Comparison of dynamic contrast-enhanced MRI and dynamic contrast-enhanced CT biomarkers in bladder cancer.

Dynamic contrast-enhanced MRI (DCE-MRI) is frequently used to provide response biomarkers in clinical trials of novel cancer therapeutics but assessment of their physiological accuracy is difficult. DCE-CT provides an independent probe of similar pharmacokinetic processes and may be modeled in the same way as DCE-MRI to provide purportedly equivalent physiological parameters. In this study, DCE-MRI and DCE-CT were directly compared in subjects with primary bladder cancer to assess the degree to which the model parameters report modeled physiology rather than artefacts of the measurement technique and to determine the interchangeability of the techniques in a clinical trial setting. The biomarker K(trans) obtained by fitting an extended version of the Kety model voxelwise to both DCE-MRI and DCE-CT data was in excellent agreement (mean across subjects was 0.085 ± 0.030 min(-1) for DCE-MRI and 0.087 ± 0.033 min(-1) for DCE-CT, intermodality coefficient of variation 9%). The parameter v(p) derived from DCE-CT was significantly greater than that derived from DCE-MRI (0.018 ± 0.006 compared to 0.009 ± 0.008, P = 0.0007) and v(e) was in reasonable agreement only for low values. The study provides evidence that the biomarker K(trans) is a robust parameter indicative of the underlying physiology and relatively independent of the method of measurement.

Pharmacokinetic and tolerability profile of once-daily zibotentan (ZD4054) in Japanese and Caucasian patients with hormone-resistant prostate cancer.

OBJECTIVE: To investigate potential differences in zibotentan pharmacokinetics between Japanese and Caucasian patients with hormone-resistant prostate cancer (HRPC) following single and multiple dosing. METHODS: In the Japanese study, 18 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 26 days' once-daily dosing. In the Caucasian study, 21 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 12 days' once-daily dosing. RESULTS: Pharmacokinetic parameters were similar between populations. Absorption of zibotentan was rapid with maximum plasma concentrations typically achieved within 3 h of dosing. Mean clearance, 17.9 and 18.7 ml/min in Japanese and Caucasian patients, respectively (range 7.0 - 36.3 ml/min in Japanese patients and 7.8 - 29.5 ml/min in Caucasian patients) and volume of distribution, 14.0 and 15.6 l for Japanese and Caucasian patients, respectively (range 7.9 - 29.1 l in Japanese patients and 9.6 - 23.8 l in Caucasian patients) were relatively low, and t1/2 was approximately 12 h (range 5.7 - 18.8 h in Japanese patients and 5.0 - 22.9 h in Caucasian patients) following single dosing. Little accumulation was observed following daily dosing and multiple-dose pharmacokinetics were predictable. Exposure levels achieved in some Japanese patients receiving zibotentan 15 mg were higher than those observed in Caucasian patients, however, this may be due to differences in body weight, as exposure levels were similar when data were normalized for body weight. Zibotentan was well tolerated in both populations. CONCLUSIONS: There are no clinically relevant differences in the disposition and pharmacokinetics of zibotentan between Japanese and Caucasian patients with HRPC.

Report on the early efficacy and tolerability of I(125) permanent prostate brachytherapy from a UK multi-institutional database.

