scholarly journals Neuropsychological outcomes on Head Start III: a prospective, multi-institutional clinical trial for young children diagnosed with malignant brain tumors

2020 ◽  
Vol 7 (3) ◽  
pp. 329-337
Author(s):  
Sharon H O’Neil ◽  
Ashley M Whitaker ◽  
Kimberly Kayser ◽  
Mary Baron Nelson ◽  
Jonathan L Finlay ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Head Start ◽  
Young Children ◽  
Pediatric Brain Tumor ◽  
The United States ◽  
Outcome Data ◽  
Individual Variability ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
Increased Risk

Abstract Background Current pediatric brain tumor treatment focuses on titrating toxicity based on risk factors while simultaneously improving survivorship. The Head Start (HS) protocols I to IV (1991-present) use high-dose chemotherapy (HDCTx) with an aim of reducing or eliminating cranial irradiation in very young children, the most vulnerable to its effects. Methods We examined estimated Full Scale IQ, overall Adaptive Functioning, Working Memory, Processing Speed, and Verbal and Nonverbal Memory outcome data for 43 HS III patients diagnosed between ages 2 months and 7 years from 15 institutions in the United States and Canada. Results At a mean of 5.12 years postdiagnosis, the HS III patients performed within the average to low-average ranges across these variables; however, individual variability was noted with scores ranging from superior to impaired, and the sample as a whole performed lower than age expectations. Performance did not significantly differ by sex or ethnicity, diagnosis, or for those treated with an intravenous methotrexate dose of 400 mg/kg vs 270 mg/kg. Additionally, performance did not significantly differ by age at diagnosis or length of follow-up. Conclusions The results, indicating overall average to low-average neurocognitive functioning, are encouraging, though significant individual variability was noted. Those who were younger at diagnosis, received more intensive methotrexate, and were further out from treatment were not at significantly increased risk of cognitive decline within our sample, suggesting a strategy of using HDCTx and autologous hematopoietic progenitor cell rescue to reduce or eliminate irradiation may allow for continued CNS development in young children treated for a brain tumor.

High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate analysis of prognostic variables.

1996 ◽  
Vol 14 (10) ◽  
pp. 2638-2645 ◽  
Author(s):  
J Beyer ◽  
A Kramar ◽  
R Mandanas ◽  
W Linkesch ◽  
A Greinix ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
The United States ◽  
High Dose Chemotherapy ◽  
Hematopoietic Progenitor Cell ◽  
Risk Category ◽  
High Dose ◽  
Prognostic Variables ◽  
Increased Risk

PURPOSE To identify prognostic variables for response and survival in male patients with relapsed or refractory germ cell tumors treated with high-dose chemotherapy (HDCT) and hematopoietic progenitor cell support. PATIENTS AND METHODS Three hundred ten patients treated with HDCT at four centers in the United States and Europe were retrospectively evaluated. Univariate and multivariate analysis of patient, disease, and treatment characteristics were used for comparisons of response rates and failure-free survival (FFS). RESULTS The actuarial FFS rate was 32% at 1, 30% at 2, and 29% at 3 years. Multivariate analysis identified progressive disease before HDCT, mediastinal nonseminomatous primary tumor, refractory or absolute refractory disease to conventional-dose cisplatin, and human chorionic gonadotropin (HCG) levels greater than 1,000 U/L before HDCT as independent adverse prognostic variables for FFS after HDCT. These variables were used to identify patients with good, intermediate, and poor prognoses. In the good-risk category, the predicted FFS rate at 2 years was 51%, compared with 27% and 5% in the intermediate-risk and poor-risk categories (P < .001). The increased risk for treatment failure was due to both a significantly lower rate of favorable responses and a significantly higher rate of relapses. Within the prognostic categories, the particular HDCT regimen or higher dosages of carboplatin or etoposide did not have a significant influence on treatment outcome. CONCLUSION Prognostic variables for treatment response after HDCT can be identified. The proposed prognostic model might help to optimize the use of HDCT in germ cell tumors and warrants validation in future trials.

scholarly journals MBCL-37. CHEMOTHERAPY STRATEGIES FOR YOUNG CHILDREN NEWLY DIAGNOSED WITH CLASSIC (CLMB) OR ANAPLASTIC/LARGE CELL (A/LCMB) MEDULLOBLASTOMA UP TO THE ERA OF MOLECULAR PROFILING – A COMPARATIVE OUTCOMES ANALYSIS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii396-iii397
Author(s):  
Jonathan Finlay ◽  
Martin Mynarek ◽  
Girish Dhall ◽  
Claire Mazewski ◽  
Richard Grundy ◽  
...  
Keyword(s):  
Head Start ◽  
Young Children ◽  
Induction Chemotherapy ◽  
Treatment Strategies ◽  
Large Cell ◽  
High Dose ◽  
Event Free Survival ◽  
Standard Chemotherapy ◽  
Outcomes Analysis ◽  
Free Survival

