Search PubMed⌕ Search

Biomedical subjects

J W Denham

Publications and source records attributed to J W Denham.

At least 55 records · Page 3Linked to original sources
PubMed1995

Acute reaction parameters for human oropharyngeal mucosa.

The purpose of this study was to determine the influence of changes in dose rate over the range 0.8-240 Gy/h on acute oropharyngeal mucosal reactions in human subjects, and to estimate the values of the important parameters that influence these reactions. Sixty-one patients requiring radiotherapy to palliate incurable head and neck cancer were treated on a telecaesium unit, using opposing lateral portals to total midline doses, varying between 30 and 42 Gy in 10 daily fractions over 2 weeks, at dose rates of 0.8, 1.8, 3.0 and 240 Gy/h according to a central composite study design. The severity and time course of reactions were charted at least twice weekly for each patient, using the EORTC/RTOG acute mucosal reaction grading system. Duration of reaction at each grade was observed to provide a more sensitive reflection of effect than the proportion of patients reaching any particular reaction grade. Analysis of duration by direct and indirect methods suggest alpha/beta ratios in the range 7-10 Gy and half-time (t1/2) values in the range 0.27-0.5 h, if mono-exponential repair kinetics are assumed. The t1/2 values are short and raise the question as to whether the repair kinetics of this tissue are well described by a mono-exponential function. Further prospective studies involving multiple daily fraction treatment regimes delivered at high dose rate, in which interfraction interval is deliberately varied, are needed to find out whether the parameters derived from this project are applicable to fractionated treatment courses at high dose rate.

Carcinoma, Squamous Cell↗
PubMed1995

Factors influencing the degree of erythematous skin reactions in humans.

Dose-response relationships have been studied using an ordinal visual scale and reflectance spectrophotometry data from 123 treatment sites on 110 patients treated with 10 dose fractions over 12-14 days. Dose rates varied between 3 and 240 Gy/h and total doses of between 25 and 41 Gy were given using teletherapy apparatus. We found qualitative scoring of erythematous skin reactions to be subject to considerable inter- and intra-observer variation. Reflectance spectrophotometry provided more reproducible information, some of which was undetectable by naked eye. Baseline erythema readings were significantly higher in male patients and at anatomical sites of previous heavy UV exposure. In addition, a pronounced decline in erythema readings during the second week of therapy and 'reciprocal vicinity' (abscopal) effects adjacent to the field, undetected by the eye, were observed in a subset of patients. Meaningful dose-response relationships could be derived only from reflectance data with peak change from the pretreatment baseline measure providing the best discrimination. Peak erythema measures following treatment were found to depend on the age and gender of the patient as well as the treatment site and its baseline erythema measurement. This was independent of the total dose administered or the instantaneous dose rate at which it was delivered. The rate of erythema development was also dose rate dependent but only weakly dependent on the biological dose intensity (Gy equiv./day) of the treatment course. The data raise the question of whether irradiation-induced erythema is exclusively a secondary phenomenon occurring as a result of basal cell killing. The short repair half time value of 0.06 h obtained by direct analysis is perplexing and may reflect a dose rate-dependent physiological vasodilatory response to irradiation and/or a multi-component cellular repair process.

Aged↗
PubMed1995

How do we bring an acceptable level of radiotherapy services to a dispersed population?

Radiotherapy referral data from four Australian States confirm that access difficulties contribute to low radiotherapy utilization rates. Access could be improved by the provision of further small treatment centres in moderately large rural or semi-rural population centres. Such a policy, however, could endanger existing standards of radiotherapeutic care unless the potential pitfalls of such an approach are addressed prospectively.

Australia↗
PubMed1994

A comparison of three electron planning algorithms for a 16 MeV electron beam.

PURPOSE: We report results of a comparison of three electron planning algorithms, an Age-Diffusion Pencil beam algorithm and two (2-D) and three dimensional (3-D) Hogstrom pencil beam algorithms, using simple 2 x 2 cm air and hard bone inhomogeneities and a complex anthropomorphic head and neck phantom. METHODS AND MATERIALS: The simple inhomogeneities have variable dimensions outside the plane of calculation to test the effects of out of plane scattering on 2-D algorithms, compared with dose measured by film below the inhomogeneity in the dose fall-off range. Comparisons are also made of a parotid treatment field for 16 MeV electrons, and the dose measured by high sensitivity thermoluminescent dosimeters in the head and neck phantom. RESULTS: Behind the simple inhomogeneities, the electron algorithms are found to underestimate the dose behind the air cavity by up to 40% and overestimated the dose behind bone by up to 30%. In the head phantom, the presence of inhomogeneities also presents problems for the algorithms, with overestimations of dose of up to 20% found behind bone-tissue interfaces, apparently due to shielding by high density bone. Overestimations of up to 17% are also found beside interfaces parallel to the beam. Underestimations of dose of up to 10% are found on the beam-side of interfaces, due to under-prediction of backscattered electrons. All three investigated algorithms underestimate the dose by up to 20% behind extreme surface curvature. One algorithm is found to underestimate the dose in the falloff region while another overestimates the dose around the 90% isodose. CONCLUSION: Clinicians should be aware of the limitations of their planning systems.

