7 research outputs found
Macromolecule Extravasation—Xenograft Size Matters: A Systematic Study Using Probe-Based Confocal Laser Endomicroscopy (pCLE)
Effect of [F-18]FMISO stratified dose-escalation on local control in FaDu hSCC in nude mice
Objective: To investigate the effect of radiation dose-escalation on local control in hypoxic versus non-hypoxic hypoxic tumours defined using [F-18]fluoromisonidazole ([F-18]FMISO) PET. Materials and methods: FaDu human squamous cell carcinomas (hSCCs) growing subcutaneously in nude mice were subjected to [F-18]FMISO PET before irradiation with single doses of 25 or 35 Gy under normal blood flow conditions. [F-18]FMISO hypoxic volume (HV) and maximum standardised uptake value (SUVmax) were used to quantify tracer uptake. The animals were followed up for at least 120 days after irradiation. The endpoints were permanent local tumour control and time to local recurrence. Results: HV varied between 38 and 291 mm(3) (median 105 mm(3)). Non-hypoxic tumours (HV below median) showed significantly better local control after single dose irradiation than hypoxic tumours (HV above median) (p = 0.046). The effect of dose was significant and not different in non-hypoxic and in hypoxic tumours (HR= 0.82 [95% Cl 0.71; 0.93], p = 0.002 and HR= 0.86 [0.78; 0.95], p = 0.001, respectively). Dose escalation resulted in an incremental increase of local tumour control from low-dose hypoxic, over low-dose non-hypoxic and high-dose hypoxic to high-dose non-hypoxic tumours. SUVmax did not reveal significant association with local control at any dose level. Conclusions: The negative effect of [F-18]FMISO HV on permanent local tumour control supports the prognostic value of the pre-treatment [F-18]FMISO HV. Making the assumption that variable [F-18]FMISO uptake in different FaDu tumours which all have the same genetic background may serve as an experimental model of intratumoural heterogeneity, the data support the concept of dose-escalation with inhomogeneous dose distribution based on pre-treatment [F-18]FMISO uptake. This result needs to be confirmed in other tumour models and using fractionated radiotherapy schedules
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SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors.
BackgroundWorse chemotherapy response for neurofibromatosis type 1- (NF1-) associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST) has been reported.MethodsWe evaluated the objective response (OR) rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%).Results34 NF1 (median age 33 years) and 14 sporadic (median age 40 years) MPNST patients enrolled. Five of 28 (17.9%) evaluable NF1 MPNST patients had a partial response (PR), as did 4 of 9 (44.4%) patients with sporadic MPNST. Stable disease (SD) was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual.ConclusionsThis trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients
Reproductive Factors and Exogenous Hormone Use in Relation to Risk of Glioma and Meningioma in a Large European Cohort Study
Background: The etiologies of glioma and meningioma tumors are largely
unknown. Although reproductive hormones are thought to influence the
risk of these tumors, epidemiologic data are not supportive of this
hypothesis; however, few cohort studies have published on this topic. We
examined the relation between reproductive factors and the risk of
glioma and meningioma among women in the European Prospective
Investigation into Cancer and Nutrition (EPIC).
Methods: After a mean of 8.4 years of follow-up, 193 glioma and 194
meningioma cases were identified among 276,212 women. Information on
reproductive factors and hormone use was collected at baseline. Cox
proportional hazard regression was used to determine hazard ratios (HR)
and 95% confidence intervals (95% CI).
Results: No associations were observed between glioma or meningioma risk
and reproductive factors, including age at menarche, parity, age at
first birth, menopausal status, and age at menopause. A higher risk of
meningioma was observed among postmenopausal women who were current
users of hormone replacement therapy (HR, 1.79; 95% CI, 1.18-2.71)
compared with never users. Similarly, current users of oral
contraceptives were at higher risk of meningioma than never users (HR,
3.61; 95% CI, 1.75-7.46).
Conclusion: Our results do not support a role for estrogens and glioma
risk. Use of exogenous hormones, especially current use, seems to
increase meningioma risk. However, these findings could be due to
diagnostic bias and require confirmation.
Impact: Elucidating the role of hormones in brain tumor development has
important implications and needs to be further examined using biological
measurements. Cancer Epidemiol Biomarkers Prev; 19(10); 2562-9. (C) 2010
AACR
Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study
Objective To compute the burden of cancer attributable to current and
former alcohol consumption in eight European countries based on direct
relative risk estimates from a cohort study.
Design Combination of prospective cohort study with representative
population based data on alcohol exposure.
Setting Eight countries (France, Italy, Spain, United Kingdom, the
Netherlands, Greece, Germany, Denmark) participating in the European
Prospective Investigation into Cancer and Nutrition (EPIC) study.
Participants 109 118 men and 254 870 women, mainly aged 37-70.
Main outcome measures Hazard rate ratios expressing the relative risk of
cancer incidence for former and current alcohol consumption among EPIC
participants. Hazard rate ratios combined with representative
information on alcohol consumption to calculate alcohol attributable
fractions of causally related cancers by country and sex. Partial
alcohol attributable fractions for consumption higher than the
recommended upper limit (two drinks a day for men with about 24 g
alcohol, one for women with about 12 g alcohol) and the estimated total
annual number of cases of alcohol attributable cancer.
Results If we assume causality, among men and women, 10% (95%
confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of
total cancer was attributable to former and current alcohol consumption
in the selected European countries. For selected cancers the figures
were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive
tract, 33% (11 to 54%) and 18% (-3 to 38%) for liver, 17% (10 to
25%) and 4% (-1 to 10%) for colorectal cancer for men and women,
respectively, and 5.0% (2 to 8%) for female breast cancer. A
substantial part of the alcohol attributable fraction in 2008 was
associated with alcohol consumption higher than the recommended upper
limit: 33 037 of 178 578 alcohol related cancer cases in men and 17 470
of 397 043 alcohol related cases in women.
Conclusions In western Europe, an important proportion of cases of
cancer can be attributable to alcohol consumption, especially
consumption higher than the recommended upper limits. These data support
current political efforts to reduce or to abstain from alcohol
consumption to reduce the incidence of cancer
Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition
The association between menopausal hormone therapy (HT) and risk of
ovarian cancer was assessed among 126,920 post-menopausal women
recruited into the European Prospective Investigation into Cancer and
Nutrition. After an average of 9-year follow-up, 424 incident ovarian
cancers were diagnosed. Cox models adjusted for body mass index, smoking
status, unilateral ovariectomy, simple hysterectomy, age at menarche,
number of full-term pregnancies, and duration of oral contraceptives
were used. Compared with baseline never use, current use of any HT was
positively associated with risk (HR [hazard ratio], 1.29; 95% CI
[confidence interval], 1.01-1.65), while former use was not (HR, 0.96;
95% CI, 0.70-1.30). Current estrogen-only HT was associated with a 63%
higher risk (HR, 1.63; 95% CI, 1.08-2.47), while current estrogen plus
progestin was associated with a smaller and non-significant higher risk
(HR, 1.20; 95% CI, 0.89-1.62). Use of tibolone was associated with a
twofold greater risk (HR, 2.19; 95% CI, 1.06-4.50), but was based on
small numbers. In conclusion, women who currently use HT have a moderate
increased risk of ovarian cancer, and which may be stronger for
estrogen-only than estrogen plus progestin preparations