Improved Outcome of Central Nervous System Germ Cell Tumors: Implications for the Role of Risk-adapted Intensive Chemotherapy
01 Mar 2010-Journal of Korean Medical Science (Korean Academy of Medical Sciences)-Vol. 25, Iss: 3, pp 458-465
TL;DR: It is suggested that risk-adapted intensive chemotherapy may improve the outcome of patients with malignant CNS-GCTs and should be considered as a first line treatment according to the clinical requirements.
Abstract: To determine the impact of treatment protocols on the outcome of central nervous system germ cell tumors (CNS-GCTs), we reviewed the medical records of 53 patients who received front-line chemotherapy from September 1997 to September 2006. Pure germinoma, normal alpha-fetoprotein level and beta-human chorionic gonadotropin level <50 mIU/mL were regarded as low-risk features and the others as high-risk. Patients from different time periods were divided into 3 groups according to the chemotherapy protocols. Group 1 (n=19) received 4 cycles of chemotherapy comprising cisplatin, etoposide and bleomycin. Group 2 (n=16) and group 3 (n=18) received 4 cycles of chemotherapy with cisplatin, etoposide, cyclophosphamide and vincristine in the former and with carboplatin, etoposide, cyclophosphamide and bleomycin in the latter. In group 2 and group 3, high-risk patients received double doses of cisplatin, carboplatin and cyclophosphamide. Radiotherapy was given after chemotherapy according to the clinical requirements. The event-free survivals of groups 1, 2, and 3 were 67.0%, 93.8%, and 100%, respectively (group 1 vs. 2, P=0.06; group 2 vs. 3, P=0.29; group 1 vs. 3, P=0.02). Our data suggest that risk-adapted intensive chemotherapy may improve the outcome of patients with malignant CNS-GCTs.
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TL;DR: Neo-adjuvant CTX for localized germinomas seems to be unnecessary as a method to reduce radiation dose in the RT protocol, however, the effective control of multifocal or disseminated germinoma can be achieved by neo- adjuvantCTX followed by response-adapted reduced dose RT.
Abstract: This prospective randomized clinical study will address the efficacy of radiation (RT)-alone and combined with pre-RT chemotherapy (CTX) treatments and propose the novel standard treatment strategy for intracranial primary pure germinoma. Between 2005 and 2008, there were 54 patients diagnosed with intracranial primary pure germinomas in a single institute. Twenty-eight patients were enrolled. The mean age of the patients was 16.2 years (range 6–31 years). There were 19 men and 9 women (men/women ratio = 2.1:1). There were 21 patients with solitary tumors and 7 with multiple tumors. These patients were randomized as RT-only treatment group (11 solitary and 3 multiple tumors) and combined (10 solitary and 4 multiple tumors, neo-adjuvant CTX followed by response-adapted RT) treatment group. The follow-up period for RT only group has a median of 58 months (mean 58.2 months, range 41–82 months), and for combine therapy group, the median was 68.5 months (mean 67.8 months, range 41–88 months). All 14 patients in the RT-only group showed complete response (CR) and no recurrence. Eleven patients in the combined group had CR and three patients had partial response after neo-adjuvant CTX. All patients responded to RT as CR without recurrence. At the time of analysis, all 28 patients were alive without evidence of disease. Neo-adjuvant CTX for localized germinomas seems to be unnecessary as a method to reduce radiation dose in our RT protocol. However, the effective control of multifocal or disseminated germinoma can be achieved by neo-adjuvant CTX followed by response-adapted reduced dose RT.
17 citations
TL;DR: Navigational tracking improved the accuracy of the neuroendoscopic approach and minimized brain trauma in pediatric patients without hydrocephalus, and the absence of ventriculomegaly in patients with brain tumor may not serve as a contraindication to neuro endoscopic tumor biopsy.
