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J L Finlay

Publications and source records attributed to J L Finlay.

At least 55 records · Page 3Linked to original sources
PubMed1996

High dose chemotherapy with autologous stem cell rescue for patients with medulloblastoma.

High-dose chemotherapy with autologous stem cell rescue (ASCR) is a promising strategy for patients with poor prognosis cerebellar medulloblastoma. For this strategy to be effective, it must be shown that the medulloblastoma tumor cells are sensitive to the chemotherapeutic agents whose dose-limiting toxicity is hematopoietic, and stem cells must be available that are free of contaminating tumor. Several protocols for high-dose chemotherapy followed by ASCR are presented in this chapter. Initial encouraging evaluations of this technique in patients with recurrent disease has prompted testing of its feasibility in infants and young children. In a reasonably short time, the role of high-dose chemotherapy with ASCR will be determined for subgroups of patients with medulloblastoma.

Age Factors↗
PubMed1996

Renal cell carcinoma in childhood and adolescence: a retrospective survey for prognostic factors in 22 cases.

To identify prognostic factors for renal carcinoma in young patients, a retrospective analysis was performed of 22 patients (< or = 21 years of age) with histologically verified renal cell carcinoma. Demographic, staging, and treatment variables were collected in a database, and their effect on survival was determined using Kaplan-Meier probability distribution. The median age was 15.5 years (range, 3 to 21 years), and the male:female ratio was 13:9. Only three patients were black. Histopathologic examination showed 15 clear cell tumors, 4 mixed cell type, 2 papillary, and one well-differentiated adenocarcinoma. The median size of the primary tumor was 10 cm (range, 5 to 20). There were seven patients with stage I tumors, one with stage II, and 14 with stage IV. Complete resection of the primary tumor was accomplished in 12 patients. The overall 5-year survival rate was 30% (confidence interval, 20% to 40%). The 5-year survival rate was better for patients who had complete resection of the primary tumor (60% v 10%). Unresectability was associated with involvement of nodes and/or occurrence of metastases, thus an independent effect of complete resection on survival could not be demonstrated. The data showed that age, tumor size, location, and histology were not predictors of outcome; tumor stage and complete surgical resection were the only meaningful prognostic factors. The presentation of renal cell carcinoma as a localized or systemic disease may reflect a twofold biological behavior. In the first group, the disease is curable with resection, in the second, it is unaffected by surgery or adjuvant therapy. In light of the very low incidence of this renal malignancy in childhood, prospective multicenter studies will be required to improve the poor therapeutic results.

Adolescent↗
PubMed1996

Brainstem gliomas in children. A Children's Cancer Group review of 119 cases.

Brainstem gliomas (BSG) with intrinsic and extensive brainstem involvement continue to have a poor outlook despite current treatment approaches. Neuroimaging studies have aided in the differentiation of malignant brainstem tumors from more 'benign' subgroups. A Children's Cancer Group protocol evaluating outcome in children with BSG after treatment with hyperfractionated radiotherapy (7,200-7,800 cGy) was recently completed. The clinical aspects of 119 children entered into this study were reviewed in an attempt to determine risk groups and prognostic indicators. The overall survival of this group was very poor and there was no statistically significant correlation of survival with age, sex, clinical symptoms and signs, or tumor grade. Longer survival was only associated with prolonged duration of brainstem symptoms and signs greater than 1 month prior to diagnosis of the tumor. Improved outlook for children with BSG will require further research in tumor biology and newer therapeutic modalities.

Adolescent↗
PubMed1996

Results of a prospective randomized trial comparing standard dose neuraxis irradiation (3,600 cGy/20) with reduced neuraxis irradiation (2,340 cGy/13) in patients with low-stage medulloblastoma. A Combined Children's Cancer Group-Pediatric Oncology Group Study.

