2006 Feb 6; [Epub ahead of print]
Intratumoral hemorrhage among children with newly
diagnosed, diffuse brainstem glioma.
Department of Hematology-Oncology, St. Jude Children's Research Hospital,
BACKGROUND: Children with diffuse brainstem glioma (BSG) commonly undergo
novel therapies because their outcome is poor with radiation therapy (RT).
Although recent clinical trials using new biologic agents documented
intratumoral hemorrhage (IH) among several children with BSG, to the
authors' knowledge little is known regarding this phenomenon. In the current
study, the authors assessed the characteristics and estimated the cumulative
incidence of IH among children with BSG. METHODS: All available brain
imaging studies and medical records of 48 consecutive patients with newly
diagnosed BSG treated at the study institution over a 10-year interval
(1992-2002) were reviewed. Treatment was comprised of RT and various
regimens of conventional chemotherapy; none of these patients received
biologic agents. At the time of last follow-up, all patients had died of
tumor progression. RESULTS: The authors reviewed 319 imaging studies (251
magnetic resonance imaging scans and 68 computed tomography scans). IH was
present in 6.25% of patients at the time of diagnosis. The 6-month and
12-month cumulative incidence estimates of IH regardless of the associated
symptoms were 15.5% +/- 5.5% and 24.4% +/- 6.5%, respectively. The same
estimates for symptomatic cases were 8.9% +/- 4% and 17.8% +/- 6%,
respectively. All cases of IH at the time of diagnosis and 78% of
symptomatic cases that developed after diagnosis were located in necrotic
areas. CONCLUSIONS: Although IH is uncommon at the time of diagnosis,
symptomatic IH may occur among nearly 20% of children after the diagnosis of
BSG. The uniform occurrence of IH among patients treated with various
chemotherapeutic regimens and its association with necrotic areas suggests
that tumor biology plays a significant role in this event. Cancer 2006. (c)
2006 American Cancer Society.
PMID: 16463390 [PubMed - as supplied by publisher]
2005 Dec 1;104(11):2473-6.
Salvage temozolomide for prior temozolomide responders.
Department of Medical Oncology, Bellaria Hospital, Bologna, Italy.
BACKGROUND: Temozolomide (TMZ) often is used as adjuvant or first-line
therapy for patients with glioma. Because of potential hematologic
complications, it usually is discontinued after 12-18 cycles, even in
responders. Subsequent salvage therapies are reported to have limited
efficacy at the time of disease recurrence. In the current study, the
authors assessed the outcome and complications of reusing TMZ at the time of
disease recurrence in patients who previously responded to treatment.
METHODS: A retrospective review of patients with recurrent/progressive
glioma who had a history of response to TMZ and were treated with the same
agent at the time of disease recurrence was conducted. RESULTS: Fourteen
patients were identified (8 men and 6 women). The median age of the patients
was 56 years (range, 25-67 yrs) at the time of diagnosis; 9 patients had
glioblastoma, 3 had anaplastic astrocytoma, and 2 patients had low-grade
oligodendroglioma. No patient developed disease progression while receiving
the initial TMZ treatment. At the time of the initial disease recurrence, 13
patients were readministered TMZ. One patient received TMZ at the time of
second disease recurrence. All patients were assessed for radiographic
response. Objective response or stable disease was achieved in 6 patients
(43%; 95% confidence interval [95% CI], 21-67%) and the 6-month
progression-free survival was 36% (95% CI, 16-61%). CONCLUSIONS: TMZ was
found to be well tolerated and effective in this setting, suggesting that
repeat use of TMZ in previous responders warrants further investigation.
PMID: 16270316 [PubMed - indexed for MEDLINE]
2005 Dec 1;104(11):2466-72.
Trends in survival from primary central nervous system
lymphoma, 1975-1999: a population-based analysis.
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering
Cancer Center, New York, New York 10021, USA.
BACKGROUND: The age-adjusted incidence of primary central nervous system
lymphoma (PCNSL) has increased since the 1970s, and treatment for this
disease has evolved considerably. The objective of this study was to examine
time trends in overall survival and disease-specific mortality in a
population-based cohort of patients with PCNSL. METHODS: We identified
patients diagnosed with PCNSL from 1975-1999 in the Surveillance,
Epidemiology, and End Results (SEER) cancer registries. To assess time
trends, year of diagnosis was classified in 5-year intervals: 1975-1980,
1981-1985, 1986-1990, 1991-1995, and 1996-1999. Overall survival
distributions were estimated via Kaplan-Meier methodology and a competing
risk analysis was used to assess PCNSL-specific mortality. We used
information on underlying cause of death to distinguish likely
immunocompetent patients from those whose PCNSL was related to human
immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). We
also examined survival stratified by age at diagnosis. RESULTS: From
1975-1999, 2462 patients were diagnosed with PCNSL in SEER. Median survival
was 4 months (95% CI 4, 5) for the entire cohort and 9 months (95% CI 8, 11)
for the immunocompetent cohort (n = 1565). In the immunocompetent cohort,
965 of 1323 (73%) deaths were attributed to PCNSL. No significant time trend
was observed in either overall or PCNSL-specific survival. CONCLUSIONS:
Overall survival for patients with PCNSL has not improved consistently in
the past three decades despite important therapeutic advances during this
time. Although results from clinical trials suggest progress in the
treatment of PCNSL, survival improvements are not reflected in this
PMID: 16240449 [PubMed - indexed for MEDLINE]
2005 Dec 1;104(11):2457-65.
Precision radiotherapy for hemangiopericytomas of the
central nervous system.