AIMS: To report the results of I(125) prostate brachytherapy from a central, prospectively collected database of three UK institutions. MATERIALS AND METHODS: All patients treated with I(125) permanent prostate brachytherapy at the Christie Hospital, Manchester (CHM), Cookridge Hospital, Leeds (CKL) and Mount Vernon Hospital, Northwood, London (MVL) since 2003 have been prospectively registered on a detailed central database. Patient, tumour, pre- and post-implant dosimetry data have been recorded. Urinary toxicity as assessed by the International Prostate Symptom Score, catheterisation and urinary stricture rates after implant have been documented and biochemical failure determined, using both the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and the Phoenix (nadir + 2 ng/ml) definition. RESULTS: In total, 1535 patients were registered on the database between January 2003 and October 2006, including 432 from CHM, 926 from CKL and 177 from MVL, with a median follow-up of 21 months (range 1-56). Patient and tumour characteristics were similar at all centres. Pre-implant dose indices were comparable between centres, except for the V150, with median values of 51.9, 64.3 and 69.8% at CHM, CKL and MVL, respectively. Median post-implant dose parameters were lower than pre-planned constraints by up to 33.0% at each centre for all values, except at CKL where the V200 was 23.9% higher. The International Prostate Symptom Score increased from a median of 5 at baseline to 18, 6 weeks after implant, but was not significantly different to baseline values by 12 months. Nine per cent of men required catheterisation after implant for a median duration of 53 days, but urinary stricture rates remained low at 1%. Neoadjuvant hormonal manipulation was used in 228 men (15%) for downsizing and 159 (10%) for intermediate/high-risk disease. Collated biochemical failure rates were low at this point of follow-up, with actuarial 2-year ASTRO and Phoenix biochemical failure-free survival rates of 94.4 and 94.5%, respectively, consistent with other large single centre reports. When post-implant dosimetric factors were assessed for a relationship to biochemical failure, no indices consistently predicted for improved ASTRO and Phoenix biochemical failure-free survival rates. CONCLUSIONS: This ongoing collaboration shows that with limited infrastructure (a single industry-sponsored data manager), a large multi-institutional database estimated to represent one-third of implants carried out in the UK during this time can be developed. Patient selection was similar across all centres and adhered to published guidelines. Early biochemical and toxicity outcomes confirm the efficacy and tolerability of I(125) prostate brachytherapy in a large cohort of patients. A further analysis is planned.

External-beam radiotherapy in T1-2 N0 penile carcinoma.

AIMS: To review the outcome of 41 patients with invasive carcinoma of the penis treated with external-beam radiotherapy using a consistent technique and dose. MATERIALS AND METHODS: Forty-one patients with carcinoma of the penis treated at Christie Hospital, Manchester, UK, between 1995 and 2000 were reviewed retrospectively. Radiotherapy was delivered using 4 MV linear accelerators with a dose of 50 Gy or 52.5 Gy in 16 fractions over 22 days. RESULTS: The distribution of patients according to stage was T1=37, T2=4, N0=40, N3=1. Median follow-up was 4.5 years. The local control rate was 62%, nodal relapse-free rate of 88%, relapse-free rate of 51% and overall survival of 88% at 5 years. All recurrences were salvaged by surgery. Penile ulceration occurred in 8% and urethral stenosis requiring dilatation in 29%. There were no penectomies for penile necrosis. CONCLUSION: EBXRT may be offered for T1-2 cancer of the penis with close surveillance to detect local recurrences early for salvage surgery without jeopardising overall survival. It remains an alternative option to penis-preserving surgery and should be discussed in a multidisciplinary setting and with the patient.

Prediction of urinary symptoms after 125iodine prostate brachytherapy.

AIMS: To evaluate the post-treatment urinary morbidity experienced by a cohort of men undergoing ultrasound-based transperineal prostate brachytherapy, as monotherapy for early stage carcinoma of the prostate. MATERIALS AND METHODS: One hundred and thirty-four consecutive patients received prostate brachytherapy between March 2000 and July 2002, and were asked to complete the International Prostate Symptom Score (IPSS) and Hospital Anxiety and Depression (HAD) questionnaires before treatment and at 1, 3, 6, 9, 12 and 18 months after implant. Data on catheterisation and surgical interventions were also recorded. Pre-treatment IPSS, dosimetry and other variables were analysed in relation to catheterisation rates and post-treatment IPSS scores at each time window. RESULTS: One hundred and eleven patients returned sufficient data for meaningful analysis. Of the patients who completed IPSS at 1 month, 85 (97%) reported deterioration in IPSS scores. This peak of symptoms, identified by a rise in median IPSS, started to improve by 3 months, and was approaching baseline by 18 months. The only significant determinants of early urinary toxicity were pre-treatment IPSS, pre-treatment prostate volume and the difficulty of implant. However, prostate volume was not significant beyond 1 month. Twenty-six patients required catheterisation at a median of 10 days after implant. Significant predictors of urinary retention were pre-treatment prostate volume and pre-treatment IPSS. Patients requiring catheterisation continued to have significantly higher IPSS at 18 months than patients who had never required a catheter. CONCLUSION: Brachytherapy was generally well tolerated, with urinary toxicity in most patients persisting for at least 3-6 months after prostate brachytherapy. Those whose pre-treatment prostate volume and IPSS were high experienced more severe urinary symptoms in the first few months.

Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix.

There is increasing evidence that hypoxia-regulated gene expression influences tumor aggressiveness, contributing to the poorer outcome of patients with hypoxic tumors. The role of the transcriptional complex hypoxia-inducible factor-1 as an important mediator of hypoxia-regulated gene expression is one of the best documented pathways. Recently, it has emerged that certain tumor-associated carbonic anhydrases (CAs) can be added to the list of known hypoxia-inducible factor-responsive genes. Here we show that the immunohistochemical expression of the tumor-associated CA IX is correlated with the level of hypoxia in human cervical tumors. We performed a prospective study in 68 patients where needle electrodes were used to make direct measurements of tumor oxygenation levels. CA IX expression was evaluated immunohistochemically in pretreatment tumor biopsies. There was a significant positive correlation between the level of tumor hypoxia (HP5) and the extent of CA IX expression. A retrospective study of 130 squamous cell cervical carcinomas demonstrated that a semiquantitative immunohistochemical analysis of CA IX expression in tumor biopsies is a significant and independent prognostic indicator of overall survival and metastasis-free survival after radiation therapy. These studies provide clinical evidence that CA IX expression is up-regulated in hypoxic human cervical tumors and is associated with a poor prognosis. CA IX may act as an intrinsic marker of tumor hypoxia and poor outcome after radiation therapy. The level of CA IX expression may be used to aid in the selection of patients who would benefit most from hypoxia-modification therapies or bio-reductive drugs.

Adjuvant and salvage treatment after radical prostatectomy: current practice in the UK.

OBJECTIVE: To survey UK urologists and radiation oncologists in the evaluation and treatment of localised prostate cancer in the adjuvant and salvage setting. METHODS: Postal questionnaires were mailed to 292 urologists and 98 radiation oncologists in the UK. RESULTS: In all, 188 (48%) questionnaires were returned. In total, 72/128 (56%) of the urologist respondents and 58/60 (97%) of the oncologist respondents perform routine radical prostate treatment. Among 43 (60%) of the urologist, 40 (69%) recommended adjuvant treatment, which could be radiotherapy, hormonal treatment or combined hormonal and radiation treatment. There is no significant difference between the modality of treatment recommended. The poor prognostic factors that would influence the decision to offer adjuvant treatment include a detectable postoperative PSA, seminal vesicle involvement, positive margins, Gleason score>8 and pathological T3. With regard to the choice of hormonal treatment, most urologists preferred antiandrogens, whereas most oncologists prefer lutienising hormone releasing hormone (LHRH) analogue (P=0.03). Regarding salvage treatment, there is a wide variation in the PSA threshold and number of PSA rises before initiation of investigations and treatment. Significantly more urologists recommended salvage radiotherapy (P=0.02), whereas oncologists recommended combined hormonal radiation therapy (P=0.03). There is a wide variation of practice regarding the duration of hormonal treatment, the type of investigations initiated, range of radiotherapy doses and treatment volumes. CONCLUSION: There is a wide variation in practice among UK clinicians.

High tumor angiogenesis is associated with poorer survival in carcinoma of the cervix treated with radiotherapy.

The purpose of this study was to examine the relationship between tumor angiogenesis and prognosis in carcinoma of the cervix treated with radiotherapy with a median follow-up time of 55 months. A retrospective study was carried out on 111 patients. Formalin-fixed, paraffin-embedded tumor biopsies were stained with anti-factor VIII using immunohistochemistry. Tumor angiogenesis was assessed by scoring the distance to the closest microvessel from random points within the tumor and the intratumor microvessel density (IMD) in the areas of highest neovascularization. High vascularity, as measured by both methods, was associated with a poor prognosis but was only significant for IMD. The 5-year survival rates for tumors with high versus low values were 50 and 65%, respectively. IMD was a significant prognostic factor within a Cox multivariate analysis. Higher tumor vascularity was associated with lower overall survival and locoregional control, but this association was not significant in the case of metastasis-free survival. The method used to assess tumor vascularity is important. The level of angiogenesis in carcinoma of the cervix is an independent prognostic parameter.

