Publications by authors named "Paul Graham Fisher"

46 Publications

50 Years Ago in TheJournal ofPediatrics: The Coincidence of Neuroblastoma and Acute Cerebellar Encephalopathy.

J Pediatr 2019 12;215:117

Departments of Neurology, Pediatrics, Neurosurgery, and Health Research and Policy, Stanford University and Lucile Packard Children's Hospital, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2019.05.059DOI Listing
December 2019

50 Years Ago in The Journal of Pediatrics: The Clinical Spectrum and Early Diagnosis of Dawson's Encephalitis.

J Pediatr 2019 10;213:102

Departments of Neurology, Pediatrics, and Human Biology, Stanford University and Lucile Packard Children's Hospital, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2019.03.049DOI Listing
October 2019

Long-term health and social function in adult survivors of paediatric astrocytoma: A report from the Childhood Cancer Survivor Study.

Eur J Cancer 2019 01 5;106:171-180. Epub 2018 Dec 5.

Division of Haematology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Division of Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Paediatrics, University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Health Policy, Management, and Evaluation, University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8, Canada.

Background: Although paediatric astrocytoma has an excellent 5-year survival rate, survivors remain at risk for morbidity and late mortality. This study aimed to estimate the risk of late mortality, chronic conditions, poor health status and social impairment in ageing paediatric astrocytoma survivors.

Methods: We longitudinally evaluated 1182 5-year astrocytoma survivors diagnosed between 1970 and 1986 and 4023 siblings enrolled in a retrospective cohort study. Kaplan-Meier estimates of late mortality and cumulative incidence of serious chronic conditions were estimated. Cox regression models provided hazard ratios (HRs) with 95% confidence intervals (CIs) for development of chronic conditions, and generalised linear models provided relative risks (RRs) of the poor health status and social outcomes.

Results: At 30 years from diagnosis, cumulative late mortality was 22.1% (CI 20.0-24.3%), primarily due to disease progression or recurrence. Compared with siblings, survivors were at increased risk of serious chronic conditions (HR 4.6, CI 3.8-5.5). Survivors reported higher rates of poor general health (RR 3.3, CI 2.8-3.8), poor mental health (RR 1.9, CI 1.7-2.1), functional impairment (RR 9.0, CI 7.7-10.5) and activity limitation (RR 3.6, CI 3.1-4.2) and lower rates of college graduation (RR 0.75, CI 0.69-0.82), marriage (RR 0.62, CI 0.58-0.66), employment (RR 0.75, CI 0.72-0.79) and household income ≥$40,000 (RR 0.68, CI 0.64-0.73). Even survivors without radiation exposure had elevated risk of chronic conditions, poor health status and social impairment compared with siblings.

Conclusions: Survivors of paediatric astrocytoma are at high risk for long-term complications of their disease and its treatment. They require lifelong monitoring for late effects.
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http://dx.doi.org/10.1016/j.ejca.2018.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647033PMC
January 2019

50 Years Ago in The Journal of Pediatrics: Significance of Leukemia Clusters.

J Pediatr 2018 07;198:130

Departments of Neurology, Pediatrics, and Human Biology Stanford University and Lucile Packard Children's Hospital Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2018.01.021DOI Listing
July 2018

It's Time for Pediatric Oncology to Grow Up.

J Clin Oncol 2018 04 9;36(10):933-934. Epub 2018 Feb 9.

Paul Graham Fisher, Stanford University, Palo Alto, CA.

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http://dx.doi.org/10.1200/JCO.2017.77.4307DOI Listing
April 2018

A New Approach to Rare Diseases of Children: The Undiagnosed Diseases Network.

J Pediatr 2018 05 11;196:291-297.e2. Epub 2018 Jan 11.

Stanford Center for Undiagnosed Diseases, Stanford University School of Medicine, Stanford, CA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA. Electronic address:

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http://dx.doi.org/10.1016/j.jpeds.2017.12.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924635PMC
May 2018

Long-term outcomes of primarily metastatic juvenile pilocytic astrocytoma in children.

J Neurosurg Pediatr 2018 01 10;21(1):49-53. Epub 2017 Nov 10.

1Division of Pediatric Neurosurgery, Department of Neurosurgery, and.