Department of Radiation Oncology, University of Heidelberg, Heidelberg,
BACKGROUND: Radiotherapy (RT) plays a major role in the management of
hemangiopericytomas (HAP). The present analysis evaluates the role of
precision RT in the management of HAP of the central nervous system (CNS)
and represents one of the largest series of HAP treated with RT that can be
found in the literature. METHODS: Of 37 consecutive patients with
histologically confirmed HAP who were treated at the institution between
1984 and 2004, the majority, 25 tumors, was localized within the skull base
(n = 25) and 4 tumors were localized at the spine. In 25 patients,
high-precision RT was delivered as fractionated stereotactic RT or intensity
modulated RT. Median age at primary diagnosis was 40.5 years (range, 10-77
yrs). After primary diagnosis, surgical resection was performed in 23
patients. A median total dose of 54 Gy was delivered in a fractionation of 5
x 1.8-2 Gy per week. The median planning target volume was 58.2 mL (range,
10-412 mL). The median follow-up time was 34 months (range, 3-166 mos).
RESULTS: Radiotherapy was well tolerated by all patients. Seventeen patients
of this series remain alive. Overall survival rates at 5 and 10 years are
100% and 64%, respectively. Actuarial survival rates after RT were 85% and
69% at 3 and 5 years, respectively. Progression-free survival after RT 80%
and 61% at 3 and 5 years, respectively. CONCLUSION: High-precision RT is an
effective and safe treatment modality for patients with HAP of the CNS and
the spine and achieves highly acceptable tumor control, while sparing normal
PMID: 16222690 [PubMed - indexed for MEDLINE]
Malignant meningioma as a second malignancy after therapy
for acute lymphatic leukemia without cranial radiation.
Department of Neurosurgery, University Medical School Essen, Hufelandstrasse
55, 45122, Essen, Germany, firstname.lastname@example.org.
RATIONALE: Meningiomas in the pediatric age group are very rare tumors,
comprising about 1-4.2% of all primary pediatric intracranial tumors. CASE
REPORT: We present a 17-year-old patient who suffered from an
intraventricular malignant meningioma. At the age of 2 years, acute
lymphatic leukemia (common ALL [cALL]) was diagnosed and successfully
treated with chemotherapy. There was no cranial radiation therapy. In
December 2001, 13 years after diagnosis of cALL, he complained of headache,
vomiting, and walking difficulties. Magnetic resonance imaging showed an
enhancing mass with cystic components in the trigone of the right lateral
ventricle. The tumor was removed completely. Histological diagnosis revealed
a malignant papillary meningioma. After removal of a recurrent meningioma 16
months later, he received local radiotherapy. CONCLUSION: Pathogenetic
mechanisms, treatment options, and prognosis of meningiomas and secondary
malignancies of this age group are discussed.
PMID: 16456690 [PubMed - in process]
Phase 1 trial of gefitinib plus sirolimus in adults with
recurrent malignant glioma.
JE 2nd, Dowell
Authors' Affiliations: AstraZeneca Pharmaceuticals, Wilmington, Delaware;
Departments of Surgery, Pediatrics, Pathology, Radiology, Medicine, and
Cancer Center Biostatistics, Duke University Medical Center, Durham, North
PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting
toxicity (DLT) of gefitinib, a receptor tyrosine kinase inhibitor of the
epidermal growth factor receptor, plus sirolimus, an inhibitor of the
mammalian target of rapamycin, among patients with recurrent malignant
glioma.Patients and Methods: Gefitinib and sirolimus were administered on a
continuous daily dosing schedule at dose levels that were escalated in
successive cohorts of malignant glioma patients at any recurrence who were
stratified based on concurrent use of CYP3A-inducing anticonvulsants
[enzyme-inducing antiepileptic drugs, (EIAED)]. Pharmacokinetic and archival
tumor biomarker data were also assessed.RESULTS: Thirty-four patients with
progressive disease after prior radiation therapy and chemotherapy were
enrolled, including 29 (85%) with glioblastoma multiforme and 5 (15%) with
anaplastic glioma. The MTD was 500 mg of gefitinib plus 5 mg of sirolimus
for patients not on EIAEDs and 1,000 mg of gefitinib plus 10 mg of sirolimus
for patients on EIAEDs. DLTs included mucositis, diarrhea, rash,
thrombocytopenia, and hypertriglyceridemia. Gefitinib exposure was not
affected by sirolimus administration but was significantly lowered by
concurrent EIAED use. Two patients (6%) achieved a partial radiographic
response, and 13 patients (38%) achieved stable disease.CONCLUSION: We show
that gefitinib plus sirolimus can be safely coadministered on a continuous,
daily dosing schedule, and established the recommended dose level of these
agents in combination for future phase 2 clinical trials.
