a minimal glucose, increased methionine and choline uptake.

The management of patients with central nervous system germ-cell tumours is evolving, and a definitive standard has not been achieved. A large amount of data indicate that radiotherapy alone results in long-term relapse free survival rates of about 90% in patients with germinoma. Various prospective trials evaluated the results of combinations of chemotherapy and reduced dose and/or volume radiotherapy. The survival rates of combined treatment approaches were similar to the rates achieved with craniospinal radiotherapy alone. Nevertheless, the relapse rates were probably higher due to the significant number of relapses that arouse outside the volume treated with radiotherapy. Additional studies are necessary to determine the appropriate radiotherapy volumes and the role of combined treatments. Chemotherapy alone results in high relapse rates and can not be recommended. Mature teratomas are benign germ cell tumours that can be controlled with complete surgical resection in over 90% of cases. Non-germinoma germ cell tumours are a heterogeneous group of tumours that includes very aggressive tumours such as mixed and pure choriocarcinomas, yolk sac tumours, and embryonal carcinomas; and tumours with intermediate aggressiveness such as mixed tumours with germinoma and teratoma, immature teratomas and teratomas with malignant transformation. Both radiotherapy alone and chemotherapy alone result in quite low rates of tumour control and current treatment approaches include chemotherapy and radiotherapy, with surgical removal of the tumour in some patients. Pineocytomas are benign tumours that are controlled in most cases by complete surgical resection or partial surgical resection and local field irradiation. Current treatment approaches for pineoblastomas include surgery, chemotherapy, and craniospinal irradiation with a local boost. Chemotherapy alone was used to delay irradiation in infants with very little success.

Germinoma of the pineal gland is a rare disease usually confined to the brain which responds well to radiotherapy. Spinal seeding occurs in approximately 4% of cases and distant metastases are extremely rare. We report on a 27-year-old female with an intracranially metastasized pineal gland germinoma, meningeal carcinomatosis and distant bone metastases. Treatment was initiated with intrathecal methotrexate (MTX) and continued with high-dose intravenous MTX. The therapy was very well tolerated apart from reversible hepatic toxicity requiring a dose reduction. The patient was in complete remission after three courses followed by two consolidation cycles; the patient has now been in continuous complete remission for more than 22 months. This is the first report to show that MTX is a potent drug in treating pineal gland germinoma. Long-term side effects of radiotherapy such as reduced mental function or hypopituitarism can probably be avoided. Single-agent high-dose MTX may provide high efficacy with limited adverse effects, especially at a more advanced tumor stage with spinal seeding and extracranial disease.

Objective: The aim of our study was to analyze patterns of care and to identify prognostic factors in patients at least 18 years of age who received radiotherapy for malignant pineal parenchymal tumors., Methods: In a multicenter, retrospective study, we analyzed data for 37 previously published cases and 64 patients treated at the participating institutions., Results: A total of 56 patients received postoperative radiotherapy, and 45 patients received primary radiotherapy. Chemotherapy was administered to 34 patients. The median follow-up period was 38 months, and median overall survival was 100 months. The variables that significantly influenced overall survival were the extent of disease (localized versus disseminated; P = 0.0002), differentiation (pineal parenchymal tumor of intermediate differentiation versus pineoblastoma; P = 0.001), and residual disease (> or = 50% versus < 50% reduction in size; P < 0.0001). In a multivariate analysis, the parameters turned out to be independent risk factors. The median survival in patients with local or spinal failure was 15 months. Local control was better in older patients (> or = 32 yr versus < 32 yr; P = 0.02). Spinal control was more successful in patients with pineal parenchymal tumors of intermediate differentiation than it was in patients with pineoblastomas (P = 0.03). Nine of 45 treatment failures occurred later than 5 years after treatment., Conclusion: Stage, histological characteristics, and response are independent risk factors in adults with malignant pineal parenchymal tumors. Late relapses are common.