OBJECTIVE Primarily metastatic juvenile pilocytic astrocytoma (JPA) is rare, likely representing 2%-3% of all cases of JPA. Due to the rarity of primarily metastatic JPA, there is currently no standard treatment paradigm and the long-term outcomes are not fully known. The goal of this case series was to add to the current understanding of this disease process. METHODS The authors searched a comprehensive database of pediatric patients with brain and spinal cord tumors treated at Lucile Packard Children's Hospital from 1997 to 2016 and identified 5 patients with primarily metastatic JPA. A retrospective chart review was performed and details of the patients' treatment and clinical course were recorded for further analysis. RESULTS For the 5 patients with primarily metastatic JPA, the mean follow-up period was 12.3 years. All patients in our series had biopsies or subtotal resections and upfront treatment. Three patients were treated with chemotherapy alone, one was treated with chemotherapy and radiotherapy, and one was treated with radiotherapy alone. Four patients had stable disease after initial treatment, and one patient had multiple episodes of progressive disease but underwent successful salvage therapy and has had stable disease for 19 years. One patient died of an intracerebral hemorrhage 10 years following initial radiation treatment believed to be secondary to radiation vasculopathy. CONCLUSIONS Evaluation of the entire neuraxis should be performed in all instances of initial JPA diagnosis to properly assess for primarily metastatic disease. Many patients with primarily metastatic JPA will have stable disease after upfront treatment, although the higher rate of stable disease found in this series relative to other reports is likely secondary to the small sample size.
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http://dx.doi.org/10.3171/2017.7.PEDS17168DOI Listing
January 2018

50 Years Ago in The Journal of Pediatrics: The Normal Achilles Tendon Reflex Time in Children as Measured with the Photomograph.

J Pediatr 2017 05;184:44

Departments of Neurology, Pediatrics, and Human Biology Stanford University Lucile Packard Children's Hospital Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2016.12.004DOI Listing
May 2017

Getting Published: A Primer on Manuscript Writing and the Editorial Process.

J Pediatr 2017 06 21;185:241-244. Epub 2017 Mar 21.

Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA; Section of Infectious Diseases, St Christopher's Hospital for Children, Philadelphia, PA.

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http://dx.doi.org/10.1016/j.jpeds.2017.02.067DOI Listing
June 2017

An Investigation of Connections between Birth Defects and Cancers Arising in Adolescence and Very Young Adulthood.

J Pediatr 2017 06 20;185:237-240. Epub 2017 Mar 20.

Cancer Prevention Institute of California, Berkeley, CA; Department of Health Research and Policy, Stanford University, Palo Alto, CA.

This study investigated the relationship between birth defects and cancer in adolescents and very young adults using California's population-based registries. Although overall cancer risk was elevated among individuals with chromosomal birth defects, this was not observed in those with nonchromosomal birth defects, as was demonstrated previously in younger children.
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http://dx.doi.org/10.1016/j.jpeds.2017.02.057DOI Listing
June 2017

50 Years Ago in TheJournal ofPediatrics: Brain Scanning in Childhood.

J Pediatr 2016 09;176:113

Departments of Neurology, Pediatrics, and Human Biology, Stanford University, Lucile Packard Children's Hospital, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2016.03.049DOI Listing
September 2016

Phase I trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in pediatric patients with recurrent or progressive central nervous system tumors: A Pediatric Brain Tumor Consortium Study.

Neuro Oncol 2016 09 28;18(9):1319-25. Epub 2016 Mar 28.

Division of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).

Background: p53 is a promising target in human cancer. p28 is a cell-penetrating peptide that preferentially enters cancer cells and binds to both wild-type and mutant p53 protein, inhibiting COP1-mediated ubiquitination and proteasomal degradation. This results in increased levels of p53, which induces cell cycle arrest at G2/M. We conducted a phase I study to determine the maximum-tolerated dose (MTD) and describe the dose-limiting toxicities (DLTs) and pharmacokinetics (PKs) of p28 in children.