PMID: 16467100 [PubMed - in process]
The Cytogenetic Relationship between Primary and
Recurrent Meningiomas Points to the Need for New Treatment Strategies in
Cases at High Risk of Relapse.
Authors' Affiliations: Unidad de Investigacion, Neurosurgery Service, and
Department of Pathology, Hospital Universitario de Salamanca and Centro de
Investigacion del Cancer, Cytometry General Service and Department of
Medicine, University of Salamanca, Salamanca, Spain.
PURPOSE: Recurrence is the major factor influencing the clinical outcome of
meningioma patients although the exact relationship between primary and
recurrent tumors still needs to be clarified. The aim of the present study
is to analyze the cytogenetic relationship between primary and subsequent
recurrent meningiomas developed within the same individual.EXPERIMENTAL
DESIGN: Multicolor interphase fluorescence in situ hybridization was done
for the identification of numerical abnormalities of 12 chromosomes in
single-cell suspensions from 59 tumor samples corresponding to 25 recurrent
meningioma patients. In 47 of these tumors, the distribution of different
tumor cell clones was also analyzed in paraffin-embedded tissue sections. In
parallel, 132 nonrecurrent cases were also studied.RESULTS: Most recurrent
meningiomas showed complex cytogenetic aberrations associated with two or
more tumor cell clones in the first tumor analyzed. Interestingly, in most
individuals (74%), exactly the same tumor cell clones identified in the
initial lesion were also detected in the subsequent recurrent tumor samples.
In the recurrent tumor samples of the remaining cases (26%), we observed
tumor cell clones related to those detected in the initial lesion but which
had acquired one or more additional chromosome aberrations associated with
either the emergence of new clones with more complex karyotypes or the
disappearance of the most representative clones from the primary lesions.
Multivariate analysis of prognostic factors showed that the Maillo et al.
prognostic score, based on age of patient, tumor grade, and monosomy 14,
together with tumor size was the best combination of independent variables
for predicting tumor recurrence at diagnosis.CONCLUSION: Overall, our
results indicate that the development of recurrent meningiomas after
complete tumor resection is usually due to regrowth of the primary tumor and
rarely to the emergence of an unrelated meningioma, underlining the need for
alternative treatment strategies in cases at high risk of relapse,
particularly those with a high Maillo et al. prognostic score and larger
PMID: 16467088 [PubMed - as supplied by publisher]
Protein p62 common in invaginations in benign meningiomas--a
possible predictor of malignancy.
Department of Pathology, Kuopio University Hospital, Finland. email@example.com
OBJECTIVE: It is known that p62 is a cytosolic conserved protein that binds
non-covalently to ubiquitin. Expression of p62 has been seen in inclusions
in neoplasias like hepatocellular and breast carcinomas but also in neuronal
inclusions of degenerative brain disorders. Dysfunction of ubiquitin system
leads to presence of p53 in cells suggested to be a predictor of future
recurrence of meningioma. MATERIAL: The study material included 45 benign
meningiomas of postmenopausal women operated in Kuopio University Hospital
between 1994 and 2002. METHODS: Patterns of p62 immunopositivity in
meningiomas was evaluated and the results were correlated to clinical and
histological parameters. RESULTS: Constant p62 labeling in at least each
field measuring 1 mm in diameter was detected consisting of 5 different
patterns. The most common labeling was seen in nuclear invaginations either
as grains or homogenous labeling, followed by Marinesco like nuclear
inclusions or rode like inclusions outside the invagination. In some cases
cytoplasmic granular staining was seen. No correlation between different p62
patterns or extent of p62 expression, histological subtypes or proliferation
marker Ki-67 was noted. CONCLUSION: Our results indicate that in the benign
not recurrent meningiomas, signs of functioning proteosomal system, can be
detected using the p62 labeling. The function of proteosomal system in
malignant and specifically invasive meningiomas needs to be further
PMID: 16465773 [PubMed - in process]
Ciliated craniopharyngioma may arise from Rathke cleft
Department of Neurosurgery, Kitasato University School of Medicine,
OBJECTIVE: The histogenesis of craniopharyngioma is not fully understood. We
encountered a ciliated craniopharyngioma, the details of which may shed
light on the histogeny of craniopharyngioma in general. PATIENT: A
74-year-old man presented with visual disturbance. Computed tomography
showed an intra-suprasellar cyst including a solid tumor. Transsphenoidal
surgery was performed. During surgery, the cyst was found to contain mucoid
milky-white fluid and a solid tumor 1 cm in diameter. Histologically, the
tumor was shown to be a papillary type craniopharyngioma with foci of
ciliated columnar epithelial cells. Ciliated craniopharyngioma was
diagnosed. CONCLUSION: Our findings in this case together with findings in
other reported cases suggest that the basal cells of Rathke cleft cyst
transform to papillary type craniopharyngioma after squamous metaplasia,
explaining the presence of the cilia and goblet cells.