PURPOSE: To determine in a prospective randomized trial the effect on survival, progression-free survival, and patterns of relapse of a decrease in the neuraxis radiation dose from 3,600 cGy in 20 fractions to 2,340 cGy in 13 fractions in patients with newly diagnosed medulloblastoma between 3 and 21 years of age with low T stage (T1, T2 and T3A), minimal postoperative residual tumor, and no evidence of dissemination (M0). METHODS AND MATERIALS: Between June 1986 and November 1990, the Children's Cancer Group and the Pediatric Oncology Group randomized 126 patients in a two-arm study comparing the two different doses of neuraxis irradiation. In both arms, the posterior fossa received 5,400 cGy in 30 fractions. All patients were staged with myelography, postoperative lumbar cerebrospinal fluid cytology, and postoperative contrast-enhanced cranial computerized tomography to ensure no evidence of dissemination and no more than 1.5 cm3 residual tumor volume. Overall survival, progression-free survival, and patterns of recurrence were carefully monitored. Prospective endocrine and psychometric studies were performed to determine the benefit of decreasing the neuraxis radiation dose. RESULTS: Following an interim analysis at a median time on study of 16 months, the study was closed, since a statistically significant increase was observed in the number of all relapses as well as isolated neuraxis relapses in patients randomized to the lower dose of neuraxis radiation. CONCLUSIONS: In patients with newly diagnosed medulloblastoma considered to have a good prognosis on the basis of low T stage, minimal residual tumor after at least subtotal resection, and no evidence of dissemination after thorough evaluation, there is an increased risk of early relapse associated with lowering the dose of neuraxis radiation from 3,600 cGy in 20 fractions to 2,340 cGy in 13 fractions.

Adolescent↗
PubMed1996

Is there a role for high-dose chemotherapy with stem cell rescue for brain stem tumors of childhood?

Diffuse pontine tumors are highly lethal and conventional therapy with irradiation provides long-term survival to a very small proportion of the patients. We have reported promising results using high-dose chemotherapy with autologous stem cell rescue in patients with recurrent high-grade astrocytomas in other anatomic locations, but our results and those of others have been very discouraging in children with brain stem tumors. Alternative strategies need to be developed for this highly lethal disease.

Adult↗
PubMed1996

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.

PURPOSE: Radiation 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 METHODS: Patients 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. RESULTS: Seventy-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. Twenty-six of 28 patients (93%) who recurred following remission underwent successful salvage therapy. Pathology was the only variable predictive of survival. The probability of surviving 2 years was .84 for germinoma patients and .62 for NGGCT. Seven of 71 patients died of toxicity associated with study chemotherapy. CONCLUSION: Forty-one percent of surviving patients and 50% of all patients were treated successfully with chemotherapy only without irradiation. Chemotherapy-only regimens for CNS GCT, although encouraging, should continue to be used only in the setting of formal clinical trials.

Adolescent↗
PubMed1996

Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children's Cancer Group.

PURPOSE: This study was designed to determine the toxicity, radiographic response rate, and outcome following high-dose thiotepa, etoposide, and autologous bone marrow rescue (ABMR) for young patients with recurrent malignant brain tumors. METHODS: Eligibility criteria required adequate renal, hepatic, and pulmonary function, and no bone marrow infiltration. Thiotepa 300 mg/m2 and etoposide 500 mg/ m2 were infused on 3 consecutive days, and autologous bone marrow was infused 72 hours following chemotherapy. RESULTS: Forty-five patients with recurrent high-grade brain tumors, aged 8 months to 36 years (median, 8 years), were treated. Seven patients (16%) died of treatment-related toxicities within 56 days of marrow reinfusion. Delayed platelet engraftment occurred in 44% of patients who survived beyond day 56. Of 35 patients with radiographically measurable disease who survived at least 28 days following ABMR, there were two complete responses (CRs) and six partial responses (PRs), for an overall response (CRs plus PRs) rate of 23% (SE = 7%). Objective responses were observed in four of 14 assessable patients with high-grade glioma and in two of six with primitive neuroectodermal tumors (PNETs)/ medulloblastoma. Survival was significantly improved in patients treated with minimal residual disease (P < .0005). Five of 18 patients (28%) with high-grade gliomas remain free of disease at 39+, 44+, 49+, 52+, and 59+ months post-ABMR. CONCLUSION: The combination of high-dose thiotepa and etoposide has activity against a variety of recurrent childhood brain tumors. These results merit further evaluation in children and young adults with both recurrent and newly diagnosed high-grade brain tumors.

Adolescent↗
PubMed1996

High-dose chemotherapy with autologous marrow rescue for malignant brain tumors: analysis of the impact of prior chemotherapy and cranio-spinal irradiation on hematopoietic recovery.