Abstract: Intraventricular endoscopic procedures to resect or biopsy peri- or intraventricular tumors may have not been used in patients with small ventricles due to the presumed difficulties with ventricular cannulation and the perceived risk of morbidity. The purpose of this study is to review the feasibility and safety of neuroendoscopic procedures in the biopsy of pediatric brain tumors with a small ventricle. Between January 2006 and January 2013, 72 children were identified with brain tumors confirmed by transventricular endoscopic biopsy. Patients were divided into non-hydrocephalus and hydrocephalus groups, and the ratio of the two groups was 20:52. In 20 pediatric brain tumors with small ventricle, the targeted lesion was successfully approached under the guidance of neuronavigation. Navigational tracking was especially helpful in entering small ventricles and in approaching the third ventricle through the narrow foramen of Monro. The histopathologic diagnosis was established in all 20 patients: nine germinomas, three mixed germ cell tumors, two pilomyxoid astrocytomas, and two pilocytic astrocytomas. The tumor biopsy sites were the suprasellar area (n = 10), pineal area (n = 4), lateral ventricular wall (n = 4), and mammillary body (n = 1). There were no major morbidities related to the endoscopic procedure. Neuroendoscopic biopsy or resection of peri- or intraventricular tumors in pediatric patients without hydrocephalus is feasible. Navigation-guided neuroendoscopic procedures improved the accuracy of the neuroendoscopic approach and minimized brain trauma. The absence of ventriculomegaly in patients with brain tumor may not serve as a contraindication to neuroendoscopic tumor biopsy.
16 citations
TL;DR: Germinoma must be considered in patients with insipidus diabetes with a sellar mass with thickening of pituitary stalk; and ectopic germinomamust be suspected in patientsWith slowly progressive hemiparesis with cerebral hemiatrophy, even with a rare condition, colocalization of midline and off-midline germinomas must be suspected.
Abstract: Germinomas are malignant intracranial germ tumors, usually found in suprasellar regions. Less than 10% are localized in off-middle structures, and synchronous involvement of both structures has only exceptionally been published. A case of an 18-year-old male patient with progressive right-sided hemiparesis and panhypopituitarism was reviewed. Brain MRI showed a solid mass involving pituitary and hypothalamus with thickening of pituitary stalk, high intensity lesions on T2-weighted imaging in left internal capsule, caudate nucleus, globus pallidus, and mild atrophy of the left internal capsule and cerebral peduncle. Nonadenomatous lesions were considered in the differential diagnosis. Alfa-fetoprotein (AFP) levels were negative in both serum and cerebrospinal fluid (CSF), while β-human chorionic gonadotrophin (β-HCG) levels were slightly increased in CSF. A transsphenoidal biopsy identified a germinoma. Four cycles of chemotherapy with bleomicine, etoposide, and cysplatin were given, followed by radiotherapy, but patients died due to a recidiva. Conclusion. Germinoma must be considered in patients with insipidus diabetes with a sellar mass with thickening of pituitary stalk; and ectopic germinoma must be suspected in patients with slowly progressive hemiparesis with cerebral hemiatrophy. Even with a rare condition, colocalization of midline and off-midline germinoma must be suspected in the presence of these typical signs of both localizations.
16 citations
Cites background from "Improved Outcome of Central Nervous..."
...However, biopsy-proven germinomas can have nongerminomatous elements among the unbiopsied sites and nonsecreting tumors can also have nongerminomatous components with a less favorable prognosis [14]....
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...The optimal management strategy for CNSGCTs remains unsettled due to a lack of prospective trials, mainly due to the infrequency of these tumors [14]....
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TL;DR: The current carboplatin-based chemotherapy protocol is safe and effective for the treatment of pediatric patients with IC-GCTs and it is concluded that no lethal hematological complications were associated with this treatment.
Abstract: Purpose
Cisplatin-based chemotherapy has been commonly used for the treatment of intracranial germ cell tumors (IC-GCTs). However, this treatment exhibits some adverse effects such as renal problems and hearing difficulty. Carboplatin-based chemotherapy was administered to pediatric patients with IC-GCTs from August 2004 at the Samsung Medical Center. In this study, we assessed the responses and adverse effects of carboplatin-based chemotherapy in pediatric IC-GCTs patients according to the risk group, and compared the results with those of the previous cisplatin-based chemotherapy.
4 citations
01 Jan 2015
TL;DR: Stereotactic radiosurgery (SRS) has advantages over other therapeutic modalities in certain settings and has a role in the management of pediatric brain tumors, however, that role is limited by the propensity of pediatric neural tumors to disseminate along cerebrospinal fluid pathways or to infiltrate surrounding brain.
