Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial.

AIMS: Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. MATERIALS AND METHODS: Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. RESULTS: Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. CONCLUSION: Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.

Interfraction patient motion and implant displacement in prostate high dose rate brachytherapy.

PURPOSE: To quantify movement of prostate cancer patients undergoing treatment, using an in-house developed motion sensor in order to determine a relationship between patient movement and high dose rate (HDR) brachytherapy implant displacement. METHODS: An electronic motion sensor was developed based on a three axis accelerometer. HDR brachytherapy treatment for prostate is delivered at this institution in two fractions 24 h apart and 22 patients were monitored for movement over the interval between fractions. The motion sensors functioned as inclinometers, monitoring inclination of both thighs, and the inclination and roll of the abdomen. The implanted HDR brachytherapy catheter set was assessed for displacement relative to fiducial markers in the prostate. Angle measurements and angle differences over a 2 s time base were binned, and the standard deviations of the resulting frequency distributions used as a metric for patient motion in each monitored axis. These parameters were correlated to measured catheter displacement using regression modeling. RESULTS: The mean implant displacement was 12.6 mm in the caudal direction. A mean of 19.95 h data was recorded for the patient cohort. Patients generally moved through a limited range of angles with a mean of the exception of two patients who spent in excess of 2 h lying on their side. When tested for a relationship between movement in any of the four monitored axes and the implant displacement, none was significant. CONCLUSIONS: It is not likely that patient movement influences HDR prostate implant displacement. There may be benefits to patient comfort if nursing protocols were relaxed to allow patients greater freedom to move while the implant is in situ.

Evolving Practice Pattern of Palliative Radiation Therapy for Bone Metastases from Lung Cancer in Australia.

AIMS: Radiation therapy is an effective treatment for bone metastases. Single-fraction conformal radiation therapy (SF-CRT) is equally effective as multifraction radiation therapy for the management of uncomplicated bone metastases. There has been a rapid development of advanced radiation therapy techniques (ART) in radiation oncology. We evaluated the changing pattern of SF-CRT and ART use for the management of bone metastases in lung cancer. MATERIALS AND METHODS: This was a state-wide population-based cohort of lung cancer patients from Victoria, Australia, who received radiation therapy for bone metastases between 2012 and 2017. The primary outcomes were proportion of radiation therapy courses using: SF-CRT and ART. We identified a subcohort in which radiation therapy was delivered at the end of life (EOL), i.e. within 30 days of death. The Cochran-Armitage test for trend was used to evaluate the change in pattern of SF-CRT and ART use over time. Multivariable analyses were used to identify factors associated with the primary outcomes. RESULTS: Of the 4335 courses of radiation therapy for bone metastases in lung cancer, 20% were SF-CRT - increasing from 19% in 2012 to 26% in 2017 (P-trend = 0.004). In multivariate analyses, treatment to the rib, shoulder, hip or extremities, and treatment in public institutions were independently associated with SF-CRT use, but the effect of year of radiation therapy was no longer significant. Five per cent of radiation therapy was delivered using ART, increasing markedly from 2016 onwards (P-trend < 0.001). In multivariate analyses, treatment in private institutions and more recent years of treatment were independently associated with the use of ART. There were 587 courses of radiation therapy delivered at the EOL, with SF-CRT more commonly used closer to death - 53%, 29% and 25% of radiation therapy within 7 days, 8-14 days and 15-30 days of death, respectively. CONCLUSION: SF-CRT continued to be underutilised for bone metastases in lung cancer in Australia, including at the EOL. We observed an increase in ART use for bone metastases from 2016, which occurred contemporaneously with changes in government funding.

Vertebral Fractures Following Stereotactic Body Radiotherapy for Spine Oligometastases: A Multi-institutional Analysis of Patient Outcomes.

