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Biomedical subjects

John D Fenwick

Publications and source records attributed to John D Fenwick.

12 recordsLinked to original sources
PubMed2006

Tomotherapy and other innovative IMRT delivery systems.

Fixed-field treatments, delivered using conventional clinical linear accelerators fitted with multileaf collimators, have rapidly become the standard form of intensity-modulated radiotherapy (IMRT). Several innovative nonstandard alternatives also exist, for which delivery and treatment planning systems are now commercially available. Three of these nonstandard IMRT approaches are reviewed here: tomotherapy, robotic linear accelerators (CyberKnife, Accuray Inc., Sunnyvale, CA), and standard linear accelerators modulated by jaws alone or by their jaws acting together with a tertiary beam-masking device. Rationales for the nonstandard IMRT approaches are discussed, and elements of their delivery system designs are briefly described. Differences between fixed-field IMRT dose distributions and the distributions that can be delivered by using the nonstandard technologies are outlined. Because conventional linear accelerators are finely honed machines, innovative design enhancement of one aspect of system performance often limits another facet of machine capability. Consequently the various delivery systems may prove optimal for different types of treatment, with specific machine designs excelling for disease sites with specific target volume and normal structure topologies. However it is likely that the delivery systems will be distinguished not just by the optimality of the dose distributions they deliver, but also by factors such as the efficiency of their treatment process, the integration of their onboard imaging systems into that process, and their ability to measure and minimize or compensate for target movement, including the effects of respiratory motion.

Humans↗
PubMed2006

Does a local bystander effect necessitate a revision of TCP models that are based on observed clinical data?

It is shown that in order to derive a general model for tumor control probability (TCP) the two assumptions that on the microscopic level (1) clonogens are non-interacting and (2) clonogen killings are uncorrelated events are not necessary. In fact, these two assumptions can be replaced with two weaker ones that only ask that (a) therapy fractions are independent and non-overlapping and (b) the probability of an event only depends on the number of incidents happening during a time interval and the length of this time interval but not on time itself. This change in assumptions implies that TCP models based on clinical data are flexible enough to include interaction of clonogens on the microscopic level and therefore also a possible bystander effect in cell killing. Based on this new set of assumptions the equation for TCP is derived, first for the homogenous case and then for the general case of a heterogeneous ensemble of tumors irradiated in-homogeneously.

Bystander Effect↗
PubMed2006

Delay differential equations and the dose-time dependence of early radiotherapy reactions.

The dose-time dependence of early radiotherapy reactions impacts on the design of accelerated fractionation schedules--oral mucositis, for example, can be dose limiting for short treatments designed to avoid tumor repopulation. In this paper a framework for modeling early reaction dose-time dependence is developed. Variation of stem cell number with time after the start of a radiation schedule is modeled using a first-order delay differential equation (DDE), motivated by experimental observations linking the speed of compensatory proliferation in early reacting tissues to the degree of tissue damage. The modeling suggests that two types of early reaction radiation response are possible, stem cell numbers either monotonically approaching equilibrium plateau levels or overshooting before returning to equilibrium. Several formulas have been derived from the delay differential equation, predicting changes in isoeffective total radiation dose with schedule duration for different types of fractionation scheme. The formulas have been fitted to a wide range of published animal early reaction data, the fits all implying a degree of overshoot. Results are presented illustrating the scope of the delay differential model: most of the data are fitted well, although the model struggles with a few datasets measured for schedules with distinctive dose-time patterns. Ways of extending the current model to cope with these particular dose-time patterns are briefly discussed. The DDE approach is conceptually more complex than earlier descriptive dose-time models but potentially more powerful. It can be used to study issues not addressed by simpler models, such as the likely effects of increasing or decreasing the dose-per-day over time, or of splitting radiation courses into intense segments separated by gaps. It may also prove useful for modeling the effects of chemoirradiation.

Animals↗
PubMed2005

Modelling simple helically delivered dose distributions.

In a previous paper, we described quality assurance procedures for Hi-Art helical tomotherapy machines. Here, we develop further some ideas discussed briefly in that paper. Simple helically generated dose distributions are modelled, and relationships between these dose distributions and underlying characteristics of Hi-Art treatment systems are elucidated. In particular, we describe the dependence of dose levels along the central axis of a cylinder aligned coaxially with a Hi-Art machine on fan beam width, couch velocity and helical delivery lengths. The impact on these dose levels of angular variations in gantry speed or output per linear accelerator pulse is also explored.