Abstract: Pediatric brain tumors encompass a heterogeneous group of diseases. For many tumors, such as low-grade glioma and standard-risk medulloblastoma, the long-term survival rate is high. Clinical investigation for these diseases in recent decades has focused on addressing late effects of therapy, in particular the neurocognitive effects of cranial radiation. Chemotherapy has been used effectively in many settings to delay radiation, to reduce radiation dose and volume, or to replace cranial irradiation entirely. For other tumors, diffuse intrinsic pontine glioma most notoriously, prognosis remains abysmal and currently available treatments are primarily palliative. Stereotactic radiosurgery (SRS) has advantages over other therapeutic modalities in certain settings and has a role in the management pediatric brain tumors. That role is limited, however, by the propensity of pediatric neural tumors to disseminate along cerebrospinal fluid (CSF) pathways or to infiltrate surrounding brain.
1 citations
References
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TL;DR: The relative incidences of germ cell tumors, neuronal tumors, and oligodendroglial tumors increased after the introduction of magnetic resonance imaging (MRI), in contrast, the incidence rates of medulloblastomas and ependymal tumors decreased.
Abstract: Objective: To investigate the age, gender, location and pathologic diagnosis of brain tumors in pediatric patients (less than 16 years old), we reviewed 677 patients who were operated on at the Department of Neurosurgery, Seoul National University Hospital (SNUH) during the period from January 1959 to June 2000 Patients and methods: Only tumors for which pathologic specimens were available were included Tumors of bone origin, purely extradural mass, nontumorous cystic lesions, and vascular malformations were excluded The mean age of the 677 patients was 78 years and the gender ratio (male-to-female ratio), 14:1 Supratentorial tumors (600%) were more common than infratentorial tumors (391%) Pathological examination showed that the most common tumors were astrocytic tumors (257%), medulloblastomas (179%), craniopharyngiomas (120%), germ cell tumors (112%), supratentorial primitive neuroectodermal tumors (ST-PNETs) (55%), and neuronal tumors (52%) Choroid plexus tumors and ependymal tumors occurred more frequently in early childhood, while pituitary adenomas and nonteratomatous germ cell tumors occurred more frequently in older children While most tumors were more predominant in males, oligodendroglial tumors and pituitary adenomas were more predominant in females Conclusions: The relative incidences of germ cell tumors, neuronal tumors, and oligodendroglial tumors increased after the introduction of magnetic resonance imaging (MRI) In contrast, the incidence rates of medulloblastomas and ependymal tumors decreased
81 citations
"Improved Outcome of Central Nervous..." refers background in this paper
...The incidence of CNS-GCTs is relatively higher in Korea as well as Japan and Taiwan (1-3)....
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TL;DR: The present study confirms the excellent result with radiotherapy alone for patients with germinomas and local control was achieved in all patients except one who died of persistent tumor after 2 months following radiotherapy.
78 citations
TL;DR: Results may bring into question the validity of the germ cell theory, since germinoma, which should be the most undifferentiated according to the theory, was the most benign and choriocarcinoma and endodermal sinus tumour were the most malignant in the follow-up study.
Abstract: We investigated 110 cases of intracranial germ cell tumours (up to the end of 1986), 56% of which showed monotypic histological patterns and 44% were shown to be mixed tumours. All these cases underwent surgery followed by radiation and/or chemotherapy. All cases of choriocarcinoma and embryonal carcinoma died within 2 yr: cases of endodermal sinus tumour also showed poor results (4 yr survival rate was 12.5%). Mature teratoma had a 5 yr survival rate (5YSR) and a 10 yr survival rate (10YSR) of 78.3% each: immature teratoma showed a 5YSR of 44.9%. Two-cell pattern tumours (PTC) showed a 5YSR of 85.8% and a 10YSR of 82.4%. They (PTC) can be divided into two groups (i) germinoma and (ii) pinealoma of pineal parenchyma origin (pineocytoma with lymphocytic infiltration) on the basis of the difference in the tumour cell-stroma relationship and also placental alkaline phosphatase stain. In the pineal region, 70% of PTC belonged to the category of pinealoma and in the suprasellar region, 92% of PTC were germinoma. Germinoma showed a 5YSR of 91.4% and a 10YSR of 91.4%, whereas those of the pinealoma were 78.2% and 68.4% respectively. This suggests that the biological characteristics of germinoma and pinealoma may be different. All these results may bring into question the validity of the germ cell theory, since germinoma, which should be the most undifferentiated according to the theory, was the most benign and choriocarcinoma and endodermal sinus tumour, which should be the most differentiated, were the most malignant in the follow-up study.(ABSTRACT TRUNCATED AT 250 WORDS)
65 citations
"Improved Outcome of Central Nervous..." refers methods in this paper
...In the past, radiation therapy was used as a single modality for the treatment of CNS-GCTs (4-12)....
