[en] Purpose: This paper describes the technique of stereolithographic biomodelling and its application to a patient who was treated using orbital brachytherapy. Methods and Materials: The process uses a moving laser beam, directed by a computer, to draw cross-sections of the model onto the surface of photo-curable liquid plastic. Using a stereolithographic apparatus (SLA), solid or surface data is sliced by software into very thin cross-sections. A helium cadmium (HeCd) laser then generates a small intense spot of ultraviolet (UV) light that is moved across the top of a vat of liquid photo monomer by a computerised optical scanning system. The laser polymerises the liquid into a solid where it touches, precisely printing each cross-section. A vertical elevator lowers the newly formed layer, and a recoating and levelling system establishes the next layer's thickness. Successive cross-sections (0.25 mm thick), each one adhering to the one below, are built one on top of the other, to form the part from the bottom up. The biomodel allowed the implant to be planned in detail prior to the surgery. The accurate placement of brachytherapy catheters was assured, and the dosimetry could be determined and optimised prior to the definitive procedure. Conclusions: Stereolithography is a useful technique in the area of orbital brachytherapy. It allows the implant to to be carried out with greater accuracy and confidence. For the patient, it minimises the risk to the eye and provides them with a greater understanding of the procedure

[en] Purpose: To analyze the results of T3N0M0 glottic carcinoma treated with radiotherapy, surgery, or both. Methods and Materials: The records were retrospectively reviewed of 97 patients with this tumor subsite and stage seen for treatment at the Queensland Radium Institute over a 29-year period. The results for radiotherapy with surgical salvage of failure ((XRT(SS))) were compared to those with surgery with or without radiotherapy ((SURG(SURG+XRT))). For those treated initially with radiotherapy alone, the results for different ranges of biologically equivalent doses were compared. These results were compared to those of other published studies. Results: The 5-year disease-specific survival rates for the (XRT(SS)) and (SURG(SURG+XRT)) groups were 50% and 58%, respectively; this difference is not significant. For the (XRT(SS)) group, there was a trend towards improved 5-year recurrence-free survival (73%) and 5-year disease-specific survival (86%) in those treated to a dose equivalent to 60-64 Gy in 2 Gy fractions, when compared with higher or lower dose equivalents. Conclusion: A group of patients with T3N0M0 glottic carcinoma is specified for which the option of radiotherapy offers a similar chance of survival to those treated surgically. More than 50% of the (XRT(SS)) survivors will retain their larynx

No abstract available

[en] The aim of this study was to assess the effect of surgery on normal tissue toxicity in head and neck cancer patients treated with accelerated radiotherapy. Toxicity data from two trials of accelerated radiotherapy were compared. The first group was taken from a phase III trial of definitive radiotherapy and the second group from a phase II trial of postoperative radiotherapy. The general eligibility criteria (apart from surgery), data collection and radiotherapy details for both trials were similar. The definitive group included 172 eligible patients and the postoperative group 52 eligible patients. At 3 weeks into treatment, by which time the dose and rate of dose accumulation were identical, there was no difference in acute toxicity. Analysis of late toxicity showed greater subcutaneous fibrosis in the postoperative group

[en] Background and purpose: A limited number of studies have suggested that oral sucralfate reduces the acute and late gastro-intestinal side-effects of pelvic radiotherapy and sucralfate enemas ameliorate symptoms of chronic proctitis. Sucralfate may act via local bFGF at the mucosal level in promoting angiogenesis and reducing epithelial associated microvascular injury. This multi-institutional study was designed to test the hypothesis that sucralfate given as an enema would have a significant protective effect against acute radiation induced rectal injury by direct application to the mucosa. Materials and methods: Eighty-six patients having radiotherapy for localised carcinoma of the prostate were randomised in a double-blind placebo-controlled study to receive either 15 ml of placebo suspension or 3 g of sucralfate in 15 ml suspension, given as a once daily enema during and for 2 weeks following radiotherapy. Assessment was based on the EORTC/RTOG acute toxicity criteria and a patient self-assessment diary. Results: There was no significant difference between placebo and sucralfate for peak incidences of EORTC/RTOG proctitis. For the placebo and sucralfate arms 95 and 88% (difference 7 ± 11%) suffered some degree of proctitis, with 71 and 61% (difference 10 ± 19%) reaching grade 2, respectively. The median period to onset of grade 2 proctitis was 33.5 and 36 days, with the median duration being 9.5 and 15 days, respectively, again these difference being non-significant. Thirty-five and 37% of patients rated the effect of radiotherapy on bowel habit as 'a lot' with a moderate or severe effect on normal daily living in 52 and 49%, respectively. Conclusion: This study suggests that sucralfate given as a once daily enema does not substantially reduce the incidence of symptoms associated with acute radiation proctitis and its routine clinical use cannot be recommended. This cohort of patients will be followed to determine if any difference develops in relation to late toxicity

