Postoperative Chemotherapy and Delayed Radiation in Children Less Than Three Years of Age with Malignant Brain Tumors

Duffner, Patricia K.; Horowitz, Marc E.; Krischer, Jeffrey P.; Friedman, Henry S.; Burger, Peter C.; Cohen, Michael E.; Sanford, Robert A.; Mulhern, Raymond K.; James, Hector E.; Freeman, Carolyn R.; Seidel, F. Glen; Kun, Larry E.

doi:10.1056/nejm199306173282401

Cited by 748 publications

(429 citation statements)

References 19 publications

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“…[1][2][3][4][5] However, relapse was a significant issue and irradiation could not be avoided in most cases. Since the 'Head Start' trials began employing AuHCR with greater irradiation avoidance, we have documented improvements in quality of life by avoiding cranial irradiation, through prospectively conducted neuropsychological and quality of life follow-up studies.…”

Section: Discussionmentioning

confidence: 99%

“…In the 1980s to mid-1990s, treatment strategies for young children with primary malignant brain central nervous system (CNS) tumors utilized standard-dose chemotherapies to attempt to delay CNS irradiation until 3 or more years of age 1 or to avoid CNS irradiation entirely. [2][3][4][5] Overall, 2-3 year PFS for children on these studies ranged from less than 10 to 34% for medulloblastoma, less than 30% for high-grade gliomas and 0-19% for other primitive neuro-ectodermal tumors.…”

Section: Introductionmentioning

confidence: 99%

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Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the ‘Head Start’ trials, 1991–2009

Altshuler

Haley

Dhall

et al. 2016

Bone Marrow Transplant

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Since 1991, three sequential prospective clinical trials have been conducted by the 'Head Start' (HS) Consortium in which young children with newly-diagnosed malignant central nervous system (CNS) tumors were treated with induction chemotherapy followed by single-cycle marrow-ablative chemotherapy and autologous hematopoietic rescue as a means of improving disease cure rate and quality of survival through avoidance (o 6 years old at diagnosis) or reduction (6-10 years old) of brain irradiation. Bone Marrow (HS I) or filgrastim-mobilized peripheral hematopoietic cells (HS II and III) were obtained following recovery from the first and/or second induction cycles. Radiotherapy was administered following all chemotherapy only for patients with residual tumor following completion of induction or with age greater than 6 years at diagnosis. Two hundred and twenty-six children were enrolled on three consecutive HS trials with primary malignant CNS tumors and underwent marrow-ablative chemotherapy. The 100-day treatment-related mortality (TRM) steadily declined as did grade IV transplant-related oropharyngeal mucositis. Factors most likely associated with the decrease in TRM and morbidity are increasing experience with the marrow-ablative chemotherapy regimen combined with improved leukapheresis and post-reinfusion supportive care techniques, contributing toward improved overall survival.Bone Marrow Transplantation (2016) 51, 945-948;

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the ‘Head Start’ trials, 1991–2009

Altshuler

Haley

Dhall

et al. 2016

Bone Marrow Transplant

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“…(2) Preradiation chemotherapy with cycles of CDP (20 mg/m 2 on days 1-5 or 90 mg/m 2 on day 1) and etoposide (75-100 mg/m 2 for 3 to 5 days) alternating with CTX (450-1580 mg/m 2 on days 1 and 2) and VCR (1.5 mg/m 2 on day 1) (Duffner et al, 1993). Seven patients were treated on this regimen based on a protocol designed by POG (Duffner et al, 1993).…”