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TL;DR: High doses of single chemotherapy agents such as cyclophosphamide and cisplatin as well the VAB6 regimen have definite activity in recurrent CNS germ cell tumors, especially germinoma.
Abstract: Gonadal germ cell tumors respond favorably to chemotherapy either at diagnosis or when they recur. Histologically similar tumors may arise in the CNS usually in the pineal or suprasellar regions. Although radiation therapy may produce a 5 year disease-free survival in excess of 60% in localized pure germinoma, gern cell tumors of other histology tend to recur. We have conducted 14 chemotherapy trials in 8 patients with recurrent CNS germ cell tumors using 3 different single agent and 2 multi-agent chemotherapy regimens. The histologic diagnoses of the patients were germinoma (4), endodermal sinus tumor (2), embryonal carcinoma (1), and mixed tumor — germinoma plus choriocarcinoma (1). There were 7 males and 1 female with a median age of 13 years. The primary tumor arose in the pineal region in 6 and was multicentric in 2. Seven patients had local recurrences and one developed an initial recurrence in the spinal canal. Three patients had CNS metastases at relapse and 2 had systemic metastases. Objective responses were documented in 7 of 14 trials (50%). Responses were observed with cyclophosphamide (80 mg/kg) in 3 of 4 patients for 2+, 3, and 5 mos, cisplatin (120 mg/m2) in 1 of 2 patients for 2+ mos, and the VAB 6 protocol (vinblastine, bleomycin, cyclophosphamide, actinomycin-d, cisplatin) in 3 of 5 patients for 5, 8, and 18 mos. The median duration of response was 5 mos. (21-18). High doses of single chemotherapy agents such as cyclophosphamide and cisplatin as well the VAB6 regimen have definite activity in recurrent CNS germ cell tumors, especially germinoma. Good palliation may be achieved with chemotherapy alone with acceptable morbidity. Adjuvant chemotherapy should be considered in patients with newly diagnosed primary intracranial germ cell tumors whose tumors are considered unlikely to be permanently controlled with radiation alone.
59 citations
"Improved Outcome of Central Nervous..." refers background in this paper
...In the 1980s, investigators began to report the effectiveness of systemic chemotherapy especially for nongerminomatous CNS-GCTs (13-15)....
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TL;DR: Although survival rate is noteworthy (66%), these tumors were not curable with this conventional chemotherapy alone and focal radiotherapy should be part of the treatment.
Abstract: Purpose: Intracranial αFP and βHCG secreting germ cell tumors have a very poor prognosis with local treatment alone. Because of efficacy of chemotherapy in extracranial forms, we tried in the SFOP (Societe Francaise d'Oncologie Pediatrique) to treat them with chemotherapeutic treatment exclusively. Patients and methods: Eighteen patients (10 αFP, 2 βHCG, 6 αFP and βHCG secretion) were enrolled from January 1988 to December 1992. After biological diagnosis patients were to receive 6 cycles of chemotherapy (vinblastine – bleomycin – carboplatin or etoposide – carboplatin/ifosfamide – etoposide). After completion of chemotherapy, surgery was to be performed in case of residual tumor. Focal radiation was only to be delivered in case of viable residual tumor. Results: All patients had biological remission and tumor reduction. Fifteen patients were treated according to the protocol by chemotherapy alone (13) or chemotherapy and radiation of residue [2]. Twelve of the 13 non irradiated patients relapsed, 8 in local and/or regional area, 3 in cerebrospinal area and 1 in undeterminated area with mild elevation of markers except in one case. Six patients are alive in second complete remission after chemotherapy and/or surgery and then a consolidation treatment with radiation and/or high dose chemotherapy (5) or craniospinal radiation (1). Three patients received radiation after 2 or 3 cycles of chemotherapy as protocol violations and didn't relapse. Thus, 12 patients out of the 18 patients are alive with a median follow up of 68 months. All but 1 had focal radiation as part of treatment. No toxic death was observed. Conclusion: Although survival rate is noteworthy (66%), these tumors were not curable with this conventional chemotherapy alone and focal radiotherapy should be part of the treatment.
55 citations