AIMS: Stereotactic body radiotherapy (SBRT) is a locally ablative therapy used for the treatment of patients with spine metastases. However, it is associated with higher rates of vertebral compression fractures (VCF) than conventionally fractionated palliative radiotherapy. The purpose of this study was to determine the rate of VCF following spine SBRT and to identify the risk factors associated with this outcome. MATERIALS AND METHODS: We retrospectively reviewed patients treated at two Australian institutions from January 2015 to March 2019. Descriptive statistics were used to assess patient, tumour and treatment factors. The Log-rank test and Cox proportional hazards model were applied in univariate and multivariable analyses to identify factors associated with VCF, local control and overall survival. RESULTS: We evaluated 113 spinal segments from 84 patients, with a median follow-up time of 11.9 months. The median dose and fractionation utilised was 30 Gy in three fractions (67.3%), with a single-fraction rate of 0.9%. The median Spinal Instability Neoplastic Score (SINS) of the lesions was 4/18, with most (84.1%) being SINS stable, scoring between 0 and 6. Five VCFs were observed (three progression of pre-existing fractures and two de novo), a cumulative VCF risk of 4.4%. Four of five fractures occurred within the first year after treatment, with a median time to VCF of 9.2 months. A pre-existing VCF (P = 0.011) was associated with subsequent fracture on multivariable analysis, whereas all VCF segments displayed lytic disease appearance. All fractures were managed conservatively with analgesia, without requirement for subsequent surgical intervention. CONCLUSION: SBRT to spine metastases is safe with respect to VCF, with rates around the lower limit observed in similar studies. Knowledge of factors that predispose to post-treatment fracture, such as pre-existing compression, lytic vertebral disease and SINS >6 will aid in the counselling and selection of patients for this therapy.

Assessment of Intrafraction Motion of the Urinary Bladder Using Magnetic Resonance Imaging (cineMRI).

AIM: To assess the intrafraction motion of the urinary bladder and delineate the appropriate margin size for radiotherapy planning, for both the full and empty bladder. MATERIALS AND METHODS: This was a single-site, single-arm study of 20 patients planned to undergo radical cystectomy for histologically confirmed muscle-invasive bladder cancer. Patients underwent magnetic resonance imaging (cineMRI) of the entire pelvis using a 3-Tesla system, prior to cystectomy. Patients first underwent a cineMRI with a full bladder, then voided and underwent a second MRI with an empty bladder. All MRI sequences were acquired over 18 min. We assessed the differences in bladder filling and subsequent bladder wall displacement, between the empty and full bladder, during a time period consistent with radiotherapy treatment delivery. RESULTS: Twenty patients underwent cineMRI of the entire pelvis. The maximum mean directional displacements of the bladder walls over the 18 min duration of the scan for the empty bladders were 9.8 mm superiorly, 1.1 mm inferiorly, 2.39 mm anteriorly, 3.73 mm posteriorly, 2.74 mm to the left and 2.48 mm to the right. The maximal mean displacements for the full bladders were 9.2 mm superiorly, 1.1 mm inferiorly, 2.28 mm anteriorly, 1.08 mm posteriorly, 1.85 mm to the left and 1.73 mm to the right. Statistically significant differences were seen in the posterior, left and right displacements but were quantitatively small. CONCLUSIONS: Intrafractional motion secondary to bladder filling showed minimal variation between the full and empty bladder. Similar clinical target volume to planning target volume margins can be applied for the delivery of radiotherapy for a full and empty bladder.

Real-time Image-guided Adaptive-predictive Prostate Radiotherapy using Rectal Diameter as a Predictor of Motion.

AIMS: To investigate a relationship between maximum rectal diameter (MRD) on pre-treatment cone beam computed tomography (CBCT) and intra-fraction prostate motion, in the context of an adaptive image-guided radiotherapy (IGRT) method. MATERIALS AND METHODS: The MRD was measured on 2125 CBCTs from 55 retrospective patient datasets and related to prostate displacement from intra-fraction imaging. A linear regression model was developed to determine a threshold MRD associated with a high probability of small prostate displacement. Standard and reduced adaptive margin plans were created to compare rectum and bladder normal tissue complication probability (NTCP) with each method. RESULTS: A per-protocol analysis carried out on 1910 fractions from 51 patients showed with 90% confidence that for a MRD≤3 cm, prostate displacement will be ≤5 mm and that for a MRD≤3.5 cm, prostate displacement will be ≤5.5 mm. In the first scenario, if adaptive therapy was used instead of standard therapy, median reductions in NTCP for rectum and bladder were 0.5% (from 9.5% to 9%) and 1.3% (from 6.6% to 5.3%), respectively. In the second scenario, the NTCP for rectum and bladder would have median reductions of 1.1% and 2.6%, respectively. CONCLUSIONS: We have identified a potential method for adaptive prostate IGRT based upon predicting small prostate intra-fraction motion by measuring MRD on pre-treatment CBCT.

