Improvement of radiotherapy treatment delivery accuracy using an electronic portal imaging device.

Reliable application of advanced external beam techniques for the treatment of patients with cancer, such as intensity modulated radiotherapy, requires an adequate quality assurance programme for the verification of the dose delivery. Accurate patient positioning is mandatory because of the steep dose gradients outside the tumour volume. Owing to the increased complexity of the treatment planning and delivery techniques, verification of the dose delivery before and during the actual patient treatment is equally important.

Fast, daily linac verification for segmented IMRT using electronic portal imaging.

Purpose: Intensity modulated radiotherapy (IMRT) requires dedicated quality assurance (QA). Recently, we have published a method for fast (1-2 min) and accurate linac quality control for dynamic multileaf collimation, using a portal imaging device. This method is in routine use for daily leaf motion verification.

Factors affecting sensitivity and specificity of screening mammography and MRI in women with an inherited risk for breast cancer.

Background: The MRISC study is a screening study, in which women with an increased risk of hereditary breast cancer are screened by a yearly mammography and MRI, and half-yearly clinical breast examination. The sensitivity found in this study was 40% for mammography and 71% for MRI and the specificity was 95 and 90%, respectively. In the current subsequent study we investigated whether these results are influenced by age, a BRCA1/2 mutation, menopausal status and breast density.

Impaired cisplatin influx in an A2780 mutant cell line: evidence for a putative, cis-configuration-specific, platinum influx transporter.

The effectiveness of platinum drugs in the treatment of cancer is hindered by intrinsic and acquired resistance. The cause of clinical resistance to platinum compounds is still unknown. In an attempt to identify new cellular mechanisms of cisplatin resistance, a one-step cisplatin-selection procedure was used to generate resistant sublines of the platinum sensitive A2780 ovarian cancer cell line.

RHyThM, a tool for analysis of PDOS formatted hyperthermia treatment data generated by the BSD2000/3D system.

One of the systems used by hyperthermia (HT) groups for heating tumours in the pelvic region is the BSD2000 system. Previous versions of the BSD2000 operate on a PDOS machine and the majority of the currently installed BSD2000/3D systems are still running under PDOS. Availability of the PDOS formatted treatment data provided by the BSD2000/3D has some difficulties.

Temperature data analysis for 22 patients with advanced cervical carcinoma treated in Rotterdam using radiotherapy, hyperthermia and chemotherapy: a reference point is needed.

Introduction: The growing interest and participation in multi-institutional trials involving deep hyperthermia treatment is an important step towards the further consolidation of hyperthermia as an oncological treatment modality. However, the differences in the clinical procedures of hyperthermia application also raises questions as how to compare the reported temperatures data obtained by the different institutes. In this study our recent developed approach, RHyThM (Rotterdam Hyperthermia Thermal Modulator), has been used for thermal data analysis to investigate the temperature dynamics behaviour of a series of deep hyperthermia treatments.

A novel approach to accurate portal dosimetry using CCD-camera based EPIDs.

A new method for portal dosimetry using CCD camera-based electronic portal imaging devices (CEPIDs) is demonstrated. Unlike previous approaches, it is not based on a priori assumptions concerning CEPID cross-talk characteristics. In this method, the nonsymmetrical and position-dependent cross-talk is determined by directly imaging a set of cross-talk kernels generated by small fields ("pencil beams") exploiting the high signal-to-noise ratio of a cooled CCD camera.

Neurocognitive functions and quality of life in haematological patients receiving haematopoietic stem cell grafts: a one-year follow-up pilot study.

Longitudinal data of neurocognitive functions and quality of life (QOL) were obtained for a cohort of 25 patients followed before transplant and through the first year after haematopoietic stem cell transplantation (SCT). A battery of neuropsychological tests and two self-report questionnaires were used to assess neurocognitive functions, QOL and psychological functioning. In comparison to normative data, up to one-fourth of the patients experienced impaired functioning on several cognitive domains before SCT.