PMID: 16465771 [PubMed - in process]
Bayesian methods for early detection of changes in
childhood cancer incidence: trends for acute lymphoblastic leukaemia are
consistent with an infectious aetiology.
Childhood Cancer Registry of Piedmont, Cancer Epidemiology Unit, CPO
Piemonte, CeRMS, S. Giovanni Hospital and University of Turin, Turin, Italy.
Published data on time trends in the incidence of childhood leukaemia show
inconsistent patterns, with some studies showing increases and others
showing relatively stable incidence rates. Data on time trends in childhood
cancer incidence from the Childhood Cancer Registry of Piedmont, Italy were
analysed using two different approaches: standard Poisson regression and a
Bayesian regression approach including an autoregressive component. Our
focus was on acute lymphoblastic leukaemia (ALL), since this is hypothesised
to have an infectious aetiology, but for purposes of comparison we also
conducted similar analyses for selected other childhood cancer sites (acute
non-lymphoblastic leukaemia (AnLL), central nervous system (CNS) tumours and
neuroblastoma (NB)). The two models fitted the data equally well, but led to
different interpretations of the time trends. The first produced
ever-increasing rates, while the latter produced non-monotonic patterns,
particularly for ALL, which showed evidence of a cyclical pattern. The
Bayesian analysis produced findings that are consistent with the hypothesis
of an infectious aetiology for ALL, but not for AnLL or for solid tumours
(CNS and NB). Although sudden changes in time trends should be interpreted
with caution, the results of the Bayesian approach are consistent with
current knowledge of the natural history of childhood ALL, including a short
latency time and the postulated infectious aetiology of the disease.
PMID: 16324832 [PubMed - indexed for MEDLINE]
Dramatic synergistic anticancer effect of clinically
achievable doses of lovastatin and troglitazone.
Division of Cancer Research, National Health Research Institutes, Taipei,
Lovastatin (an HMG-CoA reductase inhibitor) and troglitazone (a PPAR-gamma
agonist) have been intensively studied prospectively for their application
in cancer treatment. However, clinical trials of lovastatin or troglitazone
in cancer treatment resulted in only limited responses. To improve their
efficacy, lovastatin and troglitazone have, respectively, been tried to
combine with other anticancer agents with varied outcomes. In our study, we
found a dramatic synergism between lovastatin and troglitazone in anticancer
at clinically achievable concentrations. This synergism was found in far
majority of cell lines tested including DBTRG 05 MG (glioblastoma) and CL1-0
(lung). This amazing synergism was accompanied by synergistic modulation of
E2F-1 and p27(Kip1), which were reported to mediate the anticancer
activities of lovastatin and troglitazone, respectively, and other cell
cycle regulating proteins such as CDK2, cyclin A and RB phosphorylation
status. With this dramatic combination effect of lovastatin and troglitazone,
a promising regimen of cancer therapy may be materialized in the future.
Copyright 2005 Wiley-Liss, Inc.
PMID: 16094629 [PubMed - indexed for MEDLINE]
Intensity-modulated radiotherapy in high-grade gliomas:
Clinical and dosimetric results.
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center,
New York, NY, USA.
Purpose: To report preliminary clinical and dosimetric data from
intensity-modulated radiotherapy (IMRT) for malignant gliomas. Methods and
Materials: Fifty-eight consecutive high-grade gliomas were treated between
January 2001 and December 2003 with dynamic multileaf collimator IMRT,
planned with the inverse approach. A dose of 59.4-60 Gy at 1.8-2.0 Gy per
fraction was delivered. A total of three to five noncoplanar beams were used
to cover at least 95% of the target volume with the prescription isodose
line. Glioblastoma accounted for 70% of the cases, and anaplastic
oligodendroglioma histology (pure or mixed) was seen in 15% of the cases.
Surgery consisted of biopsy only in 26% of the patients, and 80% received
adjuvant chemotherapy. Results: With a median follow-up of 24 months, 85% of
the patients have relapsed. The median progression-free survival time for
anaplastic astrocytoma and glioblastoma histology was 5.6 and 2.5 months,
respectively. The overall survival time for anaplastic glioma and
glioblastoma was 36 and 9 months, respectively. Ninety-six percent of the
recurrences were local. No Grade IV/V late neurologic toxicities were noted.
A comparative dosimetric analysis revealed that regardless of tumor
location, IMRT did not significantly improve target coverage compared with
three-dimensional planning. However, IMRT resulted in a decreased maximum
dose to the spinal cord, optic nerves, and eye by 16%, 7%, and 15%,
respectively, owing to its improved dose conformality. The mean brainstem
dose also decreased by 7%. Intensity-modulated radiotherapy delivered with a
limited number of beams did not result in an increased dose to the normal
brain. Conclusions: It is unlikely that IMRT will improve local control in
high-grade gliomas without further dose escalation compared with
conventional radiotherapy. However, it might result in decreased late
toxicities associated with radiotherapy.
