Chemotherapy without irradiation--a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study.
01 Nov 1996-Journal of Clinical Oncology (American Society of Clinical Oncology)-Vol. 14, Iss: 11, pp 2908-2915
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...
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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
345 citations
TL;DR: Central nervous system (CNS) germ cell tumors (GCTs) represent approximately 3% of primary pediatric brain tumors and encompass a wide pathologic spectrum and treatment and prognosis differ greatly between groups.
Abstract: Central nervous system (CNS) germ cell tumors (GCTs) represent approximately 3% of primary pediatric brain tumors and encompass a wide pathologic spectrum. CNS GCTs are most commonly located in the pineal and suprasellar regions of the brain and can be divided into major groups including germinomas and nongerminomatous GCTs (NGGCTs), with teratomas often considered a separate category. The clinical presentation varies by location and size, and it frequently includes endocrine abnormalities, visual changes, and signs of increased intracranial pressure. Neuroimaging studies cannot differentiate GCTs from other tumors, and therefore, the diagnosis usually requires histologic confirmation. The rare exceptions are the cases where characteristic elevations of tumor markers, including alpha-fetoprotein and/or beta-human chorionic gonadotropin are documented in the serum and/or cerebrospinal fluid. In these cases, the imaging findings along with the tumor marker elevation may be diagnostic in themselves without the need for tissue confirmation. Treatment and prognosis differ greatly between groups. Germinomas have a superior prognosis than NGGCTs. Five-year overall survival rates >90% were reported initially with the use of craniospinal irradiation. More recently, the use of chemotherapy in addition to radiation therapy has afforded the ability to decrease the dose and volume of radiation therapy without affecting survival rates. NGGCTs are less radiosensitive than germinomas, but the use of adjuvant chemotherapy has improved survival rates in this group as well. The standard management for CNS GCTs remains controversial. Treatment regimens aimed to improve progression-free and overall survival times are ongoing.
338 citations
01 Oct 2007
TL;DR: An overview of current diagnostic and treatment approaches for patients with primary and metastatic brain tumors is provided.
Abstract: Central nervous system tumors are relatively common in the United States, with more than 40,000 cases annually. Although more than half of these tumors are benign, they can cause substantial morbidity. Malignant primary brain tumors are the leading cause of death from solid tumors in children and the third leading cause of death from cancer in adolescents and adults aged 15 to 34 years. Common presenting symptoms include headache, seizures, and altered mental status. Whereas magnetic resonance imaging helps define the anatomic extent of tumor, biopsy is often required to confirm the diagnosis. Treatment depends on the histologic diagnosis. Benign tumors are usually curable with surgical resection or radiation therapy including stereotactic radiation; however, most patients with malignant brain tumors benefit from chemotherapy either at the time of initial diagnosis or at tumor recurrence. Metastases to the brain remain a frequent and morbid complication of solid tumors but are frequently controlled with surgery or radiation therapy. Unfortunately, the mortality rate from malignant brain tumors remains high, despite initial disease control. This article provides an overview of current diagnostic and treatment approaches for patients with primary and metastatic brain tumors.
307 citations
TL;DR: Localized germinoma can be treated with reduced dose CSI alone or with chemotherapy and reduced-field radiotherapy, and the pattern of relapse suggests inclusion of ventricles in the radiation field.
Abstract: Germinomas contribute to about 60% of all intracranial germ cell tumors located in the pineal gland, suprasellar region, basal ganglia, and hypothalamus.1 Intracranial germinomas are highly radiosensitive, with a tendency to spread via cerebrospinal fluid (CSF), and systemic craniospinal radiation therapy has been the standard treatment for many decades.2,3 With this treatment approach, the majority of patients have been cured.4 Concerns have long been raised about the potential adverse effects of radiotherapy.4–6 Therefore, other treatment approaches were introduced to evaluate craniospinal irradiation alone, but with reduced doses, compared with previous practice, or chemotherapy either in combination with radiotherapy or alone.7,8 In the German MAKEI 89 trial, 30 Gy were applied to the craniospinal axis (CSI) with an additional tumor boost of 15 Gy.9 With this regimen, 88% of the patients remained relapse-free at 5 years. In 1990, the French Society of Paediatric Oncology initiated a trial using chemotherapy and local field radiotherapy in localized germinomas with favorable results.10 In 1998, Matsutani et al11,12 reported excellent survival for germinomas treated with surgery, followed by extended field or whole brain radiotherapy. Patients who received chemotherapy before reduced radiotherapy (30 Gy) were all alive at a median follow-up of 4.3 years. Aoyama et al13 presented promising excellent results in a second Japanese series including 16 germinomas treated with surgery, followed by chemotherapy and low-dose involved-field radiotherapy. Approaches using chemotherapy alone have not been promising.10
Because of the rarity of the disease, an international prospective study was established in 1996 in Europe to evaluate outcomes in a larger patient cohort. In this trial, the outcomes in patients with histologically proven intracranial germinomas (with or without teratoma) treated either with a reduced dose of 24 Gy CSI and additional boost to the primary and metastatic sites of 16 Gy or with combined treatment were evaluated in a nonrandomized fashion.
