Biomedical subjects
Publications and source records attributed to J D Fenwick.
Extracranial spread of meningiomas to involve the middle ear is very rare. We present the case of a 43-year-old woman with a known cerebellopontine angle meningioma who subsequently presented with left-sided otalgia and a middle-ear mass extruding through the tympanic membrane due to local invasion of the meningioma. The tumour was excised surgically. A discussion of the relevant literature is also presented.
Helical tomotherapy has been developed at the University of Wisconsin, and 'Hi-Art II' clinical machines are now commercially manufactured. At the core of each machine lies a ring-gantry-mounted short linear accelerator which generates x-rays that are collimated into a fan beam of intensity-modulated radiation by a binary multileaf, the modulation being variable with gantry angle. Patients are treated lying on a couch which is translated continuously through the bore of the machine as the gantry rotates. Highly conformal dose-distributions can be delivered using this technique, which is the therapy equivalent of spiral computed tomography. The approach requires synchrony of gantry rotation, couch translation, accelerator pulsing and the opening and closing of the leaves of the binary multileaf collimator used to modulate the radiation beam. In the course of clinically implementing helical tomotherapy, we have developed a quality assurance (QA) system for our machine. The system is analogous to that recommended for conventional clinical linear accelerator QA by AAPM Task Group 40 but contains some novel components, reflecting differences between the Hi-Art devices and conventional clinical accelerators. Here the design and dosimetric characteristics of Hi-Art machines are summarized and the QA system is set out along with experimental details of its implementation. Connections between this machine-based QA work, pre-treatment patient-specific delivery QA and fraction-by-fraction dose verification are discussed.
Geometric leaf placement strategies for multileaf collimators (MLCs) typically involve the expansion of the beam's-eye-view contour of a target by a uniform MLC margin, followed by movement of the leaves until some point on each leaf end touches the expanded contour. Film-based dose-distribution measurements have been made to determine appropriate MLC margins--characterized through an index d90--for multileaves set using one particular strategy to straight lines lying at various angles to the direction of leaf travel. Simple trigonometric relationships exist between different geometric leaf placement strategies and are used to generalize the results of the film work into d90 values for several different strategies. Measured d90 values vary both with angle and leaf placement strategy. A model has been derived that explains and describes quite well the observed variations of d90 with angle. The d90 angular variations of the strategies studied differ substantially, and geometric and dosimetric reasoning suggests that the best strategy is the one with the least angular variation. Using this criterion, the best straightforwardly implementable strategy studied is a 'touch circle' approach for which semicircles are imagined to be inscribed within leaf ends, the leaves being moved until the semicircles just touch the expanded target outline.
AIMS: Thyroid cancer is an uncommon but highly curable disease if treated optimally. The aim of this study was to determine whether clinical guidelines introduced locally at the beginning of 1999 were associated with better surgical outcome, using radioiodine uptake as a surrogate measure of completeness of thyroidectomy. MATERIALS AND METHODS: We reviewed the medical records of all patients with thyroid cancer referred to a cancer centre (n=176) 3 years before and 3 years after the introduction of guidelines. The uptake of radioiodine in the thyroid bed after thyroidectomy and before radioiodine ablation was used to assess the completeness of primary surgical treatment. RESULTS: The number of new cases referred to our centre increased from 80 in the 1996-1998 period to 94 during 1999-2001. This was largely because of an excess of papillary thyroid cancers. Documentation in the medical records of the pathological primary tumour size improved from 47.5% to 80.8% following the introduction of guidelines. A significant reduction in radioiodine uptake in the thyroid bed was observed following the introduction of guidelines (5.03% +/- 6.82 (SD) vs 2.75% +/- 5.10 (SD); P=0.005). Linear regression analysis of clinical variables indicated that the year of surgery was the only significant factor influencing radioiodine uptake in the thyroid bed (P=0.014). Twelve hospitals within the Northern Cancer Network carried out thyroid surgery for thyroid cancer in the pre-guideline era compared with seven hospitals in the post-guideline era. Surgeons who were members of the regional multidisciplinary thyroid cancer team operated on 35% of cases in the 1996-1998 period and 56.4% in the 1999-2001 period (P<0.01). CONCLUSIONS: The introduction of clinical guidelines in 1999 was associated with a reduction in the size of thyroid remnant after primary surgical treatment. This was accompanied by fewer hospitals undertaking thyroid surgery and more patients being operated on by surgeons who were members of the thyroid cancer multidisciplinary team.
