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S Webb

Publications and source records attributed to S Webb.

At least 55 records · Page 3Linked to original sources
PubMed2002

Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy.

The potential of intensity modulated radiotherapy (IMRT) to improve the therapeutic ratio in prostate cancer by dose escalation of intraprostatic tumour nodules (IPTNs) was investigated using a simultaneous integrated boost technique. The prostate and organs-at-risk were outlined on CT images from six prostate cancer patients. Positions of IPTNs were transferred onto the CT images from prostate maps derived from sequential large block sections of whole prostatectomy specimens. Inverse planned IMRT dose distributions were created to irradiate the prostate to 70 Gy and all the IPTNs to 90 Gy. A second plan was produced to escalate only the dominant IPTN (DIPTN) to 90 Gy, mimicking current imaging techniques. These plans were compared with homogeneous prostate irradiation to 70 Gy using dose-volume histograms, tumour control probability (TCP) and normal tissue complication probability (NTCP) for the rectum. The mean dose to IPTNs was increased from 69.8 Gy to 89.1 Gy if all the IPTNs were dose escalated (p=0.0003). This corresponded to a mean increase in TCP of 8.7-31.2% depending on the alpha/beta ratio of prostate cancer (p<0.001), and a mean increase in rectal NTCP of 3.0% (p<0.001). If only the DIPTN was dose escalated, the TCP was increased by 6.4-27.5% (p<0.003) and the rectal NTCP was increased by 1.8% (p<0.01). In the dose escalated DIPTN IMRT plans, the highest rectal NTCP was seen in patients with IPTNs in the posterior peripheral zone close to the anterior rectal wall, and the lowest NTCP was seen with IPTNs in the lateral peripheral zone. The ratio of increased TCP to NTCP may represent an improvement in the therapeutic ratio, but was dependent on the position of the IPTN relative to the anterior rectal wall. Improvements in prostate imaging and prostate immobilization are required before clinical implementation would be possible. Clinical trials are required to confirm the clinical benefits of these improved dose distributions.

Algorithms↗
PubMed2001

Septation and valvar formation in the outflow tract of the embryonic chick heart.

There is no agreement, in the chick, about the number of the endocardial cushions within the outflow tract or their pattern of fusion. Also, little is known of their relative contributions to the formation of the arterial valves, the subpulmonary infundibulum, and the arterial valvar sinuses. As the chick heart is an important model for studying septation of the outflow tract, our objective was to clarify these issues. Normal septation of the outflow tract was studied in a series of 60 staged chick hearts, by using stained whole-mount preparations, serial sections, and scanning electron microscopy. A further six hearts were examined subsequent to hatching. At stage 21, two pairs of endocardial cushions were seen within the developing outflow tract. One pair was positioned proximally, with the other pair located distally. By stage 25, a third distal cushion had developed. This finding was before the appearance of two further, intercalated, endocardial cushions, also distally positioned, which were first seen at stage 29. In the arterial segment, the aortic and pulmonary channels were separated by the structure known as the aortopulmonary septum. The dorsal limb of this septum penetrated the distal dorsal cushion, whereas the ventral limb grew between the remaining two distal cushions, both of which were positioned ventrally. The three distal endocardial cushions, and the two intercalated endocardial cushions, contributed to the formation of the leaflets and sinuses of the arterial roots. The two proximal cushions gave rise to a transient septum, which later became transformed into the muscular component of the subpulmonary infundibulum. Concomitant with these changes, an extracardiac tissue plane was formed which separated this newly formed structure from the sinuses of the aortic root. Our study confirms that three endocardial cushions are positioned distally, and two proximally, within the developing outflow tract of the chick. The pattern of the distal cushions, and the position of the ventral limb of the aortopulmonary septum, differs significantly from that seen in mammals.

Animals↗
PubMed2001

Potential role of intensity-modulated radiotherapy in the treatment of tumors of the maxillary sinus.

