Decreased 3D observer variation with matched CT-MRI, for target delineation in Nasopharynx cancer.

Purpose: To determine the variation in target delineation of nasopharyngeal carcinoma and the impact of measures to minimize this variation.

Materials And Methods: For ten nasopharyngeal cancer patients, ten observers each delineated the Clinical Target Volume (CTV) and the CTV elective. After 3D analysis of the delineated volumes, a second delineation was performed.

Intra-arterial versus intravenous chemoradiation for advanced head and neck cancer: Results of a randomized phase 3 trial.

Background: Chemoradiation is the preferred treatment for advanced stage IV head and neck cancer. Higher doses of chemotherapy yielded promising results in vitro and vivo, confirmed by intra-arterial (IA) cisplatin-based chemoradiation in phase 2 studies.

Methods: Two hundred and thirty-nine patients with (functionally) unresectable head and neck cancer were included, from 2000 to 2004, in a multicenter, randomized phase 3 trial, comparing IA and intravenous chemoradiation.

Target definition in prostate, head, and neck.

Target definition is a major source of errors in both prostate and head and neck external-beam radiation treatment. Delineation errors remain constant during the course of radiation and therefore have a large impact on the dose to the tumor. Major sources of delineation variation are visibility of the target including its extensions, disagreement on the target extension, and interpretation or lack of delineation protocols.

Signalling steps in apoptosis by ether lipids.

We have investigated the mechanisms of induction of apoptosis by the antineoplastic ether lipid ET-18-OCH3 (ALP) in sensitive S49wt mouse lymphoma cells and ALP-resistant S49ar variants, both with wild-type p53, and in related L1210 cells with mutated p53. Ether lipid-resistant S49ar cells were cross-resistant to extracellular stress factors (cold shock, heat shock, H2O2, dimethylsulfoxide) and to radiation-induced apoptosis but not to physiological apoptotic signals (dexamethasone, growth factor deprivation, thapsigargin, C2-ceramide) and expressed similar levels of the apoptosis-regulating proteins Bcl-2, Bcl-X, Bax, Bad and Bak as did the parent S49wt cells. The uptake of [3H]-ALP was strongly reduced in the stress-resistant cells but this was not associated with significant differences in membrane cholesterol:phospholipid content nor in membrane microviscosity.

A randomised phase II study on neo-adjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma.

The aim of this study was to examine the strategy, feasibility and outcome of neo-adjuvant chemotherapy, with doxorubicin and ifosfamide, in adult patients with 'high-risk' soft-tissue sarcomas. Patients with 'high-risk' soft-tissue sarcomas, defined as tumours > or =8 cm of any grade, or grade II/III tumours <8 cm, or grade II/III locally recurrent tumours, or grade II/III tumours with inadequate surgery performed in the previous 6 weeks and therefore requiring further surgery, were randomised between either surgery alone or three cycles of 3-weekly doxorubicin 50 mg/m(2) intravenous (i.v.

Accurate in vivo dosimetry of a randomized trial of prostate cancer irradiation.

Purpose: To guarantee an accurate dose delivery, within +/- 2.5%, in a Phase III randomized trial of prostate cancer irradiation (68 vs. 78 Gy) by means of a comprehensive in vivo dosimetry program.

In vitro differentiation characteristics of human skin fibroblasts: correlations with radiotherapy-induced breast fibrosis in patients.

Purpose: To determine whether there is an association between dermal fibroblast differentiation characteristics in vitro and breast fibrosis developing in patients following radiotherapy for breast cancer.

Materials And Methods: Three hundred and eighty-five patients had been characterized for the degree of breast fibrosis and the level of clinical risk factors for fibrosis as established by logistic regression. Early-passage fibroblasts from 79 patients with a high (HR) or low (LR) level of risk factors were studied in vitro.

Bcl-2 family members in childhood acute lymphoblastic leukemia: relationships with features at presentation, in vitro and in vivo drug response and long-term clinical outcome.

We have found that, in addition to Bcl-2 and Bax, the expression levels of apoptosis inducers (Bad, Bak) and inhibitors (Bcl-xL, Mcl-1) were highly variable in blasts from 78 children with newly diagnosed acute lymphoblastic leukemia (ALL). The patients were enrolled in the national study ALL-7 of the Dutch Childhood Leukemia Study Group. In contrast to Bcl-2 that inversely correlated with %S-phase cells and WBC, and was lower in T than in B-lineage ALL, the Bcl-2 family members were not found to be associated with features at presentation.

The importance of in situ light dosimetry for photodynamic therapy of oral cavity tumors.

Background: Photodynamic therapy (PDT) is being evaluated for treatment of localized head and neck cancer. "Light dose" is usually prescribed as incident fluence, which takes no account of reflected and scattered light. This study investigates variations in total tissue fluence for a given incident fluence in the oral cavity.

Quality of life assessment in daily clinical oncology practice: a feasibility study.

Quality of life (QL) assessments are increasingly being included in clinical trials, but their use in clinical practice is still uncommon. The objectives of this study were to investigate the feasibility of introducing individual QL assessments into the daily routine of an out-patient oncology clinic, and the potential impact of such assessments on doctor-patient communication. The study sample included six physicians and 18 of their patients from the out-patient clinic of the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital in Amsterdam, The Netherlands.

Expandable stents compared to conventional plastic endoprostheses in malignant oesophageal obstruction, especially in cardiac cancer and fistulas: the experience of the Netherlands Cancer Institute.

Background: Advanced oesophageal carcinoma usually causes debilitating dysphagia. An endoprosthesis can offer adequate palliation. The self-expandable metal stents provide several advantages over the plastic endoprostheses: less traumatic introduction and stronger attachment to the oesophageal wall.

