Does pre-operative estimation of oesophageal tumour metabolic length using F-18-fluorodeoxyglucose PET/CT images compare with surgical pathology length?

PURPOSE:
The aim of the study was to compare the pre-operative metabolic tumour length on FDG PET/CT with the resected pathological specimen in patients with oesophageal cancer.

METHODS:
All patients diagnosed with oesophageal carcinoma who had undergone staging PET/CT imaging between the period of June 2002 and May 2008 who were then suitable for curative surgery, either with or without neo-adjuvant chemotherapy, were included in this study. Metabolic tumour length was assessed using both visual analysis and a maximum standardised uptake value (SUV(max)) cutoff of 2.5.

RESULTS:
Thirty-nine patients proceeded directly to curative surgical resection, whereas 48 patients received neo-adjuvant chemotherapy, followed by curative surgery. The 95% limits of agreement in the surgical arm were more accurate when the metabolic tumour length was visually assessed with a mean difference of -0.05 cm (SD 2.16 cm) compared to a mean difference of +2.42 cm (SD 3.46 cm) when assessed with an SUV(max) cutoff of 2.5. In the neo-adjuvant group, the 95% limits of agreement were once again more accurate when assessed visually with a mean difference of -0.6 cm (SD 1.84 cm) compared to a mean difference of +1.58 cm (SD 3.1 cm) when assessed with an SUV(max) cutoff of 2.5.

CONCLUSION:
This study confirms the high accuracy of PET/CT in measuring gross target volume (GTV) length. A visual method for GTV length measurement was demonstrated to be superior and more accurate than when using an SUV(max) cutoff of 2.5. This has the potential of reducing the planning target volume with dose escalation to the tumour with a corresponding reduction in normal tissue complication probability.

18F-fluorodeoxyglucose positron emission tomography/computed tomography-based radiotherapy target volume definition in non-small-cell lung cancer: delineation by radiation oncologists vs. joint outlining with a PET radiologist?

Purpose: F-18-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has benefits in target volume (TV) definition in radiotherapy treatment planning (RTP) for non small-cell lung cancer (NSCLC); however, an optimal protocol for TV delineation has not been determined. We investigate volumetric and positional variation in gross tumor volume (GTV) delineation using a planning PET/CT among three radiation oncologists and a PET radiologist.

Out-of-field cell survival following exposure to intensity-modulated radiation fields

PURPOSE:
To determine the in-field and out-of-field cell survival of cells irradiated with either primary field or scattered radiation in the presence and absence of intercellular communication.
METHODS AND MATERIALS:
Cell survival was determined by clonogenic assay in human prostate cancer (DU145) and primary fibroblast (AGO1552) cells following exposure to different field configurations delivered using a 6-MV photon beam produced with a Varian linear accelerator.
RESULTS:
Nonuniform dose distributions were delivered using a multileaf collimator (MLC) in which half of the cell population was shielded. Clonogenic survival in the shielded region was significantly lower than that predicted from the linear quadratic model. In both cell lines, the out-of-field responses appeared to saturate at 40%-50% survival at a scattered dose of 0.70 Gy in DU-145 cells and 0.24 Gy in AGO1522 cells. There was an approximately eightfold difference in the initial slopes of the out-of-field response compared with the a-component of the uniform field response. In contrast, cells in the exposed part of the field showed increased survival. These observations were abrogated by direct physical inhibition of cellular communication and by the addition of the inducible nitric oxide synthase inhibitor aminoguanidine known to inhibit intercellular bystander effects. Additional studies showed the proportion of cells irradiated and dose delivered to the shielded and exposed regions of the field to impact on response.
CONCLUSIONS:
These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields with cellular communication between differentially irradiated cell populations playing an important role. Validation of these observations in additional cell models may facilitate the refinement of existing radiobiological models and the observations considered important determinants of cell survival.

Temporal characterization and in vitro comparison of cell survival following the delivery of 3D-conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT)

A phantom was designed and implemented for the delivery of treatment plans to cells in vitro. Single beam, 3D-conformal radiotherapy (3D-CRT) plans, inverse planned five-field intensity-modulated radiation therapy (IMRT), nine-field IMRT, single-arc volumetric modulated arc therapy (VMAT) and dual-arc VMAT plans were created on a CT scan of the phantom to deliver 3 Gy to the cell layer and verified using a Farmer chamber, 2D ionization chamber array and gafchromic film. Each plan was delivered to a 2D ionization chamber array to assess the temporal characteristics of the plan including delivery time and 'cell's eye view' for the central ionization chamber. The effective fraction time, defined as the percentage of the fraction time where any dose is delivered to each point examined, was also assessed across 120 ionization chambers. Each plan was delivered to human prostate cancer DU-145 cells and normal primary AGO-1522b fibroblast cells. Uniform beams were delivered to each cell line with the delivery time varying from 0.5 to 20.54 min. Effective fraction time was found to increase with a decreasing number of beams or arcs. For a uniform beam delivery, AGO-1552b cells exhibited a statistically significant trend towards increased survival with increased delivery time. This trend was not repeated when the different modulated clinical delivery methods were used. Less sensitive DU-145 cells did not exhibit a significant trend towards increased survival with increased delivery time for either the uniform or clinical deliveries. These results confirm that dose rate effects are most prevalent in more radiosensitive cells. Cell survival data generated from uniform beam deliveries over a range of dose rates and delivery times may not always be accurate in predicting response to more complex delivery techniques, such as IMRT and VMAT.