A Multidisciplinary Evaluation of a Web-based eLearning Training Programme for SAFRON II (TROG 13.01): a Multicentre Randomised Study of Stereotactic Radiotherapy for Lung Metastases.

AIMS: In technically advanced multicentre clinical trials, participating centres can benefit from a credentialing programme before participating in the trial. Education of staff in participating centres is an important aspect of a successful clinical trial. In the multicentre study of fractionated versus single fraction stereotactic ablative body radiotherapy in lung oligometastases (TROG 13.01), knowledge transfer of stereotactic ablative body radiotherapy techniques to the local multidisciplinary team is intended as part of the credentialing process. In this study, a web-based learning platform was developed to provide education and training for the multidisciplinary trial teams at geographically distinct sites. MATERIALS AND METHODS: A web-based platform using eLearning software consisting of seven training modules was developed. These modules were based on extracranial stereotactic theory covering the following discrete modules: Clinical background; Planning technique and evaluation; Planning optimisation; Four-dimensional computed tomography simulation; Patient-specific quality assurance; Cone beam computed tomography and image guidance; Contouring organs at risk. Radiation oncologists, medical physicists and radiation therapists from hospitals in Australia and New Zealand were invited to participate in this study. Each discipline was enrolled into a subset of modules (core modules) and was evaluated before and after completing each module. The effectiveness of the eLearning training will be evaluated based on (i) knowledge retention after participation in the web-based training and (ii) confidence evaluation after participation in the training. Evaluation consisted of a knowledge test and confidence evaluation using a Likert scale. RESULTS: In total, 130 participants were enrolled into the eLearning programme: 81 radiation therapists (62.3%), 27 medical physicists (20.8%) and 22 radiation oncologists (16.9%). There was an average absolute improvement of 14% in test score (P < 0.001) after learning. This score improvement compared with initial testing was also observed in the long-term testing (>4 weeks) after completing the modules (P < 0.001). For most there was significant increase in confidence (P < 0.001) after completing all the modules.

Neointimal hyperplasia after arterial injury is increased in a rat model of non-insulin-dependent diabetes mellitus.

BACKGROUND: The key biological determinants that promote restenosis in the setting of diabetes have not been elucidated. There is no accepted animal model to study restenosis in diabetes. METHODS AND RESULTS: We evaluated 2 models of diabetes mellitus: (1) streptozotocin (STZ)-treated Sprague-Dawley rats (type I diabetes) versus regular Sprague-Dawley rats and (2) obese Zucker rats (type II diabetes) versus lean Zucker rats. Neointimal hyperplasia was assessed after carotid balloon injury at 21 days by computerized morphometry. There was no difference in neointimal area in the STZ-treated rats compared with controls, irrespective of insulin administration or dose of STZ. Neointimal area was increased >2-fold in obese Zucker rats compared with lean Zucker rats (0.21+/-0.06 versus 0.08+/-0.03 mm(2), P<0.01). The neointimal area was markedly increased in the obese Zucker rats 7 days after injury (0.058+/-0.024 versus 0.033+/-0.009 mm(2), P<0.05) and persisted through 21 days. In both obese and lean Zucker rats, cell proliferation peaked in the media at 3 days (118.66+/-84.28 versus 27.50+/-12.75 bromodeoxyuridine-labeled cells per cross section). In the intima, cell proliferation markedly increased beginning at day 3 and persisted through day 14 in the obese and lean Zucker rats (202.27+/-98.86 versus 35.71+/-20.54 bromodeoxyuridine-labeled cells at 7 days). CONCLUSIONS: The type II diabetic rat model, typifying insulin resistance, is associated with a propensity for neointima. The obese Zucker rat model may be an ideal diabetic model to further characterize the diabetic vascular response to injury.

Efficacy of high-dose palliative radiotherapy for localised, castration-resistant prostate cancer.

