Search

AIMS: Radiotherapy is an important treatment option for paraganglioma in the head and neck region. It seems to be highly effective and avoids important surgical morbidity, which can impair quality of life. The aim of this study was to evaluate the outcomes of radiotherapy for paraganglioma of the head and neck region in order to inform our future practice. MATERIALS AND METHODS: The cohort of patients for the present study comprised 21 patients who received radiotherapy between 1998 and 2008. Follow-up ranged from 6 to 132 months, median 55 months. The mean age was 48.7 years, range 20-78 years. The female:male ratio was 2 : 1. Two patients had confirmed familial tumour syndromes. The gross tumour volume in 20 cases ranged from 1.3 to 74 cm(3), mean 23.2 cm(3), median 14.7 cm(3). Five patients were treated with intensity-modulated radiotherapy. The median dose was 50 Gy in 30 fractions. RESULTS: The crude 5-year local control rate was 95% (20/21), although the 5-year actuarial local control rate was 87%. The one patient who relapsed, at 45 months after radiotherapy, had a comparatively small tumour of 10.8 cm(3). A relationship between tumour volume and local control seems unlikely. It was possible to obtain details of side-effects from electronic records for 11 patients. Grade 3 headache, which resolved, was the most serious acute side-effect. One patient had three teeth extracted due to exacerbation of dental caries, and one had deterioration of hearing thought to be due to a combination of tumour and radiotherapy. There were two serious complications in patients who had embolisation, which we no longer use. CONCLUSIONS: Our results show a high level of efficacy for fractionated external beam radiotherapy, with minimal toxicity, in keeping with other series. This should encourage the use of radiotherapy as primary treatment for paragangliomas of the head and neck region. [ABSTRACT FROM AUTHOR]

AIMS: To identify practical intensity-modulated radiotherapy planning solutions when attempting dose escalation in the skull base. MATERIALS AND METHODS: Twenty cases of skull base meningioma were re-planned using a variation of beam number (three, five, seven and nine), beam arrangement (coplanar vs non-coplanar) and multileaf collimator (MLC) width (2.5 mm vs 10 mm) to 60 Gy/30 fractions. Plan quality and planning target volume coverage was assessed using planning target volume V(95%), equivalent uniform dose (EUD) and integral dose. RESULTS: Critical structures were maintained below clinical tolerance levels. The 2.5 mm MLC achieved an average improvement in V(95%) by 22.8% (P=0.0003), EUD by 3.7 Gy (P=0.002) and reduced the integral dose by 13.4 Gy (P=0.0001). V(95%) and the integral dose improved with five vs three beams and seven vs five beams, but did not change with nine vs seven beams. There was no effect of beam number on EUD. There was no difference in V(95%) (P=0.54), integral dose (P=0.44) or EUD (P=0.47) for beam arrangement used. Segments per plan increased by a factor of 1.5 with each addition of two beams to a plan, and by a factor of 2.5 for 2.5 mm MLC plans vs 10 mm MLC plans. CONCLUSIONS: We present evidence-based planning solutions for skull base intensity-modulated radiotherapy, and show that 2.5 mm MLC and five to seven beams can achieve safe dose escalation up to 60 Gy. This must be balanced with an increase in segmentation, which will increase treatment times. [ABSTRACT FROM AUTHOR]

AIMS: Therapeutic radiotherapy to lesions of the skull base is limited by complex target shapes and their proximity to organs at risk. Intensity-modulated radiotherapy (IMRT) using helical tomotherapy may result in improved dose distributions and safer dose escalation. The aim of this study was to compare plan efficacy and efficiency using, linac-based micro-multileaf collimator (mMLC) IMRT and helical tomotherapy. MATERIALS AND METHODS: Five cases of skull base meningioma, previously treated with three-dimensional conformal radiotherapy (50 Gy/30 fractions) were identified. They were re-planned to a dose of 60 Gy/30 fractions using IMRT with Moduleaf mMLC (2.5 mm) and helical tomotherapy. Plan efficacy was compared using measures of PTV(60) coverage (D(min), D(max), V(90%), V(95%) and V(100%)). Plan efficiency was assessed by comparing estimated beam-on times. RESULTS: The critical structure dose was limited to below predetermined tolerance levels in all cases, with similar doses obtained between techniques. The average PTV(60)D(max), D(min), D(med), D(mean), V(90%), V(95%) and V(100%) across the five cases achieved were as follows: mMLC IMRT: 64.9 Gy, 40.1 Gy, 60 Gy, 59.6 Gy, 95.4%, 88.8% and 69.2%, respectively; helical tomotherapy: 67.2 Gy, 50.3 Gy, 60 Gy, 59.9 Gy, 95.8%, 83.5% and 51.9%, respectively. The average treatment time per fraction was 18.4 min for IMRT with mMLC and 6.7 min for helical tomotherapy. DISCUSSION: This study shows that safe dose escalation to a dose of 60G y to skull base lesions can be achieved; using either mMLC- or helical tomotherapy-based IMRT. A plan comparison between the two solutions is difficult, but they seem to be similar in efficacy with any small differences being difficult to interpret and of questionable clinical significance. Helical tomotherapy has the advantage of a significantly decreased beam-on time. [ABSTRACT FROM AUTHOR]