Patient positioning using detailed three-dimensional surface data for patients undergoing conformal radiation therapy for carcinoma of the prostate: a feasibility study.

PURPOSE: The increasing complexity of radiotherapy highlights the need for accurate setup. This paper assesses the potential of position corrections, derived from the three-dimensional (3D) surface of the patient, in reducing positioning errors in patients undergoing conformal radiation therapy of the prostate. METHODS AND MATERIALS: Twenty patients undergoing conformal radiation therapy for prostate cancer had planning computed tomography (CT) scans and then weekly treatment CT scans over the course of their treatment. Patients were positioned on the CT table using three coplanar tattoo marks used for patient setup on the accelerator. Surfaces were computed from the planning CT (planning surface), and the treatment CT (treatment surfaces). Using a surface matching utility, the planning and treatment 3D surfaces were compared. The prostate was implicitly localized based on surface matching of the external contour and by matching the bony anatomy. The resultant prostate displacement after correction was assessed for the two localization methods. RESULTS: Correcting patient position via the surface comparisons reduced the standard deviation of prostate displacement with respect to the patient isocenter in the lateral and anterior/posterior directions. In the lateral direction, prostate and surface motion was highly correlated (r = 0.96). In the anterior/posterior direction the corrections from the surface data were as effective as those derived from the bony anatomy. CONCLUSION: Detailed surface data can aid the positioning of patients receiving conformal radiation therapy to the prostate by reducing the displacement of the target from the intended treatment position. This study shows that surface corrections can be as effective as those derived from bony anatomy, and may be exploited where definition of bony anatomy is difficult.

Primary malignant lymphoma of the thyroid: a clinicopathological analysis.

A retrospective analysis of 70 patients with primary malignant lymphoma of the thyroid treated at this institute between 1965-1983 has been conducted. The clinicopathological features and prognostic factors have been studied. The mean age was 67.5 years and there was a marked female:male ratio of 8:1. A total of 32 (45.7%) Stage IE and 38 (54.3%) Stage IIE patients were identified. In 64 cases histological material was reviewed and classified employing the Kiel classification. All the tumors were of B cell lineage and the majority were follicle center cell type. A biopsy only was performed in 27 patients, lobectomy in 11 patients, subtotal thyroidectomy in 27 and macroscopic thyroidectomy in 5 patients. All patients were treated with radiotherapy. The overall 5-year survival was 42%, with 63% for Stage IE and 27% for Stage IIE. The corrected overall 5-year survival was 49% with 68% for Stage IE and 36% for Stage IIE. The corresponding overall relapse free survival was 42% with 60% for Stage IE, and 31% for Stage IIE. Factors of prognostic significance for relapse and survival were stage, radiotherapy dose, stridor, retrosternal extension and fixation.

Clinical variability of target volume description in conformal radiotherapy planning.

PURPOSE: The pivotal step in radiation planning is delineation of the target volume and production of a treatment plan to encompass this. This study assesses the variation of physicians in creation of these volumes. METHODS AND MATERIALS: Three radiologists and eight radiation oncologists outlined the gross tumour volume (GTV) on the planning CT scans of four cases with T3 bladder cancer. In addition, the radiation oncologists (RO) created a planning target volume according to a set protocol for all cases. Volumes were produced and comparison of these volumes and the position of the isocenters were analysed. In addition, the margins allowed were measured and compared. RESULTS: There was a maximum variation ratio (largest to smallest volume outlined) of the GTV in the four cases of 1.74 among radiologists and 3.74 among oncologists. There was a significant difference (p = 0.01) in mean GTV between RO and the radiologists. The mean GTV of the RO exceeded the radiologists by a factor of 1.29 with a mean difference of 13.4 cm3. The variation ratio in PTV among oncologists ranged from 1.25 to 3.33. There was no significant difference in mean PTV values between the two groups of ROs divided by specialization in uro-oncology. The mean variation in location of the isocenter from the centroid of the radiologists' volume in the four cases was from 2.6 to 5.7 mm. There was, however, a wide range of values from 1.4 mm to 24.1 mm. Median margin per case ranged from 14.7 to 18.7 mm. Minimum margins allowed in each case varied from minus 7 mm to 9 mm. CONCLUSION: This study demonstrates significant interphysician variability in producing target volumes and radiation plans for conformal radiotherapy. The scale of this difference is clearly of significance, with up to 3-fold variation in volumes delineated by clinicians. The factors leading to these differences will be further addressed. The existence of such variability, however, clearly needs to be accepted as a factor in the overall uncertainty analysis in conformal radiotherapy planning.