Differences between first and subsequent rounds of the MRISC breast cancer screening program for women with a familial or genetic predisposition.

Background: Within the Dutch MRI Screening (MRISC) study, a Dutch multicenter screening study for hereditary breast cancer, the authors investigated whether previously reported increased diagnostic accuracy of magnetic resonance imaging (MRI) compared with mammography would be maintained during subsequent screening rounds.

Methods: From November 1999 to October 2003, 1909 eligible women were included in the study. Screening parameters and tumor characteristics of different rounds were calculated and compared.

TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility.

Tumor necrosis factor alpha (TNF-alpha), isolated 30 years ago, is a multifunctional cytokine playing a key role in apoptosis and cell survival as well as in inflammation and immunity. Although named for its antitumor properties, TNF has been implicated in a wide spectrum of other diseases. The current use of TNF in cancer is in the regional treatment of locally advanced soft tissue sarcomas and metastatic melanomas and other irresectable tumors of any histology to avoid amputation of the limb.

Outcome and prognostic factor analysis of 217 consecutive isolated limb perfusions with tumor necrosis factor-alpha and melphalan for limb-threatening soft tissue sarcoma.

Background: Extensive and mutilating surgery is often required for locally advanced soft tissue sarcoma (STS) of the limb. As it has become apparent that amputation for STS does not improve survival rates, the interest in limb-preserving approaches has increased. Isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF) and melphalan is successful in providing local tumor control and enables limb-preserving surgery in a majority of cases.

T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production.

EBV is associated with a broad range of malignancies. Adoptive immunotherapy of these tumors with EBV-specific CTL proved useful. We generated a panel of primary human T cells specific to various EBV antigens (i.

Technology insight: Utility of TNF-alpha-based isolated limb perfusion to avoid amputation of irresectable tumors of the extremities.

Isolated limb perfusion (ILP) with melphalan is effective in the treatment of small multiple melanoma intransit metastases and is utilized widely for this indication. The treatment is much less effective against bulky melanoma metastases and has uniformly failed in the treatment of irresectable extremity soft tissue sarcomas. The addition of tumor-necrosis factor-alpha (TNF-alpha) to this treatment approach has changed the situation dramatically.

5-Year follow-up of sentinel node negative breast cancer patients.

Aim: To report the long-term results of sentinel node negative breast cancer patients treated without axillary lymph node dissection and the 5-year follow-up results of 149 patients.

Methods: The incidence of axillary-and local recurrences and second ipsilateral primary tumours was evaluated. The added value of annual ultrasound of the treated axilla, being part of the standard follow-up, was also evaluated.

Effects of waterbolus size, shape and configuration on the SAR distribution pattern of the Lucite cone applicator.

The effects of waterbolus dimensions and configuration on the effective field size (EFS) of the Lucite cone applicator (LCA) for superficial hyperthermia are presented. The goal of the research is to develop guidelines which mark out a sub-set of optimal LCA-waterbolus set-ups. The effects of variations in (i) waterbolus thickness, (ii) waterbolus area, (iii) waterbolus length/width ratio and (iv) eccentric placement of the applicator have been investigated in an FDTD model study.

Parallel detection of transduced T lymphocytes after immunogene therapy of renal cell cancer by flow cytometry and real-time polymerase chain reaction: implications for loss of transgene expression.

We have started a phase I/II immunogene therapy study of metastatic renal cell cancer (RCC), using autologous T lymphocytes transduced ex vivo with a gene encoding a single-chain receptor based on the monoclonal antibody (mAb) G250 [scFv(G250)]. G250 recognizes carbonic anhydrase IX, which is overexpressed by RCC cells. We have developed and validated flow cytometric and real-time polymerase chain reaction (PCR) assays to quantitatively detect transduced T cells in patient blood.

On-line implant reconstruction in HDR brachytherapy.

Background And Purpose: To evaluate the accuracy of on-line planning in an Integrated Brachytherapy Unit (IBU) using dedicated image distortion correction algorithms, correcting the geometric distortion and magnetic distortion separately, and to determine the effect of the reconstruction accuracy on clinical treatment plans in terms of deviations in treatment time and dose.