The relative impact of age, sex, nucleated cell dose, prior chemotherapy, prior cranio-spinal irradiation (CSI) and bone marrow harvest (BMH) site on hematological recovery after ABMT were analyzed in a multivariate model. The study population comprised 100 patients with a median age of 9 years who underwent ABMT for malignant brain tumors. Two engraftment parameters were evaluated: number of days post ABMT before (1) an absolute neutrophil count (ANC) > or = 0.5 x 10(9)/l and (2) a platelet count > or = 50 x 10(9)/I were achieved for the third consecutive day without transfusions. Increasing cell dose correlated significantly with a more prompt recovery of platelet counts and ANC. Previous chemotherapy significantly delayed both neutrophil and platelet engraftment. The group of patients who also received CSI had a very delayed platelet recovery with a median time to engraftment of 72 days. Neutrophil engraftment was also significantly delayed and occurred at a median of 23 days. This effect of CSI was independent of cell dose or prior chemotherapy. In 20 of these patients, marrow was harvested at least partially from the posterior iliac crests, which might have received significant doses of irradiation. We conclude that engraftment is significantly faster if bone marrow is harvested prior to any chemotherapy administration, and that patients who receive prior CSI may have significant engraftment delay, particularly of the platelet lineage. In this latter group of patients, marrow should not be harvested from the posterior iliac crests. Strategies that might enhance both neutrophil and platelet count recovery should be considered in patients with irradiation damage to a substantial proportion of the total hematopoietic tissue.

Adolescent↗
PubMed1996

The role of high-dose chemotherapy and stem cell rescue in the treatment of malignant brain tumors.

The outcome for the majority of children with malignant brain tumors remains poor, despite surgery, irradiation and conventional chemotherapy. In an attempt to improve this poor outcome, strategies utilizing high-dose (potentially myeloablative) chemotherapy with autologous stem cell rescue have been developed. These studies, initially conducted in patients with recurrent brain tumors, have now been extended to patients with newly diagnosed malignant gliomas and to young children with various malignant brain tumors at diagnosis in an attempt to avoid irradiation to the brain. The results of several of these studies are summarized, demonstrating durable disease-free survival for a proportion of patients with recurrent malignant gliomas and medulloblastoma/primitive neuroectodermal tumors, as well as encouraging preliminary data in the newly-diagnosed patients.

Adult↗
PubMed1995

Survival of infants with malignant astrocytomas. A Report from the Childrens Cancer Group.

BACKGROUND: Very young children with central nervous system malignant brain tumors have a poor prognosis. As compared with older children, survival is less likely, and those children who do survive frequently have severe impairment of growth and cognitive abilities, resulting partly from treatment with radiotherapy. Therefore, an intensive chemotherapeutic regimen was used to treat children younger than 2 years of age with a diagnosis of malignant astrocytomas. PATIENTS AND METHODS: Thirty-nine children younger than 24 months of age who were diagnosed with malignant astrocytoma were treated on a Childrens Cancer Group protocol with an eight-drug chemotherapeutic regimen (vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytosine arabinoside, prednisone, and dimethyl-triazenoimidazole-carboxamide) after surgery and postoperative staging. Radiation therapy was to be deferred until the completion of chemotherapy. RESULTS: The objective response rate after two cycles of chemotherapy was 24%. Most patients did not receive radiotherapy. Progression-free survival (PFS) and survival at 3 years was 36% (standard error, 8%) and 51% (8%), respectively. The PFS of those children with anaplastic astrocytoma was 44% (11%), significantly better than that of glioblastoma multiforme (GBM) (0%). Extent of resection was not associated significantly with PFS, but tumors within the cerebral hemispheres were associated with a more favorable prognosis. Tumor progression occurred locally in almost all cases and early in treatment (median PFS, 8 months). CONCLUSION: Chemotherapy appears to be effective primary adjuvant treatment for some very young children with anaplastic astrocytomas. Overall, however, survival remains poor, especially for children with GBM. Strategies to improve outcome require early intervention, because tumor progression occurs soon after diagnosis in the majority of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group.