Irinotecan (CPT-11), a water-soluble topoisomerase I inhibitor, is metabolized by carboxylesterase enzymes to form an active metabolite, SN-38. Recent studies have shown that irinotecan also undergoes oxidative metabolism by the P450 isozyme CYP3A4, leading to the formation of a minor inactive metabolite, 7-ethyl-10-[4-N-[(5-aminopentanoic acid)-1-piperidino]-carbonyloxy-camptothecin (APC). The elucidation of this metabolic pathway suggests the potential for drug interactions when irinotecan is administered with other inducers or substrates of CYP3A4. In this report, the authors summarize the pharmacokinetic profile of irinotecan and its major metabolites with and without concomitant phenytoin administration in an individual patient. These studies revealed that concomitant phenytoin administration resulted in a marked decrease in the systemic exposure to irinotecan and SN-38 and an increase in the exposure to APC. The area under the curve of irinotecan and SN-38 decreased by 63% and 60%, respectively; the area under the curve of APC increased by approximately 16%. Further detailed pharmacokinetic studies of irinotecan in patients receiving concomitant therapy with enzyme-inducing anticonvulsants are required so that rational dosing recommendations can be provided for this patient population.

Background: Cerebral germinomas and their occasional recurrences can usually be cured by irradiation, chemotherapy, or a combination of the two treatment modalities. Late recurrences, as in our case, are distinctly rare., Case Description: This patient presented at age 24 with a calcified tumor in the pineal area. The radiological diagnosis was germinoma. No tissue diagnosis was obtained. Radiation therapy was given, and there was a complete response. The patient's symptoms reappeared 13 years later. Imaging studies revealed a lesion in the anterior corpus callosum. A germinoma was diagnosed by stereotactic biopsy. Because of complications attributed to the initial course of radiation therapy, no further radiation was given. Five courses of chemotherapy resulted in a partial remission lasting six months. The patient later died because of massive tumor progression with intracerebral, intraventricular, cerebellar, and meningeal dissemination., Conclusions: As this case illustrates, exceptional recurrences of cerebral germinomas may appear even many years after adequate initial treatment with radiation and chemotherapy.

Radiation therapy (RT) still plays a major role in the management of intracranial malignancies, together with surgical resection and, more recently, chemotherapy. This is a review of the experience with fractionated external beam RT. In medulloblastomas, combined modalities currently achieve a 5-year survival in excess of 70% in low-risk subgroups and 40% in the subgroups considered to be high risk. For the past decade, the emphasis has been on the quality of life in cured children. Recent advances have mainly aimed at limiting the toxicity of the "prophylactic" craniospinal irradiation by testing dose reductions and altered fractionations. Technical innovations have also greatly benefited gliomas: modern techniques dealing with 3D CT and MRI-based treatment combined with stereotactic positioning of the patients, achieve a high degree of conformity that might improve both local control and longterm neurocognitive and growth sequelae.

Late recurrences after therapy are rare in primitive neuro-ectodermal tumor (PNET). Most recurrences occur within the first 2 years after therapy, although a small number of recurrences may occur up to 5 years after therapy. We present a rare case of a recurrence of PNET in a 31-year-old woman 17 years after her initial presentation. The potential biological implications of this late recurrence as well as responses to subsequent therapy, including temozolomide, are discussed., (Copyright 2001 S. Karger AG, Basel)

The results of a non-resective treatment approach for pineoblastoma comprising stereotactic biopsy, cerebrospinal fluid diversion, and fractionated radiotherapy in six patients over a period of six years are presented. There were three male and three female patients, with a median age at diagnosis of 20 years. Magnetic resonance imaging of the spine, ventricular cerebrospinal fluid cytology, and tumour markers in cerebrospinal fluid were negative. Tumour response to initial radiotherapy was complete in three patients and partial in three patients. Recurrences were treated with interstitial irradiation with iodine-125 seeds in four instances, repeat radiotherapy when time elapsed was more than five years in one instance, with surgical resection in two instances, and chemotherapy in two instances. The diagnostic and therapeutic effectiveness of this management strategy is assessed. There were no complications related to surgical procedures. The median follow-up time was 48 months (range 14-70 months). Five patients were alive at 14, 45, 51, 57, and 70 months of follow-up. One patient died of disease at 28 months following diagnosis. The overall survival rate was 80 % +/- 17.89 % at 28 months. The results of this study suggest that this non-resective treatment approach is acceptable as an initial treatment alternative to radical surgical resection of pineoblastomas.