Abstract BACKGROUND/OBJECTIVE The introduction of German regimens, supplementing “standard” chemotherapy with both intravenous high-dose (HD-MTX) and intraventricular (IVENT-MTX) methotrexate, and North American regimens incorporating marrow-ablative chemotherapy with autologous hematopoietic cell rescue (HDCx+AuHCR), report encouraging outcomes for young children with medulloblastoma. We performed a comparative outcomes analysis of treatment strategies for young children with ClMB or A/LCMB. DESIGN/ METHODS Data from 12 prospective multi-center trials published between 2005 and 2019 for children &lt;six-years-old with ClMB or A/LCMB were reviewed; survivals were compared. RESULTS COG-9921, UKCCSG-CNS9204, COG-P9934 and SJYCO7 employing standard chemotherapy with either no or risk-based irradiation, reported 3-5-year event-free survival (EFS) of 17+/-5%, 33+/-28% (ClMB), 14+/-7% and 13.8+/-9% (ClMB) respectively, with reported EFS of 0% for A/LCMB in UKCCSG-CNS9204 and SJYCO7. HIT-SKK’87, HIT-SKK’92 and HIT-SKK’00 incorporating HD-MTX and IVENT-MTX reported 2-10-year EFS of 30–34+/-10–11% for ClMB and 33+/-27% (HIT-SSK’00) for A/LCMB. Head Start HS-I-II combined, CCG-99703 and HS-III employing induction chemotherapy, with or without HD-MTX, followed by single or tandem HDCx+AuHCR reported 3-5-year EFS of 42+/-14%, 50+/-11% and 27+/-6% for ClMB, with EFS for A/LCMB of 38+/-13% (HS-III). Finally, 5-year overall survivals for ACNS0334, without or with induction HD-MTX, are 39% and 69% respectively for ClMB and A/LCMB combined. CONCLUSIONS A trend towards better outcomes for young children with ClMB and A/LCMB is observed in trials including either HD-MTX and IVENT-MTX or including HD-MTX-containing induction chemotherapy and HDCx+AuHCR. Trials excluding HD-MTX, IVENT-MTX and HDCx+AuHCR have poorer outcomes.

scholarly journals Reconceptualizing civic education for young children: Recognizing embodied civic action

2019 ◽  
Vol 15 (1) ◽  
pp. 35-46
Author(s):  
Katherina A. Payne ◽  
Jennifer Keys Adair ◽  
Kiyomi Sanchez Suzuki Colegrove ◽  
Sunmin Lee ◽  
Anna Falkner ◽  
...  
Keyword(s):  
United States ◽  
Decision Making ◽  
Head Start ◽  
Young Children ◽  
Lived Experience ◽  
Civic Education ◽  
The United States ◽  
Civic Action ◽  
Civic Skills ◽  
Early Childhood Settings

Traditional conceptions of civic education for young children in the United States tend to focus on student acquisition of patriotic knowledge, that is, identifying flags and leaders, and practicing basic civic skills like voting as decision-making. The Civic Action and Young Children study sought to look beyond this narrow vision of civic education by observing, documenting, and contextualizing how young children acted on behalf of and with other people in their everyday early childhood settings. In the following paper, we offer examples from three Head Start classrooms to demonstrate multiple ways that young children act civically in everyday ways. When classrooms and teachers afford young children more agency, children’s civic capabilities expand, and they are able to act on behalf of and with their community. Rather than teaching children about democracy and citizenship, we argue for an embodied, lived experience for young children.

scholarly journals QOL-51. LISTENING BEFORE WE SPEAK: A PATIENT-CENTERED APPROACH TO DEVELOPING RESOURCES FOR PEDIATRIC BRAIN TUMOR SURVIVORS AND THEIR FAMILIES

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii440-iii440
Author(s):  
Kathy Riley
Keyword(s):  
Quality Of Life ◽  
Mental Health ◽  
United States ◽  
Brain Tumor ◽  
Mental Health Professionals ◽  
Pediatric Brain Tumor ◽  
The United States ◽  
Physical And Mental Health ◽  
Pediatric Brain