AIMS: Patients with chordoma and chondrosarcoma in the skull base present a complex multidisciplinary problem. These tumours are rare and occur in difficult anatomical regions. We reviewed the local control and survival of patients treated in our centre. MATERIALS AND METHODS: Between 1996 and 2005, 12 adult cases of chordoma (nine) and chondrosarcoma (three) in the skull base or cervical spine were treated in our centre. The median follow-up is currently 38 months. One patient was treated with palliative intent. In 10 cases the prescription dose was 65Gy in 39 fractions. The target volumes were measured, and the target maximum and minimum doses and the equivalent uniform dose (EUD) for the phase I plans were recorded. RESULTS: Local control was achieved in 11 of 12 cases. One chordoma patient failed locally, and one other died of metastatic disease despite local control. The 3- and 5-year cause-specific survival for the series was 88 and 75%, respectively. The mean phase I planning target volume (PTV) was 120.4cm(3). The median minimum dose in the phase I PTV was 81.0%. The median EUD (expressed as a percentage of the prescribed dose) for the phase I PTV, calculated using a value for the exponent a of -15, was 98.3%. The phase I EUD was below 80% in two of the 12 cases. CONCLUSIONS: Our results confirm a need for aggressive local surgery and high-dose radiotherapy, and endorse multidisciplinary working. Although charged particle therapy is accepted as providing optimal treatment plans, in eight of our patients travel abroad would not have been feasible. This series provides encouraging results for carefully planned photon conformal radiotherapy, carried out in close collaboration with a specialist surgical team. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal irradiation of tumorous calvaria (EITC) can be performed to restore function and form of the skull after resection of bone-invasive meningioma. We sought to examine the rate of tumour recurrence and other selected outcomes in patients undergoing meningioma resection and EITC., Methods: Retrospective single-centre study of adult patients undergoing meningioma resection and EITC between January 2015 and November 2022 at a tertiary neurosurgical centre. Patient demographics, surgery data, tumour data, use of adjuvant therapy, surgical complications, and tumour recurrences were collected., Results: Eighteen patients with 11 (61%) CNS WHO grade 1, 6 (33%) grade 2, and 1 (6%) grade 3 meningiomas were included. Median follow-up was 42 months (range 3-88). Five (28%) patients had a recurrence, but none were associated with the bone flap. Two (11%) wound infections requiring explant surgery occurred. Six (33%) patients required a further operation. Two operations were for recurrences, one was for infection, one was a washout and wound exploration but no evidence of infection was found, one patient requested the removal of a small titanium implant, and one patient required a ventriculoperitoneal shunt for a persistent CSF collection. There were no cases of bone flap resorption and cosmetic outcome was not routinely recorded., Conclusion: EITC is feasible and fast to perform with good outcomes and cost-effectiveness compared to other reconstructive methods. We observed similar recurrence rates and lower infection rates requiring explant compared to the largest series of cranioplasty in meningioma. Cosmetic outcome is universally under-reported and should be reported in future studies., (© 2024. The Author(s).)

In 2015, a groundswell of brain tumour patient, carer and charity activism compelled the UK Minister for Life Sciences to form a brain tumour research task and finish group. This resulted, in 2018, with the UK government pledging £20m of funding, to be paralleled with £25m from Cancer Research UK, specifically for neuro-oncology research over the subsequent 5 years. Herein, we review if and how the adult brain tumour research landscape in the United Kingdom has changed over that time and what challenges and bottlenecks remain. We have identified seven universal brain tumour research priorities and three cross-cutting themes, which span the research spectrum from bench to bedside and back again. We discuss the status, challenges and recommendations for each one, specific to the United Kingdom., (© 2024 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

Epithelioid glioblastoma multiforme (eGBM) is a rare and aggressive variant of glioblastoma multiforme (GBM) that predominantly affects younger patients and can be difficult to distinguish from other gliomas. Data on how patients with eGBM might be best treated are limited, although genomic analyses have shown that almost half of tumours harbour activating BRAF gene mutations. Here we present the case of a young female with BRAF V600E-mutant eGBM who had a prolonged response to targeted therapy with the BRAF and MEK1/2 inhibitors dabrafenib and trametinib. We review current knowledge about eGBM, including the emerging role for BRAF- ± MEK1/2- targeted therapy., (Copyright © 2021. Published by Elsevier Inc.)