PMID: 16458777 [PubMed - in process]
Impact of cranial radiotherapy on central nervous system
prophylaxis in children and adolescents with central nervous system-negative
stage III or IV lymphoblastic lymphoma.
Department of Pediatric Hematology and Oncology, Children's University
Hospital, Giessen, Germany.
PURPOSE: In the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Munster (NHL-BFM) 95
trial, we tested, against the historical control of the combined trials
NHL-BFM90 and NHL-BFM86, whether prophylactic cranial radiotherapy (PCRT)
can be omitted for CNS-negative patients with stage III or IV lymphoblastic
lymphoma (LBL) with sufficient early response. PATIENTS AND METHODS: Apart
from the removal of PCRT in NHL-BFM95, the chemotherapy of the three trials
was identical except for the amount of l-asparaginase and daunorubicin
during induction. The therapy in NHL-BFM95 was accepted to be noninferior
when compared with trials NHL-BFM90/86 if the lower limit of the one-sided
95% CI for the difference in the 2-year probability of event-free-survival (pEFS)
between target patients of NHL-BFM95 and the historical controls of
NHL-BFM90/86 did not exceed -14%. The target patient group consisted of
stage III and IV patients who were CNS negative and responded well to
induction therapy. RESULTS: The number of target patients was 156 in
NHL-BFM95 (median age, 8.6 years; range, 0.2 to 19.5 years) and 163 in
NHL-BFM90/86 (median age, 8.4 years; range, 0.6 to 16.6 years). For the
target group, the pEFS rates at 2 and 5 years were 86% +/- 3% and 82% +/-
3%, respectively, in NHL-BFM95 (median follow-up time, 5.1 years; range, 2.1
to 9.1 years) compared with 91% +/- 2% and 88% +/- 3%, respectively in
NHL-BFM90/86 (median follow-up time, 10.7 years; range, 5 to 15.4 years).
The lower limit of the one-sided 95% CI for the difference in pEFS was -11%
at 2 years and -13% at 5 years. In NHL-BFM95, one isolated and two combined
CNS relapses occurred compared with one combined CNS relapse in
NHL-BFM90/86. Five-year disease-free-survival rate was 88% +/- 3% in
NHL-BFM95 compared with 91% +/- 2% in NHL-BFM90/86. CONCLUSION: For
CNS-negative patients with stage III or IV LBL and sufficient response to
induction therapy, treatment without PCRT may be noninferior to treatment
PMID: 16421426 [PubMed - indexed for MEDLINE]
Risk factors and therapy for isolated central nervous
system relapse of pediatric acute myeloid leukemia.
Division of Hematology/Oncology, Children's Hospital of Eastern Ontario,
Ottawa, Ontario, Canada. firstname.lastname@example.org
PURPOSE: CNS relapse of pediatric acute myeloid leukemia (AML) is an
infrequent occurrence. This review examines the risk factors and therapy
used for patients with an isolated CNS relapse. PATIENTS AND METHODS:
Records of 886 patients with de novo AML were reviewed, and patients who
entered remission at the end of one course of therapy and developed an
isolated CNS relapse as their first event were analyzed (n = 690). RESULTS:
Thirty-three patients developed an isolated CNS relapse. Factors at
diagnosis significantly associated with an isolated CNS relapse, compared
with no CNS relapse, included age 0 to 2 years (70% v 27%, respectively; P
< .001), enlarged liver (79% v 39%, respectively; P < .001) or spleen
(79% v 39%, respectively; P < .001) at diagnosis, CNS disease at
diagnosis (33% v 9%, respectively; P < .001), median WBC count (79.2 v
19.3 x 10(3) microL, respectively; P < .001), French-American-British M5
morphology (45% v 15%, respectively; P < .001), and chromosome 11
abnormalities (44% v 18%, respectively; P = .022). Treatment of the isolated
CNS relapse varied from local therapy with intrathecal chemotherapy and/or
radiation therapy to systemic therapy with chemotherapy with or without bone
marrow transplantation. Survival rate in the patients treated with local
therapy was only 31.5% compared with 21.4% in patients treated with systemic
therapy. The 8-year overall survival for patients after an isolated CNS
relapse was similar to patients after a bone marrow relapse (26% +/- 16% v
21% +/- 5%, respectively). CONCLUSION: Significant predictors for isolated
CNS relapse were identified. This study demonstrated that there may be no
benefit to systemic therapy versus CNS-directed therapy in outcome. The data
support CNS-directed therapy to treat isolated CNS relapse.
PMID: 16361619 [PubMed - indexed for MEDLINE]
Clinical Cancer Advances 2005: major research advances in
cancer treatment, prevention, and screening--a report from the American
Society of Clinical Oncology.
Society of Clinical Oncology.
American Society of Clinical Oncology, Alexandria, VA 22314, USA.
