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C S Hamilton

Publications and source records attributed to C S Hamilton.

At least 19 recordsLinked to original sources
PubMed2000

Pilot study of high-frequency ultrasound to assess cutaneous oedema in the conservatively managed breast.

Cutaneous oedema is a relatively frequent complication in patients treated conservatively for breast cancer. The factors that contribute to this complication have not been precisely determined. We performed a pilot study to assess the usefulness of high-frequency ultrasound as a quantitative measure of cutaneous oedema. Eleven patients undergoing breast-conserving therapy for breast cancer were studied. Both the treated and untreated breasts were examined. Total cutaneous thickness provided a useful measure of cutaneous oedema. The treated breast was significantly thicker than the untreated breast (P < 0.001). The medial aspect of the breast was thicker than the lateral aspect in both the treated and untreated breast (P < 0.001). The increase in cutaneous thickness predated radiotherapy in those patients who had undergone an axillary dissection. Intrapatient variation in skin thickness was much less than interpatient variation in skin thickness (coefficient of variation 6.4% vs. 18.2% for the untreated breast; coefficient of variation 13.9% vs. 30.9% for the treated breast). Increasing cutaneous thickness was associated with decreasing cutaneous echodensity. We were unable to derive quantitative estimates of echodensity. Cutaneous oedema is an important outcome variable following conservative treatment of breast cancer. High-frequency ultrasound is able to quantify this accurately. It can readily detect changes invisible to the naked eye. High-frequency ultrasound should enable the effects of different treatment options (e.g., extent of surgery, radiotherapy, and chemotherapy) on cutaneous oedema to be differentiated and for the time course of oedema to be accurately characterised.

Aged↗
PubMed2000

Functional importance of motif I of pseudouridine synthases: mutagenesis of aligned lysine and proline residues.

On the basis of sequence alignments, the pseudouridine synthases were grouped into four families that share no statistically significant global sequence similarity, though some common sequence motifs were discovered [Koonin, E. V. (1996) Nucleic Acids. Res. 24, 2411-2415; Gustafsson, C., Reid, R., Greene, P. J., and Santi, D. V. (1996) Nucleic Acids Res. 24, 3756-3762]. We have investigated the functional significance of these alignments by substituting the nearly invariant lysine and proline residues in Motif I of RluA and TruB, pseudouridine synthases belonging to different families. Contrary to our expectations, the altered enzymes display only very mild kinetic impairment. Substitution of the aligned lysine and proline residues does, however, reduce structural stability, consistent with a temperature sensitive phenotype that results from substitution of the cognate proline residue in Cbf5p, a yeast homologue of TruB [Zerbarjadian, Y., King, T., Fournier, M. J., Clarke, L., and Carbon, J. (1999) Mol. Cell. Biol. 19, 7461-7472]. Together, our data support a functional role for Motif I, as predicted by sequence alignments, though the effect of substituting the highly conserved residues was milder than we anticipated. By extrapolation, our findings also support the assignment of pseudouridine synthase function to certain physiologically important eukaryotic proteins that contain Motif I, including the human protein dyskerin, alteration of which leads to the disease dyskeratosis congenita.

Amino Acid Motifs↗
PubMed1999

Is there more than one late radiation proctitis syndrome?

PURPOSE: To investigate the significance of the various late rectal symptoms that appear after radical prostatic irradiation. PATIENTS AND METHODS: Patients with localised prostate cancer treated between 1987 and 1994 at the Mater Hospital, Newcastle with radical megavoltage irradiation were recalled for examination and to complete a detailed questionnaire concerning late radiation-induced symptoms and their effects on normal daily life. The influence of patient age treatment related variables and acute proctitis symptoms occurring during therapy or the late symptoms recorded were assessed and the relationship between late symptoms and late EORTC/RTOG score and impact on normal daily life were studied. RESULTS: The presence of symptoms of acute proctitis was the only factor to predict any of three late symptoms (urgency, frequency and diarrhoea) and late EORTC/RTOG score in this series (odds ratios: 1.7-2.57, P-values: 0.009-0.0007). Cluster and discriminant function analyses revealed the presence of five subgroups of patients with varying permutations of different late rectal symptoms, including one group with minimal symptoms (P < 0.0001). While bleeding and rectal discharge were the major contributors to late EORTC/RTOG score (P < 0.0001 and 0.04), faecal urgency and bleeding were the most important factors to impact on normal daily life (P < 0.0001 and P < 0.0003). A relatively low concordance was found between late EORTC/RTOG score and the patients' self assessment on the effect of their symptoms on their normal daily lives. Some late symptoms, including bleeding and rectal discharge become less prevalent after 3 years of follow-up with a resulting improvement in EORTC/RTOG score. CONCLUSIONS: There may be more than one late (chronic) proctitis syndrome which may be linked in greater or lesser degrees to acute proctitis symptoms occurring during therapy. Urgency is a common late symptom which often has an important impact on normal daily life and deserves recognition in late normal tissue scoring systems. Assessment of the incidence of bleeding as a measure of late rectal morbidity following prostate irradiation may underestimate the impact of these chronic effects. Confirmatory studies are necessary.