PURPOSE: To assess 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) techniques to see whether doses to critical structures could be reduced while maintaining planning target volume (PTV) coverage in patients receiving conventional radiotherapy (RT) for carcinoma of the maxillary sinus because of the risk of radiation-induced complications, particularly visual loss. METHODS AND MATERIALS: Six patients who had recently received conventional RT for carcinoma of the maxillary sinus were studied. Conventional RT, 3D-CRT, and step-and-shoot IMRT plans were prepared using the same 2-field arrangement. The effect of reducing the number of segments in the IMRT beams was investigated. RESULTS: 3D-CRT and IMRT reduced the brain and ipsilateral parotid gland doses compared with the conventional plans. IMRT reduced doses to both optic nerves; for the contralateral optic nerve, 15-segment IMRT plans delivered an average maximal dose of 56.4 Gy (range 53.9-59.3) compared with 65.7 Gy (range 65.3-65.9) and 64.2 Gy (range 61.4-65.6) for conventional RT and 3D-CRT, respectively. IMRT also gave improved PTV homogeneity and improved coverage, with an average of 8.5% (range 7.0-11.7%) of the volume receiving <95% of the prescription dose (64 Gy) compared with 14.7% (range 14.1-15.9%) and 15.1% (range 14.4-16.1%) with conventional RT and 3D-CRT, respectively. Little difference was found between the 15 and 7-segment plans, but 5 segments resulted in a reduced minimal PTV dose. CONCLUSIONS: IMRT offers significant advantages over conventional RT and 3D-CRT techniques for treatment of maxillary sinus tumors. Good results can be obtained from 7 segments per beam without compromising the PTV coverage. This number of segments is practical for implementation in a busy RT department.

Humans↗
PubMed2001

Magma storage beneath Axial volcano on the Juan de Fuca mid-ocean ridge.

Axial volcano, which is located near the intersection of the Juan de Fuca ridge and the Cobb-Eickelberg seamount chain beneath the northeast Pacific Ocean, is a locus of volcanic activity thought to be associated with the Cobb hotspot. The volcano rises 700 metres above the ridge, has substantial rift zones extending about 50 kilometres to the north and south, and has erupted as recently as 1998 (ref. 2). Here we present seismological data that constrain the three-dimensional velocity structure beneath the volcano. We image a large low-velocity zone in the crust, consisting of a shallow magma chamber and a more diffuse reservoir in the lower crust, and estimate the total magma volume in the system to be between 5 and 21 km3. This volume is two orders of magnitude larger than the amount of melt emplaced during the most recent eruption (0.1-0.2 km3). We therefore infer that such volcanic events remove only a small portion of the reservoir that they tap, which must accordingly be long-lived compared to the eruption cycle. On the basis of magma flux estimates, we estimate the crustal residence time of melt in the volcanic system to be a few hundred to a few thousand years.

Journal Article↗
PubMed2001

Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst formation in the kidney, liver, and pancreas and is associated often with cardiovascular abnormalities such as hypertension, mitral valve prolapse, and intracranial aneurysms. It is caused by mutations in PKD1 or PKD2, encoding polycystin-1 and -2, which together form a cell surface nonselective cation ion channel. Pkd2-/- mice have cysts in the kidney and pancreas and defects in cardiac septation, whereas Pkd1(del34) -/- and Pkd1(L) -/- mice have cysts but no cardiac abnormalities, although vascular fragility was reported in the latter. Here we describe mice carrying a targeted mutation in Pkd1 (Pkd1(del17-21betageo)), which defines its expression pattern by using a lacZ reporter gene and may identify novel functions for polycystin-1. Although Pkd1(del17-21betageo) +/- adult mice develop renal and hepatic cysts, Pkd1(del17-21betageo) -/- embryos die at embryonic days 13.5-14.5 from a primary cardiovascular defect that includes double outflow right ventricle, disorganized myocardium, and abnormal atrio-ventricular septation. Skeletal development is also severely compromised. These abnormalities correlate with the major sites of Pkd1 expression. During nephrogenesis, Pkd1 is expressed in maturing tubular epithelial cells from embryonic day 15.5. This expression coincides with the onset of cyst formation in Pkd1(del34) -/-, Pkd1(L) -/-, and Pkd2-/- mice, supporting the hypothesis that polycystin-1 and polycystin-2 interact in vivo and that their failure to do so leads to abnormalities in tubule morphology and function.

Animals↗
PubMed2001

Heterosynaptic metaplasticity in the hippocampus in vivo: a BCM-like modifiable threshold for LTP.