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OBJECTIVE: To compare regional cerebral blood flow (rCBF) changes using 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT in subjects with dementia with Lewy bodies (DLB) and AD and in normal age-matched control subjects; to examine the utility of SPECT changes in the differential diagnosis of AD and DLB. METHOD: Whole-brain SPECT scans were acquired using a single-headed rotating gamma camera (IGE CamStar XR/T) in elderly subjects with consensus criteria DLB (n = 23; mean age = 79.4 years), National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association AD (n = 50; 81.9 years), and normal control subjects (n = 20; 78.1 years) after injection with 500 MBq of 99mTc-HMPAO. Region-of-interest analysis was performed using a SPECT template registered in Talairach space, with rCBF normalized to cerebellum. RESULTS: Both DLB and AD subjects had significantly reduced rCBF in parietal and temporal regions compared with the control subjects. The AD group also showed a significant reduction in rCBF in the frontal and medial temporal regions and the DLB in the occipital areas compared with control subjects. AD and DLB groups differed only in occipital perfusion (p < 0.01). SPECT measures (occipital and medial temporal) correctly classified 69% of all subjects, with a 65% sensitivity and 87% specificity for DLB against AD and control subjects. CONCLUSION: Temporoparietal hypoperfusion on SPECT is common to both AD and DLB. Occipital hypoperfusion is more frequently seen in DLB. Although not diagnostically specific in individual cases, occipital hypoperfusion on SPECT should raise suspicion that DLB may be the cause of dementia, prompting careful search for other features of the disorder.
BACKGROUND AND PURPOSE: In a randomized trial, the incidence of rectal bleeding among patients treated for prostate cancer using conformal radiotherapy was significantly lower (p = 0.002) than that among those treated conventionally. Here the relationship between rectal dose distributions and incidences of bleeding is assessed. METHODS AND MATERIALS: Rectal dose-surface histograms (DSHs) have been calculated for 79 trial patients. The relationship between the DSHs and incidences of Grade 1-3 bleeding has been explored using both semiempiric and biologic (parallel) model-based approaches. RESULTS: Semiempiric analysis of the trial data suggests that it is more useful to work with DSH fractional surface areas multiplied by outlined rectal lengths than with either raw DSH fractional areas or fractional areas multiplied by absolute total outlined rectal surface area. Fitting the parallel model to length-multiplied rectal DSHs and complication data reveals the existence of a significant volume effect, the rate of Grade 1-3 bleeding falling by 1.1% (95% confidence interval [0.04, 2.2]%) for each 1% decrease in the fraction of rectal wall (outlined over an 11-cm length) receiving a dose of more than 57 Gy. CONCLUSION: The existence of this volume effect suggests that dose escalation can be achieved using conformal techniques, although the extent to which doses may be safely escalated cannot be reliably estimated from the trial data.
Yaes and Kalend have noted that if functional subunit size is determined by factors such as cell migration lengths or biochemical diffusion lengths, rather than by fixed anatomical boundaries, then the conventional series normal tissue complication probability (ntcp) model should be conceptually modified. Here a von Mises-type formula describing the ntcp for such a modified model is derived, using a methodology based on that of Feller.