Assessing software upgrades, plan properties and patient geometry using intensity modulated radiation therapy (IMRT) complexity metrics

Purpose: The aim of this study is to compare the sensitivity of different metrics to detect differences in complexity of intensity modulated radiation therapy (IMRT) plans following upgrades, changes to planning parameters, and patient geometry. Correlations between complexity metrics are also assessed.

Systematic review of reviews of risk factors for intracranial aneurysms

Systematic reviews of systematic reviews identify good quality reviews of earlier studies of medical conditions. This article describes a systematic review of systematic reviews performed to investigate factors that might influence the risk of rupture of an intracranial aneurysm. It exemplifies the technique of this type of research and reports the finding of a specific study. The annual incidence of subarachnoid haemorrhage resulting from the rupture of intracranial aneurysms is estimated to be nine per 100,000. A large proportion of people who have this bleed, will die or remain dependent on the care of others for some time. Reliable knowledge about the risks of subarachnoid haemorrhage in different populations will help in planning, screening and prevention strategies and in predicting the prognosis of individual patients. If the necessary data were available in the identified reviews, an estimate for the numerical relationship between a particular characteristic and the risk of subarachnoid haemorrhage was included in this report. The identification of eligible systematic reviews relied mainly on the two major bibliographic databases of the biomedical literature: PubMed and EMBASE. These were searched in 2006, using specially designed search strategies. Approximately 2,000 records were retrieved and each of these was checked carefully against the eligibility criteria for this systematic review. These criteria required that the report be a systematic review of studies assessing the risk of subarachnoid haemorrhage in patients known to have an unruptured intracranial aneurysm or of studies that had investigated the characteristics of people who experienced a subarachnoid haemorrhage without previously being known to have an unruptured aneurysm. Reports which included more than one systematic review were eligible and each of these reviews was potentially eligible. The quality of each systematic review was assessed. In this review, 16 separate reports were identified, including a total of 46 eligible systematic reviews. These brought together research studies for 24 different risk factors. This has shown that the following factors appear to be associated with a higher risk of subarachnoid haemorrhage: being a woman, older age, posterior circulation aneurysms, larger aneurysms, previous symptoms,

Gamma Knife Radiosurgery as a Therapeutic Strategy for Intracranial Sarcomatous Metastases

Purpose: To determine the indication and outcomes for Gamma Knife stereotactic radiosurgery (GKSRS) in the care of patients with intracranial sarcomatous metastases. Methods and Materials: Data from 21 patients who underwent radiosurgery for 60 sarcomatous intracranial metastases (54 parenchymal and 6 dural-based) were studied. Nine patients had radiosurgery for solitary tumors and 12 for multiple tumors. The primary pathology was metastatic leiomyosarcoma (4 patients), osteosarcoma (3 patients), soft-tissue sarcoma (5 patients), chondrosarcoma (2 patients), alveolar soft part sarcoma (2 patients), and rhabdomyosarcoma, Ewing's sarcoma, liposarcoma, neurofibrosarcoma, and synovial sarcoma (1 patient each). Twenty patients received multimodality management for their primary tumor, and 1 patient had no evidence of systemic disease. The mean tumor volume was 6.2 cm 3 (range, 0.07-40.9 cm 3), and a median margin dose of 16 Gy was administered. Three patients had progressive intracranial disease despite fractionated whole-brain radiotherapy before SRS. Results: A local tumor control rate of 88% was achieved (including patients receiving boost, up-front, and salvage SRS). New remote brain metastases developed in 7 patients (33%). The median survival after diagnosis of intracranial metastasis was 16 months, and the 1-year survival rate was 61%. Conclusions: Gamma Knife radiosurgery was a well-tolerated and initially effective therapy in the management of patients with sarcomatous intracranial metastases. However, many patients, including those who also received fractionated whole-brain radiotherapy, developed progressive new brain disease. © 2010 Elsevier Inc. All rights reserved.

pcDNA3.1tdTomato is superior to pDsRed2-N1 for optical fluorescence imaging in the F344/AY-27 rat model of bladder cancer

PURPOSE: Animal models are important for pre-clinical assessment of novel therapies in metastatic bladder cancer. The F344/AY-27 model involves orthotopic colonisation with AY-27 tumour cells which are syngeneic to F344 rats. One disadvantage of the model is the unknown status of colonisation between instillation and sacrifice. Non-invasive optical imaging using red fluorescence reporters could potentially detect tumours in situ and would also reduce the number of animals required for each experiment.