245 citations
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,...
234 citations
References
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01 Mar 1972
3,283 citations
TL;DR: It is argued that the problem of estimation of failure rates under the removal of certain causes is not well posed until a mechanism for cause removal is specified, and a method involving the estimation of parameters that relate time-dependent risk indicators for some causes to cause-specific hazard functions for other causes is proposed for the study of interrelations among failure types.
Abstract: Distinct problems in the analysis of failure times with competing causes of failure include the estimation of treatment or exposure effects on specific failure types, the study of interrelations among failure types, and the estimation of failure rates for some causes given the removal of certain other failure types. The usual formation of these problems is in terms of conceptual or latent failure times for each failure type. This approach is criticized on the basis of unwarranted assumptions, lack of physical interpretation and identifiability problems. An alternative approach utilizing cause-specific hazard functions for observable quantities, including time-dependent covariates, is proposed. Cause-specific hazard functions are shown to be the basic estimable quantities in the competing risks framework. A method, involving the estimation of parameters that relate time-dependent risk indicators for some causes to cause-specific hazard functions for other causes, is proposed for the study of interrelations among failure types. Further, it is argued that the problem of estimation of failure rates under the removal of certain causes is not well posed until a mechanism for cause removal is specified. Following such a specification, one will sometimes be in a position to make sensible extrapolations from available data to situations involving cause removal. A clinical program in bone marrow transplantation for leukemia provides a setting for discussion and illustration of each of these ideas. Failure due to censoring in a survivorship study leads to further discussion.
1,429 citations
TL;DR: In this paper, a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin was used to treat 50 patients with disseminated testicular cancer.
Abstract: Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin. Three patients were considered inevaluable due to early death. This chemotherapy regimen produced 74% complete and 26% partial remissions. Furthermore, five patients with partial remission became disease-free after surgical removal of residual disease, producing an overall 85% disease-free status. Toxicity, although significant during remission induction with cis-platinum, vinblastine, and bleomycin, was usually manageable, although there were two drug-related deaths during this period. Thirty-eight of these patients remain alive and 32 remain alive and disease-free at 6 + to 30 + months. We believe this regimen represents a major advance in the management of patients with disseminated testicular cancer.
1,355 citations
01 Jan 2002
TL;DR: Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin, producing an overall 85% disease-free status.
Abstract: (Reprinted with permission from Ann Intern Med, 87: 293–298, 1997) Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin. Three patients were considered inevaluable due to early death. This chemotherapy regimen produced 74% complete and 26% partial remissions. Furthermore, five patients with partial remission became diseasefree after surgical removal of residual disease, producing an overall 85% disease-free status. Toxicity, although significant during remission induction with cis-platinum, vinblastine, and bleomycin, was usually manageable, although there were two drug-related deaths during this period. Thirty-eight of these patients remain alive and 32 remain alive and disease-free at 6 to 30 months. We believe this regimen represents a major advance in the management of patients with disseminated testicular cancer. Although testicular cancer accounts for only 1% of all malignant tumors in men, it ranks first in incidence of cancer deaths in the 25 to 34 age group. 1 Thus cancer of the testis has a significant impact on the social, economic, and emo
1,340 citations
TL;DR: The pathogenesis of GCT's may be revealed by their specificity of origin within the positive (suprasellar cistern-suprachiasmatic nucleus) and negative (pineal) regulatory centers for gonadotropin secretion within the diencephalon.
Abstract: ✓ The natural history of primary intracranial germ-cell tumors (GCT's) is defined from 389 previously published cases, of which 65% were germinomas, 18% teratomas, 5% embryonal carcinomas, 7% endodermal sinus tumors, and 5% choriocarcinomas. Intracranial GCT's display specificity in site of origin. Ninety-five percent arise along the midline from the suprasellar cistern (37%) to the pineal gland (48%), and an additional 6% involve both sites. The majority of germinomas (57%) arise in the suprasellar cistern, while most nongerminomatous GCT's (68%) preferentially involve the pineal gland (p < 0.0001). The age distribution of afflicted patients is unimodal, centering with an abrupt surge in frequency in the early pubertal years; 68% of patients are diagnosed between 10 and 21 years of age. Nongerminomatous GCT's demonstrate an earlier age of onset than do germinomas (p < 0.0001). Prolonged symptomatic intervals prior to diagnosis are common in germinomas (p = 0.0007), in suprasellar GCT's (p = 0.001), and a...
732 citations