Comparison of NMR lipid profiles in mitotic arrest and apoptosis as indicators of paclitaxel resistance in cervical cell lines.

This study aimed to characterize changes in lipid saturation using magnetic resonance spectroscopy of sensitive (HeLa) and resistant (C33A; Me180) cervical cancer cell lines following exposure to paclitaxel to explore lipid profiles as biomarkers of drug resistance. Spectra were acquired at 11.74 T.

Parameters for the Lyman Kutcher Burman (LKB) model of Normal Tissue Complication Probability (NTCP) for specific rectal complications observed in clinical practise.

Background And Purpose: The Normal Tissue Complication Probability (NTCP) for rectum is usually defined for late rectal bleeding. This study calculates NTCP parameter values for additional rectal toxicity endpoints observed in clinical practise.

Materials And Methods: 388 patients from the multicentre MRC-RT01 prostate conformal radiotherapy trial (ISRCTN 47772397) were used to derive independent Lyman Kutcher Burman model (LKB) parameters for five late rectal toxicity endpoints: rectal bleeding, proctitis, stool frequency, loose stools and rectal urgency.

Computerized detection of breast lesions in multi-centre and multi-instrument DCE-MR data using 3D principal component maps and template matching.

In this study, we introduce a novel, robust and accurate computerized algorithm based on volumetric principal component maps and template matching that facilitates lesion detection on dynamic contrast-enhanced MR. The study dataset comprises 24,204 contrast-enhanced breast MR images corresponding to 4034 axial slices from 47 women in the UK multi-centre study of MRI screening for breast cancer and categorized as high risk. The scans analysed here were performed on six different models of scanner from three commercial vendors, sited in 13 clinics around the UK.

MLC tracking for Elekta VMAT: a modelling study.

A model has been developed to simulate volumetric modulated arc therapy (VMAT) delivery for Elekta control systems. The model was experimentally validated for static-tumour VMAT delivery and has been applied to the investigation of motion compensation with dynamic multileaf collimator (dMLC) delivery tracking for a series of VMAT lung treatment plans at various control point spacings for five patients. The relative increase in treatment time with dMLC tracking was calculated for four 1D rigid-body motion trajectories, and the effect of the control point spacing, the MLC leaf speed and an increased number of dose levels on the dMLC tracking delivery time evaluated.

Dosimetric consequences of inter-fraction breathing-pattern variation on radiotherapy with personalized motion-assessed margins.

The data from eight patients who had undergone stereotactic body radiotherapy were selected due to their 4D-CT planning scans showing that their tumours had respiratory induced motion trajectories of large amplitude (greater than 9 mm in cranio-caudal direction). Radiotherapy plans with personalized motion-assessed margins were generated for these eight patients. The margins were generated by inverse 4D planning on an eight-bin phase-sorted 4D-CT scan.

A 4-bank multileaf collimator provides a decomposition advantage for delivering intensity-modulated beams by step-and-shoot.

During the delivery of intensity-modulated radiation therapy (IMRT) by the multileaf collimator (MLC) step-and-shoot technique, it is required to sequence the two-dimensional intensity-modulated beams (2D IMBs) into a series of components that can be shaped with the MLC. In this paper it is shown that the use of an MLC that has four banks of leaves (in two orthogonal pairs) instead of two banks only is advantageous for this purpose.

Exploiting tumor metabolism for non-invasive imaging of the therapeutic activity of molecularly targeted anticancer agents.

Rational drug discovery and development requires biomarkers to inform on target modulation and treatment efficacy. Many aspects of metabolism are altered in cancer, compared to normal tissues, and are often regulated by oncogene activation. Non-invasive imaging of spatio-temporal effects of molecularly targeted anticancer agents on tumor metabolism has considerable potential in the development and use of personalized molecular medicine approaches to cancer treatment.

Assessing response in bone metastases in prostate cancer with diffusion weighted MRI.

Objectives: To determine whether changes in ADC of bone metastases secondary to prostate carcinoma are significantly different in responders compared with progressors on chemotherapy.

Methods: Twenty-six patients with known bone metastases secondary to prostate carcinoma underwent diffusion-weighted MRI of the lumbar spine and pelvis at baseline and 12 weeks following chemotherapy. RECIST assessment of staging CT and PSA taken at the same time points were used to classify patients as responders, progressors or stable.