Changes in oxygenation during radiotherapy in carcinoma of the cervix.

PURPOSE: The aim of this study was to investigate changes in tumor oxygenation, assessed by polarographic needle electrode measurements, following fractionated external beam radiotherapy in carcinoma of the cervix. METHODS AND MATERIALS: Normal and tumor tissue oxygenation was measured in 19 patients prior to radiotherapy and after 40-45 Gy of external beam radiotherapy delivered in 20 fractions over 4 weeks. All measurements were performed during anesthesia. RESULTS: There was no significant difference in the level of normal tissue oxygenation pre- and post radiotherapy. The individual patient median tumor pO2 values ranged from 0 to 31 mmHg pre-radiotherapy and 1 to 61 mmHg post-radiotherapy. The mean of the 19 median pO2 values increased from 8 (SD +/- 10) mmHg to 20 (+/- 20) mmHg following external beam radiotherapy. The increase was significant by paired Wilcoxon test (p = 0.011). There was also a significant fall in the proportion of values < 5 mmHg (p = 0.040). Although this value remained constant, or fell, in the majority of patients (15/19), it increased in 4 tumors. Tumor size pre- and postradiotherapy did not correlate with the level of pretreatment oxygenation; neither did the change in tumor size and change in level of oxygenation. CONCLUSION: The level of tumor oxygenation increased in the majority of patients (15/19) following 40-45 Gy of radiotherapy in carcinoma of the cervix.

Clinical implementation of dynamic multileaf collimation for compensated bladder treatments.

BACKGROUND AND PURPOSE: To describe the clinical implementation of dynamic multileaf collimation (DMLC). Custom compensated four-field treatments of carcinoma of the bladder have been used as a simple test site for the introduction of intensity modulated radiotherapy. MATERIALS AND METHODS: Compensating intensity modulations are calculated from computed tomography (CT) data, accounting for scattered, as well as primary radiation. Modulations are converted to multileaf collimator (MLC) leaf and jaw settings for dynamic delivery on a linear accelerator. A full dose calculation is carried out, accounting for dynamic leaf and jaw motion and transmission through these components. Before treatment, a test run of the delivery is performed and an absolute dose measurement made in a water or solid water phantom. Treatments are verified by in vivo diode measurements and real-time electronic portal imaging. RESULTS: Seven patients have been treated using DMLC. The technique improves dose homogeneity within the target volume, reducing high dose areas and compensating for loss of scatter at the beam edge. A typical total treatment time is 20 min. CONCLUSIONS: Compensated bladder treatments have proven an effective test site for DMLC in an extremely busy clinic.

Animation and radiobiological analysis of 3D motion in conformal radiotherapy.

PURPOSE: To allow treatment plans to be evaluated against the range of expected organ motion and set up error anticipated during treatment. METHODS: Planning tools have been developed to allow concurrent animation and radiobiological analysis of three dimensional (3D) target and organ motion in conformal radiotherapy. Surfaces fitted to structures outlined on CT studies are projected onto pre-treatment images or onto megavoltage images collected during the patient treatment. Visual simulation of tumour and normal tissue movement is then performed by the application of three dimensional affine transformations, to the selected surface. Concurrent registration of the surface motion with the 3D dose distribution allows calculation of the change in dose to the volume. Realistic patterns of motion can be applied to the structure to simulate inter-fraction motion and set-up error. The biologically effective dose for the structure is calculated for each fraction as the surface moves over the course of the treatment and is used to calculate the normal tissue complication probability (NTCP) or tumour control probability (TCP) for the moving structure. The tool has been used to evaluate conformal therapy plans against set up measurements recorded during patient treatments. NTCP and TCP were calculated for a patient whose set up had been corrected after systematic deviations from plan geometry were measured during treatment, the effect of not making the correction were also assessed. RESULTS: TCP for the moving tumour was reduced if inadequate margins were set for the treatment. Modelling suggests that smaller margins could have been set for the set up corrected during the course of the treatment. The NTCP for the rectum was also higher for the uncorrected set up due to a more rectal tissue falling in the high dose region. CONCLUSION: This approach provides a simple way for clinical users to utilise information incrementally collected throughout the whole of a patient's treatment. In particular it is possible to test the robustness of a patient plan against a range of possible motion patterns. The methods described represent a move from the inspection of static pre-treatment plans to a review of the dynamic treatment.