Patients And Methods: The reconstruction accuracy has been measured using 20 markers, positioned at well known locations in a QA phantom. Treatment plans of two phantoms representing clinical implant geometries, have been compared with reference plans to determine the effect of the reconstruction accuracy on the treatment plan.

The palliative value of tumor necrosis factor alpha-based isolated limb perfusion in patients with metastatic sarcoma and melanoma.

Background: Both patients with soft tissue sarcoma (STS) and patients with melanoma have limited treatment possibilities once the tumor has metastasized systemically. In patients with extremity STS or bulky melanoma in-transit metastases, the local tumor burden may be so problematic that, even in patients with systemically metastasized disease, an amputation may be inevitable. Isolated limb perfusion (ILP) has proven to be an excellent, local, limb-saving treatment option in patients with locally advanced extremity tumors.

Survival and prognostic factors in BRCA1-associated breast cancer.

Background: Studies comparing survival in BRCA1-associated and sporadic breast cancer (BC) report inconsistent results and frequently concern small sample sizes. Further, the prognostic impact of the classical tumour and treatment factors is unclear in BRCA1-associated BC.

Patients And Methods: We selected 223 BC patients diagnosed between 1980 and 2001 within families with a deleterious germline BRCA1-mutation ascertained at the Rotterdam Family Cancer Clinic.

Phoenix-ampho outperforms PG13 as retroviral packaging cells to transduce human T cells with tumor-specific receptors: implications for clinical immunogene therapy of cancer.

We have designed a transgene that encodes a scFv(G250) chimeric receptor, which is specific for carboxyanhydrase IX (G250-ligand, G250L), a molecule overexpressed by renal cell cancer (RCC). Retroviral transduction of this transgene into primary human T lymphocytes confers these cells with specific functional responses towards G250L-positive RCC cells. In preparation of a clinical phase (I/II) study in RCC patients, we set up a protocol for gene transduction and expansion of primary human T cells.

Radiation therapy for prostate cancer and erectile (dys)function: the role of imaging.

Incidence of erectile dysfunction (ED) after radiotherapy reported in the literature varies from 7 to 72% after external-beam radiotherapy to 5-51% after brachytherapy. Most of these studies are retrospective, the definition of ED is variable and sexual functioning is frequently assessed by asking only one question. Already in the 1980's it was suggested that post-radiation ED was attributable to vascular damage.

Salvage abdominoperineal resection and perineal wound healing in local recurrent or persistent anal cancer.

The primary treatment for anal cancer is chemoradiation (CRT). Failures after CRT are potentially curable with an abdominoperineal resection (APR). A major problem of surgery in the anal area is poor healing of the perineal wound.

TNF dose reduction in isolated limb perfusion.

Aims: Isolated limb perfusion with TNF and melphalan (TM-ILP) is highly effective in the local treatment of advanced sarcoma and melanoma of the limb. The optimal dose of TNF for this procedure is not well established. The aim of this study was to assess the efficacy and toxicity of TM-ILPs with reduced TNF dose.

Potential for improvement of docetaxel-based chemotherapy: a pharmacological review.

Since the introduction of docetaxel, research has focused on various approaches to overcome treatment limitations and improve outcome. This review discusses the pharmacological attempts at treatment optimisation, which include reducing interindividual pharmacokinetic and pharmacodynamic variability, optimising schedule, route of administration, reversing drug resistance and the development of structurally related second-generation taxanes.

Primary and secondary reconstruction after surgery of the irradiated pelvis using a gracilis muscle flap transposition.

Introduction: The aim of this study is to describe our experience with reconstruction of pelvic defects after surgery for previously irradiated malignancies using a gracilis muscle flap transposition.

Patients And Methods: Between 1993 and 2002, 25 patients were treated by primary (n=7) or secondary reconstruction (n=18) using a gracilis muscle transfer. All patients were previously irradiated with a median dosage of 50 Gy.