[en] Purpose: To assess the potential for sucralfate administered rectally to reduce the risk of late rectal morbidity in patients undergoing nonconformal radiotherapy (RT) for carcinoma of the prostate and to study the variables potentially contributing to late rectal morbidity and particularly to explore the relationship between acute and late toxicity. Methods and Materials: Eighty-six patients with localized prostate carcinoma were randomized in a double-blind, placebo-controlled study to a daily enema of 3 g of sucralfate in a 15-mL suspension or the same suspension without sucralfate. The enema began the first day of RT and was continued for 2 weeks after treatment completion. The primary end point of the study was acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) toxicity; however, the patients were followed for an additional 5 years on a 6-month basis. The evaluation included late RTOG/EORTC toxicity and a patient self-assessment questionnaire. Results: With a median follow-up of 5 years, the Kaplan-Meier probability of late Grade 2 RTOG/EORTC toxicity was 12% (95% confidence interval [CI] 2-22%) for placebo and 5% (95% CI 0-12%) for sucralfate (p=0.26). The probability of late rectal bleeding was 59% (95% CI 45-73%) for placebo and 54% (95% CI 40-68%) for sucralfate. No statistically significant difference was found between the treatment arms for the peak incidence of any of the other patient self-assessment variables. Cox proportional hazards modeling indicated acute RTOG/EORTC toxicity of Grade 2 or greater was associated with a hazard ratio of 2.74 (95% CI 1.31-5.73) for the development of late toxicity of Grade 1 or greater. Substituting the patient self-assessment variables for acute RTOG/EORTC toxicity revealed that rectal pain of a moderate or severe grade during RT was the best predictor of the subsequent development of late toxicity, with a hazard ratio of 3.44 (95% CI 1.68-7). Conclusion: The results of this study do not support the use of sucralfate administered rectally as a method for reducing the late toxicity of nonconformal RT for prostate cancer. There appears to be an association between the development of acute and subsequent late toxicity, although the nature of this association remains to be determined

[en] Purpose: The aims of this analysis were to determine the effect of anaemia on loco-regional control, relapse-free survival, cause-specific survival, overall survival, and acute and late radiation therapy toxicity in patients with Stage III and IV squamous cell carcinoma of the head and neck treated with radiotherapy. Patients and methods: Between 1991 and 1998, 350 patients were randomly assigned to either conventional radiotherapy, (70 Gy in 35 fractions in 49 days) or to accelerated radiotherapy (59.4 Gy in 33 fractions in 24 days). Patients were divided into two groups according to their haemoglobin level: a normal haemoglobin group (≥13 g/dl in males, ≥12 g/dl in females) and a low haemoglobin group (<13 g/dl in males, <12 g/dl in females). The influence of anaemia on cause-specific survival and the development of confluent mucositis independent of other variables was tested using Cox proportional hazards model. Results: Of 350 patients recruited to the trial, 238 had haemoglobin measurements and were eligible for inclusion in this secondary analysis. One hundred and ninety-three were considered to have normal haemoglobin, and 45 patients were considered to be anaemic. There were significant differences between the groups in loco-regional control, relapse-free survival, cause-specific survival and overall survival, with hazards ratios of 0.56 (95% confidence interval (CI) 0.34-0.94), 0.57 (95% CI 0.35-0.92), 0.49 (95% CI 0.29-0.85) and 0.43 (95% CI 0.26-0.70) in favour of the normal haemoglobin group. Using Cox proportional hazards modelling, haemoglobin level was a significant predictor of cause-specific survival in addition to disease site, stage, and Eastern Cooperative Oncology Group status. There were no statistically significant differences between the groups in the development of acute or late reactions. Conclusion: Significant reductions in loco-regional control, disease-free survival, cause-specific survival and overall survival occur in the presence of anaemia. No significant differences in normal tissue toxicity have been identified in this analysis