Imaging cervical cancer: recent advances and future directions.

Purpose Of Review: There has been considerable progress in the imaging of cervical cancer over the last 5 years. In countries with access to cross-sectional imaging resources, technical advances have enabled a range of imaging techniques to become increasingly employed and established in the detection, staging and treatment planning of cervical cancer and for identifying disease recurrence. This review highlights these developments and summarizes recent significant articles.

A population-based study of prostate cancer chemotherapy.

The use of chemotherapy in the treatment of prostate cancer is a relatively recent development, with no published data on the patterns of care in the UK. We carried out a population-based study to assess variation in the use of prostate cancer chemotherapy over time in a UK cancer network.

The CT flare response of metastatic bone disease in prostate cancer.

Background: New or worsening bone lesions in patients responding to treatment, known as the flare phenomenon is well described on (99m)Tc-MDP bone scintigraphy, but to our knowledge has not previously been described on CT. The appearance of new or worsening bone sclerosis on CT in patients with prostate cancer may therefore be erroneously classified as disease progression.

Purpose: To assess the incidence of osteoblastic healing flare response at 3-month CT assessment in patients with castrate-resistant prostate cancer and to identify associated features that enable differentiation from progressive metastatic bone disease at 3 months.

Optimising diffusion weighted MRI for imaging metastatic and myeloma bone disease and assessing reproducibility.

Objectives: To establish normal bone marrow values of apparent diffusion coefficient (ADC) over an age range, compare them with metastatic and myelomatous involvement, to establish reproducibility and to optimise b values.

Methods: The ADCs of bone marrow in 7 volunteers (mean age 29.7 years), 34 volunteers (mean age 63.

Optimising stereotactic body radiotherapy for non-small cell lung cancer with volumetric intensity-modulated arc therapy--a planning study.

Aims: The potential advantages of stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC) over conventional fractionated radiotherapy include a higher biological effective dose, a reduction in accelerated repopulation, greater patient convenience and reduced demand on radiotherapy resources. Before introducing SBRT in our department, a review of planning and delivery was undertaken, starting with an assessment of optimum beam number and arrangement.

Materials And Methods: Radiotherapy planning computed tomography scans for five patients previously treated for T1 peripheral NSCLC were selected.

Modeling late rectal toxicities based on a parameterized representation of the 3D dose distribution.

Many models exist for predicting toxicities based on dose-volume histograms (DVHs) or dose-surface histograms (DSHs). This approach has several drawbacks as firstly the reduction of the dose distribution to a histogram results in the loss of spatial information and secondly the bins of the histograms are highly correlated with each other. Furthermore, some of the complex nonlinear models proposed in the past lack a direct physical interpretation and the ability to predict probabilities rather than binary outcomes.

New strategies in metastatic prostate cancer: targeting the androgen receptor signaling pathway.

Recent data report that abiraterone acetate, a specific inhibitor of CYP17 that is key to androgen and estrogen synthesis, improves survival in metastatic castration-resistant prostate cancer (CRPC), confirming the continued dependency of CRPC on the androgen receptor (AR) signaling pathway. MDV3100 is a novel antagonist of AR that is also in phase III clinical trials. In addition, several other agents targeting the AR axis are undergoing evaluation in early clinical studies.

Removal and effects of scatter-glare in cone-beam CT with an amorphous-silicon flat-panel detector.

Scatter in a detector and its housing can result in image degradation. Typically, such scatter leads to a low-spatial frequency 'glare' superimposed on the primary signal. We infer the glare-spread function (GSF) of an amorphous-silicon flat-panel detector via an edge-spread technique.

Diffusion-weighted magnetic resonance imaging for monitoring prostate cancer progression in patients managed by active surveillance.

Objectives: We studied patients managed by active surveillance to determine whether there was a difference over time in apparent diffusion coefficients (ADCs) derived from diffusion-weighted MRI in those who progressed to radical treatment (progressors, n = 17) compared with those who did not (non-progressors, n = 33).