Body Burden↗
PubMed2004

A challenge to traditional radiation oncology.

PURPOSE: To investigate and compare the biologically effective doses, equivalent doses in 2-Gy fractions, log tumor cells killed, and late effects that can be estimated for the large fractions in short overall times that are now being delivered in various clinically used schedules in several countries for the treatment of cancer in human lungs, liver, and kidney. METHODS AND MATERIALS: Linear quadratic (LQ) modeling is employed with only the standard assumptions that tumor alpha/beta ratio is 10 Gy, pneumonitis and late complication alpha/beta ratios are 3 Gy, that intrinsic radiosensitivity of tumor cells is 0.35 ln/Gy, that no tumor repopulation occurs within 2 weeks, and that LQ modeling is valid up to 23 Gy per fraction. As well as the planning target volume (PTV), we propose a practical term called the prescription isodose volume (PIV) to be used in this discussion. In the ideal case of 100% conformity, PIV equals PTV, but usually PIV is larger than the PTV. Biologically effective doses (BED) in Gy(10) for tumors or Gy(3) for normal lung are calculated and converted to equivalent doses in 2 Gy fractions (= normalized total doses [NTD]), and to estimated log cell kill. How such large biologic doses might be delivered to tissues is discussed. RESULTS: Tumor cell kill varies between 16 and 27 logs to base 10 for schedules from 4F x 12 Gy to 3F x 23 Gy. The rationale for the high end of this scale is the possible presence of hypoxic or otherwise extraordinarily resistant cells, but how many tumors and which ones require such doses is not known. How can such large doses be tolerated? In "parallel type organs," it is shown to be theoretically possible, provided that suitably small volumes are irradiated, with rapid fall-off of dose outside the PTV, and a mean dose (excluding PTV and allowing for local fraction size) to both lungs of less than 19 Gy NTD. If suitably small PTVs were used, local late BEDs have been given which were as large as 600 Gy(3), equivalent to 2 Gy x 180F = 360 Gy in 2-Gy fractions, with remarkably few complications reported clinically. Questions of concurrent chemotherapy and microscopic extension of lung tumor cells are discussed briefly. CONCLUSIONS: Such large doses can apparently be given, with suitable precautions and experience. Ongoing clinical trials from an increasing number of centers will be reporting the results of tumor control and complications from this new modality of biologically higher doses.

Algorithms↗
PubMed2004

The application of statistical parametric mapping to 123I-FP-CIT SPECT in dementia with Lewy bodies, Alzheimer's disease and Parkinson's disease.

Dopaminergic loss can be visualised using (123)I-FP-CIT single photon emission computed tomography (SPECT) in several disorders including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Most previous SPECT studies have adopted region of interest (ROI) methods for analysis, which are subjective and operator-dependent. The purpose of this study was to investigate differences in striatal binding of (123)I-FP-CIT SPECT using the automated technique of statistical parametric mapping (SPM99) in subjects with DLB, Alzheimer's disease (AD), PD and healthy age-matched controls. This involved spatial normalisation of each subject's image to a customised template, followed by smoothing and intensity normalisation of each image to its corresponding mean occipital count per voxel. Group differences were assessed using a two-sample t test. Applying a height threshold of P <or= 0.05 corrected, the SPM[t] maps showed a significant bilateral reduced uptake in caudate, anterior and posterior putamen in DLB and PD subjects compared to AD subjects and controls. Significant reduction in binding was also observed bilaterally in the caudate nucleus in AD compared to controls. Striatal binding was indistinguishable between patients with DLB and PD. To investigate the usefulness of SPM as a decision aid in the evaluation of visually rated normal and abnormal patterns of uptake, receiver operator characteristic (ROC) curve analysis was performed using data from single-subject SPMs. The areas under the ROC curves were greater than 0.92, demonstrating comparable discriminatory power with visual rating. The automated voxel-based approach is a viable alternative to the subjective and often time-consuming method of ROI and, in addition, may have the potential to differentiate between normal and abnormal patterns of uptake in a manner similar to visual inspection.