AIMS: There are limited outcome data after radiotherapy treatment for clinically localised, castration-resistant prostate cancer. We report our single institution experience on patient outcomes in this group using high-dose palliative radiotherapy (HDPRT). MATERIALS AND METHODS: A retrospective review of patient hospital records was conducted in prostate cancer patients treated with palliative intent radiotherapy and restricted to those who had castration-resistant disease, no evidence of regional or distant disease and who received a local radiotherapy dose equivalent to 40 Gy or greater. RESULTS: Fifty-one patients met the study criteria, 88% of these had high-risk disease at initial diagnosis. The median time to delivery of HDPRT was 66 months and the median follow-up from HDPRT was 54 months. Grade 3 or worse toxicity was experienced in 8%. The estimated freedom from local failure, cause-specific survival and overall survival at 5 years were 81, 65 and 35%, respectively. Local procedures were a significant contributor to local morbidity, with the most common procedure a transurethral resection of the prostate (27% patients). Only two patients died from complications of local failure. CONCLUSION: HDPRT was well tolerated and provided a high rate of local control in a clinically localised castration-resistant prostate cancer population. Although prostate cancer remained the most frequent cause of death, some patients had extended survival without evidence of disease progression.

Predictors of respiratory-induced lung tumour motion measured on four-dimensional computed tomography.

AIMS: The delivery of radical radiotherapy in lung cancer is complicated by respiratory-induced tumour motion. The aim of the study was to correlate tumour motion characteristics with tumour and patient factors, particularly the anatomical lobe and pulmonary zone. MATERIALS AND METHODS: Lung tumour volumes on four-dimensional computed tomography were delineated by a single observer at maximal expiration and propagated through all 10 phases of the breathing cycle. Movements were tracked in the superior-inferior (SI), anterior-posterior (AP) and medio-lateral (ML) directions by changes in the tumour centroid coordinates. Tumour motion characteristics were correlated with anatomical lobe, pulmonary zone, tumour volume, T-stage, smoking status and spirometry. RESULTS: In 101 consecutive patients, the median magnitude of tumour motion in the SI direction was significantly larger in tumours located in lower lobes compared with upper lobes and middle/lingular lobes (0.70 cm versus 0.09 cm versus 0.26 cm, P < 0.01). No significant difference was found in median tumour motion between lower, upper and middle/lingular lobes in the AP (0.16 cm versus 0.13 cm versus 0.16 cm, P = 0.45) and ML (0.08 cm versus 0.08 cm versus 0.13 cm, P = 0.32) directions, respectively. When assessed by zone, the median tumour displacement in the SI direction was significantly larger in the lower zones (0.81 cm) as compared with the middle zones (0.30 cm) and upper zones (0.11 cm), P < 0.01. No difference was observed in the AP (P = 0.45) and ML (P = 0.73) directions. Tumour volume, T-stage and forced expiratory ratio were not statistically significant predictors of respiratory-induced tumour motion. CONCLUSION: Respiratory-induced tumour motion in the SI direction was significantly greater in lower lobe and lower pulmonary zone tumours compared with apical tumours. Tumour volume, T-stage and spirometry did not correlate with the magnitude or direction of respiratory-induced tumour motion. During curative radiotherapy in lung cancer, attention should be paid to motion management, especially for lower lobe tumours.

Comparison of Single-fraction and Multi-fraction Stereotactic Radiotherapy for Patients with 18F-fluorodeoxyglucose Positron Emission Tomography-staged Pulmonary Oligometastases.

AIM: To compare outcomes of single-fraction and multi-fraction stereotactic ablative body radiotherapy (SABR) for pulmonary metastases. MATERIALS AND METHODS: A retrospective review from two academic institutions of patients with one to three pulmonary metastases staged with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans. For single-fraction SABR, 26 Gy was prescribed for peripheral targets and 18 Gy for central targets. In the multi-fraction cohort, 48 Gy/4 or 50 Gy/5 was prescribed for peripheral targets and 50 Gy/5 was prescribed for central targets. Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were delivered using heterogeneity corrections. Conformity indices at an intermediate dose (R50%) and at a high dose (R100%) were used to assess a relationship with the planning target volume (PTV). Overall survival, local and distant progression and toxicity rates were analysed from the date of treatment completion. RESULTS: Between February 2010 and June 2013, 65 patients with 85 pulmonary metastases were reviewed. The median follow-up was 2.1 years. Metastases most commonly originated from colorectal cancer (31%), followed by non-small cell lung cancer (25%). 3D-CRT was used in 52 targets, IMRT in 21 and VMAT in 12. 3D-CRT showed a lower median R50% (P=0.01), but a higher median R100% than IMRT/VMAT (P=0.04). The R50% index was inversely correlated to the PTV with all techniques (P=0.01). Overall survival at 1 and 2 years in all patients was 93% (95% confidence interval 87-100%) and 71% (95% confidence interval 58-86%), respectively. The 2 year freedom from local and distant progression was 93% (95% confidence interval 86-100%) and 38% (95% confidence interval 27-55%), respectively. There were no significant differences between overall survival (P=0 .14), time to distant progression (P=0.06) or toxicity rates (P=0.75) between single- and multi-fraction cohorts. CONCLUSION: We report comparable local control, overall survival and toxicity rates between single-fraction and multi-fraction SABR treatments in patients with FDG-PET-staged pulmonary oligometastases. We propose a guideline for R50% conformity incorporating 3D-CRT/IMRT/VMAT techniques with heterogeneity corrected planning algorithms.