Abstract In the United States, more than 28,000 children and teenagers live with the diagnosis of a primary brain tumor (Porter, McCarthy, Freels, Kim, & Davis, 2010). In 2017, an estimated 4,820 new cases of childhood primary brain and other central nervous system tumors were expected to be diagnosed in children ages 0 – 19 in the United States (Central Brain Tumor Registry of the United States, 2017). Survivors suffer from lifelong side effects caused by their illness or by various treatments. Commonly identified late effects of treatment include a decline in intellectual functioning and processing speed, performance IQ deficits, memory deficits, psychological difficulties, deficits in adaptive functioning (daily life skills), and an overall decrease in health-related quality of life (Castellino, Ullrich, Whelen, & Lange, 2014). To address the ongoing challenges these survivors and their families face, the Pediatric Brain Tumor Foundation (PBTF) met extensively with working groups comprised of survivors and caregivers to develop the outline for a comprehensive Survivorship Resource Guidebook. In 2019, the PBTF published the guidebook which categorizes survivor and caregiver needs into three primary areas: physical and mental health, quality of life, and working the system. Expert authors included survivors and caregivers themselves in addition to medical and mental health professionals. Key outcomes discovered during the creation and production of this resource highlight how caregivers, survivors and professionals can collaborate to provide needed information and practical help to one segment of the pediatric cancer population who experience profound morbidities as a result of their diagnosis and treatment.

scholarly journals SWK-03. CAREGIVER EXPERIENCES FOR PEDIATRIC BRAIN TUMOR PATIENTS AND THEIR FAMILIES AT A DEDICATED MEDICAL SPECIALTY CAMP

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii465-iii465
Author(s):  
Ryan Brownfield ◽  
Barb Galantowicz ◽  
Claire Russell ◽  
Jennifer Chabot ◽  
Scott Coven
Keyword(s):  
Brain Tumor ◽  
Pediatric Brain Tumor ◽  
Medical Specialty ◽  
The United States ◽  
Structured Interview ◽  
Non Profit ◽  
Institutional Review ◽  
The Future ◽  
Horse Farms ◽  
Pediatric Brain

Abstract BACKGROUND Medical specialty camps have provided children with unique psychosocial experiences; however, dedicated pediatric brain tumor camps are rare in the United States, except in limited locations. This study aimed to glean caregiver perceptions from a dedicated family brain tumor camp, and to learn about the family experience with navigating a neuro-oncology diagnosis. DESIGN: Flying Horse Farms is a non-profit organization located in Mt. Gilead, Ohio and a member of the SeriousFun Children’s Network, a global community of camps and programs serving children with serious illnesses and their families, at no cost. The institutional review board at Ohio University approved this project at Flying Horse Farms in September 2017. Consent from caregivers was obtained prior to participation in the study, which provided the opportunity to complete three separate phases: a pre-camp survey, attend a semi-structured interview during the weekend, and complete a post-camp survey. RESULTS 11 families were present for the weekend, and 10 families consented to participate in all three phases. For 6 families, this was their first experience at Flying Horse Farms. For 9 of the 10 families, the camp met their expectations. Additionally, 9 out of 10 families reported they would be interested in attending a diagnosis specific camp again in the future. CONCLUSIONS This work demonstrates the feasibility of conducting research at a medical specialty camp without restricting the camp experience. Better understanding of the attendee’s attitudes toward camp may enhance the experience and the neuro-oncology journey in the future.

Abstract 12427: Racial Disparities in Hospitalization for Atrial Fibrillation: The Nationwide Inpatient Sample 2001-09

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Gene F Kwan ◽  
Danielle M Enserro ◽  
Allan J Walkey ◽  
Renda S Wiener ◽  
Emelia J Benjamin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Racial Differences ◽  
Nationwide Inpatient Sample ◽  
The United States ◽  
Census Bureau ◽  
Outcome Data ◽  
Hospitalization Rates ◽  
Increased Risk ◽  
Modifiable Factors