Methods: Children aged 3-21 years with recurrent or progressive central nervous system tumors were eligible. Intravenous p28 was administered 3 times weekly for 4 consecutive weeks of a 6-week cycle at 4.16 mg/kg/dose (the adult recommended phase II dose) using a rolling-6 study design. Expression status of p53 was characterized by immunohistochemistry, and serum PK parameters were established on the second dose.

Results: Of the 18 eligible patients enrolled in the study, 12 completed the DLT monitoring period and were evaluable for toxicity. p28 was well-tolerated; 7 participants received ≥2 courses, and the most common adverse event attributed to the drug was transient grade 1 infusion-related reaction. PK analysis revealed a profile similar to adults; however, an increased area under the curve was observed in pediatric patients. High p53 expression in tumor cell nuclei was observed in 6 of 12 available tissue samples. There were no objective responses; 2 participants remained stable on the study for >4 cycles.

Conclusions: This phase I study demonstrated that p28 is well-tolerated in children with recurrent CNS malignancies at the adult recommended phase II dose.
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http://dx.doi.org/10.1093/neuonc/now047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999001PMC
September 2016

50 Years Ago in The Journal of Pediatrics: Neonatal Myasthenia Gravis.

J Pediatr 2016 Apr;171:201

Departments of Neurology, Pediatrics, and Human Biology, Stanford University Lucile Packard Children's Hospital, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2015.10.053DOI Listing
April 2016

50 Years Ago in The Journal of Pediatrics: Hydrocephalus.

J Pediatr 2015 Dec;167(6):1286

Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2015.06.004DOI Listing
December 2015

50 Years Ago in The Journal of Pediatrics: Treatment of Hydrocephalus with Acetazolamide: Results in 15 Cases.

J Pediatr 2015 Jun;166(6):1369

Departments of Neurology, Pediatrics, and Human Biology, Stanford University, Lucile Packard Children's Hospital, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2014.12.043DOI Listing
June 2015

50 Years ago in the Journal of Pediatrics: brain tumors in early infancy--probably congenital in origin.

J Pediatr 2014 Nov 21;165(5):978. Epub 2014 Oct 21.

Departments of Neurology, Pediatrics, and Human Biology, Stanford University, Lucile Packard Children's Hospital, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2014.05.033DOI Listing
November 2014

Quality of life outcomes in proton and photon treated pediatric brain tumor survivors.

Radiother Oncol 2014 Oct 7;113(1):89-94. Epub 2014 Oct 7.

Center for Child and Adolescent Health Policy, Massachusetts General Hospital, Department of Pediatrics, Harvard Medical School, Boston, United States.

Background: Radiotherapy can impair Health Related Quality of Life (HRQoL) in survivors of childhood brain tumors, but proton radiotherapy (PRT) may mitigate this effect. This study compares HRQoL in PRT and photon (XRT) pediatric brain tumor survivors.

Methods: HRQoL data were prospectively collected on PRT-treated patients aged 2-18 treated at Massachusetts General Hospital (MGH). Cross-sectional PedsQL data from XRT treated Lucile Packard Children's Hospital (LPCH) patients provided the comparison data.

Results: Parent proxy HRQoL scores were reported at 3 years for the PRT cohort (PRT-C) and 2.9 years (median) for the XRT cohort (XRT-C). The total core HRQoL score for the PRT-C, XRT-C, and normative population differed from one another and was 75.9, 65.4 and 80.9 respectively (p=0.002; p=0.024; p<0.001). The PRT-C scored 10.3 and 10.5 points higher than the XRT-C in the physical (PhSD) and psychosocial (PsSD) summary domains of the total core score (TCS, p=0.015; p=0.001). The PRT-C showed no difference in PhSD compared with the normative population, but scored 6.1 points less in the PsSD (p=0.003). Compared to healthy controls, the XRT-C scored lower in all domains (p<0.001).

Conclusions: The HRQoL of pediatric brain tumor survivors treated with PRT compare favorably to those treated with XRT and similar to healthy controls in the PhSD.
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http://dx.doi.org/10.1016/j.radonc.2014.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288853PMC
October 2014

50 years ago in the Journal of Pediatrics: cerebrospinal fluid and blood electrolytes in 62 mentally defective infants and children.