Low predictive value of intrinsic fibroblast radiosensitivity for fibrosis development following radiotherapy for breast cancer.

Purpose: To test whether the intrinsic radiosensitivity of skin fibroblasts from breast cancer patients correlates with the degree of breast fibrosis after breast conserving therapy.

Methods: In a systematic study design, 79 patients were selected from an earlier study group of 385 patients based on observed fibrosis and seven identified clinical risk factors for fibrosis development. In vitro radiosensitivity of patients' dermal fibroblasts was determined by clonogenic assay of early passage cultures.

Mutational analysis of Bax and Bcl-2 in childhood acute lymphoblastic leukaemia.

In childhood acute lymphoblastic leukaemia there are large interpatient variations in levels of the apoptosis-regulating proteins Bax and Bcl-2, but the molecular basis for this variation is unknown. Point-mutations in bax have been reported in cell lines derived from haematological malignancies. Frameshift mutations, which result in reduced Bax levels, have also been found in colon cancer of the microsatellite mutator phenotype.

Monoclonal antibodies against the nonmucin domain of MUC1/episialin.

We have tested the reactivity of the monoclonal antibodies submitted to the ISOBM TD-4 Workshop for reactivity with a hybrid molecule consisting of the bacterial beta-galactosidase and most of the extracellular nonrepeat domain of MUC1/episialin. Two monoclonal antibodies submitted to the Workshop, 232A1 and M29, were directed against the protein moiety of this domain as shown by immunoblotting and immunoprecipitation.

Treatment and outcome of brain metastasis as first site of distant metastasis from breast cancer.

Twenty-eight consecutive patients with breast cancer were analyzed who presented with a single brain metastasis as first site of distant metastasis. The response to surgery with postoperative radiation therapy (RT) (9 patients) and to non-surgical therapy as first-line treatment was 100% and 89% respectively with a significant difference in median recurrence-free intervals of 23 months and of 5 months respectively (p = 0.033).

The Bax alpha:Bcl-2 ratio modulates the response to dexamethasone in leukaemic cells and is highly variable in childhood acute leukaemia.

Bcl-2 over-expression has been shown to inhibit apoptosis induced by a variety of stimuli, whereas a predominance of Bax alpha to Bcl-2 accelerates apoptosis upon apoptotic stimuli. We sought to study the relevance of these apoptotic regulating gene products in leukaemia. In a panel of leukaemia and lymphoma cell lines (HL60, DoHH2, CEM C7, L1210 and S49), the Bax alpha-to-Bcl-2 ratio as assessed by Western-blot analysis correlated with sensitivity to dexamethasone treatment.

The role of radiotherapy in the local management of dermatofibrosarcoma protuberans. Soft Tissue Tumours Working Group.

Dermatofibrosarcoma protuberans (DFSP), a fibrohistiocytic tumour of intermediate malignancy, has a strong tendency to recur locally. Wide local excision is the recommended treatment modality. A retrospective analysis was performed on 38 consecutive DFSP patients presenting to The Netherlands Cancer Institute, to define the role of radiotherapy.

Chemical characterization and comparative cellular effects of meta-iodobenzyl guanidine and benzyl guanidine.

meta-Iodobenzyl guanidine (MIBG) combines the structural properties of the neuron-blocking agents bretylium and guanethidine and is being used increasingly for various clinical applications. Different samples of MIBG were assayed for possible contamination with benzyl guanidine (BG). Fast-atom-bombardment mass spectrometry (FAB-MS) analysis showed a prominent but variable m/z 150 signal, corresponding to a protonated BG.

Central nervous system metastasis in breast cancer.

Background And Purpose: Central nervous system (CNS) metastasis occurs in at least 30% of patients with breast cancer. Standard treatment is the same as in other solid tumors, though clinical behavior, and sensitivity to radiation therapy (RT) and to chemotherapy may differ considerably. Most of these patients die within a few months, but a substantial subgroup may survive a year or more.

Influence of fractionation and fluence rate in photodynamic therapy with Photofrin or mTHPC.

Various schedules of fractionated photodynamic therapy (PDT), delivered at two different light fluence rates, were investigated in the RIF1 tumor model in an attempt to minimize the development of hypoxia during PDT and thereby improve tumor response relative to single treatments. The photosensitizers Photofrin and meta-tetrahydroxyphenylchlorin (mTHPC) were used in combination with either interstitial or superficial illumination. For both methods of illumination, equal volumetric light doses gave similar tumor responses, as measured by tumor regrowth times and number of cures.

A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1.

Episialin (MUC1, PEM, EMA, CA15-3 antigen) is a sialylated, membrane-associated glycoprotein with an extended mucin-like ectodomain. This domain mainly consists of 30-90 homologous 20-amino acid repeats that are rich in O-glycosylation sites (serines and threonines). It is likely that this part forms a polyproline beta-turn helix.

Unchanged pharmacokinetics of etoposide given by intra-arterial hepatic infusion as compared with i.v. infusion.

We investigated the pharmacokinetics of etoposide given to a patient suffering from multifocal liver metastases from an unknown primary tumor. The drug was given either by i.v.

Radioimmunotherapy of small-cell lung cancer xenografts using 131I-labelled anti-NCAM monoclonal antibody 123C3.

We have studied the therapeutic efficacy of 131I-labelled monoclonal antibody 123C3 in human small-cell lung carcinoma xenografts established from the NCI-H69 cell line in nude mice. Several radiation doses were administered intraperitoneally and different treatment schedules were tested. The maximal tolerated dose, 2 x 500 microCi, resulted in complete remission of tumours smaller than 200 mm3 and long-lasting remission (more than 135 days) of the larger tumours.