Aged↗
PubMed2004

Helical tomotherapy as a means of delivering accelerated partial breast irradiation.

A novel treatment approach utilizing helical tomotherapy for partial breast irradiation for patients with early-stage breast cancer is described. This technique may serve as an alternative to high dose-rate (HDR) interstitial brachytherapy and standard linac-based approaches. Through helical tomotherapy, highly conformal irradiation of target volumes and avoidance of normal sensitive structures can be achieved. Unlike HDR brachytherapy, it is noninvasive. Unlike other linac-based techniques, it provides image-guided adaptive radiotherapy along with intensity modulation. A treatment planning CT scan was obtained as usual on a post-lumpectomy patient undergoing HDR interstitial breast brachytherapy. The patient underwent catheter placement for HDR treatment and was positioned prone on a specially designed position-supporting mattress during CT. The planning target volume (PTV) was defined as the lumpectomy bed plus a 20 mm margin. The prescription dose was 34 Gy (10 fx of 3.4 Gy) in both the CT based HDR and on the tomotherapy plan. Cumulative dose-volume histograms (DVHs) were generated and analyzed for the target, lung, heart, skin, pectoralis muscle, and chest wall for both HDR brachytherapy and helical tomotherapy. Dosimetric coverage of the target with helical tomotherapy was conformal and homogeneous. "Hot spots" (> or =150% isodose line) were present around implanted dwell positions in brachytherapy plan whereas no isodose lines higher than 109% were present in the helical tomotherapy plan. Similar dose coverage was achieved for lung, pectoralis muscle, heart, chest wall and breast skin with the two methods. We also compared our results to that obtained using conventional linac-based three dimensional (3D) conformal accelerated partial breast irradiation. Dose homogeneity is excellent with 3D conformal irradiation, and lung, heart and chest wall dose is less than for either HDR brachytherapy or helical tomotherapy but skin and pectoral muscle doses were higher than with the other techniques. Our results suggest that helical tomotherapy can serve as an effective means of delivering accelerated partial breast irradiation and may offer superior dose homogeneity compared to HDR brachytherapy.

Brachytherapy↗
PubMed2003

Discordant serum thyroglobulin results generated by two classes of assay in patients with thyroid carcinoma: correlation with clinical outcome after 3 years of follow-up.

BACKGROUND: Serum thyroglobulin measurement is an integral part of monitoring patients with thyroid carcinoma, but analytic problems pose serious difficulties in the utility of this test. METHODS: Between 1997 and 1998, serum samples from 83 patients with differentiated thyroid carcinoma were collected. Serum thyroglobulin was assayed by both radioimmunoassay and by an immunoradiometric assay. The disease status of patients with discordant serum thyroglobulin results was assessed in June 2001. Therefore, the predictive value of a single thyroglobulin measurement was assessed by evaluating the clinical status of patients 3 years later. RESULTS: Discordant serum thyroglobulin results were noted in 17 (20.4%) patients. Of the 17 patients with discordant results, 16 had adequate clinical follow-up data. Of these 16 patients, 11 patients had detectable levels of serum thyroglobulin by immunoradiometric assay (range, 1.4-350 microg/L) whereas levels were undetectable by radioimmunoassay (< 1 microg/L). All 11 patients had evidence of metastases 3 years later. Two patients had undetectable serum thyroglobulin levels using the immunoradiometric assay (< 1 microg/L), whereas they had detectable levels using radioimmunoassay (serum thyroglobulin 7.2-30 microg/L). The serum samples from both patients had normal recoveries and positive antithyroglobulin antibodies. Both patients developed metastases 3 years later. CONCLUSIONS: False-negative serum thyroglobulin results were significantly higher with the radioimmunoassay method compared with the immunoradiometric assay. The immunoradiometric assay is more reliable than the radioimmunoassay, particularly in patients who have no thyroglobulin antibodies. This finding is novel in that traditional immunoradiometric assay systems compared with radioimmunoassays usually have a higher incidence of false-negative results when assessed against clinical status. The immunoradiometric assay is subject to false-negative results in some patients with thyroglobulin antibodies, even when recovery experiments indicate the absence of interference. Thyroglobulin antibodies should be measured in all patients with differentiated thyroid carcinoma and if positive, results should be interpreted with extreme caution.