PURPOSE: In a previous randomized trial, the addition of adjuvant chemotherapy to postoperative radiotherapy proved beneficial in the treatment of childhood high-grade astrocytomas. The present study tests the hypothesis that an eight-drug adjuvant chemotherapy regimen would improve survival in such children compared with the three-drug regimen of the prior study. PATIENTS AND METHODS: Between April 1985 and May 1990, patients between the ages of 18 months and 21 years with newly diagnosed high-grade astrocytomas were eligible for this study, as determined by the treating institution's histopathologic diagnosis. Treatment consisted of postoperative local-field radiotherapy and adjuvant chemotherapy, either lomustine (CCNU), vincristine, and prednisone (control regimen) or eight-drugs-in-1-day chemotherapy (experimental regimen). Two cycles of postoperative preirradiation chemotherapy were administered in the experimental regimen. Patients were evaluated radiographically every 3 months after irradiation. RESULTS: Eighty-five eligible patients were randomized to the control regimen and 87 to the experimental regimen. The progression-free survival (PFS) and overall survival (OS) at 5 years were 33% (SE = 5%) and 36% (SE = 6%), respectively. There was no statistical difference in outcome between the two chemotherapy regimens. In patients with confirmed diagnoses of anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM), anaplastic astrocytoma, greater than 90% resection, and nonmidline tumor location were characteristics predictive of an improved PFS. There was a difference in toxicity between the two chemotherapeutic regimens, with greater myelosuppression and hearing loss in the experimental regimen. Tumor recurrence occurred primarily within the primary tumor site. CONCLUSIONS: There is no benefit to the treatment of high-grade astrocytomas in children with eight-drugs-in-1-day chemotherapy compared with CCNU, vincristine, and prednisone. Extent of tumor resection and histopathologic diagnosis are significant prognostic variables. The overall outcome for children with high-grade astrocytomas remains poor.

Adolescent↗
PubMed1995

Prognostic factors and treatment results for supratentorial primitive neuroectodermal tumors in children using radiation and chemotherapy: a Childrens Cancer Group randomized trial.

PURPOSE: To determine clinical characteristics and response to treatment for children with supratentorial primitive neuroectodermal tumors (S-PNETs). PATIENTS AND METHODS: After surgery and staging, 55 patients aged 1.5 to 19.3 years with S-PNETs were randomized to receive craniospinal radiotherapy (RT) followed by eight cycles of 1-(2-chloro-ethyl)-3-cyclohexylnitrosourea (CCNU), vincristine (VCR), and prednisone (standard treatment) or two cycles of 8-in-1 chemotherapy followed by RT and then eight additional cycles of 8-in-1. RESULTS: Three-year Kaplan-Meier estimates (estimate +/- SE) of survival and progression-free survival (PFS) rates for patients with confirmed diagnoses of S-PNET were 57% +/- 8% and 45% +/- 8%, respectively; survival and PFS rates for children with PNETs located in the pineal region were 73% +/- 12% and 61% +/- 13%, respectively, and were significantly different from the other S-PNETs (P < .03). The 8-in-1 arm had greater toxicity than the standard-treatment arm. Distributions of PFS between the two treatment groups were not significantly different (P > .5). Other univariate prognostic factors that influenced PFS included metastasis (M) stage (P < .03: M0 50% +/- 9% v M1-4 0%) and age (P < .02: 1.5 to 2 years 25% +/- 13% v > or = 3 years 53% +/- 9%). CONCLUSION: In this first randomized treatment trial for S-PNETs in children, no significant differences were detected between the two treatment groups. M0 and pineal site of involvement were independent predictors of a better outcome. However, survival was better than previously reported.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Outcome of children with brain stem gliomas after treatment with 7800 cGy of hyperfractionated radiotherapy. A Childrens Cancer Group Phase I/II Trial.

