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Journal ArticleDOI

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.

AbstractTo 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.

Topics: Carboplatin (60%), Chemotherapy (56%), Germ cell tumors (56%), Etoposide (56%), Germinoma (55%)

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Citations
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Journal ArticleDOI
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.

15 citations


Journal ArticleDOI
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.

14 citations


Journal ArticleDOI
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.

12 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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Journal ArticleDOI
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


Book ChapterDOI
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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Journal ArticleDOI
TL;DR: Germinomas have a good prognosis, as over 90% of patients can be effectively treated with radiation therapy, and recent reports suggest that the dose and volume of radiation therapy required for disease control can be lessened with the addition of adjuvant chemotherapy.
Abstract: Intracranial germ cell tumors are a heterogeneous group of lesions which occur in children and adults. Within the classification of intracranial germ cell tumors, there are a variety of different tumor types which carry different prognoses. The diagnosis of an intracranial germ cell tumor usually requires histological information, but a subgroup of tumors will secrete specific tumor markers, including α-fetoprotein and β-human chorionic gonadotropin, which may obviate the need for surgical intervention. The management of intracranial germ cell tumors in both children and adults remains unsettled. Germinomas have a good prognosis, as over 90% of patients can be effectively treated with radiation therapy. The dose and volume of radiation therapy needed for disease control is not well established, and controversy exists concerning the need for whole brain or craniospinal radiation therapy for localized tumors. Germinomas are also chemosensitive and recent reports suggest that the dose and volume of radiation therapy required for disease control can be lessened with the addition of adjuvant chemotherapy. The outcome for patients with nongerminomatous germ cell tumors is less favorable. Radiation therapy alone will result in disease control in 40%-60% of patients. The addition of chemotherapy to radiation therapy may improve the rate of survival. The Oncologist 2000;5:312-320

323 citations


"Improved Outcome of Central Nervous..." refers background in this paper

  • ...However, such classifications have limitations since biopsy-proven germinomas can have nongerminomatous elements among the unbiopsied sites and non-secreting tumors can also have nongerminomatous components such as immature teratoma with less favorable prognosis (16)....

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Journal ArticleDOI
TL;DR: Chemotherapy-only regimens for CNS GCT, although encouraging, should continue to be used only in the setting of formal clinical trials.
Abstract: PURPOSERadiation therapy for CNS germ cell tumors (GCT) is commonly associated with neurologic sequelae. We designed a therapeutic trial to determine whether irradiation could be avoided.PATIENTS AND METHODSPatients received four cycles of carboplatin, etoposide, and bleomycin. Those with a complete response (CR) received two further cycles; others received two cycles intensified by cyclophosphamide.RESULTSSeventy-one patients were enrolled (45 with germinoma and 26 with nongerminomatous GCT [NGGCT]). Sixty-eight were assessable for response. Thirty-nine of 68 (57%) achieved a CR within four cycles. Of 29 patients with less than a CR, 16 achieved CR with intensified chemotherapy or second surgery. Overall, 55 of 71 (78%) achieved a CR without irradiation. The CR rate was 84% for germinomas and 78% for NGGCT. With a median follow-up duration of 31 months, 28 of 71 patients were alive without relapse or progression. Thirty-five showed tumor recurrence (n = 28) or progression (n = 7) at a median of 13 months...

312 citations


Journal ArticleDOI
TL;DR: Radiotherapy directed toward the craniospinal axis or tumor site alone at decreased dose levels is effective and further attempts to decrease total doses are justified to reduce the risk of late side effects.
Abstract: PURPOSE: A multicenter prospective trial was conducted (Maligue Keimzelltumoren [MAKEI] 83/86/89) to assess outcome in intracranial germinoma after treatment with radiotherapy alone at reduced doses. PATIENTS AND METHODS: Between 1983 and 1993, 60 patients with histologically (n = 58) or cytologically (n = 2) confirmed germinoma were enrolled onto the study. Patients received radiotherapy alone (craniospinal axis/local boost). In the MAKEI 83/86 study (involving 11 patients), the dose to the craniospinal axis was 36 Gy and the dose to the tumor region was 14 Gy. In the MAKEI 89 study (involving 49 patients), doses were 30 and 15 Gy, respectively. RESULTS: Median patient age was 13 years (range, 6 to 31 years). Complete remission was achieved in all patients. The estimated (Kaplan-Meier) 5-year relapse-free survival rate was 91.0% ± 3.9% at a mean follow-up of 59.5 months (range, 3 to 180 months); the estimated overall survival rate was 93.7% ± 3.6%. Relapse occurred in five patients 10 to 33 months (mean,...

215 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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Journal ArticleDOI
TL;DR: Sixty-one patients with midline pineal tumors and 16 patients with suprasellar germinomas were treated with surgical decompression and relatively high-dose radiotherapy of the primary site, and there were no long-term complications.
Abstract: Sixty-one patients with midline pineal tumors and 16 patients with suprasellar germinomas were treated with surgical decompression and relatively high-dose radiotherapy of the primary site Results were excellent, and there were no long-term complications Ten per cent of midline pineal tumors and 37% of suprasellar germinomas metastasized to the cerebral or spinal subarachnoid space within 6 months to 5 years Irradiation of the entire neural axis is recommended for locally extensive tumors, simultaneous pineal and hypothalamic lesions, and all biopsy-proved germinomas The five-year survival rate was 79% for midline pineal tumors and 77% for suprasellar germinomas

207 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)....

    [...]