Calculating radiotherapy margins based on Bayesian modelling of patient specific random errors.

Collected real-life clinical target volume (CTV) displacement data show that some patients undergoing external beam radiotherapy (EBRT) demonstrate significantly more fraction-to-fraction variability in their displacement ('random error') than others. This contrasts with the common assumption made by historical recipes for margin estimation for EBRT, that the random error is constant across patients. In this work we present statistical models of CTV displacements in which random errors are characterised by an inverse gamma (IG) distribution in order to assess the impact of random error variability on CTV-to-PTV margin widths, for eight real world patient cohorts from four institutions, and for different sites of malignancy. We considered a variety of clinical treatment requirements and penumbral widths. The eight cohorts consisted of a total of 874 patients and 27 391 treatment sessions. Compared to a traditional margin recipe that assumes constant random errors across patients, for a typical 4 mm penumbral width, the IG based margin model mandates that in order to satisfy the common clinical requirement that 90% of patients receive at least 95% of prescribed RT dose to the entire CTV, margins be increased by a median of 10% (range over the eight cohorts -19% to +35%). This substantially reduces the proportion of patients for whom margins are too small to satisfy clinical requirements.

Occult breast carcinoma presenting as axillary metastases.

PURPOSE: Breast carcinoma presenting with axillary lymphadenopathy and no clinical or radiological evidence of a primary tumor is a rare presentation. We aimed to examine the management of the breast by observation, radiation therapy, or mastectomy. METHODS AND MATERIALS: Departmental records from 1979 to 1996 of unknown primary presentations and cases of T0N1-2M0 breast carcinoma were reviewed to find cases of occult breast carcinoma presenting as axillary lymphadenopathy with no clinical or imaging evidence of a primary tumor. RESULTS: There were 6047 presentations of breast carcinoma with 20 cases of occult breast carcinoma meeting the criteria. The breast was treated by observation in 6 cases, mastectomy in 2 cases, and radiotherapy to the intact breast in 12 cases. Eighty-three percent of patients (5 of 6 patients) who had observation of the breast had a local recurrence, compared to 25% who had radiotherapy to the intact breast (3 of 12 patients) and 0% who had a mastectomy (0 of 2 patients). The median recurrence-free survival was 7 months in patients who had observation of the breast, compared to 182 months in patients who had local treatment. Three of the 6 patients who underwent breast observation have died whereas 1 of the 14 who had local treatment have died, with a mean follow-up of 73 months. It was found that patients having observation of the breast had a poorer recurrence-free survival (p = 0.003) and overall survival (p = 0.05) compared to those having local treatment of the breast. CONCLUSIONS: Patients with such a presentation should have a complete physical examination, mammography, ultrasound, and MRI of the breasts. If there remains no evidence of a primary tumor, an axillary dissection should be carried out and the breast treated by radiotherapy or mastectomy. Observation of the breast is not a recommended option.

Cost-minimization analysis: radiation treatment with and without a multi-leaf collimator.