The homeostatic maintenance of the "modification threshold" for inducing long-term potentiation (LTP) is a fundamental feature of the Bienenstock, Cooper, and Munro (BCM) model of synaptic plasticity. In the present study, two key features of the modification threshold, its heterosynaptic expression and its regulation by postsynaptic neural activity, were tested experimentally in the dentate gyrus of awake, freely moving rats. Conditioning stimulation ranging from 10 to 1,440 brief 400-Hz trains, when applied to medial perforant path afferents, raised the threshold for LTP induction heterosynaptically in the neighboring lateral perforant path synapses. This effect recovered slowly over a 7- to 35-day period. The same conditioning paradigms, however, did not affect the reversal of long-term depression. The inhibition of LTP by medial-path conditioning stimulation was N-methyl-D-aspartate (NMDA) receptor-dependent, but antidromic stimulation of the granule cells could also inhibit lateral path LTP induction, independently of NMDA receptor activation. Increased calcium buffering is a potential mechanism underlying the altered LTP threshold, but the levels of two important calcium-binding proteins did not increase after conditioning stimulation, nor was de novo protein synthesis required for generating the threshold shift. These data confirm, in an in vivo model, two key postulates of the BCM model regarding the LTP threshold. They also provide further evidence for the broad sensitivity of synaptic plasticity mechanisms to the history of prior activity, i.e., metaplasticity.

Animals↗
PubMed2001

SPG15, a new locus for autosomal recessive complicated HSP on chromosome 14q.

The authors studied two families with autosomal recessive hereditary spastic paraplegia (HSP) complicated by the presence of additional symptoms of pigmented maculopathy, distal amyotrophy, dysarthria, mental retardation, and further intellectual deterioration. Evidence was obtained for linkage to a locus on chromosome 14q that is distinct from the SPG3 locus for autosomal dominant HSP (D14S77: lod score of 4.20 at zero recombination). Haplotype construction of nearby markers confirms the existence of this novel HSP locus (SPG15) and narrows it to a 19-cM interval flanked by D14S1038 and D14S61.

Chromosomes, Human, Pair 14↗
PubMed2001

Role of MEKK2-MEK5 in the regulation of TNF-alpha gene expression and MEKK2-MKK7 in the activation of c-Jun N-terminal kinase in mast cells.

Cross-linking of the high-affinity IgE receptor (FcepsilonRI) on mast cells with IgE and multivalent antigen triggers mitogen-activated protein (MAP) kinase activation and cytokine gene expression. We report here that MAP kinase kinase 4 (MKK4) gene disruption does not affect either MAP kinase activation or cytokine gene expression in response to cross-linking of FcepsilonRI in embryonic stem cell-derived mast cells. MKK7 is activated in response to cross-linking of FcepsilonRI, and this activation is inhibited by MAP/ERK kinase (MEK) kinase 2 (MEKK2) gene disruption. In addition, expression of kinase-inactive MKK7 in the murine mast cell line MC/9 inhibits c-Jun NH(2)-terminal kinase (JNK) activation in response to cross-linking of FcepsilonRI, whereas expression of kinase-inactive MKK4 does not affect JNK activation by this stimulus. However, FcepsilonRI-induced activation of the tumor necrosis factor-alpha (TNF-alpha) gene promoter is not affected by expression of kinase-inactive MKK7. We describe an alternative pathway by which MEKK2 activates MEK5 and big MAP kinase1/extracellular signal-regulated kinase 5 in addition to MKK7 and JNK, and interruption of this pathway inhibits TNF-alpha promoter activation. These findings suggest that JNK activation by antigen cross-linking is dependent on the MEKK2-MKK7 pathway, and cytokine production in mast cells is regulated in part by the signaling complex MEKK2-MEK5-ERK5.

Cell Line↗
PubMed2001

Marine risk assessment: linear alkylbenzenesulponates (LAS) in the North Sea.