Background Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers with 5-ALA-guided surgery. Methods We conducted a multicentre feasibility study of 5-ALA with BCNU wafers followed by standard-of-care chemoradiotherapy (chemoRT) in patients with suspected GBM. Patients judged suitable for radical resection were administered 5-ALA pre-operatively and BCNU wafers at the end resection. Post-operative treatment continued as per routine clinical practice. The primary objective was to establish if combining 5-ALA and BCNU wafers is safe without compromising patients from receiving standard chemoRT. Results Seventy-two patients were recruited, sixty-four (88.9%) received BCNU wafer implants, and fifty-nine (81.9%) patients remained eligible following formal histological diagnosis. Seven (11.9%) eligible patients suffered surgical complications but only two (3.4%) were not able to begin chemoRT, four (6.8%) additional patients did not begin chemoRT within 6 weeks of surgery due to surgical complications. Eleven (18.6%) patients did not begin chemoRT for other reasons (other toxicity ( n = 3), death ( n = 3), lost to follow-up/withdrew ( n = 3), clinical decision ( n = 1), poor performance status ( n = 1)). Median progression-free survival was 8.7 months (95% CI: 6.4-9.8) and median overall survival was 14.7 months (95% CI: 11.7-16.8). Conclusions Combining BCNU wafers with 5-ALA-guided surgery in newly diagnosed GBM patients is both feasible and tolerable in terms of surgical morbidity and overall toxicity. Any potential therapeutic benefit for the sequential use of 5-ALA and BCNU with chemoRT requires further investigation with improved local delivery technologies.

Purpose: Glioblastoma prognosis is poor. Treatment options are limited at progression. Surgery may benefit, but no quality guidelines exist to inform patient selection. We sought to describe variations in surgical management at progression, highlight where further evidence is needed, and build towards a consensus strategy., Methods: Current practice in selection of patients with progressive GBM for second surgery was surveyed online amongst specialists in the UK and Europe. We complemented this with an assessment of practice in a retrospective cohort study from six United Kingdom neurosurgical units. We used descriptive statistics to analyse the data., Results: 234 questionnaire responses were received. Maintaining or improving patient quality of life was key to decision making, with variation as to whether patient age, performance status or intended extent of resection was relevant. MGMT methylation status was not important. Half considered no minimum time after first surgery. 288 patients were reported in the cohort analysis. Median time to second surgery from first surgery 390 days. Median overall survival 815 days, with no association between time to second surgery and time to death (p = 0.874)., Conclusions: This is the most wide-ranging examination of contemporaneous practice in management of GBM progression. Without evidence-based guidelines, the variation is unsurprising. We propose consensus guidelines for consideration, to reduce heterogeneity in decision making, support data collection and analysis of factors influencing outcomes, and to inform clinical trials to establish whether second surgery improves patient outcomes, or simply selects to patients already performing well.

Background and Purpose: The impact of weight loss and anatomical change during head and neck (H&N) radiotherapy on spinal cord dosimetry is poorly understood, limiting evidence-based adaptive management strategies., Materials and Methods: 133 H&N patients treated with daily mega-voltage CT image-guidance (MVCT-IG) on TomoTherapy, were selected. Elastix software was used to deform planning scan SC contours to MVCT-IG scans, and accumulate dose. Planned (D P ) and delivered (D A ) spinal cord D 2% (SCD 2% ) were compared. Univariate relationships between neck irradiation strategy (unilateral vs bilateral), T-stage, N-stage, weight loss, and changes in lateral separation (LND) and CT slice surface area (SSA) at C1 and the superior thyroid notch (TN), and ΔSCD 2% [(D A - D P ) D 2% ] were examined., Results: The mean value for (D A - D P ) D 2% was -0.07 Gy (95%CI -0.28 to 0.14, range -5.7 Gy to 3.8 Gy), and the mean absolute difference between D P and D A (independent of difference direction) was 0.9 Gy (95%CI 0.76-1.04 Gy). Neck treatment strategy (p = 0.39) and T-stage (p = 0.56) did not affect ΔSCD 2% . Borderline significance (p = 0.09) was seen for higher N-stage (N2-3) and higher ΔSCD 2% . Mean reductions in anatomical metrics were substantial: weight loss 6.8 kg; C1LND 12.9 mm; C1SSA 12.1 cm 2 ; TNLND 5.3 mm; TNSSA 11.2 cm 2 , but no relationship between weight loss or anatomical change and ΔSCD 2% was observed (all r 2  < 0.1)., Conclusions: Differences between delivered and planned spinal cord D 2% are small in patients treated with daily IG. Even patients experiencing substantial weight loss or anatomical change during treatment do not require adaptive replanning for spinal cord safety., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: L'Hermitte's sign (LS) after chemoradiotherapy for head and neck cancer appears related to higher spinal cord doses. IMRT plans limit spinal cord dose, but the incidence of LS remains high., Methods: One hundred seventeen patients treated with TomoTherapy™ between 2008 and 2015 prospectively completed a side-effect questionnaire (VoxTox Trial Registration: UK CRN ID 13716). Baseline patient and treatment data were collected. Radiotherapy plans were analysed; mean and maximum spinal cord dose and volumes receiving 10, 20, 30 and 40 Gy were recorded. Dose variation across the cord was examined. These data were included in a logistic regression model., Results: Forty two patients (35.9%) reported LS symptoms. Concurrent weekly cisplatin did not increase LS risk (p = 0.70, OR = 1.23 {95% CI 0.51-2.34}). Of 13 diabetic participants (9 taking metformin), only 1 developed LS (p = 0.025, OR = 0.13 {95% CI 0.051-3.27}). A refined binary logistic regression model showed that patients receiving unilateral radiation (p = 0.019, OR = 2.06 {95% CI 0.15-0.84}) were more likely to develop LS. Higher V 40Gy (p = 0.047, OR = 1.06 {95% CI 1.00-1.12}), and younger age (mean age 56.6 vs 59.7, p = 0.060, OR = 0.96 {95% CI 0.92-1.00}) were associated with elevated risk of LS, with borderline significance., Conclusions: In this cohort, concomitant cisplatin did not increase risk, and LS incidence was lower in diabetic patients. Patient age and dose gradients across the spinal cord may be important factors.