Introduction: Racial differences in atrial fibrillation (AF) prevalence and disparities in treatment are well established; however, racial differences in outcomes among patients hospitalized with AF are less clear. We assessed racial differences in complications related to AF in a representative sample of AF hospitalization in the United States. Methods: We identified adults (≥ 40 years) with a principal diagnosis of AF and length of stay (LOS) among survivors of 1-30 days using weighted national estimates from the Nationwide Inpatient Sample. We excluded patients undergoing cardiac surgery or with missing covariates. Annual AF hospitalization rates by race were calculated using the total US population obtained from the US Census Bureau. We used multivariable regression models (covariates listed in Table) to examine associations of race with heart failure and hospital mortality among patients admitted with AF. Results: 2,244,036 AF hospitalizations (85% White, 6.7% Black, 5.0% Hispanic and 1.4% Asian/Pacific Islander) were analyzed from 2001-09. Hospitalization and outcome data by year are summarized in the table. Across all studied years, Blacks had lower AF hospitalization rates than Whites. Yet in all study years, mean LOS was longer for Blacks (range 4.2-4.6 days) than Whites (range 3.4-3.6 days). Blacks consistently had increased risk of in-hospital heart failure (Odds Ratio [OR] ranged from 1.5 [1.4, 1.7] to 1.7 [1.6, 1.9] across years) and death (OR, 1.5 [1.1, 2.1] to 2.3 [1.7, 3.0]) compared with Whites after adjustment for comorbidities. Conclusions: Although Blacks have lower incidence of hospitalizations for AF, they experience higher risk of heart failure, longer LOS, and greater mortality compared with Whites hospitalized with AF. Further public health investigation is warranted to examine the causes for disparities in outcomes among Blacks with AF and identify modifiable factors that may improve outcomes of Blacks with AF.

Craniotomy for Resection of Pediatric Brain Tumors in the United States, 1988 to 2000: Effects of Provider Caseloads and Progressive Centralization and Specialization of Care

Neurosurgery ◽  
2004 ◽  
Vol 54 (3) ◽  
pp. 553-565 ◽  
Author(s):  
Edward R. Smith ◽  
William E. Butler ◽  
Fred G. Barker
Keyword(s):  
United States ◽  
Brain Tumor ◽  
Mortality Rate ◽  
Multivariate Analyses ◽  
Pediatric Brain Tumor ◽  
High Volume ◽  
The United States ◽  
Mortality Rates ◽  
Discharge Disposition ◽  
Pediatric Brain

Abstract OBJECTIVE Large provider caseloads are associated with better patient outcomes after many complex surgical procedures. Mortality rates for pediatric brain tumor surgery in various practice settings have not been described. We used a national hospital discharge database to study the volume-outcome relationship for craniotomy performed for pediatric brain tumor resection, as well as trends toward centralization and specialization. METHODS We conducted a cross sectional and longitudinal cohort study using Nationwide Inpatient Sample data for 1988 to 2000 (Agency for Healthcare Research and Quality, Rockville, MD). Multivariate analyses adjusted for age, sex, geographic region, admission type (emergency, urgent, or elective), tumor location, and malignancy. RESULTS We analyzed 4712 admissions (329 hospitals, 480 identified surgeons) for pediatric brain tumor craniotomy. The in-hospital mortality rate was 1.6% and decreased from 2.7% (in 1988–1990) to 1.2% (in 1997–2000) during the study period. On a per-patient basis, median annual caseloads were 11 for hospitals (range, 1–59 cases) and 6 for surgeons (range, 1–32 cases). In multivariate analyses, the mortality rate was significantly lower at high-volume hospitals than at low-volume hospitals (odds ratio, 0.52 for 10-fold larger caseload; 95% confidence interval, 0.28–0.94; P = 0.03). The mortality rate was 2.3% at the lowest-volume-quartile hospitals (4 or fewer admissions annually), compared with 1.4% at the highest-volume-quartile hospitals (more than 20 admissions annually). There was a trend toward lower mortality rates after surgery performed by high-volume surgeons (P = 0.16). Adverse hospital discharge disposition was less likely to be associated with high-volume hospitals (P &lt; 0.001) and high-volume surgeons (P = 0.004). Length of stay and hospital charges were minimally related to hospital caseloads. Approximately 5% of United States hospitals performed pediatric brain tumor craniotomy during this period. The burden of care shifted toward large-caseload hospitals, teaching hospitals, and surgeons whose practices included predominantly pediatric patients, indicating progressive centralization and specialization. CONCLUSION Mortality and adverse discharge disposition rates for pediatric brain tumor craniotomy were lower when the procedure was performed at high-volume hospitals and by high-volume surgeons in the United States, from 1988 to 2000. There were trends toward lower mortality rates, greater centralization of surgery, and more specialization among surgeons during this period.