PURPOSE: To compare the costs of radiation treatment on a linear accelerator with a multileaf collimator (MLC) versus treatment on a linear accelerator without an MLC. The study was designed to determine whether the increased throughput of fields and decreased block cutting made the MLC cost effective from an institutional perspective. METHODS AND MATERIALS: The number of fields, basic treatment equivalent, equivalent simple treatment visits, and blocks were prospectively collected for the four linear accelerators. Building, equipment, staffing, and service costs were all obtained in 1999 Australian dollars from the manufacturers and hospital department heads. The Joint Radiation Oncology Centre at Westmead and Nepean Hospitals, which are Australian public hospitals, runs as one unit, with the same staff, and currently operates five linear accelerators. Currently, four of the linear accelerators are used for general radiotherapy, operating for exactly the same hours; the final machine operates more limited hours and is used for specialized radiotherapy techniques and emergency cases. RESULTS: The two machines with MLCs, on average, treated 5,169 fields each, while the two machines without MLCs treated 4,543 fields in a 3-month period, a 12% increase in throughput. The two non-MLC machines required 155 premounted trays (PMTs) in total, while the MLC machines required 17 PMTs. Linear accelerators with MLCs were demonstrably more efficient, and while their capital costs were higher, the reduction in labor costs associated with block cutting and, particularly the increased throughput, more than offset these initial costs. The total cost of a radiation field with an MLC was found to be $A101.69 compared to $A106.98 without an MLC. A multiway sensitivity analysis showed the results to be robust. The worst-case scenario was a departmental savings of $A168,000 per year; the best-case scenario was a savings of $A680,000 per year. CONCLUSION: Under the conditions pertaining to the radiation oncology department in this group of hospitals, and in similar departments, the use of an MLC can be justified.

A comparison of the needle biopsy post mortem with the conventional autopsy.

Tru-cut biopsy post mortems were compared with the standard full autopsy at a large city mortuary. Subjects consisted of coronial cases excluding suspicious deaths, obvious trauma cases and children under the age of 14 yrs. The following comparisons were made: the ability to collect tissue from each of the organs; any abnormalities detected on histology; correlation of the Tru-cut biopsy results with the results of the conventional post mortem; and determination of cause of death with both techniques. Twenty-one cases were examined by both techniques. Tissue collection by biopsy varied from 100% for liver to 9.5% for kidney with heart, lung and brain giving intermediate results. The cause of death was determined in 9 cases (43%) by biopsy and in 20 cases (95%) by conventional post mortem; the cause of death was not ascertainable in 1 case. In 8 of the 9 cases (89%) where death could be determined by biopsy the cause of death was consistent with the findings of the full autopsy. The cause of death at needle biopsy examination was incorrect in 1 case (11%) compared to the findings of the standard post mortem. Clearly the needle post mortem is inferior to the conventional autopsy in determining the cause of death.

Splenosis mimicking metastases from breast carcinoma.

The case history is presented of a patient with breast cancer who was extensively investigated for presumed hepatic metastases, which were finally diagnosed as splenosis, the heterotopic autotransplantation of splenic tissue after traumatic rupture of the spleen. This case history highlights the importance of obtaining a pathological diagnosis prior to labelling a patient as having metastatic disease. This is especially important for patients who have an unusual pattern or appearance of metastases or for whom the risk of metastatic disease is presumed to be minimal.

Radiation therapy for cervix carcinoma: benefits of individualized dosimetry.

This study is a presentation of the prospective collection of data on patients treated by radical radiotherapy at Westmead Hospital between December 1989 and December 1998. The impact of the routine use of individualized dosimetry and lower brachytherapy dose on patients was examined, by comparing the historical series of patients treated between 1989 to 1991 to the later patients treated with inividualised dosimetry. There were 163 patients treated with external beam and intracavitary radiotherapy during this period. Histology was squamous carcinoma in 80% (132 patients), adenocarcinoma in 13% (22 patients), and adenosquamous carcinoma in 6% (9 patients). Patients were generally treated with 50 Gy in 25 fractions to the pelvis followed by 1 low dose rate caesium intracavitary brachytherapy insertion. Patients who had dosimetry generally received 20 Gy to point A via the insertion compared to 30 Gy in the non-dosimetry group. Median follow-up was 62 months. Only 22% (18) of patients failed with disease outside the pelvis. Pelvic control was similar in the patients who had dosimetry as opposed to no dosimetry (P=0.8). In the dosimetry group there were less grade III or higher bowel toxicity (P=0.01) and less vaginal fistulae (P=0.03). The actuarial two-year survival was 56.2% in the no dosimetry group and 68.6% in the dosimetry group. When controlled for stage and performance status patients who had dosimetry had a statistically significant greater overall survival (P=0.02). Thus we found that the routine use of dosimetry was associated with a lower brachytherapy dose, decreased complications, without any decrease in local control or survival.

The appropriate rate of breast conserving surgery: an evidence-based estimate.