Algorithms↗
PubMed1994

Dosimetry of high energy electron therapy to the parotid region.

Well-known inadequacies in currently available electron planning systems, and two cases of temporal lobe necrosis following electron therapy of the parotid stimulated a comprehensive head and neck phantom dosimetric study of the use of high energy electrons for parotid treatments. A typical electron field employed for the treatment of parotid malignancy was examined in an anthropomorphic head phantom from which air cavities had been excavated. Thermoluminescent dosimeter measurements were compared with predicted point doses obtained from a Theraplan Treatment planning system (V05). Data was examined for three different electron energies: 12, 16 and 20 MeV and with the addition of contoured bolus for 20 MeV. A number of significant discrepancies between the measured and predicted dose were observed. Measured doses were seen to exceed predicted doses by up to 23% in the temporal lobe. Further under-predictions of dose were found behind the mandible and in the nasal cavity. Over-predictions of dose by the planning algorithm of up to 22% were observed beside the oropharynx. Some of these discrepancies were found to relate to Theraplan under-estimation of the dose in the fall-off region. Other errors are attributable to the difficulties in predicting dose at density interfaces. Localised over- and under-predictions of this magnitude must be accounted for by the clinician prescribing treatment in terms of possible late effects on the temporal lobe and, in particular, the nominated dose specification point.

Adenocarcinoma, Papillary↗
PubMed1993

Objective decision-making following a portal film: the results of a pilot study.

PURPOSE: To discriminate between random and systematic treatment setup errors using portal films. METHODS AND MATERIALS: A bi-dimensional analytic techniques using multiple analyses of variance based on Hotelling's T2 statistics to derive numerical and graphical measures of daily portal film accuracy and precision has been trialed using 88 daily portal films from seven patients' treatment. RESULTS: A demonstration is provided of how a reasonable approximation of random variation from the intended (Simulator) field center, and systematic displacement of the mean position of the portal film centers may be derived from a minimum number of portal films. If a random error as great as 10 mm exists, at least six or seven portal films are considered necessary to reliably detect and quantify the size of a systematic error. CONCLUSION: Our results suggest that a modest systematic error could go undetected until the end of a 5 or 6 week course of treatment if only one portal film is obtained each week. A greater number of portal films should be performed during the first week of treatment to reduce the frequency of such errors. Efforts to separate and quantify both random and systematic errors in setup are worthwhile and will lead to improvements in outcome at the individual patient level and at a departmental level in the development of quality assurance programs.

Humans↗
PubMed1993

Phase I/II study of concurrent weekly carboplatin and radiation therapy in advanced head and neck cancer.

Thirty-two patients with locally advanced head and neck cancer have been treated with concurrent weekly carboplatin and conventional radiation therapy (RT) (2 Gy fractions 4-5 days/week to a total dose of 64-70 Gy over 7-8 weeks) in a Phase I/II study. Carboplatin was administered weekly during RT at doses of 75-150 mg/m2/wk as a 1-hour infusion. The maximum tolerated dose of carboplatin was 130 mg/m2/wk, with myelosuppression, predominantly neutropenia, being dose limiting. Other systemic toxicities were insignificant and no overlapping toxicity was evident. Ultimate locoregional control and survival probabilities were disappointing. It is suggested that either further studies using radiation and carboplatin at the dose 130 mg/m2/wk, or variations on dose and scheduling be performed prior to the instigation of Phase III studies.

Adult↗
PubMed1993

Pelvic radiotherapy with concurrent 5-fluorouracil modulated by leucovorin for rectal cancer: a phase II study.

