Getting a “Head Start”: Neuropsychological functioning of young children treated for brain tumors with delayed or no cranial radiation therapy

2009 ◽  
Vol 54 (3) ◽  
pp. 346-347
Author(s):  
Deborah P. Waber
Keyword(s):  
Radiation Therapy ◽  
Head Start ◽  
Young Children ◽  
Brain Tumors ◽  
Neuropsychological Functioning ◽  
Cranial Radiation

Newly diagnosed high-risk malignant brain tumors with leptomeningeal dissemination in young children: A final update on Head Start II Regimen A2 intensified with high-dose methotrexate

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9552-9552
Author(s):  
S. Chi ◽  
S. Gardner ◽  
L. Y. Ji ◽  
R. Sposto ◽  
G. Dhall ◽  
...  
Keyword(s):  
High Risk ◽  
Head Start ◽  
Young Children ◽  
Brain Tumors ◽  
Response Rate ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Leptomeningeal Dissemination ◽  
Newly Diagnosed ◽  
Dose Methotrexate

9552 Background: The prognosis for young children with newly diagnosed malignant brain tumors with leptomeningeal dissemination remains poor. From Jan 1997 to Mar 2003, “Head Start II” Regimen A2, intensified with high-dose methotrexate, was offered to this high-risk population. Methods: Eligibility: patients < 10 yrs of age; confirmed diagnosis of medulloblastoma (MB), primitive neuroectodermal tumor (PNET), ependymoma and choroid plexus carcinoma (CPC); and high-risk status as determined by neuroaxis dissemination. Patients with atypical teratoid/rhabdoid tumor (ATRT), regardless of stage, were also eligible. Treatment: 5 cycles of vincristine (0.05 mg/kg/week × 3 doses), cisplatin (3.5 mg/kg), etoposide (4 mg/kg/day × 2 days), cyclophosphamide (65 mg/kg/day × 2 days), and methotrexate (400 mg/kg) with leucovorin. Children without progressive disease (PD) by the end of induction underwent a single consolidation cycle (carboplatin, etoposide, thiotepa) with autologous stem cell rescue. Reduced dose RT (2340cGy CSI and focal boost) was reserved for any with residual disease at the end of induction or for the older patient (>6 yrs of age). Results: 40 patients were enrolled (MB, 22; PNET, 6; ependymoma, 5; AT/RT, 6; CPC, 1), med age at diagnosis 38 mos (range 5 to 119 mos). Significant toxicities of this intensified regimen included GI toxicities and infections. Among the entire cohort, there were 26 CR, 6 PR, 2 with stable disease and 4 with PD (and 2 toxic deaths), for a CR +PR response rate of 82%. For disseminated MB (4 M1; 2 M2; 16 M3), the CR rate alone is 77% (17/22). The 5-year EFS and OS for disseminated MB are 45% (95% CI, 24 % to 64%) and 54% (95% CI, 31% to 72%), respectively. Of note, 6/12 MB survivors (all M3) did not receive RT and all are NED >5 years from diagnosis. In addition, there are 3 AT/RT survivors, 12, 54 and 66 mos post-diagnosis who did not receive RT. Conclusions: This intensified regimen is feasible and tolerable. For patients with disseminated MB, the majority of whom had M3 disease at diagnosis, the impressive response rate and outcomes suggest that the addition of methotrexate is justified for future studies. Long- term neuropsychological outcomes are being studied at this time. No significant financial relationships to disclose.

Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols: Final report

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9507-9507
Author(s):  
G. Dhall ◽  
H. Grodman ◽  
L. Ji ◽  
S. Sands ◽  
S. Gardner ◽  
...  
Keyword(s):  
Head Start ◽  
Young Children ◽  
Cognitive Functioning ◽  
Neuropsychological Functioning ◽  
Residual Tumor ◽  
Emotional Behavior ◽  
Final Report ◽  
Intensive Chemotherapy ◽  
Social And Emotional