BACKGROUND: Brain stem gliomas remain the childhood brain tumors most resistant to treatment. Treatments with hyperfractionated radiotherapy at doses as high as 7560 cGy have been fairly well tolerated. This study was undertaken to determine the toxicity and possible efficacy of hyperfractionated radiotherapy in children with brain stem gliomas using 100 cGy of radiation twice daily, to a total dose of 7800 cGy. METHODS: Sixty-six children (mean age at diagnosis, 7.5 years) with diffuse intrinsic brain stem gliomas were treated. Patients were evaluated for potential toxicity of treatment, progression-free survival, survival, and response to treatment. RESULTS: Objective response to treatment was documented in 20 of 58 (34%) evaluable patients, with 8 (14%) patients having a greater than 50% reduction in tumor size. Overall survival was 35% plus or minus 6% at 1 year and 11% plus or minus 6% at 3 years. Intralesional cystic/necrotic radiographic changes developed in nine patients 6 weeks after radiation, and three of these patients subsequently improved without antitumor intervention. Six of 14 autopsied patients had evidence of probable radiation-induced intralesional necrotic damage, and in 1, necrosis may have played a role in death. Thirty-three of 66 patients were treated with steroids for prolonged periods. CONCLUSIONS: The results of this treatment regimen demonstrate that hyperfractionated radiotherapy, as delivered in this study to a total dose of 7800 cGy, is relatively well tolerated, but may result in prolonged steroid-use dependency and possible radiation-associated damage. Objective responses to treatment were seen in 34% of patients, but these results were not better than those seen at lower doses of hyperfractionated radiotherapy. There is no evidence that radiation to 7800 cGy results in improved survival for patients with diffuse intrinsic brain stem gliomas.

Adolescent↗
PubMed1994

Disseminated nonlymphoblastic lymphoma of childhood: a Childrens Cancer Group study, CCG-552.

PURPOSE: To assess the efficacy of a chemotherapy-only regimen in pediatric patients with disseminated non-lymphoblastic lymphoma and acute B-cell leukemia (B-ALL). PATIENTS AND METHODS: Sixty-eight eligible patients with previously untreated disseminated non-lymphoblastic lymphoma were enrolled on a Childrens Cancer Group study. Therapy included cycles of chemotherapy, systemic and intrathecal (IT), ever 3 weeks for a total maximal duration of 57 weeks. Fifty-five patients had small non-cleaved cell lymphoma (SNCCL) and 13 had diffuse large cell lymphoma (DLCL). Forty-seven were stage III, six were stage IV, and 15 had B-ALL; 13 had central nervous system (CNS) involvement. RESULTS: Four year event-free survival (EFS) was 53% (SE +/- 12%). Stage III SNCCL patients with LDH < 500 IU/L achieved an improved EFS compared to other SNCCL patients (86% vs. 42% 4 year EFS, P = .072). The primary site of failure for advanced stage SNCCL patients was the CNS. All Ki-1-positive DLCL patients relapsed. Patterns of failure, time to relapse, and outcome following relapse differed between SNCCL and DLCL patients. CONCLUSIONS: Advanced stage SNCCL requires better CNS-directed chemotherapy to reduce the CNS failure rate; however, the achievement of durable disease-free survival in four of 11 patients with CNS disease without use of cranial irradiation suggests merit for further evaluation of chemotherapy-only strategies. DLCL patients do not need intensive CNS-directed chemotherapy.

Adolescent↗
PubMed1994

Pre-irradiation chemotherapy in children with high-grade astrocytoma: tumor response to two cycles of the '8-drugs-in-1-day' regimen. A Childrens Cancer Group study, CCG-945.

PURPOSE: This study was undertaken to evaluate the radiographic response to two cycles of chemotherapy prior to irradiation in newly diagnosed children with high-grade astrocytomas. PATIENTS AND METHODS: One hundred and thirty children less than 21 years of age with newly-diagnosed high-grade astrocytoma were treated with the 'eight-drugs-in-one-day' chemotherapy regimen as part of a phase III multi-institutional Childrens Cancer Group (CCG) trial. Computerized Tomographic (CT) or Magnetic Resonance Image (MRI) scans, obtained after two cycles of chemotherapy had been administered, were compared with post-operative scans to determine treatment response. Scans were evaluated by institutional radiologists, and were reviewed centrally by a single neuroradiologist. RESULTS: Of 79 patients with evaluable post-operative residual tumor on CT or MRI scans, 26 (33%) were determined on institutional evaluation to have had an objective response. However, central review of scans documented responses on only 14/79 (18%). A significantly higher response rate on central review was observed for those children 36 months of age or less at study entry than for older children (33% v 11%; p < 0.001). However, a higher disease progression rate was also observed for those children 36 months of age or less than for older children (21% v 2.6%; p < 0.001). CONCLUSION: In this study, the largest yet reported in newly-diagnosed children with high-grade astrocytomas, the chemotherapy regimen has activity in younger children. The differences in response rates reported by institutional and central review highlight the difficulties inherent in assessing response to brain tumor therapy. However, the study does demonstrate the consistent ability of radiologists to identify disease progression within the institutional and central reviews.