This year, for the first time, the American Society of Clinical Oncology (ASCO)
is publishing Clinical Cancer Advances 2005: Major Research Advances in
Cancer Treatment, Prevention, and Screening, an annual review of the most
significant clinical research presented or published over the past year
across all cancer types. ASCO embarked on this project to provide the
public, patients, policymakers, and physicians with an accessible summary of
the year's most important research advances. While not intended to serve as
a comprehensive review, this report provides a year-end snapshot of research
that will have the greatest impact on patient care. As you will read, there
is much good news from the front lines of cancer research. These pages
report on new chemotherapy regimens that sharply reduce the risk of
recurrence for very common cancers; the "coming of age" of
targeted cancer therapies; promising studies of drugs to prevent cancer; and
improvements in quality of life for people living with the disease, among
many other advances. Survival rates for cancer are on the rise, increasing
from 50% to 64% over the last 30 years. Cancer still exacts an enormous
toll, however. Nearly 1.4 million Americans will be diagnosed this year, and
some 570,000 will die of the disease. Clearly, more research is needed to
find effective therapies for the most stubborn cancer types and stages. We
need to know more about the long-term effects of newer, more targeted cancer
therapies, some of which need to be taken over long periods of time. And we
need to devote far greater attention to tracking and improving the care of
the nearly 10 million cancer survivors in the United States today. Despite
these and other challenges, the message of this report is one of hope.
Through the dedicated, persistent pursuit of clinical research and
participation in clinical trials by people with cancer, we steadily uncover
new and better ways of treating, diagnosing, and preventing a disease that
touches the lives of so many. I want to thank the Editorial Board members,
the Specialty Editors, and the ASCO Cancer Communications Committee for
their dedicated work to develop this report, and I hope you find it useful.
PMID: 16326753 [PubMed - indexed for MEDLINE]
Efaproxiral: should we hold our breath?
PMID: 16314614 [PubMed - indexed for MEDLINE]
OTX1 and OTX2 Expression Correlates With the
Clinicopathologic Classification of Medulloblastomas.
Haas T, Oussoren
Sluis P, Pietsch
From the Departments of Human Genetics (TdH, PvS, RV, MK), NeuroGenetics (EO,
FB), and Neuropathology (DT), Academic Medical Center, Amsterdam, the
Netherlands; the Departments of Pathology (WG) and Oncology, Children's
Memorial Health Institute, Warsaw, Poland; the Institute of Pathology (MP),
Medical Faculty (MP, LZ-Z), University of Ljubljana, Ljubljana, Slovenia;
the IST- National Institute for Cancer Research and the Department of
Oncology, Biology, and Genetics (MP, GC), University of Genoa, Genoa, Italy;
and the Department of Neuropathology (OW, TP), University of Bonn, Bonn,
OTX1 and OTX2 are transcription factors with an essential role in the
development of the cerebellum. We previously described a high OTX2
expression in medulloblastoma. Here, we analyzed amplification and mRNA
expression of OTX1 and OTX2 in a series of human medulloblastomas. In
addition, OTX2 protein expression was analyzed on tissue arrays. The OTX2
gene was amplified in the medulloblastoma cell line D425 and mRNA and
protein data showed expression in 114 of 152 medulloblastomas (75%), but not
in postnatal cerebellum. Northern blot (n = 10) and reverse
transcriptase-polymerase chain reaction (n = 45) analyses demonstrated that
virtually all medulloblastomas expressed OTX1, OTX2, or both. OTX2 mRNA
expression correlated with a classic medulloblastoma histology (29 of 34
cases), whereas expression of OTX1 mRNA only was correlated with a nodular/desmoplastic
histology (9 of 11 cases). Immunohistochemical analysis of a series of
classic medulloblastomas detected OTX2 protein expression in 83 of 107 (78%)
cases. The OTX2-positive tumors of this series were preferentially localized
in the vermis of the cerebellum, whereas OTX2-negative tumors more
frequently occurred in the hemispheres of the cerebellum. In addition,
OTX2-positive tumors were mainly found in children, but OTX2-negative tumors
occurred in 2 patient groups: very young patients (<5 years) and adults
(>20 years). Nodular/desmoplastic medulloblastomas are thought to arise
from the external granular layer (EGL). However, it is unclear whether
classic medulloblastomas also originate from the EGL or from the ventricular
matrix. Analysis of human fetal brain showed OTX2 protein expression in a
small number of presumptive neuronal precursor cells of the EGL, but not in
precursor cells of the ventricular matrix. Combined with data from rodents,
our results therefore suggest that both nodular/desmoplastic and at least
part of the classic medulloblastomas originate from cells of the EGL, albeit
from different regions.
PMID: 16462208 [PubMed - as supplied by publisher]
TRAIL-Induced Apoptosis in U-1242 MG Glioma Cells.
From the Department of Pathology, The Ohio State University, Columbus, Ohio.