The fate of linear alkylbenzenesulponates (LAS) in estuaries and coastal areas of the North Sea has been characterized with simple environmental models. The predicted concentration range in the estuaries around the North Sea (0.9-9 microg LAS l(-1)) was validated by monitoring data (1-9 microg LAS l(-1)). In offshore sites of the North Sea, it is estimated--and experimentally verified for a few sites--that the LAS concentration is below analytical detection limit (i.e., 0.5 microg LAS l(-1)). The effects of LAS on marine organisms have been reviewed. For short-term acute tests, there was no significant difference (p = 0.83) between the mean LC50 values of freshwater and marine organisms (mainly pelagic species tested, 4.1 and 4.3 mg LAS l(-1), respectively). For longer-term chronic tests, it appeared that the sensitivity (mean no-observed effect concentration (NOEC) value) of marine and freshwater organisms (0.3 and 2.3 mg LAS l(-1), respectively) was significantly different pt-test = 0.007). The predicted no-effect-concentrations (PNEC) were 360 and 31 microg LAS l(-1), for freshwater and marine pelagic communities, respectively. Given that the maximum expected estuarine and marine concentrations are 3 to > 30 times lower than the PNEC, the risk of LAS to pelagic organisms in these environments is judged to be low.

Animals↗
PubMed2001

A comparison of multileaf collimator with conformal blocks for the boost phase of dose-escalated conformal prostate radiotherapy.

A multileaf collimator (MLC) is compared with conformal blocks for delivering the boost phase of dose-escalated conformal prostate radiotherapy. When using conformal blocks, the volume of rectum irradiated to 90% (V90) is lower (1.4+/-1.3%, 1 SD) for a three-field plan with gantry angles 0 degree, 90 degrees, 270 degrees than for a six-field plan with gantry angles 50 degrees, 90 degrees, 130 degrees, 230 degrees, 270 degrees, 310 degrees (2.1 +/- 1.3%, P = 0.002). However, when using an MLC in which the leaves and wedge are oriented at right angles, V90 is higher (4.7 +/- 3.0%) for a three-field plan than for a six-field plan (2.7 +/- 1.6%, P=0.05). The larger increase in V90 for the three-field plan when changing from conformal blocks to MLC is mainly due to the limitation imposed upon the MLC orientation by the use of wedges.

Dose-Response Relationship, Radiation↗
PubMed2001

Beam-orientation optimization of intensity-modulated radiotherapy: clinical application to parotid gland tumours.

BACKGROUND AND PURPOSE: An optimization algorithm has been developed to determine the best beam-arrangement for a small number of intensity-modulated radiotherapy (IMRT) fields. The algorithm is designed to avoid, if possible, beam-orientations that pass through organs-at-risk (OARs) with low radiation tolerance. MATERIALS AND METHODS: An independent, fast IMRT algorithm based on the Bortfeld algorithm was developed to determine the profile of the intensity-modulated beams (IMBs) for each beam-arrangement and a fast-simulated-annealing algorithm finds the 'optimal' beam-arrangement. The final beam-arrangement was transferred to the CORVUS (NOMOS Corporation) treatment planning system, and the IMBs were re-optimized for comparison with a standard nine-field, equi-spaced arrangement. The algorithm has been initially tested on a single example patient, with a parotid gland carcinoma. RESULTS: The nine-field, IMRT plan for an example patient with a parotid gland tumour significantly reduced the dose to the cochlea compared with the conformal radiotherapy plan. In addition, the planning-target-volume (PTV) homogeneity was improved, but the plan produced a higher dose to the contralateral parotid (73% of the OAR received more than 6 Gy). The beam-orientation optimization algorithm produced a three-field plan that greatly reduced the dose to the contralateral parotid (maximum dose of 2 Gy), whilst maintaining the PTV dose homogeneity and the reduced cochlear dose of the nine-field plan. Some changes in the dose to the other OARs, namely the brain and the oral cavity, were seen, but were deemed not to be clinically significant. CONCLUSIONS: In conclusion, IMB-orientation optimization for head and neck treatment sites can produce improvements in treatment plans with only a few fields.

Algorithms↗
PubMed2001

The dosimetric consequences of inter-fractional patient movement on three classes of intensity-modulated delivery techniques in breast radiotherapy.