Autotransplants for Multiple Myeloma (MM) – An Update of the Arkansas Experience Since 1989 In Almost 4000 Patients with Special Emphasis on Third and Further Transplants.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1352-1352
Author(s):  
Bijay Nair ◽  
Elias J. Anaissie ◽  
Sarah Waheed ◽  
Yazan Alsayed ◽  
Rachael Sexton ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Outcome Data ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
Front Line ◽  
High Dose Therapy ◽  
Free Survival ◽  
Treatment Groups ◽  
Dose Therapy ◽  
Previously Treated

Abstract Abstract 1352 Background: The Arkansas program has emphasized high hematopoietic progenitor cell (HPC) yields since its inception in 1989, in order to enable further high-dose therapy for relapse, rescue patients from hematopoietic compromise due to extensive cumulative genotoxic or novel agent dosing, and provide a fall-back option in the case MDS develops. Here we are examining the overall outcome data among 3888 patients undergoing HPC-supported therapy since 1989. Patients and Methods: Patients were grouped according to whether they received front-line Total Therapy (TT) protocols (TT-P, n=1452), non-TT protocols for previously treated MM (non-TT-P, n= 1155) or non-protocol therapies (non-P, n=1281). Overall survival (OS) and event free survival (EFS) were measured from the 1st high-dose therapy (Tx-1) intervention and examined in the context of baseline variables present prior to Tx-1, the aforementioned 3 treatment groups, and intervals between successive Tx interventions. Results: OS/EFS from Tx-1 was longest with TT-P (5-yr estimates, 67%/52%) followed by non-TT-P (5-yr estimates, 43%/30%) and non-P (5-yr estimates, 36%/27%) (p<0.0001, p<0.0001). Among all 3888 patients, 2773 (71%) received Tx-2 including 2385 (86%) within 6 months of Tx-1; 405 (10%) received Tx-3 including 140 (35%) within 2yr of Tx-2; 58 (1.5%) received Tx-4 including 44 (76%) within 2yr form Tx-3; 12 (0.3%) received Tx-5 all within 2yr from Tx-4; and 3 patients had Tx-6. When examined in the context of the 3 different treatment groups, 1157/1231 (94%) of the TT-P group had Tx-2 within 6mo, 51/169 (30%) had Tx-3 within 2yr of Tx-2, 51/169 (30%) had Tx-4 within 2yr of Tx-3, and 7/7 (100%) had a Tx-5 within 2 yr of Tx-4. Among 1155 non-TT-P patients, 646/822 (79%) had Tx-2 within 6mo of Tx-1, 37/129 (29%) had Tx-3 within 2yr of Tx-2, 14/18 (78%) had Tx-4 within 3yr of Tx-3, and all 4 (100%) receiving Tx-5 had done so within 2yr of Tx-4. Among 1281 non-P patients, 582/720 (81%) had received Tx-2 within 6mo of Tx-1, 52/107 (49%) had received Tx-3 within 2yr of Tx-2, 7/10 (70%) had received Tx-4 within 2yr of Tx-3, and 1 patient received Tx-5 within 2yr of Tx-4. KM plots from Tx-3 were similar among the 3 treatment groups with median OS of 16mo for TT-P, 14mo for non-TT-P and 11mo for non-P (p=0.13); median EFS were 7, 8, and 6 months (P=0.17). Timely application within 6mo resulted in superior OS and EFS from Tx-2 (OS: 79 v 23 months, EFS: 48 v 14 months; both P<0.0001). Multivariate Cox analyses examining post-Tx EFS and OS revealed TT-P superiority from Tx-1 and Tx-2 over non-TT-P and non-P; Tx-2 within 6mo of Tx-1 provided superior post-Tx-2 EFS and OS; while benefit from Tx-3 was not apparent until at least 2yr had elapsed since Tx-2. CA within 1 year of Tx-1 adversely affected EFS and OS from Tx-1, Tx-2 and Tx-3. Other adverse baseline parameters included low albumin for EFS and OS post-Tx-1; and B2M >=3.5mg/L for EFS and OS post-Tx-1 and post-Tx-2. Conclusions: We confirm that front-line TT-P provides superior clinical outcomes in comparison with back-up/salvage non-TT-P and non-P Tx, emphasizing the benefit from planned upfront protocol therapy. Timely application of Tx-2 within 6 months of Tx-1 extended both EFS and OS from Tx-2, validating our concept of maximum tumor cyto-reduction and avoiding MM re-growth. Tx-3 was useful when applied beyond 2yr from Tx-2, in support of the notion that longer disease control prior to relapse favorably impacts subsequent salvage Tx. Disclosures: No relevant conflicts of interest to declare.

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.

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