J Pediatr 2014 Sep;165(3):515

Departments of Neurology, Pediatrics, and Human Biology, Stanford University Lucile Packard Children's Hospital, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2014.03.028DOI Listing
September 2014

50 years ago in the Journal of Pediatrics: an etiologic and diagnostic study of cerebral palsy.

J Pediatr 2014 Aug;165(2):273

Departments of Neurology, Pediatrics, and Human Biology, Stanford University, Lucile Packard Children's Hospital, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2014.02.059DOI Listing
August 2014

Pilot undergraduate course teaches students about chronic illness in children: an educational intervention study.

Educ Health (Abingdon) 2014 Jan-Apr;27(1):34-8

Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.

Background: Recent data question whether medical education adequately prepares physicians to care for the growing number of children with chronic medical conditions. We describe a 10-week course designed to provide undergraduate students with the knowledge and skills required to understand and care for children with chronic or catastrophic illnesses. The course presented the illness experience from the child's perspective and thus presented information in a manner that was efficient, conducive, and memorable. The curriculum was designed like a graduate-level seminar that included workshops, lectures, readings, writing, and lively discussions.

Methods: This is an educational intervention study that used survey data to assess changes in attitudes among and between participants completing this course versus students not exposed to this course. We used Somers' D test and Fisher's z-transformation to perform both pre- and post-nonparametric comparisons.

Results: Course participants were more likely to change their attitudes and agree that chronically ill children "feel comfortable talking with their peers about their condition" (P=0.003) and less likely to agree that these children "want to be treated differently," "want more sympathy," or "care less about romantic relationships" (P = 0.003, 0.002 and 0.02, respectively). Controls were more likely to continue to agree that chronically ill children "want to be treated differently" (P = 0.009) and "care less about romantic relationships" (P = 0.02), and less likely to agree that these children "talk openly" or "feel comfortable talking with their peers about their condition" (P = 0.04).

Conclusions: This classroom-based course serves as a feasible and cost-effective model for universities and medical schools to aid in improving student attitudes toward treating chronically ill children. The course provides the unique opportunity to learn directly from those who care for and those who have lived with chronic illness.
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http://dx.doi.org/10.4103/1357-6283.134305DOI Listing
April 2015

50 Years ago in The Journal of Pediatrics: the hypotonic infant.

J Pediatr 2014 Mar;164(3):565

Departments of Neurology, Pediatrics, and Human Biology, Stanford University, Lucile Packard Children's Hospital, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2013.09.052DOI Listing
March 2014

50 years ago in the Journal of Pediatrics: central nervous system complications of children with acute leukemia: an evaluation of treatment methods.

J Pediatr 2014 Jan;164(1):33

Departments of Neurology, Pediatrics, and Human Biology, Lucile Packard Children's Hospital, Stanford University, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2013.08.003DOI Listing
January 2014

50 Years ago in The Journal of Pediatrics: cigarettes, school children, and lung cancer.

J Pediatr 2013 Nov;163(5):1371

Departments of Neurology, Pediatrics, and Human Biology, Stanford University, Lucile Packard Children's Hospital, Palo Alto, California.

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http://dx.doi.org/10.1016/j.jpeds.2013.04.064DOI Listing
November 2013

Risk of subsequent cancer following a primary CNS tumor.

J Neurooncol 2013 Apr 8;112(2):285-95. Epub 2013 Feb 8.

Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.

Improvements in survival among central nervous system (CNS) tumor patients has made the risk of developing a subsequent cancer an important survivorship issue. Such a risk is likely influenced by histological and treatment differences between CNS tumors. De-identified data for 41,159 patients with a primary CNS tumor diagnosis from 9 Surveillance, Epidemiology and End Results (SEER) registries were used to calculate potential risk for subsequent cancer development. Relative risk (RR) and 95 % confidence interval (CI) of subsequent cancer was calculated using SEER*Stat 7.0.9, comparing observed number of subsequent cancers versus expected in the general United States population. For all CNS tumors studied, there were 830 subsequent cancers with a RR of 1.26 (95 % CI, 1.18-1.35). Subsequent cancers were observed in the CNS, digestive system, bones/joints, soft tissue, thyroid and leukemia. Radiotherapy was associated with an elevated risk, particularly in patients diagnosed with a medulloblastoma/primitive neuroectodermal tumor (MPNET). MPNET patients who received radiotherapy were at a significant risk for development of cancers of the digestive system, leukemia, bone/joint and cranial nerves. Glioblastoma multiforme patients who received radiotherapy were at lower risks for female breast and prostate cancers, though at an elevated risk for cancers of the thyroid and brain. Radiotherapy is associated with subsequent cancer development, particularly for sites within the field of radiation, though host susceptibility and post-treatment status underlie this risk. Variation in subsequent cancer risk among different CNS tumor histological subtypes indicate a complex interplay between risk factors in subsequent cancer development.
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http://dx.doi.org/10.1007/s11060-013-1063-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777246PMC
April 2013