Aims: To evaluate the long-term outcomes of patients with chordoma and low-grade chondrosarcoma after surgery and high-dose radiotherapy., Materials and Methods: High-dose photon radiotherapy was delivered to 28 patients at the Neuro-oncology Unit at Addenbrooke's Hospital (Cambridge, UK) between 1996 and 2016. Twenty-four patients were treated with curative intent, 17 with chordoma, seven with low-grade chondrosarcoma, with a median dose of 65 Gy (range 65-70 Gy). Local control and survival rates were calculated using the Kaplan-Meier method., Results: The median follow-up was 83 months (range 7-205 months). The 5 year disease-specific survival for chordoma patients treated with radical intent was 85%; the local control rate was 74%. The 5 year disease-specific survival for chondrosarcoma patients treated with radical intent was 100%; the local control rate was 83%. The mean planning target volume (PTV) was 274.6 ml (median 124.7 ml). A PTV of 110 ml or less was a good predictor of local control, with 100% sensitivity and 63% specificity. For patients treated with radical intent, this threshold of 110 ml or less for the PTV revealed a statistically significant difference when comparing local control with disease recurrence (P = 0.019, Fisher's exact test). Our data also suggest that the probability of disease control may be partly related to both target volume and radiotherapy dose., Conclusion: Our results show that refined high-dose photon radiotherapy, following tumour resection by a specialist surgical team, is effective in the long-term control of chordoma and low-grade chondrosarcoma, even in the presence of metal reconstruction. The results presented here will provide a useful source for comparison between high-dose photon therapy and proton beam therapy in a UK setting, in order to establish best practice for the management of chordoma and low-grade chondrosarcoma., (Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: Craniospinal irradiation (CSI) remains a crucial treatment for patients with medulloblastoma. There is uncertainty about how to manage meningeal surfaces and cerebrospinal fluid (CSF) that follows cranial nerves exiting skull base foramina. The purpose of this study was to assess plan quality and dose coverage of posterior cranial fossa foramina with both photon and proton therapy., Materials and Methods: We analysed the radiotherapy plans of seven patients treated with CSI for medulloblastoma and primitive neuro-ectodermal tumours and three with ependymoma (total n = 10). Four had been treated with a field-based technique and six with TomoTherapy™. The internal acoustic meatus (IAM), jugular foramen (JF) and hypoglossal canal (HC) were contoured and added to the original treatment clinical target volume (Plan&#95;CTV) to create a Test&#95;CTV. This was grown to a test planning target volume (Test&#95;PTV) for comparison with a Plan&#95;PTV. Using Plan&#95;CTV and Plan&#95;PTV, proton plans were generated for all 10 cases. The following dosimetry data were recorded: conformity (dice similarity coefficient) and homogeneity index (D 2  - D 98 /D 50 ) as well as median and maximum dose (D 2% ) to Plan&#95;PTV, V 95% and minimum dose (D 99.9% ) to Plan&#95;CTV and Test&#95;CTV and Plan&#95;PTV and Test&#95;PTV, V 95% and minimum dose (D 98% ) to foramina PTVs., Results: Proton and TomoTherapy™ plans were more conformal (0.87, 0.86) and homogeneous (0.07, 0.04) than field-photon plans (0.79, 0.17). However, field-photon plans covered the IAM, JF and HC PTVs better than proton plans (P = 0.002, 0.004, 0.003, respectively). TomoTherapy™ plans covered the IAM and JF better than proton plans (P = 0.000, 0.002, respectively) but the result for the HC was not significant. Adding foramen CTVs/PTVs made no difference for field plans. The mean D min dropped 3.4% from Plan&#95;PTV to Test&#95;PTV for TomoTherapy™ (not significant) and 14.8% for protons (P = 0.001)., Conclusions: Highly conformal CSI techniques may underdose meninges and CSF in the dural reflections of posterior fossa cranial nerves unless these structures are specifically included in the CTV., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

The VoxTox research programme has applied expertise from the physical sciences to the problem of radiotherapy toxicity, bringing together expertise from engineering, mathematics, high energy physics (including the Large Hadron Collider), medical physics and radiation oncology. In our initial cohort of 109 men treated with curative radiotherapy for prostate cancer, daily image guidance computed tomography (CT) scans have been used to calculate delivered dose to the rectum, as distinct from planned dose, using an automated approach. Clinical toxicity data have been collected, allowing us to address the hypothesis that delivered dose provides a better predictor of toxicity than planned dose.