PURPOSE: The objective of the present study was to estimate the proportion of incident cases of breast cancer that should receive breast conserving surgery (BCS), using an evidence-based approach. METHODS: An extensive search of the literature was undertaken to identify eligibility criteria for BCS. The eligibility criteria for BCS were combined with the information about case mix and patient preference to estimate the need for BCS. An epidemiological approach was then used to estimate the incidence of each eligibility criterion for BCS in a typical North American population of breast cancer patients. The effect of sampling error on the estimated appropriate rate of BCS was calculated, and the effect of systematic error using alternative sources of information, was estimated by sensitivity analysis. RESULTS: The analysis showed that 69.6% of breast cancer cases are eligible for BCS, and that 48.0 +/- 6.0% of breast cancer patients are both eligible for BCS and prefer it to mastectomy. Based on sensitivity analysis, the plausible range of the appropriate rate was 42.1% to 49.43%. The proportion of breast cancer cases in which BCS was appropriate was stage dependent; 63.0 +/- 11.5% in ductal carcinoma in-situ; 57.0 +/- 9.9% in stage I; 52.2 +/- 9.4% in stage II, and 27.2 +/- 5.2% in stage III. CONCLUSIONS: This model suggests that BCS is appropriate in 48% of all breast cancer patients. This information may be useful in auditing surgical practice, and may serve as a basis for planning of ancillary services, including radiotherapy.

Radiation induced mucositis: co-ordinating a research agenda.

AIMS: A one-day workshop was hosted by the Symptom Control Committee of the National Cancer Institute of Canada, Clinical Trials Group (NCIC-CTG), in conjunction with the October 2002 annual meeting of the Canadian Association of Radiation Oncologists in Toronto, Ontario. The primary intention of the workshop was to direct the future research agenda of the Symptom Control Committee. Large group presentations were held initially to review the contemporary research issues of four selected areas of interest: fatigue, brain metastasis, bone metastasis and radiation-induced mucositis. Panel members were then charged with the identification of specific research proposals that could be considered for further development. Research questions were to be clinically relevant and currently appropriate. Any additional information needed before the launch of any potential trial was also requested. In this paper, we will review and summarise the outcomes from the radiation-induced mucositis sessions. MATERIALS AND METHODS: Thirty-four participants participated in the large group sessions and contributed to one of four panel discussions on selected supportive care issues relevant to radiation oncologists. RESULTS: Three potential and non-overlapping research questions were identified; two involving mucositis management in patients receiving radical radiation for head and neck cancer, and a third for patients with advanced lung cancer undergoing combined radiation and chemotherapy and at risk for the development of symptomatic oesophagitis. CONCLUSION: The workshop successfully identified three potential research questions. The large group and the smaller panel discussions successfully established consensus on important aspects of future study designs. The current 'standard of care', appropriate experimental treatments, primary outcomes of interest and study population parameters were each important issues that were discussed. The importance of developing meaningful biological assays was reviewed, as was the need to ensure the appropriate storage of biological samples from patients for future study.

A review of kidney motion under free, deep and forced-shallow breathing conditions: implications for stereotactic ablative body radiotherapy treatment.

Motion management strategies are important during stereotactic ablative body radiotherapy for abdominal targets. The kidney is a mobile retroperitoneal organ that moves with respiration. A review of the literature was performed to investigate the reported degree of kidney motion associated with various breathing conditions. A structured search was performed using Medline from January 1970 to May 2013 for all publications describing cranial-caudal kidney motion. Relevance to radiotherapy practice was reviewed based on any breathing instructions and/or immobilization equipment that could affect breathing pattern. Studies were categorized under three types of breathing conditions: Forced-shallow, breath-hold/deep and free. A total of 25 publications were identified describing cranial-caudal kidney motion with a combined total of 415 participants. Three publications described forced-shallow breathing using prone positioning or abdominal compression plates. Prone positioning, compared to supine positioning, did little to minimise kidney motion, however use of compression plates can result in kidney motion of less than 5 mm. Eight publications described deep breathing/breath hold techniques that showed average kidney motion ranging between 10 mm-40 mm. Fifteen publications investigated kidney motion under free breathing with the majority reporting mean motion of less than 10 mm. Kidney movement of up to 8.1 mm in the anterior posterior direction and 6.2 mm laterally were reported with no indications that breathing technique can influence the extent of this motion. In summary, kidney movement is complex and consideration should be made to ensure that motion management strategies provide the desired radiotherapy benefit. There are limited publications on the effectiveness of abdominal compression on reducing kidney motion which warrant further investigation in this area.