BACKGROUND AND PURPOSE: A comparison between three classes of intensity-modulated delivery techniques was undertaken to examine the dosimetric consequences of using a multileaf collimator (MLC) reshaped on each imaged fraction as opposed to compensators designed on the first day of treatment potentially giving a treatment technique whose accuracy is thus degraded by movement. MATERIALS AND METHODS: The effects of inter-fractional patient movement for a cohort of six breast patients were studied. Five treatment techniques were evaluated, two using a compensator, two using multiple static fields (MSF) and one using a dynamic multileaf collimator (DMLC). The compensated techniques consisted of (i) the use of compensators designed on day 1 only and used each fraction thereafter and (ii) the use of a compensator redesigned for each imaged fraction. The two MSF techniques were (i) a four-field-component design and (ii) a method where the fluence interval between the MLC field components was set so they were equivalent to the compensator ('quantized' MSF-MLC). The final technique investigated was the DMLC. Plans were produced for each of the five methods and a paired t-test was used to assess the reduction in the breast volume outside the dose range 95-105% between sets of pairs of techniques. An on-line correction strategy was simulated to determine the number of treatments that required intervention. The action levels were calculated using the difference between the volume outside the dose range 95-105% calculated for treatments where the DMLC was designed on day 1 only and for each imaged fraction. Differences of greater than 2%, greater than 5% and greater than 10% were investigated. RESULTS: Thirty-five plans were evaluated for each technique. Results showed that a statistically significant mean reduction in the volume of the breast outside the dose range 95-105% could be achieved if the compensators were designed on each imaged fraction rather than on day 1 only (P=0.0045). When the comparison was made between the 'quantized' MSF-MLC and the technique where the compensators were designed on day 1 only, a statistically significant mean reduction in the volume of the breast tissue outside the dose range 95-105% was not achieved (P=0.21). Comparison of the DMLC technique to the technique where the compensators were designed on day 1 only results in a statistically significant mean reduction in the volume outside the dose range 95-105% (P=0.024). This corresponds to a mean reduction in the volume outside 95-105% dose of 1.94%. The 2% action level showed the greatest reduction in the volume outside 95-105% dose and intervention was only required in approximately one-third of the treatments investigated. CONCLUSIONS: Redesigning MSFs for each imaged fraction did not provide a statistically significant mean reduction in the volume outside the dose range 95-105%. However, using the DMLC technique creates a statistically significant mean reduction in the volume outside the dose range 95-105%.

Breast Neoplasms↗
PubMed2001

Optimisation of radiotherapy for carcinoma of the parotid gland: a comparison of conventional, three-dimensional conformal, and intensity-modulated techniques.

BACKGROUND AND PURPOSE: To compare external beam radiotherapy techniques for parotid gland tumours using conventional radiotherapy (RT), three-dimensional conformal radiotherapy (3DCRT), and intensity-modulated radiotherapy (IMRT). To optimise the IMRT techniques, and to produce an IMRT class solution. MATERIALS AND METHODS: The planning target volume (PTV), contra-lateral parotid gland, oral cavity, brain-stem, brain and cochlea were outlined on CT planning scans of six patients with parotid gland tumours. Optimised conventional RT and 3DCRT plans were created and compared with inverse-planned IMRT dose distributions using dose-volume histograms. The aim was to reduce the radiation dose to organs at risk and improve the PTV dose distribution. A beam-direction optimisation algorithm was used to improve the dose distribution of the IMRT plans, and a class solution for parotid gland IMRT was investigated. RESULTS: 3DCRT plans produced an equivalent PTV irradiation and reduced the dose to the cochlea, oral cavity, brain, and other normal tissues compared with conventional RT. IMRT further reduced the radiation dose to the cochlea and oral cavity compared with 3DCRT. For nine- and seven-field IMRT techniques, there was an increase in low-dose radiation to non-target tissue and the contra-lateral parotid gland. IMRT plans produced using three to five optimised intensity-modulated beam directions maintained the advantages of the more complex IMRT plans, and reduced the contra-lateral parotid gland dose to acceptable levels. Three- and four-field non-coplanar beam arrangements increased the volume of brain irradiated, and increased PTV dose inhomogeneity. A four-field class solution consisting of paired ipsilateral coplanar anterior and posterior oblique beams (15, 45, 145 and 170 degrees from the anterior plane) was developed which maintained the benefits without the complexity of individual patient optimisation. CONCLUSIONS: For patients with parotid gland tumours, reduction in the radiation dose to critical normal tissues was demonstrated with 3DCRT compared with conventional RT. IMRT produced a further reduction in the dose to the cochlea and oral cavity. With nine and seven fields, the dose to the contra-lateral parotid gland was increased, but this was avoided by optimisation of the beam directions. The benefits of IMRT were maintained with three or four fields when the beam angles were optimised, but were also achieved using a four-field class solution. Clinical trials are required to confirm the clinical benefits of these improved dose distributions.