Objective: There is no consensus approach to covering skull base meningeal reflections-and cerebrospinal fluid (CSF) therein-of the posterior fossa cranial nerves (CNs VII-XII) when planning radiotherapy (RT) for medulloblastoma and ependymoma. We sought to determine whether MRI and specifically fast imaging employing steady-state acquisition (FIESTA) sequences can answer this anatomical question and guide RT planning., Methods: 96 posterior fossa FIESTA sequences were reviewed. Following exclusions, measurements were made on the following scans for each foramen respectively (left, right); internal acoustic meatus (IAM) (86, 84), jugular foramen (JF) (83, 85) and hypoglossal canal (HC) (42, 45). A protocol describes measurement procedure. Two observers measured distances for five cases and agreement was assessed. One observer measured all the remaining cases., Results: IAM and JF measurement interobserver variability was compared. Mean measurement difference between observers was -0.275 mm (standard deviation 0.557). IAM and JF measurements were normally distributed. Mean IAM distance was 12.2 mm [95% confidence interval (CI) 8.8-15.6]; JF was 7.3 mm (95% CI 4.0-10.6). The HC was difficult to visualize on many images and data followed a bimodal distribution., Conclusion: Dural reflections of posterior fossa CNs are well demonstrated by FIESTA MRI. Measuring CSF extension into these structures is feasible and robust; mean CSF extension into IAM and JF was measured. We plan further work to assess coverage of these structures with photon and proton RT plans. Advances in knowledge: We have described CSF extension beyond the internal table of the skull into the IAM, JF and HC. Oncologists planning RT for patients with medulloblastoma and ependymoma may use these data to guide contouring.

Intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy offer significant opportunities to improve outcomes for our patients, although they are not yet as widely used as they might be. IMRT allows better target coverage and lower organ at risk doses than conformal therapy. It also allows inhomogeneous dose plans to be developed, where these can provide benefit, either to dose escalate the tumour or reduce dose to adjacent or overlapping organs at risk. Image guidance adds precision and the possibility of careful reduction in planning target volume margins. The technologies can be valuable both for patients with highly malignant tumours, such as glioblastoma, and those with less malignant or benign tumours. In glioblastoma, temozolomide chemotherapy and surgical developments have improved survival, and developments in radiotherapy techniques should also be used to optimise outcome. Target volume delineation, including calculation of the planning target volume margin is critical. Clear definitions of the gross tumour and clinical target volumes are essential, following established guidelines. Normal tissue volume delineation is also essential for IMRT. The planning organ at risk volume has become a valuable tool to manipulate dose away from organs at risk to avoid toxicities. This is distinct from 'optimising volumes' used to drive the computer optimiser during planning. Hard data on central nervous system (CNS) normal tissue tolerance is surprisingly slight, reflecting the clinical imperative to avoid serious complications in neurological tissues. The effect of chemotherapy on radiotherapy tolerance in the CNS remains obscure, and more needs to be done to develop the knowledge base. IMRT provides better conformation of the high dose treatment to the shape of the target, and reduces the dose to normal tissue structures. Image guidance improves the accuracy of dose delivery, which is particularly important where steep dose gradients are present. These technologies should be regarded as the state-of-the-art for our CNS patients., (Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: To review the treatment of squamous carcinoma of the temporal bone at a regional skull base unit for the period 1982-2012., Study Design: Retrospective case review., Setting: Tertiary referral center., Patients: Sixty patients with primary squamous carcinoma of the temporal bone., Interventions: Multidisciplinary team approach including surgical resection, reconstruction, and postoperative radiotherapy., Main Outcome Measures: Disease-specific survival, overall survival., Results: The 5-year disease-specific survival for the whole cohort was 44% (CI, 37%-51%). Multivariable analysis revealed nodal status, poorly differentiated squamous cell histology, and carotid involvement to be poor prognostic indicators., Conclusion: Although the survival figures in this series are comparable with the best outcomes from other units, our experience would suggest improvements can still be achieved by reconsidering the selection of patients for neck dissection and temperomandibular joint excision in early stage disease. We also conclude that postoperative radiotherapy should be delivered to all patients, including surgical salvage cases who may have received previous irradiation. Finally, the minority of patients with poor prognostic features should be offered a more palliative therapeutic approach.

