Cone beam CT verification for oesophageal cancer - impact of volume selected for image registration.

PURPOSE: Oesophageal cancers are difficult to visualise on volumetric imaging and reliable surrogate are needed for accurate tumour registration. The aim of this investigation is to evaluate the effect of a user defined volume with automated registration techniques using commercially available software with the on-board volumetric imaging for treatment verification of oesophageal cancer and determine the optimum location of this volume. MATERIAL AND METHODS: In 20 patients four 'clipbox'(C) volumes were defined: C-planning target volume (PTV), C-carina, C-vertebrae, C-thorax. The set-up corrections (translational and rotational) for C-PTV were compared to the corrections using C-carina, C-vertebrae and C-thorax. RESULTS: Six hundred and eight registrations were performed. The best concordance in set-up corrections was found in the superior/inferior direction between C-PTV and C-carina (76%). In the right/left and anterior/posterior direction, better agreement was found between C-PTV and C-thorax with 80% and 76% agreement, respectively. Automatic 'bone' registration using C-vertebrae failed in 28% of scans. The correlation ratio between C-PTV and C-carina (n = 4) for mid-oesophageal tumours was 0.88, 0.79, and 0.95 in the right/left, superior/inferior and anterior/posterior directions, respectively. CONCLUSION: The defined volume for matching is important for oesophageal tumours. The alignment 'clipbox' and registration method selected can affect the displacements obtained. This may best be determined by tumour location and highlights the need to diversify protocols within one tumour treatment site. Further analysis is required to validate carina as a tumour surrogate for mid-oesophageal tumours.

Treatment of lung cancer using volumetric modulated arc therapy and image guidance: a case study.

BACKGROUND: Volumetric modulated arc therapy (VMAT) is a radiotherapy technique in which the gantry rotates while the beam is on. Gantry speed, multileaf collimator (MLC) leaf position and dose rate vary continuously during the irradiation. For optimum results, this type of treatment should be subject to image guidance. The application of VMAT and image guidance to the treatment of a lung cancer patient is described. MATERIAL AND METHODS: In-house software AutoBeam was developed to facilitate treatment planning for VMAT beams. The algorithm consisted of a fluence optimisation using the iterative least-squares technique, a segmentation and then a direct-aperture optimisation. A dose of 50 Gy in 25 fractions was planned, using a single arc with 35 control points at 10 degrees intervals. The resulting plan was transferred to a commercial treatment planning system for final calculation. The plan was verified using a 0.6 cm(3) ionisation chamber and film in a rectangular phantom. The patient was treated supine on a customised lung board and imaged daily with cone-beam CT for the first three days then weekly thereafter. RESULTS: The VMAT plan provided slightly improved coverage of the planning target volume (PTV) and slightly lower volume of lung irradiated to 20 Gy (V(20)) than a three-field conformal plan (PTV minimum dose 85.0 Gy vs. 81.8 Gy and lung V(20) 31.5% vs. 34.8%). The difference between the measured and planned dose was -1.1% (measured dose lower) and 97.6% of the film passed a gamma test of 3% and 3mm. The VMAT treatment required 90 s for delivery of a single fraction of 2 Gy instead of 180 s total treatment time for the conformal plan. CONCLUSION: VMAT provides a quality dose distribution with a short treatment time as shown in an example of a lung tumour. The technique should allow for more efficient delivery of high dose treatments, such as used for hypofractionated radiotherapy of small volume lung tumours, and the technique may also be used in conjunction with Active Breathing Control, where fewer breath holds will be required.

District nurses' triggers for referral of patients to the Macmillan nurse.

This study aimed to identify the triggers which motivate district nurses to refer patients to the Macmillan nursing service and resulted from observation within the researcher's clinical practice, when it was noted that referral patterns from district nurses to the Macmillan nursing service were very inconsistent. A qualitative exploratory descriptive design was utilised and the analysis of the findings identified three 'key' themes, which motivate district nurses to refer: knowledge and skills, interprofessional issues and perception of Macmillan. Within each theme emerged an amalgam of triggers which were complex in nature, pertaining not only to patient need, but also to the needs of the district nursing service. However, it became apparent during the analysis that there was also a lack of knowledge regarding the role of the Macmillan nurse. This lack of knowledge relating to the Macmillan nurse role had been affirmed previously by several authors (Graves and Nash 1993, Clark et al 2002, Ahmed et al 2004) but the literature also reported that the Macmillan nurse role was open to confusion (Clark et al 2002, Corner 2003). This confusion may potentially affect referrals and prevent patients from receiving the services of the Macmillan nurse. This study has established a need for the development of referral criteria into the Macmillan nursing service and that there is also an identified need for further research, providing scope for the Macmillan nurse and district nurse to work collaboratively to improve palliative services in the community.