Adult↗
PubMed2002

A comparison of (99m)Tc-HMPAO SPET changes in dementia with Lewy bodies and Alzheimer's disease using statistical parametric mapping.

Differences in regional cerebral blood flow (rCBF) between subjects with Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and healthy volunteers were investigated using statistical parametric mapping (SPM99). Forty-eight AD, 23 DLB and 20 age-matched control subjects participated. Technetium-99m hexamethylpropylene amine oxime (HMPAO) brain single-photon emission tomography (SPET) scans were acquired for each subject using a single-headed rotating gamma camera (IGE CamStar XR/T). The SPET images were spatially normalised and group comparison was performed by SPM99. In addition, covariate analysis was undertaken on the standardised images taking the Mini Mental State Examination (MMSE) scores as a variable. Applying a height threshold of P < or = 0.001 uncorrected, significant perfusion deficits in the parietal and frontal regions of the brain were observed in both AD and DLB groups compared with the control subjects. In addition, significant temporoparietal perfusion deficits were identified in the AD subjects, whereas the DLB patients had deficits in the occipital region. Comparison of dementia groups (height threshold of P < or = 0.01 uncorrected) yielded hypoperfusion in both the parietal [Brodmann area (BA) 7] and occipital (BA 17, 18) regions of the brain in DLB compared with AD. Abnormalities in these areas, which included visual cortex and several areas involved in higher visual processing and visuospatial function, may be important in understanding the visual hallucinations and visuospatial deficits which are characteristic of DLB. Covariate analysis indicated group differences between AD and DLB in terms of a positive correlation between cognitive test score and temporoparietal blood flow. In conclusion, we found evidence of frontal and parietal hypoperfusion in both AD and DLB, while temporal perfusion deficits were observed exclusively in AD and parieto-occipital deficits in DLB.

Age Factors↗
PubMed2002

Reversible ischemia around intracerebral hemorrhage: a single-photon emission computerized tomography study.

OBJECT: A zone of perilesional ischemia has been demonstrated around intracerebral hemorrhage (ICH) in numerous experimental models and in human studies. There is potential for perfusion recovery in the zone of perilesional oligemia around ICH. The authors sought to demonstrate, quantify, and study the chronological evolution of perilesional ischemic change in ICH in humans by measuring cerebral blood flow. METHODS: Eleven patients with spontaneous supratentorial ICH underwent two technetium-99m hexamethylpropyleneamine oxime single-photon emission computerized tomography (SPECT) scanning, one in the acute stage (within days of ictus) and the other in the late stage (6-9 months postictus). All patients in this study were treated nonsurgically. Methods of SPECT data analysis based on count differences in regions of interest can be difficult to apply to images with large space-occupying lesions such as ICH, because of the distortion of intracranial anatomy, midline shift, and alterations in the three-dimensional (3D) characteristics of the lesion over time (that is, absorption of the hematoma on the later studies). The authors used the following method: the late and early images were registered and aligned to a common 3D orientation and were normalized to maximal counts. The late images were then compared voxel by voxel with the early ones. The region-growing algorithm was used to discern the difference between the two images, outlining voxels in the perihematoma region, with a signal improvement of at least 15% on the late image. Discrete brain regions around the hematoma with at least a 15% improvement in radiotracer uptake (and hence perfusion) in the late images were observed in all cases. The mean volume of brain with a greater than 15% improvement in perfusion between the two studies was 34.8 cm3 (range 7.2-71.3 cm3). These volumes represent regions of the brain that were poorly perfused in the initial studies. This may represent a zone of reversible perilesional oligemia (penumbra) in ICH in humans. CONCLUSIONS: This is the first study in which it is documented that some of the perilesional hypoperfused tissue around human ICH regains its perfusion in the long term, leading the authors to suggest that there may be a penumbra in human ICH. Medical or surgical therapeutic interventions could increase the volume of perilesional brain that recovers after the initial insult. The results of this study therefore support the concept that intervention in ICH has the potential to reduce the ultimate neurological deficit and improve outcome.

Adult↗