Aged↗
PubMed1997

Response of human hair cortical cells to fractionated radiotherapy.

Hair cortical cell counting (HCCC) represents a non-invasive, in-vivo measure of cell kill in the human integument. Sixty-six patients undergoing conventionally fractionated, external beam radiotherapy for early stage carcinoma of the prostate had groin hair samples counted. This technique is a sensitive and reproducible measure of radiation effect and may have applicability as an in-vivo prediction tool or in the field of biological dosimetry. A repopulative follicular response occurring at 3-4 weeks may explain flattening of the dose response curve.

Dose-Response Relationship, Radiation↗
PubMed1996

Assessment of mucosal underdosing in larynx irradiation.

PURPOSE: Mucosal underdosing as a result of electron disequilibrium at the air cavity may affect local recurrence rates for T1 and T2 larynx cancers. Secondary build-up properties of high-energy beams have been demonstrated in a slab phantom. It was the aim of this investigation to determine whether significant surface underdosing exists for the mucosa under clinical conditions. METHODS AND MATERIALS: Measurements were made using a thermoluminescent dosimetry (TLD) extrapolation technique in an anatomic larynx phantom. The larynx phantom was constructed using tissue and cartilage equivalent material, based on patient cross-sectional anatomy. Three different thicknesses of LiF ribbons, 0.14, 0.39, and 0.89 mm, were placed reproducibly at 12 different positions at the anterior, posterior, and lateral walls on the endolarynx surface. Measured doses were plotted and an extrapolation was made back to the mucosal depth to obtain the dose received at each of the positions. Results were obtained for two different field configurations, opposed laterals and oblique fields, for 6-MV X rays and opposed lateral fields from a telecesium unit. In addition, the larynx surface doses of field sizes from 4 x 6 cm2 to 7 x 6 cm2 were investigated. RESULTS: Surface underdosing was observed owing to the secondary build-up and build-down effect of the air cavity, and the dose measured for the three extrapolation TLDs at any position varied by up to 18%. An average variation of 6% was observed. The surface underdosing was most apparent for the 6-MV opposed lateral beam technique, where mucosa doses down to 76% of the prescribed dose were observed. Mucosal underdosing at the measurement positions was less marked with oblique techniques, telecesium treatment, and increasing field size. CONCLUSION: Because of underdosing, some surface positions receive < 80% of the prescribed dose. This may contribute to the potential for higher recurrence rates observed with high-energy photons.

Air↗
PubMed1996

Factors influencing outcome following radio-chemotherapy for oesophageal cancer. The Trans Tasman Radiation Oncology Group (TROG)

BACKGROUND AND PURPOSES: To define new directions, the Trans Tasman Radiation Oncology Group (TROG) has conducted a detailed analysis of its unrandomised experience with radio-chemotherapy in oesophageal cancer. METHODS AND PATIENTS: Since 1984, 373 patients with oesophageal cancer have been treated on three prospective, but unrandomised, protocols involving radiation with concurrent cisplatin and infusional fluorouracil. Centres in Australia and New Zealand have contributed patients. Reasons for case selection have been examined in detail and prognostic models have been examined in the light of biases exposed. RESULTS: Cause specific survival in 92 patients treated pre-operatively with 35 Gy, infusional fluorouracil and cisplatin was 25.5 +/- 6.0% at 5 years and similar to the 5 year expectations of 169 patients treated with 60 Gy and two courses of the same chemotherapy (23.8 +/- 4.7%). Analysis of failure in these groups suggests that local relapse precedes the development of metastases and competes as a cause for ultimate failure. Although patients treated surgically were less likely to relapse locally, survival was no better because more developed metastases. Some of the 112 patients treated "palliatively" with 30-35 Gy concurrent with chemotherapy without surgery have become long-term survivors with 5 year survival figure in this group 7.7 +/- 3.4%. Apart from variables related to disease stage and performance status at presentation, tumour site emerged as a strong predictor of outcome. Prognosis worsens the nearer the tumour is to the stomach. In addition, indications of a radiation dose response relationship emerged. CONCLUSIONS: Concurrent radio-chemotherapy protocols can improve outcome in patients fit enough to tolerate these approaches. New strategies remain necessary, however.