Working with several mechanisms of critical local tissue damage, formulae are analytically derived that describe normal tissue complication probabilities (ntcps) for series-type radiotherapy complications arising in heterogeneous patient populations. Using the formulae, values are calculated for deltaD50(10)-the increase in dose leading to a 50% series-type complication rate (D50) when irradiated organ volume is reduced tenfold. From the structure of the ntcp formulae derived, it follows that dose-levels leading to clinically relevant serious complication rates (less than 5%) will change less with irradiated volume than will D50. Calculated values of deltaD50(10) for the heterogeneous series model are low-generally less than 6 Gy; such values are much lower than those calculated for the non-heterogeneous series model (27-37 Gy). These results suggest that if the dose-limiting toxicity of a radiotherapy treatment is a series-type complication with a local damage mechanism similar to any of those studied in this work, then even very substantial improvements in technique-leading to large reductions in highly dosed normal tissue volumes-would be unlikely to allow a useful degree of escalation of the dose delivered to the tumour, unless highly dosed normal tissue volumes can be reduced below the length-scale of a functional subunit.
A trial of nonescalated conformal versus conventional radiotherapy treatment of prostate cancer has been carried out at the Royal Marsden NHS Trust (RMH) and Institute of Cancer Research (ICR), demonstrating a significant reduction in the rate of rectal bleeding reported for patients treated using the conformal technique. The relationship between planned rectal dose-distributions and incidences of bleeding has been analyzed, showing that the rate of bleeding falls significantly as the extent of the rectal wall receiving a planned dose-level of more than 57 Gy is reduced. Dose-distributions delivered to the rectal wall over the course of radiotherapy treatment inevitably differ from planned distributions, due to sources of uncertainty such as patient setup error, rectal wall movement and variation in the absolute rectal wall surface area. In this paper estimates of the differences between planned and treated rectal dose-distribution parameters are obtained for the RMH/ICR nonescalated conformal technique, working from a distribution of setup errors observed during the RMH/ICR trial, movement data supplied by Lebesque and colleagues derived from repeat CT scans, and estimates of rectal circumference variations extracted from the literature. Setup errors and wall movement are found to cause only limited systematic differences between mean treated and planned rectal dose-distribution parameter values, but introduce considerable uncertainties into the treated values of some dose-distribution parameters: setup errors lead to 22% and 9% relative uncertainties in the highly dosed fraction of the rectal wall and the wall average dose, respectively, with wall movement leading to 21% and 9% relative uncertainties. Estimates obtained from the literature of the uncertainty in the absolute surface area of the distensible rectal wall are of the order of 13%-18%. In a subsequent paper the impact of these uncertainties on analyses of the relationship between incidences of bleeding and planned rectal dose-distributions is explored.
A trial of nonescalated conformal versus conventional radiotherapy treatment of prostate cancer has been carried out at the Royal Marsden NHS Trust (RMH) and Institute of Cancer Research (ICR), demonstrating a significant reduction in the rate of rectal bleeding reported for patients treated using the conformal technique. The rate of bleeding has been shown to fall significantly as the extent of rectal wall receiving a planned dose-level in excess of 57 Gy is reduced. Dose-distributions delivered to the rectal wall over the course of radiotherapy treatment inevitably differ from planned distributions. In a previous paper estimates were obtained of the uncertainties in some planned rectal dose-distribution parameters generated by patient setup error, rectal wall movement and the variable degree of rectal wall distension. Here these uncertainties are combined to obtain estimates of the total planning uncertainties in rectal dose-distribution parameters thought likely, on the basis of mechanistic biological modeling, to correlate strongly with the complication rate. Working from these totaled uncertainty values, together with values of patient-to-patient and technique-to-technique differences in planned dose-distribution parameters, it can be inferred that the rectal dose-distribution uncertainties: (i) Have only a marginal impact on fits of a normal tissue complication probability (ntcp) model to RMH/ICR dose-distribution and grade 1, 2, 3 bleeding data (slightly flattening observed volume-response curves); (ii) only slightly reduce the power of a 2 x 100 patient trial of conformal versus conventional prostate radiotherapy to detect a significantly lower rate of grade 1,2,3 rectal bleeding amongst conformally treated patients; (iii) do not diminish the information content of individual planned patient dose-distribution data to the point where the fitting of technique-averaged data would provide as sensitive a test of the existence of a volume effect as the fitting of individual patient data.