A young woman presented with a pineoblastoma treated initially with whole neuraxis radiotherapy. She had biopsy confirmed metastatic disease to the left lateral pelvis which was treated on 2 separate occasions, and biopsy confirmed metastatic disease to the subcutaneous tissues of the left thigh. She currently remains well 8 years after the primary diagnosis and 6 years after the first systemic relapse.

Background: The outcome of a child with a primitive neuroectodermal tumors arising supratentorially (SPNET) is not well characterized and may differ from the outcome of a patient with a histologically similar cerebellar tumor (medulloblastoma [MB]). Recently, 5-year progression free survival rates as high as 80% have been reported for children with MB treated with craniospinal radiation (CRT) and chemotherapy including cisplatin, lomustine (CCNU), and vincristine (VCR)., Methods: The authors reviewed the outcome of 22 consecutive patients age 3 years and older (mean age, 10 years; range, 3-18 years) with SPNET who were treated at the study institutions between 1981 and 1996. Tumor location included was 13 pineal, 6 cortical, and 3 thalamic or suprasellar. Five patients had disease dissemination at diagnosis. All patients underwent surgery and staging, followed by CRT and chemotherapy with cisplatin, CCNU, and VCR., Results: Of the 22 patients, 13 had developed disease progression and 10 had died at the time of last follow-up. Overall progression free survival (PFS) was 47% +/- 11% at 3 years and 37% +/- 11% at 5 years. There was a significant difference in PFS between patients with localized disease versus those with disseminated disease (P = 0.04). There was no statistical association between tumor location and survival. Although not significant (P = 0.21), there was a trend toward better survival of those patients with complete or near-complete resection compared with those with partial resection or biopsy., Conclusions: The results of the current study demonstrate that the outcome for children with SPNET treated with radiation and chemotherapy appears worse than for children with MB treated with identical therapy. This suggests that there may be biologic differences between supratentorial and infratentorial primitive neuroectodermal tumors, thus requiring refinements in treatment.

Purpose: To provide evidence that radiation therapy alone in the form of craniospinal irradiation (CSI) and a boost to the primary site of disease provides effective disease control and limited additional morbidity for patients with CNS germinoma., Methods and Materials: Twelve patients with a median age of 12 years (range 9-16 years) with CNS germinoma were treated with CSI (median 25.6 Gy, range 23.4-32 Gy) and a boost to the primary site of disease (50.4 Gy, range 45-54 Gy) between January 1987 and June 1998. All patients were biopsied prior to radiation therapy and none received chemotherapy. No patients were lost to follow-up and the majority had long-term (> 45 month) pre- and postirradiation endocrine and psychology assessment., Results: All 12 patients are alive and no failures have occurred with a median follow-up of 69 months (range 14-143 months). Preirradiation endocrine deficiencies were present in 6 of 6 suprasellar tumors and 1 of 6 pineal tumors; with follow-up there was no substantial difference between age and gender adjusted pre- and postirradiation stature and weight. With long-term follow-up, there were no significant differences between pre- and postirradiation full-scale, verbal, and performance IQ scores., Conclusions: This study confirms the ability of radiation therapy alone to achieve disease control with a high rate of success in pediatric patients and demonstrates that the treatment toxicity faced by these patients may be less than anticipated. Because these patients present with substantial preexisting morbidity at diagnosis and may be of an age where the potential for radiation-related side effects is relatively small, the superiority of treatment alternatives may be difficult to prove.