Section: Methodsmentioning

confidence: 99%

Adult medulloblastoma: Multiagent chemotherapy

Greenberg¹

2001

Neuro-Oncology

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In this study, the records of 17 adult patients with medulloblastoma treated with craniospinal radiation and 1 of 2 multiagent chemotherapy protocols were reviewed for progression-free survival, overall survival, and toxicity, and the patients were compared with each other and with similarly treated children and adults. Records of patients treated at 3 institutions were reviewed. Seventeen medulloblastoma patients (11 female, 6 male) with a median age of 23 years (range, 18-47 years) were treated with surgery, craniospinal radiation (CSRT) plus local boost, and 1 of 2 adjuvant chemotherapy regimens. All tumors were infratentorial (10 in 4th ventricle and 7 in left or right hemisphere). Ten patients presented with hydrocephalus, and 7 of them were shunted. Eight patients had gross total resection, 7 had subtotal resection (>50% removed), and 2 had partial resection (<50% removed). Postoperatively, 3 patients had positive cytology and 3 had positive spinal MRI. Five patients were classi ed as good risk and 12 were classi ed as poor risk (Chang staging system). Ten patients were treated with the "Packer protocol," consisting of CSRT plus weekly vincristine followed by 8 cycles of cisplatin, lomustine, and vincristine. Seven patients were treated with the Pediatric Oncology Group (POG) protocol, consisting of alternating courses of cisplatin/etoposide and cyclophosphamide/vincristine, followed by CSRT. Eight of 17 patients relapsed, with all 8 relapsing at the primary site. Other relapse sites included the leptomeninges (5), bone (1), and brain (1). The estimated median relapse-free survival (Kaplan-Meier) for all patients was 48 months (95% con dence interval, >26 months to ¥). Median relapse-free survival for patients on the Packer protocol was 26 months, and for those on the POG regimen was 48 months (P = 0.410). Five of 10 on the Packer protocol were relapse-free, while 4 of 7 were relapse-free on the POG regimen. Two patients relapsed during chemotherapy and 6 relapsed after completing all therapy at 18, 18, 26, 30, 40, and 48 months. The estimated median survival of all patients was 56 months (95% con dence interval, 27 to ¥) with 11 patients alive; for the Packer protocol, median survival was 36 months, and for the POG protocol, it was 57 months (P = 0.058). The hazard ratio was 0 (95% con dence interval, 0 to ¥). Toxicity during the Packer protocol was moderately severe, with only 1 of 10 patients able to complete all therapy. Two patients had severe abdominal pain during CSRT + vincristine, and 5 had peripheral neuropathy during vincristine therapy. Hearing loss (>20 dB) occurred in 7, neutropenia (<500 µl) in 6, thrombocytopenia (<50,000 µl) in 6, nephrotoxicity (>25% ¯by creatinine clearance) in 2, and decreased pulmonary function (diffusing capacity for carbon monoxide ¯>40%) in 1. On the POG protocol, only 1 patient had persistent nausea and vomiting, 2 had peripheral neuropathy, and 3 had hearing de cit (>20 dB) or tinnitus. The POG and Packer protocols did not have a statistically signi cant differenc...

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“…In a large multicenter study in patients < 3 years of age with malignant brain tumors (although not AA and GBM), 39% of 102 evaluable patients had an objective response after only 2 cycles of cyclophosphamide plus vincristine (Duffner et al, 1993). Patients continued to receive chemotherapy for up to 1 or 2 years, depending on their age at diagnosis and response to treatment, before receiving radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of temozolomide in patients with newly diagnosed supratentorial malignant glioma before radiation therapy

Gilbert¹,

Friedman²,

Kuttesch³

et al. 2002

Neuro-Oncol

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Temozolomide is a novel second-generation oral alkylating agent with demonstrated ef cacy and safety in patients with recurrent glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). A multicenter phase II trial was conducted to determine the ef cacy and safety of temozolomide before radiotherapy in patients with newly diagnosed GBM and AA. Fifty-seven patients (51 adult, 6 pediatric) with newly diagnosed supratentorial GBM or AA were treated with temozolomide (200 mg/m 2 per day for 5 consecutive days every 28 days) for a maximum of 4 cycles. All patients were then treated with external beam radiotherapy. Twenty-two patients (39%) achieved objective response, including 6 (11%) with complete response (CR) and 16 (28%) with partial response (PR). Additionally, 18 (32%) patients had stable disease (SD Abbreviations used are as follows: AA, anaplastic astrocytoma; CR, complete response; GBM, glioblastoma multiforme; Gd-MRI, gadolinium-enhanced magnetic resonance imaging; KPS, Karnofksy performance score; PR, partial response; SD, stable disease. adult patients with AA, the median progression-free and overall survival rates were 7.6 and 23.5 months, respectively. Among 36 patients (33 adult, 3 pediatric) with GBM, 4 (11%) had CR, 11 (31%) had PR, and 10 (28%) had SD. The median progression-free and overall survival rates among adult patients with GBM were 3.9 and 13.2 months, respectively. Temozolomide was safe and well tolerated in adult and pediatric patients. Grades 3 and 4 adverse events were reported in 16 (28%) and 7 (12%) patients, respectively. Temozolomide was safe and effective in treating newly diagnosed GBM and AA before radiotherapy. This pre-irradiation treatment approach appears promising, but will require additional evaluation in comparative studies. Neuro-Oncology 4, 261-267, 2002 (Posted to Neuro-Oncology [serial online], Doc. 02-009, July 12, 2002

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Postoperative Chemotherapy and Delayed Radiation in Children Less Than Three Years of Age with Malignant Brain Tumors

Cited by 748 publications

References 19 publications

Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the ‘Head Start’ trials, 1991–2009

Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the ‘Head Start’ trials, 1991–2009

Adult medulloblastoma: Multiagent chemotherapy

A phase II study of temozolomide in patients with newly diagnosed supratentorial malignant glioma before radiation therapy

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