[en] Purpose: The acute and late toxicities of synchronous carboplatin, etoposide, and radiation therapy were prospectively assessed in a group of patients with high-risk Milkier cell carcinoma of the skin. Patients and Methods: Forty patients from six different centers throughout Australia were entered into a Phase II study under the auspices of the Trans-Tasman Radiation Oncology Group. The trial was activated in 1996 and continues to accrue. Patients are eligible if they have disease localized to the primary site and nodes and are required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, gross residual disease after surgery, or occult primary with nodes. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (area under curve [Auc] 4.5) and etoposide (80 mg/M² i.v.) were given on days 1-3 during weeks 1, 4, 7, and 10. The median age of the group was 67 years (43-78). Results: The median duration of follow-up was 22 months (2-45). There were no treatment-related deaths. Grade 3 or 4 skin toxicity occurred in 63% of patients (95% CI 48, 78). The most serious acute effect was on neutrophils with Grade 3 or 4 (neutrophils <1x10⁹/L), occurring in 60% (95% CI 45, 75) of cases. Complications from neutropenia (fever and sepsis) occurred in 16 patients (40% of cases). The median time for neutropenic complications was 27 days (9-35), and 10/16 (62%) cases of neutropenic fever occurred after the second cycle of chemotherapy. The probability of Grade 3 or 4 late effects on platelets (<50x10⁹/L) and hemoglobin (<8 g/dl) was 10% (95% CI 1, 20) and 6% (95% CI 2, 15), respectively. Of the 40 patients, 35 were able to complete 4 cycles of chemotherapy. There were no factors predictive for neutropenic toxicity at a p value < 0.05. Conclusions: The protocol has acceptable toxicity, and the treatment has been deliverable in a multi-institutional trial setting. Neutropenia is likely to occur with synchronous carboplatin/etoposide and radiation in this population of patients. The risk of a febrile neutropenia was greatest at the time of the second cycle of chemotherapy, when there was moist desquamation of skin or mucosal membranes that provided a portal for infection. This should be considered in the design of subsequent protocols with chemoradiotherapy

[en] 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

[en] Purpose: The aims of this randomized controlled trial were to determine whether there were differences in the disease-free survival (DFS) and toxicity between conventional radiotherapy (CRT) and a continuous 3 week accelerated radiotherapy regimen (ART) in stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx. Patients and methods: Patients from 14 centres throughout Australia and New Zealand were randomly assigned to either CRT, using a single 2 Gy/day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. The accrual began in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. Results: The median potential follow-up time was 53 months (range, 14-101). The DFS at 5 years was 41% (95% CI, 33-50%) for ART and 35% (95% CI, 27-43%) for CRT (P=0.323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66-1.15). The 5-year disease-specific survival rates were 40% for CRT and 46% for ART (P=0.398) and the loco-regional control was 47% for CRT vs. 52% for ART (P=0.300). The respective hazard ratios were 0.88 (95% CI, 0.65-1.2) and 0.85 (0.62-1.16), favouring the accelerated arm. In the ART arm, confluent mucositis was more severe (94 vs. 71%; P<0.001) and peaked about 3 weeks earlier than in the CRT arm, but healing appeared complete in all cases. There were statistically significant reductions in the probability of grade 2 or greater late soft tissue effects over time in the ART arm (P<0.05), except for the mucous membrane where late effects were similar in both arms. Conclusions: Differences in DFS, disease-specific survival and loco-regional control have not been demonstrated. ART resulted in more acute mucosal toxicity, but this did not result in greater prolongation of the treatment time compared with the CRT arm. There were less late effects in the ART arm, with the exception of late mucosal effects. This trial has confirmed that tumour cell repopulation occurs during conventionally fractionated radiotherapy for head and neck cancer. However, it has also provided additional evidence that overall improvements in the therapeutic ratio using accelerated fractionation strategies are seriously constrained by the need to limit total doses to levels that do not exceed acute mucosal tolerance. The accelerated schedule tested has been shown in this trial to be an acceptable alternative to conventionally fractionated irradiation to 70 Gy