ABSTRACT: Tumor necrosis factor related apoptosis-inducing ligand (TRAIL)
induces apoptosis in U-1242 MG cells. To investigate the molecular events
involved in this process, we studied the effects of TRAIL on the
localization within membrane fractions of molecules critical to the
extrinsic apoptotic pathway. We report here that death receptor-5 (DR5),
tumor necrosis factor receptor-1 (TNF-R1), and Fas receptor (FasR) are all
located in the caveolin-1-enriched membrane fractions, and TRAIL caused the
translocation of DR5, FasR, and TNF-R1 to the caveolar fractions. Caspase-8
is mainly located outside of caveolae, but TRAIL caused it to redistribute
to the caveolin-1-enriched fractions where it was cleaved. Within 6 hours,
the cleaved caspase-8 appeared in the high-density, noncaveolin fractions.
Using confocal microscopy, we found that DR5, caspase-8, and caveolin-1
became progressively concentrated in blebs of plasmalemma as they formed in
response to TRAIL. Our results provide the first evidence for the caveolar
localization of TNF-R1 and DR5 and the coordinated redistribution among
membrane fractions of several death receptors in response to TRAIL. We
propose that the coordinated movement of these molecules among membrane
compartments is probably an important component of the mechanisms regulating
and initiating the extrinsic apoptotic pathway in human glioma cells.
PMID: 16462206 [PubMed - in process]
Risk of Ventriculoperitoneal Shunt Infections due to
Gastrostomy Feeding Tube Insertion in Pediatric Patients with Brain Tumors.
Divisions of Pediatric Neuro-Oncology, Image-Guided Therapy and Neurosurgery,
Hospital for Sick Children, University of Toronto, Toronto, Canada.
Objective: To determine the risk of ventriculoperitoneal (VP) shunt
infections after percutaneous retrograde gastrostomy feeding tube (GT)
placement in children with brain tumors. Patients and Methods: All children
(age 0-18 years) with primary brain tumors diagnosed and treated at the
Hospital for Sick Children, Toronto, Canada, were subjected to a
retrospective analysis. Two groups were identified: the study group included
children with a VP shunt and a GT; the control group included children with
VP shunts only. Each study patient was matched with 2 controls to compare
the rate of infections (cohort comparative study). Results: There were 1,167
children diagnosed and treated with primary brain tumors during the study
period (1988-2003); 174 (15%) had a VP shunt and 23 (2%) children had both,
a VP shunt and a GT. In the study group (n = 17), GTs were inserted at a
median time of 80 days (range 6-204 days) after VP shunts. VP shunt
infection rate was 23.5% (4/17) compared to 8.8% (3/34) in the control group
(OR 3.18; 95% CI 0.622-16.54, p = 0.16). Three (75%) of the infection
episodes in the study group presented with an ascending VP shunt infection
directly related to the GT insertion or manipulation in the first 6 weeks.
These GTs were inserted at 13, 47 and 49 days after VP shunt insertion.
Conclusion: Placement of percutaneous retrograde GTs, in the acute phase, in
children with brain tumors and VP shunts may increase the risk of ascending
meningitis especially if there are early GT-related complications. Copyright
(c) 2006 S. Karger AG, Basel.
PMID: 16465078 [PubMed - in process]
Stereotactic radiation therapy with chemotherapy in the
management of recurrent medulloblastomas.
Department of Neurosurgery, Faculty of Medicine, Saga University, Saga,
Medulloblastomas are highly lethal tumors when they recur. Very few patients
survive with conventional treatment. This report documents the preliminary
study results of a treatment for recurrent medulloblastomas consisting of
stereotactic radiation therapy (SRT) with chemotherapy. Four patients had
local recurrence without apparent metastases and 8 patients had metastases
with or without local recurrence. Twelve patients with 18 lesions underwent
SRT as a single session (n = 8) or in a hypofractionated manner (n = 10)
using a gamma knife or modified linear accelerator. All patients then
received systemic chemotherapy. Five patients were treated with one to two
sequential courses of high-dose chemotherapy with peripheral blood stem cell
transplantation. The reduction in tumor size after SRT was often remarkable.
Fourteen of 18 lesions treated disappeared 1-6 months after SRT. Two of 4
patients who had local recurrences without apparent metastasis at the time
of SRT are alive without evidence of disease 70 and 72 months after SRT,
respectively. In contrast, all 8 patients with metastasis had new lesions
either in the spinal canal or on the surface of the brain outside the target
area of SRT. Median progression-free survival and overall survival from the
time of SRT were 9 and 19 months, respectively. The Kaplan-Meier estimates
of PFS and overall survival at 3 years were 17 and 25%, respectively. One
patient had brainstem edema after SRT causing bulbar palsy and quadriparesis.
One patient died of toxicity of chemotherapy. Our experience suggests that
local recurrence can be controlled by SRT with chemotherapy but survival of
patients with metastases can not be improved effectively by SRT in
conjunction with aggressive chemotherapy. Copyright (c) 2006 S. Karger AG,
PMID: 16465076 [PubMed - in process]
Survival analysis of children with primary malignant
brain tumors in England and wales: a population-based study.