9507 Background: The use of dose-intensive chemotherapy with autologous hematopoietic cell rescue (AuHCR) is a potentially curative approach to the management of infants and young children with non-metastatic (M-0) medulloblastoma, with the additional benefit of avoiding the late effects of irradiation. We report the results of the “Head Start” I (1991 to 1997) and “Head Start” II (1997 to 2002) clinical trials, using this approach, to treat children with M-0 medulloblastoma, who were less than three years of age at diagnosis. Methods: Twenty one children were enrolled on these two serial studies. After surgery, patients received a uniform induction chemotherapy regimen consisting of five cycles of vincristine, cisplatin, cyclophosphamide and etoposide. Following completion of induction, all patients underwent myeloablative consolidation chemotherapy using carboplatin, thiotepa and etoposide followed by AuHCR, and did not receive irradiation. Irradiation was used only at relapse. Quality of life (QoL) and social and emotional behavior were evaluated on “Head Start” I, and cognitive functioning was evaluated on “Head Start” II survivors. Results: The five-year event-free (EFS) and overall survival (OS) rates (±SE) for all patients, patients with gross total resection, and patients with residual tumor were 52 ± 11% and 70 ± 10%, 64 ± 13% and 79 ± 17%, and 29 ± 17% and 57 ± 19%, respectively. The five-year EFS and OS (±SE) for patients with desmoplastic and classical medulloblastoma were 67 ± 16% and 78 ± 14%, and 42 ± 14 and 67 ± 14%, respectively. Young age (<2 years versus 2 to 3 years) at diagnosis did not appear to impact adversely upon outcome. There were four treatment related deaths. A majority of survivors (71%) avoided irradiation altogether. Neuropsychological functioning in children surviving without irradiation was well within the normal range for most patients. Conclusions: The strategy of brief intensive chemotherapy without irradiation for young children with M-0 medulloblastoma has eliminated the need for craniospinal irradiation in over half (52%) of the patients, with preservation of QoL and cognitive functioning in the majority. No significant financial relationships to disclose.

Magnetic resonance imaging evaluation of radiation: Cranial radiation therapy-induced diffuse white matter injury

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13033-e13033
Author(s):  
T. Z. Mohran ◽  
M. M. Omar ◽  
M. A. Hameed ◽  
M. S. Elnaggar
Keyword(s):  
Radiation Therapy ◽  
White Matter ◽  
Brain Tumors ◽  
Spin Echo ◽  
White Matter Injury ◽  
High Signal ◽  
Imaging Evaluation ◽  
Post Contrast ◽  
Diffuse White Matter ◽  
Cranial Radiation

e13033 Background: To study the value of MRI in detection and grading of diffuse white matter injury induced by cranial radiation therapy for brain tumors and to evaluate the influence of various risk factors for its development. Methods: This study included 60 patients who had primary brain tumors and received external beam conventionally fractionated radiotherapy. Twenty-three out of 60 patients received chemotherapy after radiotherapy. Post radiotherapy follow-up MRI examination was performed for all patients at 6 weeks, 3, 6, 9, 12 months, and at more than 1 year from completion of radiotherapy. MR imaging was performed with T2-weighted turbo spin echo, fast fluid-attenuated inversion- recovery (FLAIR), T1-weighted spin-echo, and T1-weighted post-contrast spin-echo sequences. Results: Twenty-one of 60 patients (35%) developed diffuse white matter injury at a mean of 15.3 + 7.6 months from the completion of radiotherapy (range, 5–36 months). Radiation-related diffuse white matter changes were characterized as diffuse high signal intensity in the periventricular deep white matter on T2WI and FLAIR sequences. The MRI grading system of these periventricular hyperintensity (PVH) were as follow: 39 patients (65%) had no WMI (grade 0), four had grade 1 changes, three patients had grade 2 changes, nine patients had grade 3, and five patients had grade 4. They were symmetrical in 13 of 21 patients (61.9%), and asymmetrical in eight out of 21 patients (38.1%). The prevalence of diffuse matter injury found to be significantly related to the volume of irradiation (p = 0.02), fraction size (p = 0.008), and concomitant use of chemotherapy (p > 0.02)Conclusions: Diffuse white matter injury is a known consequence of radiation therapy, and the capability of detecting and grading such damage is optimally provided by MRI. No significant financial relationships to disclose.