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Lack of an effective treatment for spontaneous intracerebral haemorrhage (ICH) is partly because the mechanism of neuronal damage in ICH is not fully understood. Animal experiments have shown that there is a zone of ischaemia and oedema around the haematoma which can be reduced by early evacuation of the mass lesion. We set out to study Cerebral Blood Flow (CBF) changes in patients with ICH. We present data on 13 patients (mean age 60). SPECT scans were performed within 48 hours of ictus and 4-7 days later. Four patients had surgical evacuation of the clot; 9 were managed conservatively. The ratio of uptake of the isotope in the cerebral hemisphere containing the haematoma to the isotope uptake in the contra-lateral (un-affected) cerebral hemisphere was taken as an index of perfusion of the affected cerebral hemisphere. The perfusion index of the affected hemisphere improved between the first and the second scans in all the surgically treated patients; in the conservatively managed group, it was worse in 6 patients, the same in 1 and very slightly better in 2. There was an overall mean improvement of 3.87% in the surgical group, and an overall mean deterioration of 3.61% in the medical group. This data suggests that surgical evacuation of the clot may improve perfusion in the ipsilateral cerebral hemisphere in ICH. It underlines the importance of a prospective randomised trial to assess the value of surgery in patients with ICH. The Surgical Trial in Intracerebral Haemorrhage (STICH) is currently underway worldwide. We also describe the application of Difference Based Region Growing (DBRG) to SPECT image analysis. This method overcomes the difficulties posed by 1) the presence of a mass lesion and 2) surgical evacuation of haematoma.
Despite advances in neuro-otological techniques permanent complete facial palsy may still occur in up to 10% of patients undergoing removal of cerebellopontine angle tumours. Hypoglossal-facial nerve anastomosis is the procedure of choice in our unit for facial reanimation in such patients and below we report the results of hypoglossal-facial nerve anastomosis performed on 29 patients. Assessment of patient benefit from hypoglossal-facial nerve anastomosis was obtained using a questionnaire based on the Glasgow Benefit Inventory. The results showed all patients to have an improvement in their House Brackmann grade following hypoglossal-facial anastomosis with 65% achieving grade III or better. Of the 20 patients who completed the questionnaire, 18 showed a positive benefit (median score 59.5, range 40-77). There was a significant correlation (P < 0.045) between the Glasgow benefit inventory score and House Brackmann grade. Outcome was not affected by the time interval between the acoustic neuroma surgery and performing the hypoglossal-facial nerve anastomosis, sex or length of follow-up. However the Glasgow benefit score was significantly influenced by age (P = 0.023) with younger patients showing more benefit independent of improvement in facial nerve function.
The dependence of local tumor control probability (tcp) on tumor volume is analyzed and discussed with the help of radiobiological modeling; in particular the impact of possible correlations between mean tumor radiosensitivity and tumor dimensions on the tcp volume dependence is explored. The linear-quadratic Poissonian tumor control probability (tcp) model was modified to account for the possible dependence of clonogenic cell density and radiosensitivity parameters on tumor volume; then the original and modified versions of the model were fitted to published clinical and laboratory tumor control data. These different versions of the tcp model often fitted tumor control data equally well, because of the high degree of correlation between the parameters. Nevertheless the results were very different from a physical point of view and we suggest that sometimes it is possible to choose between equally good fits on the basis of physical considerations. Possible links between the volume dependence of the mean radiosensitivity and the degree of tumor hypoxia were also analyzed through a comparison of the results of the tcp fit to published measurements of oxygen tension in tumors.
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The Plummer-Vinson syndrome is characterized by an association of dysphagia, iron-deficiency anemia, and esophageal webs. The authors report the case of a 6 year old with Plummer-Vinson syndrome. Plummer-Vinson syndrome usually occurs in adults, rarely in adolescents, however, there have been no previous reports in the English-language literature of the syndrome occurring in childhood.
Metastasis to the tonsils from malignant melanoma is rare. This paper describes one such case in a woman with synchronous breast adenocarcinoma and cutaneous malignant melanoma who had a most unusual clinical course.