Objective: To illustrate the wider potential scope of image-guided intensity-modulated radiotherapy (IG-IMRT), outside of the "standard" indications for IMRT., Methods: Nine challenging clinical cases were selected. All were treated with radical intent, although it was accepted that in several of the cases the probability of cure was low. IMRT alone was not adequate owing to the close proximity of the target to organs at risk, the risk of geographical miss, or the need to tighten planning margins, making image-guided radiotherapy an essential integral part of the treatment. Discrepancies between the initial planning scan and the daily on-treatment megavoltage CT were recorded for each case. The three-dimensional displacement was compared with the margin used to create the planning target volume (PTV)., Results: All but one patient achieved local control. Three patients developed metastatic disease but benefited from good local palliation; two have since died. A further patient died of an unrelated condition. Four patients are alive and well. Toxicity was low in all cases. Without daily image guidance, the PTV margin would have been insufficient to ensure complete coverage in 49% of fractions. It was inadequate by >3 mm in 19% of fractions, and by >5 mm in 9%., Conclusion: IG-IMRT ensures accurate dose delivery to treat the target and avoid critical structures, acting as daily quality assurance for the delivery of complex IMRT plans. These patients could not have been adequately treated without image guidance., Advances in Knowledge: IG-IMRT can offer improved outcomes in less common clinical situations, where conventional techniques would provide suboptimal treatment.

Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard chemotherapy regimens showing limited efficacy. Recent evidence suggests that temozolomide (TMZ), an orally-active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. A low level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) predicts TMZ responsiveness in glioblastomas, and a similar correlation has been observed in the majority of aggressive pituitary adenomas/carcinomas reported to date. Here, we report a case of a silent pituitary corticotroph adenoma, which subsequently re-presented with Cushing's syndrome due to functioning hepatic metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ therapy (200 mg/m² for 5 days every 28 days-seven cycles) resulted in marked clinical, biochemical [>50% fall in adrenocorticotrophic hormone (ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral adrenalectomy. However, despite reintroduction of TMZ therapy (further eight cycles) ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ therapy in glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of pituitary adenomas/carcinomas are also considered.

Background: Antithyroglobulin antibodies are a prevalent cause of interference in serum thyroglobulin immunoassays. Current guidelines recommend that antithyroglobulin antibodies should be measured concurrently with thyroglobulin when monitoring thyroid cancer patients post-thyroidectomy. However, the concordance between different antithyroglobulin assays has been questioned despite the availability of an international thyroglobulin antibody Reference Preparation., Methods: Four antithyroglobulin assays currently in use in UK laboratories (Siemens Immulite(®), Brahms GmbH, PerkinElmer AutoDELFIA and Siemens ADVIA Centaur(®)) were compared in a cohort of 145 thyroid cancer patients., Results: Using reference data provided by the kit manufacturer, concordance between the assays was 74%. Adjusting the cut-offs to maximize agreement increased concordance to 90%. Recovery of exogenous thyroglobulin using the Brahms Tg-plus immunoradiometric assay was neither a specific nor a sensitive test for the presence of a positive antibody result by any assay., Conclusions: Despite the availability of an international reference preparation, current antithyroglobulin assays show unacceptable variance.

Background: Brain tumours account for <2% of all primary neoplasms but are responsible for 7% of the years of life lost from cancer before age 70 years. The latest survival trends for patients with CNS malignancies have remained largely static. The objective of this study was to evaluate the change in practice as a result of implementing the Improving Outcomes Guidance from the UK National Institute for Health and Clinical Excellence (NICE)., Methods: Patients were identified from the local cancer registry and hospital databases. We compared time from diagnosis to treatment, proportion of patients discussed at multidisciplinary team (MDT) meetings, treatment received, length of inpatient stay and survival. Inpatient and imaging costs were also estimated., Results: Service reconfiguration and implementation of NICE guidance resulted in significantly more patients being discussed by the MDT--increased from 66 to 87%, reduced emergency admission in favour of elective surgery, reduced median hospital stay from 8 to 4.5 days, increased use of post-operative MRI from 17 to 91% facilitating early discharge and treatment planning, and reduced cost of inpatient stay from £2096 in 2006 to £1316 in 2009. Patients treated with optimal surgery followed by radiotherapy with concomitant and adjuvant temozolomide achieved outcomes comparable to those reported in clinical trials: median overall survival 18 months (2-year survival 35%)., Conclusions: Advancing the management of neuro-oncology patients by moving from an emergency-based system of patient referral and management to a more planned elective outpatient-based pattern of care improves patient experience and has the potential to deliver better outcomes and research opportunities.