Humans↗
PubMed2001

Cardiac avoidance in breast radiotherapy: a comparison of simple shielding techniques with intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: Adjuvant breast radiotherapy (RT) is now part of the routine care of patients with early breast cancer. However, analysis of the Early Breast Cancer Trialists' Collaborative suggests that patients with the lowest risk of dying of breast cancer are at significant risk of cardiac mortality due to longer relapse-free survival. Patients with a significant amount of heart in the high-dose volume have been shown to be at risk of fatal cardiac events. This study was designed to assess whether conformal planning or intensity-modulated radiotherapy (IMRT) techniques allow reduced cardiac irradiation whilst maintaining full target coverage. MATERIAL AND METHODS: Ten patients with early breast cancer were available for computed tomography (CT) planning. Each had at least 1 cm maximum heart depth within the posterior border of conventional tangents. For each patient, plans were generated and compared using dose volume histograms for planning target volume (PTV) and organs at risk. The plans included conventional tangents with and without shielding. The shielding was designed to either completely spare the heart or to shield as much heart as possible without compromising PTV coverage. IMRT plans were also prepared using two- and four-field tangential and six-field arc-like beam arrangements. RESULTS: PTV homogeneity was better for the tangential IMRT techniques. For all patients, cardiac irradiation was reduced by the addition of partial cardiac shielding to conventional tangents, without compromise of PTV coverage. The two- and four-field IMRT techniques also reduced heart doses. The average percentage volume of heart receiving >60% of the prescription dose was 4.4% (range 1.0-7.1%) for conventional tangents, 1.5% (0.2-3.9%) for partial shielding, 2.3% (0.5-4.6%) for the two-field IMRT technique and 2.2% (0.4-5.6%) for the four-field IMRT technique. For patients with larger maximum heart depths the four-field IMRT plan achieved greater heart sparing than the partial shielding, although irradiation of the contralateral breast was increased. Full cardiac shielding resulted in the most complete heart sparing but with compromise of the PTV coverage; the mean volume receiving less than 95% of the prescription dose was 4% (range 1.5-8.7%). CONCLUSION: All patients undergoing adjuvant tangential breast RT in whom the heart is seen to be in the high-dose volume should be considered for the addition of cardiac-sparing lead blocks. Three-dimensional CT planning and alternative beam arrangements with IMRT optimization enables more complete cardiac sparing without compromise of PTV coverage in certain patients.

Breast Neoplasms↗
PubMed2001

Improvements in target coverage and reduced spinal cord irradiation using intensity-modulated radiotherapy (IMRT) in patients with carcinoma of the thyroid gland.

BACKGROUND AND PURPOSE: External beam radiotherapy for thyroid carcinoma poses a significant technical challenge as the target volume lies close to or surrounds the spinal cord. The potential of intensity-modulated radiotherapy (IMRT) to improve the dose distributions was investigated. MATERIALS AND METHODS: A planning study was performed on patients with thyroid carcinoma. Plans were generated to irradiate the thyroid bed alone or to treat the thyroid bed and the loco-regional lymph nodes in two phases. Conventional plans with minimal beam shaping were compared to three-dimensional conformal radiotherapy (3DCRT) and inverse-planned IMRT plans to assess target coverage and normal tissue sparing. IMRT techniques were optimized to find the minimum number of equispaced beams required to achieve the clinical benefit and a concomitant boost technique was explored. RESULTS: For the thyroid bed alone and the thyroid bed plus loco-regional lymph nodes, conventional and conformal techniques produced low minimum doses to the planning target volume (PTV) if spinal cord tolerance was respected. 3DCRT reduced the irradiated volume of normal tissue (P=0.01). IMRT plans achieved the goal dose to the PTV (P<0.01) and also reduced the spinal cord maximum dose (P<0.01). IMRT, using a concomitant boost technique, produced better target coverage than a two-phase technique. For both the two-phase and concomitant boost techniques, IMRT plans with seven and five equispaced fields produced similar dose distributions to nine fields, but three fields were significantly worse. CONCLUSIONS: 3DCRT reduced normal tissue irradiation compared to conventional techniques, but did not improve PTV or spinal cord doses. IMRT improved the PTV coverage and reduced the spinal cord dose. A simultaneous integrated boost technique with five equispaced fields produced the best dose distribution. IMRT should reduce the risk of myelopathy or may allow dose escalation in patients with thyroid cancer.