50 years ago in The Journal of Pediatrics: Sensory neuropathy in a child.

J Pediatr 2012 Dec;161(6):1034

Department of Neurology, Stanford University, Palo Alto, California, USA.

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http://dx.doi.org/10.1016/j.jpeds.2012.06.061DOI Listing
December 2012

In memoriam: Donald W. Lewis, MD (1951-2012 ).

J Child Neurol 2012 Oct;27(10):1355-9

Departments of Pediatrics and Neurology, Eastern Virginia School of Medicine, Norfolk, VA, USA.

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http://dx.doi.org/10.1177/0883073812457464DOI Listing
October 2012

50 years ago in The Journal of Pediatrics: the surgical management of meningoceles and meningomyeloceles.

J Pediatr 2012 Oct;161(4):734

Departments of Neurosurgery and Neurology, Stanford University, Lucile Packard Children's Hospital, Palo Alto, California, USA.

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http://dx.doi.org/10.1016/j.jpeds.2012.05.019DOI Listing
October 2012

50 years ago in The Journal of Pediatrics: the effect of degree of hypoxia on the electroencephalogram in infants.

J Pediatr 2012 Oct;161(4):614

Division of Child Neurology, Stanford University Lucile Packard Children's Hospital, Palo Alto, California, USA.

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http://dx.doi.org/10.1016/j.jpeds.2012.05.018DOI Listing
October 2012

Concurrent cyclophosphamide and craniospinal radiotherapy for pediatric high-risk embryonal brain tumors.

J Neurooncol 2012 Nov 2;110(2):287-91. Epub 2012 Sep 2.

Division of Child Neurology, Department of Neurology, Stanford University, Palo Alto, CA 94304, USA.

Embryonal tumors are an aggressive subtype of high-grade, pediatric central nervous system (CNS) tumors often with dismal survival rates. The 5-year survival for highest-risk embryonal tumors may be as low as 10 %. We report feasibility and efficacy from our experience using intravenous (IV) cyclophosphamide concurrently with craniospinal radiation (CSI) in high-risk embryonal CNS tumors of childhood. Ten consecutive children (aged: 3.5-15.5 years, median: 10.2 years, six male) with high-risk embryonal tumors, including: large cell/anaplastic medulloblastoma (6), atypical teratoid rhabdoid tumor (1), and leptomeningeal primitive neuroectodermal tumor (3), were treated with IV cyclophosphamide 1 g/M(2) on days 1 and 2 of CSI. Following a median of 36 Gy CSI plus tumor boosts, adjuvant treatment consisted of 21 doses of oral etoposide (7) and alkylator based chemotherapy from five to eight cycles in all. Of the ten patients thus treated, six remain alive with no evidence of disease and four are deceased. Median survival was 3.3 years, with a 3-year progression-free survival of 50 % (5/10). Median follow-up was: 3.3 years (range: 5 months-12.9 years) in the five patients with progression, median time-to-progression was: 1.3 years (range: 1 month-3 years). Median follow-up in the patients without progression is 8.8 years (range: 3-12.9 years). Complications due to adjuvant chemotherapy were typical and included myelosupression (10), necessitating shortened duration of chemotherapy in three, and hemorrhagic cystitis (1). In high-risk embryonal CNS tumors, cyclophosphamide given concurrently with CSI is well tolerated. Early results suggest that a phase II trial is warranted.
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http://dx.doi.org/10.1007/s11060-012-0969-2DOI Listing
November 2012