Aims: High-dose radiotherapy after surgical debulking is the treatment of choice for chordomas and chondrosarcomas. This study reviewed our outcomes, in relation to residual tumour volume and radiation dose, in order to inform our future practice., Patients and Methods: Nineteen patients referred to the Neuro-Oncology Unit at Addenbrooke's Hospital (Cambridge, UK) between 1996 and 2009 and treated with photon radiotherapy were reviewed. Seventeen of the 19 were treated with curative intent. The median follow-up was 53 months. The tumours in the study had a mean gross tumour volume (GTV) of 17.2 cm(3) (median 10.5 cm(3)) and a range of 0-76.3 cm(3). The median dose was 65Gy in 39 fractions., Results: The 5 year cause-specific survival for radically treated patients with chordomas was 92% and the 5 year local control rate was 83%. The 5 year cause-specific survival and local control rates with chondrosarcomas were both 100%. A planning target volume (PTV) below 90 cm(3) is predictive of local control, but volumes above this are not. The GTV seems to be a better predictor of outcome: among the 17 of 19 patients treated curatively, a GTV threshold of 30 cm(3) distinguished local failures from the 15 patients with local control, with sensitivity to detect local control of 100% (95% confidence interval 78-100%), specificity 100% (95% confidence interval 16-100%) and positive predictive value 100% (95% confidence interval 78-100%)., Conclusions: Our results show a high level of efficacy for fractionated photon radiotherapy after surgery, in keeping with other series. In addition, we found that although surgical debulking is essential, a small residual tumour volume may still be controlled with high-dose photon radiotherapy. This information may be relevant during neurosurgical planning, possibly allowing a reduction in risk of serious neurological deficits. This should encourage the further development of sophisticated photon radiotherapy, for patients unsuitable for proton therapy., (Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia., Methods: We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1-4, N0-3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537., Findings: 47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0-59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56-87] of 34 patients given conventional radiotherapy vs 15 [38%; 23-55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23-61] of 44 patients given conventional radiotherapy vs 35 [74%; 55-89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63-95] of 24 patients given conventional radiotherapy vs nine [29%; 14-48] of 31 given IMRT; p<0·0001). At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with conventional radiotherapy, as were clinically significant improvements in dry-mouth-specific and global quality of life scores. At 24 months, no significant differences were seen between randomised groups in non-xerostomia late toxicities, locoregional control, or overall survival., Interpretation: Sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck., Funding: Cancer Research UK (CRUK/03/005)., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aims: To quantify the changes in contours of the target and organs at risk and the differences between planned and delivered doses to the target and organs at risk during the course of radiotherapy in head and neck cancer patients treated with intensity-modulated radiotherapy on the TomoTherapy HiArt™ system., Materials and Methods: Five patients with squamous cell carcinoma of the head and neck treated with radical chemoradiotherapy using the TomoTherapy HiArt system were included in the study. The target volumes were treated to three different dose levels depending on the level of clinical risk for harbouring disease. Patient positions were assessed daily with megavoltage computed tomography (MVCT) and positional correction made before each treatment when necessary. MVCTs were superimposed on to the planning kilovoltage computed tomography images for each patient and target volumes and organ at risk volumes were re-outlined on MVCT images. Doses to clinical target volumes and organs at risk were recalculated to show the actual delivered doses., Results: There was shrinkage in the volume of the parotid glands during treatment in all cases. The mean volume reduction in the ipsilateral parotid gland was more marked at 30.2%, compared with the contralateral parotid glands. However, the mean percentage dose per fraction increase was higher in the contralateral parotid glands at 24%, compared with the ipsilateral parotids. The calculated doses were higher than the planned doses in all CTV-54, CTV-60 and CTV-68, but the mean dose differences were modest, in the range 1.3-2.4%., Conclusions: We have shown that there were considerable changes in the volume and dose to the parotids during treatment. The changes in volume and dose to the clinical target volume were more modest in comparison. Adaptive radiotherapy planning can be helpful in improving the dose to the parotid glands. However, its role in the optimisation of the dosage to the clinical target volume is less likely to result in a significant clinical benefit., (Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Glioblastoma is the most frequent and malignant brain tumour. For many years, the conventional treatment has been maximal surgical resection followed by radiotherapy (RT), with a median survival time of less than 10 months. Previously, the use of adjuvant chemotherapy (given after RT) has failed to demonstrate a statistically significant survival advantage. Recently, a randomized phase III trial has confirmed the benefit of temozolomide (TMZ) and has defined a new standard of care for the treatment of patients with high-grade brain tumours. The results showed an increase of 2.5 months in median survival, and 16.1% in 2 year survival, for patients receiving RT with TMZ compared with RT alone. It is not clear whether the major benefit of TMZ comes from either concomitant administration of TMZ with RT, or from six cycles of adjuvant TMZ, or both. The objectives were to develop our original model, which addressed survival after RT, to construct a new module to assess the potential role of TMZ from clinical data, and to explore its synergistic contribution in addition to radiation. The model has been extended to include radiobiological parameters. The addition of the linear quadratic equation to describe cellular response to treatment has enabled us to quantify the effects of radiation and TMZ in radiobiological terms. The results indicate that the model achieves an excellent fit to the clinical data, with the assumption that TMZ given concomitantly with RT synergistically increases radiosensitivity. The alternative, that the effect of TMZ is due only to direct cell killing, does not fit the clinical data so well. The addition of concomitant TMZ appears to change the radiobiological parameters. This aspect of our results suggests possible treatment developments. Our observations need further evaluations in real clinical trials, may suggest treatment strategies for new trials, and inform their design.

