http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16455477&dopt=Abstract

Lancet Oncol. 2006 Feb;7(2):132-40.

Survival from rare cancer in adults: a population-based study.

Gatta G, Ciccolallo L, Kunkler I, Capocaccia R, Berrino F, Coleman MP,
De Angelis R, Faivre J, Lutz JM, Martinez C, Moller T, Sankila R;
EUROCARE Working Group.

Epidemiology Unit, National Cancer Institute, Milan, Italy.
gemma.gatta@istitutotumori.mi.it

BACKGROUND: Rare cancers are a challenge to clinical practice, and
treatment experience, even in major cancer centres to which rare
cancers are usually referred, is often limited. We aimed to study the
epidemiology of rare cancers in a large population of several
countries. METHODS: We analysed survival by age, sex, subsite, and
morphology in 57,144 adults with 14 selected rare cancers diagnosed
1983-94. Variations in survival over time and between European regions
were also assessed for variations in quality of care. We also estimated
the adjusted relative excess risk of death for every rare cancer.
FINDINGS: Overall 5-year relative survival was good (ie, >65%) for
placental choriocarcinoma (85.4% [95% CI 81.4-89.5]), thyroid medullary
carcinoma (72.4% [69.2-75.5]), ovarian germ-cell cancer (73.0%
[70.0-76.0]), lung carcinoid (70.1% [67.3-72.9]), and cervical
adenocarcinoma (65.5% [64.3-66.6]); intermediate (ie, 35-65%) for
testicular cancer at age 65 years or older (64.0% [59.3-68.7]), sarcoma
of extremities (60.0% [58.9-61.2]), digestive-system endocrine cancers
(55.6% [54.9-56.3]), anal squamous-cell carcinoma (53.1% [51.5-54.8]),
and uterine sarcoma (43.5% [42.0-44.9]); low for carcinoma of
adrenal-gland cortex (32.7% [28.3-37.2]) and bladder squamous-cell
carcinoma (20.4% [18.8-22.0]); and poor for angiosarcoma of liver (6.4%
[1.8-11.0]) and mesothelioma (4.7% [4.3-5.2]). Survival was usually
better for women than men and poor in those aged 75 years or older.
Survival significantly improved over time for ovarian germ-cell cancer,
sarcomas of extremities, digestive-system endocrine tumours, anal
squamous-cell carcinoma, and angiosarcoma of liver. Survival in
northern Europe was higher than in the other geographic groupings for
most cancers. INTERPRETATION: Because effective treatments are
available for several of the rare cancers we assessed, further research
is needed to ascertain why survival is lower in some European countries
than in others, particularly in older patients. Audit of best practice
for rare cancers with treatment protocols would be useful.

PMID: 16455477 [PubMed – in process]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16400337&dopt=Abstract

Bone Marrow Transplant. 2006 Feb;37(4):345-51.

Population pharmacokinetics of intravenous busulfan in
patients undergoing hematopoietic stem cell transplantation.

Takama H, Tanaka H, Nakashima D, Ueda R, Takaue Y.

1Product Development Department, Pharmaceutical Division, Kirin Brewery
Company Ltd, Shibuya-ku, Tokyo, Japan.

A population pharmacokinetic analysis was performed in 30 patients who
received an intravenous busulfan and cyclophosphamide regimen before
hematopoietic stem cell transplantation. Each patient received 0.8
mg/kg as a 2 h infusion every 6 h for 16 doses. A total of 690
concentration measurements were analyzed using the nonlinear mixed
effect model (NONMEM) program. A one-compartment model with an additive
error model as an intraindividual variability including an
interoccasion variability (IOV) in clearance (CL) was sufficient to
describe the concentration-time profile of busulfan. Actual body weight
(ABW) was found to be the determinant for CL and the volume of
distribution (V) according to NONMEM analysis. In this limited study,
the age (range 7-53 years old; median, 30 years old) had no significant
effect on busulfan pharmacokinetics. For a patient weighting 60 kg, the
typical CL and V were estimated to be 8.87 l/h and 33.8 l,
respectively. The interindividual variability of CL and V were 13.6 and
6.3%, respectively. The IOV (6.6%) in CL was estimated to be less than
the intraindividual variability. These results indicate high
interpatient and intrapatient consistency of busulfan pharmacokinetics
after intravenous administration, which may eliminate the requirement
for pharmacokinetic monitoring.Bone Marrow Transplantation (2006) 37,
345-351. doi:10.1038/sj.bmt.1705252; published online 9 January 2006.

PMID: 16400337 [PubMed – in process]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16450380&dopt=Abstract

Int J Cancer. 2006 Jan 31; [Epub ahead of print] 

Generation of tumoricidal PAX3 peptide antigen specific cytotoxic T
lymphocytes.