MATERIALS AND METHODS: AY-27 cells were stably transfected with either pDsRed2-N1 or pcDNA3.1tdTomato. The intensity and stability of fluorescence in the resultant AY-27/DsRed2-N1 and AY-27/tdTomato stable cell lines were compared using Xenogen IVIS®200 and Olympus IX51 systems.

RESULTS: AY-27/tdTomato fluorescence intensity was 60-fold brighter than AY-27/DsRed2-N1 and was sustained in AY-27/tdTomato cells following freezing and six subsequent sub-cultures. After sub-cutaneous injection, fluorescence intensity from AY-27/tdTomato cells was threefold stronger than that detected from AY-27/DsRed2-N1 cells. IVIS®200 detected fluorescence from AY-27/tdTomato and AY-27/DsRed2-N1 cells colonising resected and exteriorised bladders, respectively. However, the deep-seated position of the bladder precluded in vivo imaging. Characteristics of AY-27/tdTomato cells in vitro and in tumours colonising F344 rats resembled those of parental AY-27 cells. Tumour transformation was observed in the bladders colonised with AY-27/DsRed2-N1 cells.

CONCLUSIONS: In vivo whole-body imaging of internal red fluorescent animal tumours should use pcDNA3.1tdTomato rather than pDsRed2-N1. Optical imaging of deep-seated organs in larger animals remains a challenge which may require proteins with brighter red or far-red fluorescence and/or alternative approaches.

Conventional 3D staging PET/CT in CT simulation for lung cancer: impact of rigid and deformable target volume alignments for radiotherapy treatment planning

Objective: Positron emission tomography (PET)/CT scans can improve target definition in radiotherapy for non-small cell lung cancer (NSCLC). As staging PET/CT scans are increasingly available, we evaluated different methods for co-registration of staging PET/CT data to radiotherapy simulation (RTP) scans.

Methods: 10 patients underwent staging PET/CT followed by RTP PET/CT. On both scans, gross tumour volumes (GTVs) were delineated using CT (GTVCT) and PET display settings. Four PET-based contours (manual delineation, two threshold methods and a source-to-background ratio method) were delineated. The CT component of the staging scan was co-registered using both rigid and deformable techniques to the CT component of RTP PET/CT. Subsequently rigid registration and deformation warps were used to transfer PET and CT contours from the staging scan to the RTP scan. Dice’s similarity coefficient (DSC) was used to assess the registration accuracy of staging-based GTVs following both registration methods with the GTVs delineated on the RTP PET/CT scan.

Results: When the GTVCT delineated on the staging scan after both rigid registration and deformation was compared with the GTVCT on the RTP scan, a significant improvement in overlap (registration) using deformation was observed (mean DSC 0.66 for rigid registration and 0.82 for deformable registration, p50.008). A similar comparison for PET contours revealed no significant improvement in overlap with the use of deformable registration.

Conclusions: No consistent improvements in similarity measures were observed when deformable registration was used for transferring PET-based contours from a staging PET/CT. This suggests that currently the use of rigid registration remains the most appropriate method for RTP in NSCLC.

A Robust Curve-Fitting Procedure for the Analysis of Plasmid DNA Strand Break Data from Gel Electrophoresis

A robust method for fitting to the results of gel electrophoresis assays of damage to plasmid DNA caused by radiation is presented. This method makes use of nonlinear regression to fit analytically derived dose response curves to observations of the supercoiled, open circular and linear plasmid forms simultaneously, allowing for more accurate results than fitting to individual forms. Comparisons with a commonly used analysis method show that while there is a relatively small benefit between the methods for data sets with small errors, the parameters generated by this method remain much more closely distributed around the true value in the face of increasing measurement uncertainties. This allows for parameters to be specified with greater confidence, reflected in a reduction of errors on fitted parameters. On test data sets, fitted uncertainties were reduced by 30%, similar to the improvement that would be offered by moving from triplicate to fivefold repeats (assuming standard errors). This method has been implemented in a popular spreadsheet package and made available online to improve its accessibility. (C) 2011 by Radiation Research Society

Assessing the image quality of pelvic MR images acquired with a flat couch for radiotherapy treatment planning

Objectives: To improve the integration of MRI with radiotherapy treatment planning, our department fabricated a flat couch top for our MR scanner. Setting up using this couch top meant that the patients were physically higher up in the scanner and, posteriorly, a gap was introduced between the patient and radiofrequency coil.