Department of Surgery, Division of Neurosurgery, National Taiwan University
Hospital, Taipei, Taiwan.
Primary malignant brain tumor is the second most common cancer in children.
To investigate factors affecting children's survival at a population level,
data of 3,169 patients (age <15 years) from the Cancer Registry in
England and Wales were used. They were diagnosed during 1971-1990 and
followed up until 1995. Variables including age, gender, morphology, WHO
grade, tumor site, socioeconomic status, geographical region, and period of
diagnosis were available for analysis using the Kaplan-Meier method and the
Cox hazards ratio (HR) regression. Results showed that the median survival
and the 1-, 5-, and 10-year crude survival rate for this population were 8.7
years, 72.4, 54.0, and 49.2% respectively. Survival was influenced by age
(HR 0.88/5 years), morphology (ependymoma HR 2.43), WHO grades (HR
1.42/grade), tumor sites (brain stem HR 2.11), and periods of diagnosis (HR
0.88/5 years). Gender, socioeconomic status, and geographical region did not
affect their survival. Results from this population-based data are very
helpful for comparison with other hospital-based studies and for public
health purposes. Copyright (c) 2006 S. Karger AG, Basel.
PMID: 16465074 [PubMed - in process]
Dual occurrence of pineal germinoma and testicular
seminoma. Case report and review of the literature.
Department of Neurosurgery, Heilig Hart Ziekenhuis, Roeselare, Belgium.
A 16-year-old male presented with obstructive hydrocephalus secondary to
pineal germinoma. There have been many reported cases of abdominal
metastasis of pineal germinoma after ventriculoperitoneal shunting.
Endoscopic ventriculostomy was preferred in our case, thus avoiding
iatrogenic peritoneal seeding, but spinal metastasis was unavoidable.
Metastatic infiltration of the ventricular system and spinal meninges is the
commonest mode of spread. Later, the patient underwent orchidectomy for an
asymptomatic left testicular seminoma. He responded to chemotherapy, and had
a complete recurrence-free remission for more than 10 years. As far as we
know there are only a handful of reported cases of dual occurrence of two
primary germ cell tumors (GCT), i.e. gonadal seminoma and pineal germinoma
with spinal seeding. We also addressed the controversial subject of
radiation versus chemotherapy in the management of patients with pineal
germinomas. A review of the relevant literature and recommendations for
future treatment of similar cases are discussed. Copyright 2006 S. Karger
PMID: 16357500 [PubMed - indexed for MEDLINE]
Spinal intradural-intramedullary cavernous malformation.
Case report and literature review.
Department of Neurosurgery, Mevki Military Hospital, Ankara, Turkey. email@example.com
Cavernous angiomas or cavernomas are uncommon vascular malformations of the
central nervous system and spinal involvement is much rarer especially in
pediatric patients. We report a case of spinal intradural-intramedullary
cavernous angioma in a 14-year-old male child. The cavernoma was located at
the level of C6-C7 at the dorsal part of the spinal cord. The diagnosis was
made with MRI and the patient underwent surgical treatment. The cavernoma
was totally removed with laminotomy and microsurgical techniques.
Somatosensory evoked potential monitoring was also used peroperatively. The
clinical, radiological and surgical features of this rare case were
presented and discussed with reference to the literature. Copyright 2006 S.
Karger AG, Basel
PMID: 16357499 [PubMed - indexed for MEDLINE]
Cancer. 2006 Feb 2;6(1):32 [Epub ahead of print]
Nestin expression in the cell lines derived from
ABSTRACT: BACKGROUND: Nestin is a protein belonging to class VI of
intermediate filaments that is produced in stem/progenitor cells in the
mammalian CNS during development and is consecutively replaced by other
intermediate filament proteins (neurofilaments, GFAP). Down-regulated nestin
may be re-expressed in the adult organism under several pathological
conditions (brain injury, ischemia, inflammation, neoplastic
transformation). Our work focused on a detailed study of the nestin
cytoskeleton in cell lines derived from glioblastoma multiforme, because
re-expression of nestin together with down-regulation of GFAP has been
previously reported in this type of brain tumors. METHODS: Two cell lines
were derived from the tumor tissue of patients treated for glioblastoma
multiforme. Nestin and other cytoskeletal proteins were visualized using
immunocytochemical methods: indirect immunofluorescence and
immunogold-labelling. RESULTS: Using epifluorescence and confocal
microscopy, we described the morphology of nestin-positive intermediate
filaments in glioblastoma cells of both primary cultures and the derived
cell lines, as well as the reorganization of nestin during mitosis. Our most
important result came through transmission electron microscopy and provided
clear evidence that nestin is present in the cell nucleus. CONCLUSIONS:
Detailed information concerning the pattern of the nestin cytoskeleton in
glioblastoma cell lines and especially the demonstration of nestin in the
nucleus represent an important background for further studies of nestin
re-expression in relationship to tumor malignancy and invasive potential.
PMID: 16457706 [PubMed - as supplied by publisher]