Rodeberg DA, Nuss RA, Elsawa SF, Erskine CL, Celis E.

Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

The transcription factor PAX3 is expressed during early embryogenesis
and in multiple cancer types, including embryonal rhabdomyosarcoma
(ERMS), Ewing sarcoma (ES) and malignant melanoma (MEL), suggesting
that it could function as a general tumor associated antigen. Major
histocompatibility complex (MHC) peptide binding algorithms were used
to predict potential epitopes in PAX3 capable of stimulating in vitro
naive HLA-A0201 restricted cytotoxic T-lymphocytes (CTLs). Two
peptides, PAX3-282 (QLMAFNHLI) and a modified version of this peptide
PAX3-282.9V (QLMAFNHLV), were capable of inducing antigen-specific
CTLs. Of these peptides, PAX3-282.9V was the most efficient inducer of
primary CTL response. These CTLs were able to lyse HLA-A0201 expressing
target cells that were pulsed with peptide, and more importantly, were
effective in killing tumor cells that express PAX3, including ERMS, ES
and MEL cell lines. These findings provide compelling evidence that
peptide PAX3-282 is naturally processed by tumors and is presented in
the context of HLA-A0201 in adequate amounts to allow CTL recognition.
Also, PAX3-282.9V is an effective immunogenic peptide able to induce
CTL recognition of PAX3-containing tumors and may be used as an
antitumor peptide vaccine. (c) 2006 Wiley-Liss, Inc.

PMID: 16450380 [PubMed – as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16446642&dopt=Abstract

Ann Dermatol Venereol. 2005 Dec;132(12 Pt 1):986-9.

Primary cutaneous extraskeletal Ewing's sarcoma

[Article in French]

Kourda M, Chatti S, Sfia M, Kraiem W, Ben Brahim E.

Service de Dermatologie, Hopital de Nabeul, Tunisie.
kourda_mouna@yahoo.fr

BACKGROUND: Cutaneous extraskeletal Ewing's sarcoma is rare, being seen
principally in children. We report a case of cutaneous sarcoma in the
sole of the foot in a child. CASE REPORT: A 9-year-old child with no
medical history of note was presenting a skin tumor for 3 months on the
heel of the right foot. This tumor was burgeoning and painful and
measured 3.5 cm in diameter; it was ulcerative at the surface and
covered with a crust. Histological and immunohistochemical examinations
confirmed the diagnosis of Ewing's sarcoma. Staging examinations proved
negative and the patient underwent polychemotherapy, resulting in
complete regression of the tumor. COMMENTS: Until 1998, 37 cases of
cutaneous and subcutaneous Ewing's sarcoma were reported, being seen in
21 girls and 16 boys. Mean age at diagnosis was 15 years and mean tumor
size was 3 cm (range: 1 to 12 cm). The tumors were observed throughout
the body, being seen in the sole of the foot in 2 cases. Confirmation
of the diagnosis was made by histological examination (malignant
proliferation of small round cells in the dermis), immunohistochemical
examination (CD99+) and cytogenetic analysis (translocation between
chromosomes 22 and 11). The prognosis for cutaneous Ewing's sarcoma
appears more favorable than that of Ewing's sarcoma in bone. Of the 37
patients treated, 7 had metastases and 2 presented relapse. Treatment
for cutaneous Ewing's sarcoma, though not codified, consists of
polychemotherapy associated with surgery and/or radiotherapy.

PMID: 16446642 [PubMed – in process]

http://www.pedresearch.org/cgi/content/abstract/59/2/259

CLINICAL INVESTIGATIONS

Patterns of Growth and Body Proportions After Total-Body
Irradiation and Hematopoietic Stem Cell Transplantation During Childhood

BOUDEWIJN BAKKER, WILMA OOSTDIJK, RONALD B. GESKUS, W. HENRIËTTE
STOKVIS-BRANTSMA, JAAK M. VOSSEN and JAN M. WIT

Department of Pediatrics [B.B., W.O., W.H.S.-B., J.M.V., J.M.W.],
Department of Medical Statistics [R.B.G.], Leiden University Medical
Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands

Patterns of growth and body proportions were studied in 75 children
receiving total-body irradiation (TBI) and hematopoietic stem cell
transplantation (SCT) before onset of puberty. Of the 19 patients
receiving GH, only data obtained before onset of GH were included.
Thirty-two patients reached final height (FH). Median change in height
SD score (SDS) between SCT and FH was –1.7 in boys and –1.1 in girls.
Peak height velocity (PHV) was decreased in the majority of the
patients (median PHV 5.7 cm/y in boys and 5.3 cm/y in girls), even
though it occurred at appropriate ages. Changes in body proportions
were analyzed by linear mixed-effects models. Decrease in sitting
height SDS did not differ between boys and girls. In boys, decrease in
leg length SDS was of comparable magnitude, whereas, in girls, decrease
in leg length was less pronounced, leading to a significant decrease in
SDS for sitting height/height ratio in girls only. The sex-specific
effects of several variables on height SDS were analyzed by linear
mixed-effects modeling, showing a slightly faster decrease in younger
children and a more pronounced decrease during puberty in boys compared
with girls. We conclude that 1) younger children are more susceptible
to growth retardation after TBI and SCT, 2) pubertal growth is more
compromised in boys, and 3) leg growth is relatively less affected in
girls, possibly due to a high incidence of gonadal failure in girls.

Abbreviations:
FH, final height
PHV, peak height velocity
SCT, stem cell transplantation
SDS, standard deviation score
TBI, total-body irradiation

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16394892&dopt=Abstract

J Pediatr Hematol Oncol. 2006 Jan;28(1):40-2.
   
Long-term survival following a phase I/II trial with VETOPEC
for solid tumors in childhood

Ziegler DS, McCowage G, Cohn RJ, White L.

Centre for Children's Cancer and Blood Disorders, Sydney Children's
Hospital, Randwick, NSW, Australia.

The objective of this study was to evaluate long-term survival after
treatment during a phase I/II trial with a specific regimen of
vincristine, etoposide, and escalating cyclophosphamide (VETOPEC).
Fifty-six children with poor-prognosis solid tumors were enrolled on
study between May 1991 and May 1994. All had tumors that had relapsed
on, or were refractory to, conventional treatment, or for whom existing
treatment options were considered ineffective. The records of all
surviving patients were reviewed to ascertain their disease and health
status. Of the 56 patients, 10 patients (18%) remain alive with no
further disease progression at a median follow-up of 11 years (range
7-13 years). Eight patients (14%) remain completely free of disease.
None of the patients show long-term side effects directly attributable
to the VETOPEC regimen, apart from one patient with ovarian failure.
The VETOPEC regimen can offer not only good tumor responses but also
the chance of cure for a surprisingly large number of children with
very-poor-prognosis solid tumors. This regimen warrants continuing
development and consideration for use in future trials.

PMID: 16394892 [PubMed – in process]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16425266&dopt=Abstract

Pediatr Blood Cancer. 2006 Jan 19; [Epub ahead of print]
 
Analysis of biologic surrogate markers from a
Children's Oncology Group Phase I trial of gefitinib in pediatric
patients with solid tumors.

Jimeno A, Daw NC, Amador ML, Cusatis G, Kulesza P, Krailo M, Ingle AM,
Blaney SM, Adamson P, Hidalgo M.

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University,
Baltimore, Maryland.

This trial evaluated the effect of gefitinib on the plasma circulating
levels of epidermal growth factor receptor (EGFR), vascular endothelial
growth factor (VEGF), matrix metalloproteinases (MMP)-2 and -9 of
patients treated on a pediatric Phase I trial. Complete plasma
correlative studies were obtained from 16 of the 25 enrolled patients.
There was a trend for lower MMP-2 baseline levels in patients with
partial response or stable disease. The Ewing sarcoma from the only
patient with partial response lacked egfr mutations. Gefitinib did not
induce any significant variation in the levels of the assessed
parameters, and none of these determinations showed significant
predictive or prognostic value. Pediatr Blood Cancer (c) 2006
Wiley-Liss, Inc.

PMID: 16425266 [PubMed – as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16435380&dopt=Abstract

Pediatr Blood Cancer. 2006 Jan 24; [Epub ahead of print]   

Topotecan by 21-day continuous infusion in
children with relapsed or refractory solid tumors: A Children's
Oncology Group study.

Hawkins DS, Bradfield S, Whitlock JA, Krailo M, Franklin J,
Blaney SM, Adamson PC, Reaman G.

Children's Hospital and Regional Medical Center, Seattle,
Washington.