Tumour oxygenation levels correlate with dynamic contrast-enhanced magnetic resonance imaging parameters in carcinoma of the cervix.

BACKGROUND AND PURPOSE: The Eppendorf pO(2) histograph is the 'gold standard' method for measuring tumour oxygenation. The method is not suitable for widespread application because its use is limited to accessible tumours. A non-invasive imaging technique would be an attractive alternative. Therefore, the relationships between tumour oxygenation and dynamic contrast-enhanced magnetic resonance imaging (MRI) parameters were investigated. MATERIALS AND METHODS: The study comprised 30 patients with carcinoma of the cervix. Tumour oxygenation was measured pre-treatment as median pO(2) and the proportion of values less than 5 mmHg (HP5) using a pO(2) histograph. Repeat measurements were obtained for nine patients following 40-45 Gy external beam radiotherapy giving a total of 39 measurements. Dynamic contrast-enhanced MRI using gadolinium was performed prior to obtaining the oxygenation data. Time/signal intensity curves were generated to obtain two standard parameters: maximum enhancement over baseline (SI-I) and the rate of enhancement (SI-I/s). RESULTS: Using the 39 measurements, there was a significant correlation between SI-I and both median pO(2) (r=0.59; P<0.001) and HP5 (r=-0. 49; P=0.002). There was a weak, borderline significant correlation between SI-I/s and both median pO(2) (r=0.29; P=0.071) and HP5 (r=-0. 34; P=0.037). There was a significant relationship between tumour size and SI-I (r=0.54; P<0.001), but not SI-I/s. In 29 tumours, where data were available, there was no relationship between histological assessment of tumour angiogenesis (intra-tumour microvessel density; IMD) and either MRI parameter. CONCLUSIONS: Tumour oxygenation levels measured using a pO(2) histograph correlate with dynamic contrast-enhanced MRI parameters. Therefore, non-invasive dynamic MRI may be a method for measuring hypoxia in human tumours.

Tumour size as a prognostic factor in carcinoma of the cervix: assessment by transrectal ultrasound.

Transrectal ultrasound (TRUS) was used to measure tumour size in patients with carcinoma of the cervix and to assess its prognostic significance. Clinical staging was conducted and at the time of examination under anaesthesia, TRUS was used to assess maximum transverse diameter of the tumour. Eighty-one patients were studied. FIGO stages were 1B 34 patients, IIA seven patients, IIB 31 patients, IIIA two patients and IIIB seven patients. Mean tumour diameters by stage were IB 37 mm, IIA 37 mm, IIB 49 mm, IIIA 42 mm and IIIB 50 mm. There was a significant correlation between size and stage (p = 0.001). With a median follow-up of 18 months, 16 relapses have occurred. The actuarial relapse rates at median follow-up by stage were IB 10%, IIA 17%, IIB 22%, IIIA 0% and IIIB 35%. The actuarial relapse rates by size grouping at median follow-up were less than 30 mm 0%, greater than 30 and less than 40 mm 11%, greater than 40 and less than 50 mm 22%, and greater than 50 mm 38%. There was a significant difference between the mean recorded size of the tumours in the relapsed group and the relapse-free group (p = 0.02). Despite the small number of patients and short follow-up, tumour size as measured by TRUS appears to predict relapse.

Development of a simultaneous boost IMRT class solution for a hypofractionated prostate cancer protocol.