Adenocarcinoma↗
PubMed1996

Underprediction of human skin erythema at low doses per fraction by the linear quadratic model.

BACKGROUND AND PURPOSE: The erythematous response of human skin to radiotherapy has proven useful for testing the predictions of the linear quadratic (LQ) model in terms of fractionation sensitivity and repair half time. No formal investigation of the response of human skin to doses less than 2 Gy per fraction has occurred. This study aims to test the validity of the LQ model for human skin at doses ranging from 0.4 to 5.2 Gy per fraction. MATERIALS AND METHODS: Complete erythema reaction profiles were obtained using reflectance spectrophotometry in two patient populations: 65 patients treated palliatively with 5, 10, 12 and 20 daily treatment fractions (varying thicknesses of bolus, various body sites) and 52 patients undergoing prostatic irradiation for localised carcinoma of the prostate (no bolus, 30-32 fractions). RESULTS AND CONCLUSIONS: Gender, age, site and prior sun exposure influence pre- and post-treatment erythema values independently of dose administered. Out-of-field effects were also noted. The linear quadratic model significantly underpredicted peak erythema values at doses less than 1.5 Gy per fraction. This suggests that either the conventional linear quadratic model does not apply for low doses per fraction in human skin or that erythema is not exclusively initiated by radiation damage to the basal layer. The data are potentially explained by an induced repair model.

Aged↗
PubMed1996

Mucosal regeneration during radiotherapy. Trans Tasman Radiation Oncology Group (TROG).

BACKGROUND AND PURPOSE: Regeneration of the aerodigestive mucosa is known to occur during conventionally fractionated radiotherapy. The circumstances surrounding its time of onset and magnitude are not well understood, however. MATERIAL AND METHODS: Mucosal reactions were observed in 100 patients undergoing conventionally fractionated treatment at 2 Gy/day over 7 weeks and 88 receiving accelerated treatment at 1.8 Gy twice daily over 3 1/2 weeks on the Trans Tasman Radiation Oncology Group head and neck cancer trials. Similar observations in 61 patients treated palliatively at dose rates between 0.8 and 240 Gy/h using ten 3.0-4.2 Gy fractions over 2 weeks are compared. RESULTS: Several findings emerged from these studies: 1. Reactions evolved more quickly at oropharyngeal sites than in the hypopharynx. 2. Reactions at both sites evolved more rapidly at greater rates of dose accumulation. 3. The timing of reactions suggested the presence of a strong regenerative mucosal response that started before the manifestation of "patchy' (grade II) mucosal reactions. 4. The regenerative response was strong enough to "make good' damage accumulated at a rate of 2 Gy/day in over a third of cases. 5. The linear quadratic model without time correction failed to provide an adequate prediction of the frequency or intensity of mucosal reactions produced by any of the regimes. A simple model of the regenerative response is presented. CONCLUSIONS: This study suggests that the timing and magnitude of the regenerative response vary between sites and individuals but are linked to the amount of epithelial cellular depletion occurring during treatment.

Head and Neck Neoplasms↗
PubMed1996

Low dose rate teletherapy: updated tumour response.

This report presents an update of tumour response experience in patients with locally advanced head and neck cancer treated on the low dose rate teletherapy project at the Mater Misericordiae Hospital, Newcastle. Long-term progression-free survival figures are disappointing in all dose rate/total dose groupings and offer little encouragement that an improvement in therapeutic ratio can be achieved for head and neck cancer patients using teletherapy apparatus adjusted to treat at low and intermediate dose rates.

Cesium Radioisotopes↗
PubMed1995

Clinical use of carbon-loaded thermoluminescent dosimeters for skin dose determination.

PURPOSE: Carbon-loaded thermoluminescent dosimeters (TLDs) are designed for surface/skin dose measurements. Following 4 years in clinical use at the Mater Hospital, the accuracy and clinical usefulness of the carbon-loaded TLDs was assessed. METHODS AND MATERIALS: Teflon-based carbon-loaded lithium fluoride (LiF) disks with a diameter of 13 mm were used in the present study. The TLDs were compared with ion chamber readings and TLD extrapolation to determine the effective depth of the TLD measurement. In vivo measurements were made on patients receiving open-field treatments to the chest, abdomen, and groin. Skin entry dose or entry and exit dose were assessed in comparison with doses estimated from phantom measurements. RESULTS: The effective depth of measurement in a 6 MV therapeutic x-ray beam was found to be about 0.10 mm using TLD extrapolation as a comparison. Entrance surface dose measurements made on a solid water phantom agreed well with ion chamber and TLD extrapolation measurements, and black TLDs provide a more accurate exit dose than the other methods. Under clinical conditions, the black TLDs have an accuracy of +/- 5% (+/- 2 SD). The dose predicted from black TLD readings correlate with observed skin reactions as assessed with reflectance spectroscopy. CONCLUSION: In vivo dosimetry with carbon-loaded TLDs proved to be a useful tool in assessing the dose delivered to the basal cell layer in the skin of patients undergoing radiotherapy.