PURPOSE: The Children's Oncology Group conducted a phase II trial of
21-day continuous infusion topotecan to determine the response rate in
pediatric patients with recurrent or refractory malignant solid tumors.
PROCEDURE: Patients with Ewing sarcoma family of tumors (ESFT),
osteosarcoma (OS), soft tissue sarcomas (STS), medulloblastoma
(MB)/primitive neuroectodermal tumor (PNET), astrocytoma, or
neuroblastoma (NB) recurrent or refractory to conventional therapy,
measurable disease, and adequate organ function were treated with
topotecan 0.3 mg/m(2)/day by continuous intravenous infusion for 21
consecutive days, followed by 7 days without therapy prior to response
assessment. RESULTS: Fifty-five patients were enrolled; two were
ineligible, two were removed from protocol therapy prior to evaluation
for response, and one was inevaluable for response, leaving 53 and 50
patients evaluable for toxicity and response, respectively. Objective
responses were seen in 2/20 patients with ESFT (both partial responses,
4 and 19 courses), 0/10 OS patients, and 0/12 STS patients. There were
insufficient patients enrolled to determine the response rate for the
MB/PNET, astrocytoma, and NB strata. The most common Grade 3 or 4
toxicities during the first course of therapy were thrombocytopenia
(12/53), neutropenia (8/53), and fatigue (7/53). CONCLUSION:
Intravenous topotecan by 21-day continuous infusion is tolerable in
pediatric patients with recurrent or refractory solid tumors. Limited
activity was seen in ESFT and further development of this topotecan
schedule as a single agent is not warranted. Pediatr Blood Cancer (c)
2006 Wiley-Liss, Inc.

PMID: 16435380 [PubMed – as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16421909&dopt=Abstract

Pediatr Blood Cancer. 2006 Jan 18; [Epub ahead of print]

An analysis of primary site control and late effects
according to local control modality in non-metastatic Ewing sarcoma.

Paulino AC, Nguyen TX, Mai WY.

Department of Radiology, Division of Radiation Oncology, Baylor College
of Medicine and Methodist Hospital, Houston, Texas.

PURPOSE: To examine prognostic factors for primary site control and
analyze late effects according to local treatment modality in
non-metastatic Ewing sarcoma (ES). MATERIALS AND METHODS: From 1976 to
2001, 76 patients with localized ES and a median age of 14.5 years were
seen and treated at one institution. Tumors were located in the
extremity in 38, pelvis in 13, spine in 11, trunk in 8, and head and
neck in 6. Tumor size was </=8 cm in 44 and >8 cm in 32. Local
therapy included radiotherapy (RT) alone in 40, surgery (S) alone in
27, and surgery followed by postoperative radiotherapy (S + RT) in 9.
Chemotherapy (CT) was delivered to 65 patients (86%). Median follow-up
for surviving patients was 9.7 years. RESULTS: The 5- and 10-year
overall survival rates were 57.5% and 52.1% while the 5- and 10-year
local control rate was 79.2%. The 5- and 10-year local control rates
were 78.2% for RT, 77.6% for surgery, and 88.9% for S + RT (P = 0.68).
Multivariate analysis showed that only the use of CT was found to be a
prognostic factor for local control (P = 0.014). The 5- and 10-year
local control rates were 83.7% for those receiving CT and 51.1% for
those not receiving CT. For patients followed at least 5 years from
diagnosis, late effects were seen in 10 of 19 (52.6%) receiving RT, 2
of 5 (40%) receiving S + RT, and 4 of 16 (25%) receiving surgery alone.
The most common late effects with RT were muscular atrophy, limb length
growth delay, and development of second malignancy. Scoliosis and
decrease range of motion of an extremity were seen regardless of local
treatment modality. Three patients who had surgery alone had an
amputation whereas two who had RT had an amputation secondary to
relapse or development of osteosarcoma. CONCLUSION: In this single
institution study, the use of CT was the only factor found to impact on
local control. Late effects were common regardless of local control
strategy. Pediatric Blood Cancer (c) 2006 Wiley-Liss, Inc.
PMID: 16421909 [PubMed – as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16411221&dopt=Abstract

Pediatr Blood Cancer. 2006 Jan 12; [Epub ahead of print]

Second and third malignant solid tumor in a girl
with ovarian Sertoli-Leydig tumor.

Panagiotou JP, Polychronopoulou S, Sofou K, Vanvliet-Constantinidou C,
Papandreou E, Haidas S.

Department of Pediatric Hematology/Oncology, “Aghia Sophia” Children's
Hospital, Athens, Greece.

We report a Sertoli-Leydig cell (SLC) tumor of the right ovary in a
10-year-old girl, which was dealt with surgical removal. Three months
after resection, she presented with a new episode of acute abdomen
because of an abdominal mass, which histologically was compatible with
an undifferentiated embryonal rhabdomyosarcoma. Chemotherapy, according
to SIOP-??? 89 protocol, was administered additionally to radiotherapy
(3,960 cGy). Three years after completing treatment, the patient
developed a painful swelling at her left upper arm. The diagnosis was
Ewing sarcoma of the humerus, which was confirmed by identification of
the typical 11; 22 translocation on cytogenetic and molecular analysis
of the tumor tissue. The patient died 14 months from Ewing diagnosis
due to progressive disease. Pediatr Blood Cancer (c) 2006 Wiley-Liss,
Inc.

PMID: 16411221 [PubMed – as supplied by publisher]