Cranial Radiation Therapy Induces Acute Cognitive Impairments in Patients with Brain Tumors Only

2005 ◽  
Vol 63 ◽  
pp. S155-S156
Author(s):  
G. Welzel ◽  
K. Fleckenstein ◽  
D. Thoennessen ◽  
B. Hermann ◽  
U. Kraus-Tiefenbacher ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Tumors ◽  
Cognitive Impairments ◽  
Cranial Radiation

A phase I study of cranial radiation therapy with concomitant continuous infusion paclitaxel in children with brain tumors

2001 ◽  
Vol 37 (4) ◽  
pp. 390-392 ◽  
Author(s):  
Li Liu ◽  
Neha Vapiwala ◽  
Louis K. Munoz ◽  
Naomi J. Winick ◽  
Steven Weitman ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Tumors ◽  
Phase I ◽  
Continuous Infusion ◽  
Phase I Study ◽  
Cranial Radiation

Neuropsychological Functioning after Surgery in Children Treated for Brain Tumor

Neurosurgery ◽  
2003 ◽  
Vol 52 (6) ◽  
pp. 1348-1357 ◽  
Author(s):  
Sarah C. Carpentieri ◽  
Deborah P. Waber ◽  
Scott L. Pomeroy ◽  
R. Michael Scott ◽  
Liliana C. Goumnerova ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Tumors ◽  
Verbal Memory ◽  
Neuropsychological Functioning ◽  
Poor Performance ◽  
School Age ◽  
Stereotactic Radiation Therapy ◽  
Stereotactic Radiation ◽  
Dana Farber Cancer Institute ◽  
Normative Expectations

Abstract OBJECTIVE To describe the neuropsychological functioning of children treated with surgery only for localized brain tumors in Dana-Farber Cancer Institute Protocol 92-077. Subsequent reports will describe the neuropsychological functioning of children treated with surgery and stereotactic radiation therapy on Dana-Farber Cancer Institute 92-077. METHODS The intellectual functioning of 106 patients was evaluated within 3 months after surgery. An in-depth assessment of the neuropsychological functioning, including an impairment index, was conducted for a subset of 77 school-age children (6–16 yr old) across six functional domains. Descriptive statistics were generated; binomial distribution analyses were performed to assess whether the proportion of individuals with impaired performance on each measure exceeded normative expectations. The impairment index assessed whether poor performance was attributable to a few children or reflected the performance of the cohort as a whole. RESULTS Although the Full Scale IQ was within normative expectations, the Verbal IQ was higher than the Performance IQ with 45% of individuals showing a significant discrepancy (P &lt; 0.01) between these scales. There was an increased prevalence of poor performance for measures of motor output, verbal memory, and visuospatial organization. The distribution of the impairment index indicated moderate impairment across the school-age cohort rather than severe impairment in a few patients. CONCLUSION The results document a moderate level of neuropsychological morbidity among children with brain tumors before stereotactic radiation therapy, presumably referable to the tumor itself and the surgery. The extent to which stereotactic radiation therapy may increase this burden will be assessed in follow-up studies evaluating the longitudinal neuropsychological data.

Neurodevelopmental status of infants and young children treated for brain tumors with preirradiation chemotherapy.

1989 ◽  
Vol 7 (11) ◽  
pp. 1660-1666 ◽  
Author(s):  
R K Mulhern ◽  
M E Horowitz ◽  
E H Kovnar ◽  
J Langston ◽  
R A Sanford ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Young Children ◽  
Brain Tumors ◽  
Performance Status ◽  
Cranial Irradiation ◽  
Multiple Risk Factors ◽  
Probable Interaction ◽  
Normal Performance ◽  
Infants And Young Children

In an effort to reduce the severity of late neurotoxicities associated with cranial irradiation, 14 infants and young children with malignant brain tumors were given preirradiation chemotherapy for 2 to 22 months (median, 8 months). Prospective neurodevelopmental evaluations were routinely conducted and now extend from 35 to 60 months (median, 41 months) postdiagnosis, and 10 to 52 months (median, 31 months) postirradiation in the 12 surviving children. At the initiation of chemotherapy, less than one fourth of the patients displayed normal performance status or mental functioning on age-corrected tests; the majority remained stable or declined while receiving chemotherapy. Declining mental development and adaptive behavior were noted in six patients following radiation therapy with only two patients now functioning in the normal range for age. The analysis suggests that neurodevelopmental progress is a function of multiple factors, including neurologic and sensorimotor deficits associated with the tumor, surgical intervention, and chemotherapy that antedated radiation therapy. This implies that delaying irradiation will not necessarily improve the patients' functional status. Whether the interval of postponement of irradiation evidenced in this sample will translate into an ultimately better quality of life remains unknown. Given the probable interaction of multiple risk factors, well-controlled prospective clinical trials are needed to definitively analyze this issue.

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