Humans↗
PubMed2001

A comparison of conformal and intensity-modulated techniques for oesophageal radiotherapy.

BACKGROUND AND PURPOSE: To investigate the potential of intensity-modulated radiotherapy (IMRT) to reduce lung irradiation in the treatment of oesophageal carcinoma with radical radiotherapy. MATERIALS AND METHODS: A treatment planning study was performed to compare two-phase conformal radiotherapy (CFRT) with IMRT in five patients. The CFRT plans consisted of anterior, posterior and bilateral posterior oblique fields, while the IMRT plans consisted of either nine equispaced fields (9F), or four fields (4F) with orientations equal to the CFRT plans. IMRT plans with seven, five or three equispaced fields were also investigated in one patient. Treatment plans were compared using dose-volume histograms and normal tissue complication probabilities. RESULTS: The 9F IMRT plan was unable to improve on the homogeneity of dose to the planning target volume (PTV), compared with the CFRT plan (dose range, 16.9+/-4.5 (1 SD) vs. 12.4+/-3.9%; P=0.06). Similarly, the 9F IMRT plan was unable to reduce the mean lung dose (11.7+/-3.2 vs. 11.0+/-2.9 Gy; P=0.2). Similar results were obtained for seven, five and three equispaced fields in the single patient studied. The 4F IMRT plan provided comparable PTV dose homogeneity with the CFRT plan (11.8+/-3.3 vs. 12.4+/-3.9%; P=0.6), with reduced mean lung dose (9.5+/-2.3 vs 11.0+/-2.9 Gy; P=0.001). CONCLUSIONS: IMRT using nine equispaced fields provided no improvement over CFRT. This was because the larger number of fields in the IMRT plan distributed a low dose over the entire lung. In contrast, IMRT using four fields equal to the CFRT fields offered an improvement in lung sparing. Thus, IMRT with a few carefully chosen field directions may lead to a modest reduction in pneumonitis, or allow tumour dose escalation within the currently accepted lung toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Development of the human pulmonary vein and its incorporation in the morphologically left atrium.

OBJECTIVE: Using a newly acquired archive of previously prepared material, we sought to re-examine the origin of the pulmonary vein in the human heart, aiming to determine whether it originates from the systemic venous sinus ("sinus venosus"), or appears as a new structure draining to the left atrium. In addition, we examined the temporal sequence of incorporation of the initially solitary pulmonary vein to the stage at which four venous orifices opened to the left atrium. METHODS: We studied 26 normal human embryos, ranging from 3.8 mm to 112 mm crown-rump length, and representing the period from the 12th Carnegie stage to 15 weeks of gestation. RESULTS: The pulmonary vein canalised as a solitary vessel within the mediastinal tissues so as to connect the intraparenchymal pulmonary venous networks to the heart, using the regressing dorsal mesocardium as its portal of cardiac entry. The vein was always distinct from the tributaries of the embryonic systemic venous sinus. The orifice of the solitary vein became committed to the left atrium by growth of the vestibular spine. During development, a marked disparity was seen between the temporal and morphological patterns of incorporation of the left-sided and right-sided veins into the left atrium. The pattern of the primary bifurcation was asymmetrical, a much longer tributary being formed on the left than on the right. Contact between the atrial wall and the venous tributary on the left initially produced a shelf, which became effaced with incorporation of the two left-sided veins into the atrium. CONCLUSIONS: The initial process of formation of the human pulmonary vein is very similar to that seen in animal models. The walls of the initially solitary vein in humans become incorporated by a morphologically asymmetric process so that four pulmonary veins eventually drain independently into the left atrium. Failure of incorporation on the left side may provide the substrate for congenital division of the left atrium.

Crown-Rump Length↗