The purpose of this work was to develop a robust technique for planning intensity-modulated radiation therapy (IMRT) for prostate cancer patients who are to be entered into a proposed hypofractionated dose escalation study. In this study the dose escalation will be restricted to the prostate alone, which may be regarded as a concurrent boost volume within the overall planning target volume (PTV). The dose to the prostate itself is to be delivered in 3 Gy fractions, and for this phase of the study the total prostate dose will be 57 Gy in 19 fractions, with 50 Gy prescribed to the rest of the PTV. If acute toxicity results are acceptable, the next phase will escalate doses to 60 Gy in 20 x 3 Gy fractions. There will be 30 patients in each arm. This work describes the class solution which was developed to create IMRT plans for this study, and which enabled the same set of inverse planning parameters to be used during optimization for every patient with minimal planner intervention. The resulting dose distributions were compared with those that would be achieved from a 3D conformal radiotherapy (3DCRT) technique that used a multileaf collimator (MLC) but no intensity modulation to treat the PTV, followed by a sequential boost to raise the prostate to 57 Gy. The two methods were tested on anatomical data sets for a series of 10 patients who would have been eligible for this study, and the techniques were compared in terms of doses to the target volumes and the organs at risk. The IMRT method resulted in much greater sparing of the rectum and bladder than the 3DCRT technique, whilst still delivering acceptable doses to the target volumes. In particular, the volume of rectum receiving the minimum PTV dose of 47.5 Gy was reduced from a mean value of 36.9% (range 23.4% to 61.0%) to 18.6% (10.3% to 29.0%). In conclusion, it was found possible to use a class solution approach to produce IMRT dose escalated plans. This IMRT technique has since been implemented clinically for patients enrolled in the hypofractionated dose escalation study.

Radioiodine ablation of residual tissue in thyroid cancer: relationship between administered activity, neck uptake and outcome.

A retrospective review was performed to evaluate the effectiveness of radioiodine in the ablation of residual thyroid tissue after surgery for differentiated thyroid cancer. 121 patients were treated at the Princess Margaret Hospital, Toronto, Canada between 1977 and 1989, with the activity of radioiodine determined empirically. Ablation of residual thyroid was determined by 131I nuclear scans, using absent visible uptake (compared with background) as the criterion for successful ablation. 97 patients (80%) had successful ablation of residual thyroid tissue after the first administration of radioiodine. Patients with higher iodine uptake in the neck had a tendency to receive higher activities of 131I. There were no statistically significant differences in age, sex, type of surgery, initial iodine uptake in the neck and administered radioiodine activity between those successfully ablated and those that were not. Patients receiving less than 3.7 GBq (100 mCi) tended to have lower iodine uptake (< 5% at 24 or 48 h), but their rate of thyroid ablation was just as high as those given 3.7 GBq or more. In order to take advantage of this, we have formalized our approach by deriving guidelines to the empiric determination of radioiodine activity based on the iodine uptake in the neck. Among the 11 patients treated with lobectomy only, the ablation rate was 64%. Although this was not significantly lower than for other forms of surgery, we continue to recommend completion thyroidectomy for this group of patients, if the goal of treatment is to ablate all thyroid tissue.

Carcinoma of the nasal cavity and paranasal sinuses: an analysis of radical radiotherapy.

A retrospective analysis was conducted of 152 patients with carcinoma of the nasal cavity and paranasal sinuses who were treated with radical radiotherapy between 1975-1984. Stages at presentation were T1 11%, T2 18%, T3 27%, and T4 44%. The median follow-up was 61 months. The overall corrected 5-year survival was 47% and by T stage, T1 86%, T2 82%, T3 49%, T4 25%. Local control was achieved in 45% of cases following radiotherapy. Salvage surgery was attempted in 20 patients where radiotherapy failed and was successful in eight. Nodal disease was present in 6.5% of patients at presentation and 10.5% developed nodal disease after treatment. Nodal disease as sole relapse occurred in four patients and was associated with prolonged survival following radical salvage treatment. Distant metastatic disease occurred in 25 patients and of these 17 (68%) also had locoregional failure. Osteoradionecrosis occurred in three cases, and a further three cases developed bilateral blindness. We conclude that radical radiotherapy achieves results comparable to published data for combined surgery and radiotherapy with acceptable toxicity.

Nasoethmoidal adenocarcinoma in woodworking twins.

The occurrence of nasoethmoidal adenocarcinoma in twins has not previously been reported. This paper describes the concurrent presentation in twins over 50 years after their first occupational exposure to hardwoods. There was a remarkable similarity in presentation.