Adolescent↗
PubMed1994

Neuropsychologic effects of cranial irradiation, intrathecal methotrexate, and systemic methotrexate in childhood cancer.

PURPOSE: To investigate the neuropsychologic effects of cranial irradiation (CRT), intrathecal methotrexate (IT-MTX), and systemic methotrexate (SYS-MTX) in a cohort of pediatric patients with cancer who had either received no, moderate, or high doses of these treatments alone or in various combinations. PATIENT AND METHODS: Data were collected on 120 pediatric cancer patients from a large variety of diagnostic groups. Patients completed a comprehensive neuropsychologic test battery designed to assess most areas of cognitive functioning. In analyzing cancer treatment effects, the following variables were statistically controlled: (1) age, (2) socioeconomic status (SES), (3) age at diagnosis, (4) months since both onset and cessation of CNS treatments, (5) time missed from schooling, and (6) presence/type of CNS cancer. RESULTS: CRT, largely in combination with IT-MTX, was significantly associated with deficits in several, primarily nondominant, hemispheric neuropsychologic functions, even after control and other treatment variables were addressed. This relationship was somewhat, but not highly, dose-dependent at CRT doses greater than approximately 18 Gy, at least over the first several years posttreatment. While there was statistically significant evidence for cognitive impairment, absence from school during treatment and age at diagnosis were more predictive of reading and spelling academic achievement than having received CRT. IT-MTX and SYS-MTX alone were not associated with significant degrees of neuropsychologic involvement. CONCLUSION: CRT, especially when administered with IT-MTX, at currently used dosages was associated with significant neuropsychologic impairment in children. These impairments are most likely to be reflected in nonverbal intelligence, perceptual abilities, and susceptibility to distraction. IT-MTX and SYS-MTX did not result in a consistent pattern of cognitive deficit.

Absenteeism↗
PubMed1994

Survival of infants with primitive neuroectodermal tumors or malignant ependymomas of the CNS treated with eight drugs in 1 day: a report from the Childrens Cancer Group.

PURPOSE: Very young children with CNS primitive neuroectodermal tumors (PNETs) and ependymomas have a poor prognosis and commonly have impairment of growth and cognitive abilities, in part resulting from radiotherapy. Thus, an intensive chemotherapeutic regimen was used to treat children less than 18 months of age at diagnosis. PATIENTS AND METHODS: Children were treated on a Childrens Cancer Group (CCG) protocol with an eight-drug chemotherapeutic regimen (vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytarabine, prednisone, and cyclophosphamide) following surgery and postoperative staging. Delayed or reduced-volume radiotherapy was to be administered to all patients, but, in fact, was omitted in most cases. RESULTS: On central review of pathology, 82 children had diagnosis concordant with study entry criteria. Of these, 46 (56%) had posterior fossa (PF) PNET, eight (10%) had pineal PNET, 11 (12%) had nonpineal supratentorial PNET, 15 (18%) had ependymoma, and two had rhabdoid tumors. Fifty percent of tumor resections were complete, as verified by postoperative computed tomographic (CT) scan, and 23% of patients had metastatic disease at the time of diagnosis. Objective tumor response was documented following two cycles of chemotherapy in 28% of assessable patients. Toxicity of chemotherapy was primarily hematopoietic. Five children died of chemotherapy-related complications. Radiotherapy was administered to only nine patients before tumor progression. The 3-year progression-free survival (PFS) rates for PF PNET, pineal PNET, supratentorial nonpineal PNET, and ependymoma are 22% (SE = 6%), 0%, 55% (16%), and 26% (11%), respectively. The 3-year PFS rate for those children without metastatic disease was 29% (6%), as compared with 11% (6%) for those with metastatic disease. The only independent predictors of PFS were metastasis stage and location of the tumor within the pineal region. The median time to progression was 6 months. Twenty-four children completed the chemotherapeutic regimen without tumor progression; 19 are event-free survivors more than 2 years from diagnosis, only three of whom received radiation therapy. CONCLUSION: While overall survival in this group of very young patients is poor, a subset of children who have received only chemotherapy as adjuvant treatment remain free from tumor recurrence.

Antineoplastic Combined Chemotherapy Protocols↗