Carbon↗
PubMed1995

Combined modality therapy for esophageal carcinoma: preliminary results from a large Australasian multicenter study.

PURPOSE: This report updates local control and survival experience and focuses on treatment toxicity in 294 patients with esophageal cancer who have been treated at six Australasian centers using three prospective unrandomized protocols that used concurrent radiation, cisplatin, and modest dose infusional fluorouracil. METHODS AND MATERIALS: Protocol 1--"definitive" chemoradiation. One hundred and thirty-seven patients have been treated with "definitive" radiation to 60 Gy in 6 weeks plus two courses of cisplatin (80 mg/m2) and infusional fluorouracil (800 mg/m2/day over 4 days) during the first and fourth weeks of radiation. Protocol 2--"preoperative" chemoradiation and surgery. Seventy-eight patients received chemoradiation using the same chemotherapy, but 30-35 Gy in 3-4 weeks prior to surgery. Protocol 3--"palliative" chemoradiation. Seventy-nine patients deemed incurable were treated "palliatively" with the same chemoradiation protocol without surgery. Follow-up ranges from 6 months to 7 years (mean 22 months) in live patients. RESULTS: Durable palliation of dysphagia in all three treatment groups has been reflected by encouraging 3-year survival expectations of 43.2 +/- 5% in definitively treated patients, 40.3 +/- 7.65% in surgically treated patients, and 8.5% +/- 3.9% in the palliatively treated patients. There are early indications that female patients have fared better than males. Toxicity levels were modest in all three groups. Following definitive treatment, severe myelotoxicity (World Health Organization grades 3 and 4) occurred in 19%, severe esophagitis (World Health Organization grade 3) in 11%, and moderate or severe benign stricture in 17%, depending upon age and sex of the patient (being worse in female patients). CONCLUSIONS: These studies demonstrate that the concurrent addition of modest dose cisplatin and infusional dose fluorouracil to radiation in the definitive, preoperative, and palliative settings contribute to high rates of durable dysphagia-free survival, with overall survival comparable to (and possibly better than) the chemoradiation arm of the recently reported Intergroup Study, but at the cost of less morbidity.

Adenocarcinoma↗
PubMed1995

Simultaneous adjuvant radiation therapy and chemotherapy in high-risk breast cancer--toxicity and dose modification: a Transtasman Radiation Oncology Group Multi-Institution study.

PURPOSE: To establish the toxicity profile of simultaneously administered postoperative radiation therapy and CMF chemotherapy as a prelude to a randomized controlled study addressing the sequencing of the two modalities. METHODS AND MATERIALS: One hundred and thirty eight breast cancer patients at high risk of locoregional, as well as systemic relapse, who were referred to three centers in Australia and New Zealand were treated with postoperative radiation therapy and chemotherapy simultaneously. Acute toxicity and dose modifications in these patients were compared with 83 patients treated over the same time frame with chemotherapy alone. In a separate study the long-term radiation and surgical effects in 24 patients treated simultaneously with radiation therapy and chemotherapy at Newcastle (Australia) following conservative surgery were compared with 23 matched patients treated at Newcastle with radiation therapy alone. RESULTS: Myelotoxicity was increased in patients treated simultaneously with radiation therapy and chemotherapy. The effect was not great, but may have contributed to chemotherapy dose reductions. Lymphopenia was observed to be the largest factor in total white cell depressions caused by the simultaneous administration of radiation therapy. Postsurgical appearances were found to so dominate long-term treatment effects on the treated breast that the effect of radiation therapy dose and additional chemotherapy was difficult to detect. CONCLUSION: Studies addressing the sequencing of radiation therapy and chemotherapy will necessarily be large because adverse effects from administering the two modalities simultaneously are not great. The present study has endorsed the importance in future studies of stratification according to the extent and type of surgery and adherence to a single strict policy of chemotherapy dose modification.

Adult↗
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↗