Methods: 50 consecutive patients (Stage T1/2a, Gleason grade ≤ 3+4, prostate-specific antigen (PSA) <15 ng ml⁻¹, <50% cores positive) were imaged endorectally (baseline and 1-3 years follow-up) with T₂ weighted (T₂W) and echo-planar diffusion-weighted MRI sequences. Regions of interest drawn on ADC maps with reference to the T₂W images yielded ADC(all) (b = 0-800), ADC(fast) (b = 0-300) and ADC(slow) (b = 300-800) for whole prostate (minus tumour) and tumour (low signal-intensity peripheral zone lesion in biopsy-positive octant).

Endovaginal magnetic resonance imaging of stage 1A/1B cervical cancer with A T2- and diffusion-weighted magnetic resonance technique: effect of lesion size and previous cone biopsy on tumor detectability.

Objective: To evaluate the effects of previous cone biopsy and lesion size on detectability of stage 1a/1b cervical cancer using endovaginal T2- and diffusion-weighted magnetic resonance imaging.

Methods: One hundred and thirteen patients with cervical tumor were imaged using an endovaginal coil with T2-weighted (T2-W) and diffusion-weighted single-shot echo-planar sequences; 85 managed surgically (58 with prior cone biopsy/LLETZ) were evaluated. T2-W images and ADC maps viewed simultaneously were scored positive or negative for tumor and compared with histology at surgery.

Intensity-modulated radiation therapy (IMRT) by a dynamic-jaws-only (DJO) technique in rotate-translate mode.

In this note it is shown how the use of a rotate-translate methodology employing only jaws, which move dynamically with the beam continuously on, can lead to a delivery of a two-dimensional intensity-modulated beam wherein the modulation is spatially slowly varying. All that is necessary is that a pair of jaws sweep across the face of an accelerator with the aperture between them suitably varying in width and defined by a position-time trajectory function for each jaw. This is then repeated, at the same gantry angle, with the jaws rotated to a different head twist and with a different jaw-pair trajectory for a number of sequential head twists.

Noninvasive detection of carboxypeptidase G2 activity in vivo.

The pseudomonad protein, carboxypeptidase G2 (CPG2), is a prodrug-activating enzyme utilized in the targeted chemotherapy strategies of antibody- and gene-directed enzyme prodrug therapy (ADEPT and GDEPT). We have developed a noninvasive imaging approach to monitor CPG2 activity in vivo that will facilitate the preclinical and clinical development of CPG2-based ADEPT and GDEPT strategies. Cleavage of the novel reporter probe, 3,5-difluorobenzoyl-L-glutamic acid (3,5-DFBGlu), by CPG2, in human colon adenocarcinoma WiDr xenografts engineered to stably express CPG2, was monitored using (19)F MRSI.

CT reconstruction from portal images acquired during volumetric-modulated arc therapy.

Volumetric-modulated arc therapy (VMAT), a form of intensity-modulated arc therapy (IMAT), has become a topic of research and clinical activity in recent years. As a form of arc therapy, portal images acquired during the treatment fraction form a (partial) Radon transform of the patient. We show that these portal images, when used in a modified global cone-beam filtered backprojection (FBP) algorithm, allow a surprisingly recognizable CT-volume to be reconstructed.

Initial management of low-risk localized prostate cancer in the UK: analysis of the British Association of Urological Surgeons Cancer Registry.

Objective: to assess the patterns of care for low-risk localized prostate cancer. Management of this condition is highly controversial, with a range of treatment options, but there are no published UK data.

Methods: data from the British Association of Urological Surgeons (BAUS) Cancer Registry were linked to the UK Association of Cancer registries postcode directory.

Does the option to rotate the Elekta Beam Modulator MLC during VMAT IMRT delivery confer advantage?--a study of 'parked gaps'.

When delivering intensity-modulated radiation therapy (IMRT) using the volumetric modulated arc therapy (VMAT) technique on an Elekta accelerator equipped with the Elekta Beam Modulator multileaf collimator (MLC), the orientation of the MLC, relative to the accelerator head, is generally fixed during the delivery. However, it has the ability to rotate about its axis as the gantry simultaneously rotates. This note shows that this can confer a potential advantage when planning and delivering IMRT via VMAT.

Imaging ovarian cancer and peritoneal metastases--current and emerging techniques.

Peritoneal metastases are often the first presentation of ovarian malignancy. Evaluating the extent of disease critically determines tumor resectability and can also predict outcome. Standard CT, however, frequently fails to identify small sites of peritoneal spread.