Comparison of setup accuracy and intrafraction motion using stereotactic frame versus 3-point thermoplastic mask-based immobilization for fractionated cranial image guided radiation therapy.

PURPOSE: Prospectively compare patient setup accuracy and intrafraction motion of a standard 3-point thermoplastic mask with the Gill-Thomas-Cosman relocatable stereotactic frame, during fractionated cranial radiation therapy using the ExacTrac system (Brainlab AG Feldkirchen, Germany) for daily online correction. METHODS AND MATERIALS: The number of fractions with all postcorrection and post-treatment errors <2 mm was assessed in 21 patients undergoing fractionated stereotactic radiation therapy (13 frame setup, 8 mask setup) using daily online correction. Achievable patient setup accuracy and total intrafraction motion were evaluated. The relative contributions of movement during floor rotation and patient movement to intrafraction motion were calculated. RESULTS: With daily online correction, patient setup margins can be reduced from 1, 5, and 4 mm in the lateral, longitudinal, and vertical axes for mask setup and from 1-2, 2, and 1 mm, respectively, for frame setup to <1 mm isotropically for either immobilization system. Intrafraction movement was small for frame setup (mean [SD], -0.3 [0.3], -1.1[0.4], and -0.2 [0.6] in lateral, longitudinal and vertical axes, respectively; maximum, -2.7 mm [longitudinal axis]), and mask-setup (mean [SD], -0.4 [0.5], -0.8 [0.7], and 0.0 [0.3], respectively; maximum, -2.0 mm [longitudinal axis]) and is mainly due to floor rotation. Postcorrection and post-treatment errors were all <2 mm in 95% and 99% of fractions in the mask and frame, respectively, meeting the criteria for a 3-mm clinical target volume-planning target volume margin for either immobilization method. CONCLUSIONS: Daily online correction can compensate for less precise immobilization and permits stereotactic margins to be used for standard thermoplastic masks without the need for specialized mask systems.

Set-up errors in radiotherapy for oesophageal cancers--is electronic portal imaging or conebeam more accurate?

PURPOSE: To compare kV computed tomography (CBCT) with electronic portal imaging (EPI) and evaluate set-up variations in the anterior-posterior (AP), right-left (LR) and cranio-caudal (CC) directions and rotational variations: pitch, roll, and yaw, for oesophageal cancer patients treated with radical radiotherapy. METHODS AND MATERIALS: Twenty patients with locally advanced oesophageal cancer treated with chemoradiation were consented for this prospective ethics approved protocol. Patients were positioned using skin marks/tattoos, kV-CBCT scans (XVI) and EPI's were performed prior to treatment and registered to the planning CT scans and digitally reconstructed radiographs, respectively. XVI data was used to adjust patient setups before treatment delivery. A total of 122 EPI pairs and 207 CBCT scans were analysed. The systematic and random errors were calculated. RESULTS: The systematic and random errors (mm) for XVI were 1.3, 1.7, 1.4 and 2.6, 3.9, 2.0 in RL, CC and AP direction, respectively, with EPI of similar magnitude. There was no correlation between the 2 modalities of imaging as 31.7% of all image pairs were discordant >3 mm and 12.5% >5 mm. XVI identified rotations >3° in 44 images. CONCLUSIONS: EPI results in different position correction for verification of radiotherapy in oesophageal malignancies when compared with CBCT. CBCT verification offers adequate 3D volumetric image quality to improve the accuracy of treatment delivery for oesophageal malignancies in radiotherapy and should be used for image guidance.

Quantification of organ motion during chemoradiotherapy of rectal cancer using cone-beam computed tomography.