Combined modality treatment for cancer of the rectum has been shown to reduce recurrences and improve overall survival. We wished to find out if we could safely give concurrent radiotherapy and 5-fluorouracil (5-FU) modulated by leucovorin (LV) in 3 settings: pre-operatively, adjuvantly and in recurrent disease. A total of 39 patients were treated, 11 preoperatively, 17 adjuvantly and 11 with recurrent disease. There were 26 males and 13 females with a median age of 64 years. The median radiotherapy (RT) dose was 45 Gy/25 fractions/1.8 Gy per fraction (range 25-63 Gy). Chemotherapy consisted of LV 80 mg/m2 i.v. infusion over 1.5 hours followed by 5-FU 400 mg/m2 i.v. bolus, both given once a week. The median number of cycles was 8 (range 3-12). Diarrhoea was the main toxicity, and was encountered in 30 patients (77%): grade 1 in 3 (8%), grade 2 in 12 (30%), grade 3 in 11 (28%), and grade 4 in 4 (10%). This required 18 (46%) patients to have modifications to their RT (20% had breaks and 26% ceased at doses < 45 Gy). Nine patients (23%) had modifications in the chemotherapy (10% had breaks and 13% received < 6 cycles). Encouraging responses were seen in the preoperative setting. Concurrent RT and 5-FU/LV, as given in this schedule, results in an unacceptable incidence of diarrhoea, limiting both the total dose of RT and chemotherapy that can be delivered, particularly in patients who have had previous surgery.

Adenocarcinoma↗
PubMed1993

Low dose rate teletherapy and tumour response.

Tumour responses in 25 patients with locally advanced head and neck cancer, treated on an experimental fractionated low dose rate (FLDR) teletherapy program are reported. Treatment was given at dose rates ranging from 1.8 to 3 Gy/h to a range of total doses from 32-38 Gy, with palliative intent. The total doses delivered have been predicted by the linear quadratic formula to be equivalent to 33-41 Gy using conventionally fractionated high dose rate treatment, in terms of acute normal tissue effects. A complete response rate (no visible or palpable disease 2 months after treatment) was observed in 28% of cases. Analysis of these response rates suggests that the linear quadratic formula may underestimate the anti-tumour effect of FLDR teletherapy at the various dose rates and total dose permutations in this study.

Carcinoma, Squamous Cell↗
PubMed1992

A practical evaluation of five dose-volume histogram reduction algorithms.

A unifying approach to cumulative dose-volume histogram (CDVH) reduction analysis is presented, utilising two weighted linear interpolation models (VWD, DWV), two weighted probability models (VWP, DWP) and a novel integral probability model (IPM). As a test of their predictive value these algorithms were applied to CDVH data generated from lung doses, measured by TLD arrays in a female anthropomorphic phantom. Three arbitrary configurations of breast size and location of "target volume" within the breast were "treated", using an appropriate electron field (Varian Clinac 1800) or double-plane iridium-192 implant. Calculated effective doses from each of the reduction algorithms showed the iridium implant to be dosimetrically the most favourable in two the three configurations. Likewise, complication probabilities, based on a logistic dose-volume response function showed lung complication probabilities to be lower for the interstitial technique in the same situations. All algorithms tested showed reasonable consistency, with the exception of the VWD. The rationale and value of comparative rather than absolute dose-volume histogram analyses are discussed.

Algorithms↗
PubMed1992

Tangential breast irradiation: simple improvements.

A series of studies using phantom and in vivo dosimetry measurements with diodes and thermoluminescent dosimetry were undertaken to establish whether simple methods are available to obtain improvements in homogeneity of dose in the treated breast, and reductions of dose to tissues outside it, when using tangential 6MV photon fields. These studies confirmed that the use of an appropriate lung density correction factor in the planning process is likely to cause a reduction in the amount of wedge compensation predicted to be necessary to produce reasonable dose homogeneity in the central axis of the beam. This was shown to be of value in eliminating potential areas of overdosage in the chest wall medial and lateral to the breast mound, and also in reducing unwanted doses to the contralateral breast and lung. Further reductions in dose to contralateral breast were confirmed to occur when the majority, or all, of the wedge compensation predicted necessary is placed on the lateral field and when the lateral tangential field is angled anteriorly in such a way as to align the posterior beam edges. Skin does above, below, and over the breast mound were observed to depend critically upon angle of incidence of the beam, with its consequent effect upon electron build-up, and the position of the breast contour in the beam. Skin doses above and below the breast mound were shown to exceed over the mound itself. This differential effect was observed to increase with increasing wedge compensation. In some situations skin doses below the breast mound nearly reached prescribed dose within the breast. The design and use of simple lead attenuators to reduce these areas of high dosage is discussed.

Breast Neoplasms↗