PURPOSE: There has been no previously published data related to the quantification of rectal motion using cone-beam computed tomography (CBCT) during standard conformal long-course chemoradiotherapy. The purpose of the present study was to quantify the interfractional changes in rectal movement and dimensions and rectal and bladder volume using CBCT and to quantify the bony anatomy displacements to calculate the margins required to account for systematic (Σ) and random (σ) setup errors. METHODS AND MATERIALS: CBCT images were acquired from 16 patients on the first 3 days of treatment and weekly thereafter. The rectum and bladder were outlined on all CBCT images. The interfraction movement was measured using fixed bony landmarks as references to define the rectal location (upper, mid, and low), The maximal rectal diameter at the three rectal locations was also measured. The bony anatomy displacements were quantified, allowing the calculation of systematic (Σ) and random (σ) setup errors. RESULTS: A total of 123 CBCT data sets were analyzed. Analysis of variance for standard deviation from planning scans showed that rectal anterior and lateral wall movement differed significantly by rectal location. Anterior and lateral rectal wall movements were larger in the mid and upper rectum compared with the low rectum. The posterior rectal wall movement did not change significantly with the rectal location. The rectal diameter changed more in the mid and upper than in the low rectum. No consistent relationship was found between the rectal and bladder volume and time, nor was a significant relationship found between the rectal volume and bladder volume. CONCLUSIONS: In the present study, the anterior and lateral rectal movement and rectal diameter were found to change most in the upper rectum, followed by the mid rectum, with the smallest changes seen in the low rectum. Asymmetric margins are warranted to ensure phase 2 coverage.

Cone beam computed tomography-derived adaptive radiotherapy for radical treatment of esophageal cancer.

PURPOSE: To investigate the potential for reduction in normal tissue irradiation by creating a patient specific planning target volume (PTV) using cone beam computed tomography (CBCT) imaging acquired in the first week of radiotherapy for patients receiving radical radiotherapy. METHODS AND MATERIALS: Patients receiving radical RT for carcinoma of the esophagus were investigated. The PTV is defined as CTV(tumor, nodes) plus esophagus outlined 3 to 5 cm cranio-caudally and a 1.5-cm circumferential margin is added (clinical plan). Prefraction CBCT are acquired on Days 1 to 4, then weekly. No correction for setup error made. The images are imported into the planning system. The tumor and esophagus for the length of the PTV are contoured on each CBCT and 5 mm margin is added. A composite volume (PTV1) is created using Week 1 composite CBCT volumes. The same process is repeated using CBCT Week 2 to 6 (PTV2). A new plan is created using PTV1 (adaptive plan). The coverage of the 95% isodose of PTV1 is evaluated on PTV2. Dose-volume histograms (DVH) for lungs, heart, and cord for two plans are compared. RESULTS: A total of 139 CBCT for 14 cases were analyzed. For the adaptive plan the coverage of the 95% prescription isodose for PTV1 = 95.6% +/- 4% and the PTV2 = 96.8% +/- 4.1% (t test, 0.19). Lungs V20 (15.6 Gy vs. 10.2 Gy) and heart mean dose (26.9 Gy vs. 20.7 Gy) were significantly smaller for the adaptive plan. CONCLUSIONS: A reduced planning volume can be constructed within the first week of treatment using CBCT. A single plan modification can be performed within the second week of treatment with considerable reduction in organ at risk dose.

Evidence for a role for Galphai1 in mediating weak agonist-induced platelet aggregation in human platelets: reduced Galphai1 expression and defective Gi signaling in the platelets of a patient with a chronic bleeding disorder.

We have examined platelet functional responses and characterized a novel signaling defect in the platelets of a patient suffering from a chronic bleeding disorder. Platelet aggregation responses stimulated by weak agonists such as adenosine diphosphate (ADP) and adrenaline were severely impaired. In comparison, both aggregation and dense granule secretion were normal following activation with high doses of collagen, thrombin, or phorbol-12 myristate-13 acetate (PMA). ADP, thrombin, or thromboxane A2 (TxA2) signaling through their respective Gq-coupled receptors was normal as assessed by measuring either mobilization of intracellular calcium, diacylglycerol (DAG) generation, or pleckstrin phosphorylation. In comparison, Gi-mediated signaling induced by either thrombin, ADP, or adrenaline, examined by suppression of forskolin-stimulated rise in cyclic AMP (cAMP) was impaired, indicating dysfunctional Galphai signaling. Immunoblot analysis of platelet membranes with specific antiserum against different Galpha subunits indicated normal levels of Galphai2,Galphai3,Galphaz, and Galphaq in patient platelets. However, the Galphai1level was reduced to 25% of that found in normal platelets. Analysis of platelet cDNA and gDNA revealed no abnormality in either the Galphai1 or Galphai2 gene sequences. Our studies implicate the minor expressed Galphai subtype Galphai1 as having an important role in regulating signaling pathways associated with the activation of alphaIIbbeta3 and subsequent platelet aggregation by weak agonists.