Aims: Radiotherapy is an important treatment modality for meningioma. We aimed to review the clinical outcomes for meningioma patients treated with radiotherapy in the Addenbrooke's Hospital Oncology Department., Materials and Methods: A retrospective chart review was carried out on patients with meningioma referred and treated in the department between 1 November 1996 and 31 October 2006. Patient details and outcomes were recorded and the results were analysed to assess survival outcomes. Survival data were confirmed by the Eastern Cancer Registration and Information Centre., Results: In total, 174 patients were referred to the department for an oncology opinion. Of these, 128 proceeded to radiotherapy. The median follow-up was 5.3 years (range 2.1-11.9 years). Sixty-seven per cent of the patients were older than 50 years, and the female: male ratio was 2.2: 1. Overall survival was 78% at the time of follow-up, with death related to meningioma in 7% of the total cohort. Local control was 85% overall, 93% for grade 1 disease, 45% for grade 2 disease and 82% for grade 3 disease. Patients with non-benign disease were more likely to receive >50Gy (27% of grade 1 lesions vs 65% of grade 2/3 lesions), but despite this local control remained poor, even with the higher dose delivered (local control 60 and 40% for grade 2 lesions treated with 50 and >50Gy, respectively, and 100 and 75% for grade 3 lesions treated with 50 and >50Gy, respectively)., Conclusions: Our cohort of patients had an overall local control and survival similar to those documented from other departments. Grade was an important prognostic factor. Patients treated with >50Gy had worse local control outcomes, probably due to selection bias. Dose escalation may still be appropriate for high-risk disease, and may be more effective with more conformal techniques, such as intensity-modulated radiotherapy.

Aims: To assess the effectiveness of different on-treatment correction strategies on set-up accuracy in patients with head and neck cancer (HNC) treated on a TomoTherapy HiArt system. To assess the adequacy of clinical target volume (CTV) to planning target volume (PTV) treatment planning margins when treating with intensity-modulated radiotherapy without daily image guidance., Materials and Methods: The set-up accuracy measured by daily online volumetric imaging was retrospectively reviewed for the first 15 patients with HNC treated on the TomoTherapy unit at Addenbrooke's Hospital. For each fraction, megavoltage computed tomography was carried out, any discrepancy from the planning scan was noted, and corrected, before treatment. These data were used to evaluate imaging correction protocols using three different action levels. The first three fractions were imaged and used to correct for systematic error, using a 5 mm action level (5 mmAL), a 3 mm action level (3 mmAL), and no action level (NAL). All imaging strategies were applied, to assess the number of fractions that would potentially have exceeded a 5 and 3 mm margin. Systematic and random errors were calculated for the population, assuming the NAL protocol had been applied, and minimum CTV-PTV margins, required to allow for errors attributable only to set-up, were calculated using van Herk's formula., Results: In total, 490 fractions were analysed. Using a 5 mmAL imaging protocol, potentially 198/490 fractions (40%) were outside a 5 mm CTV-PTV margin and 400/490 (82%) were outside a 3 mm margin. Using a 3 mmAL imaging protocol, potentially 67/490 fractions (14%) were outside a 5 mm CTV-PTV margin and 253/490 (52%) were outside a 3 mm margin. A small systematic error was identified in the system; once corrected this would improve these results. Using the NAL imaging protocol, potentially 31/490 fractions (6%) were outside a 5 mm CTV-PTV margin and 143/490 fractions (29%) were outside a 3 mm margin. Estimated minimum CTV-PTV margins to account only for set-up errors, with three-fraction image-guided radiotherapy and a NAL protocol, were 2.8, 3.1 and 4.1 mm in the mediolateral, superior-inferior and anterior-posterior directions, respectively., Conclusion: Reducing the action level at which the systematic error is corrected improves the probability of treatment delivery accuracy. Using the NAL correction protocol reduces the number of fractions that have set-up displacements outside a 5 mm CTV-PTV margin. Although a 5 mm margin is probably sufficient for standard HNC radiotherapy, change to a 3 mm margin is not favoured at our centre without access to daily image-guided radiotherapy.

Introduction: There is ambiguity in pathological grading of high grade gliomas within the WHO 2000 classification, especially those with predominant oligodendroglial differentiation., Patients and Methods: All adult high grade gliomas treated radically, 1996-2005, were assessed. Cases in which pathology was grade III but radiology suggested glioblastoma (GBM) were classified as 'grade III/IV'; their pathology was reviewed., Results: Data from 245 patients (52 grade III, 18 grade III/IV, 175 GBM) were analysed using a Cox Proportional Hazards model. On pathology review, features suggestive of more aggressive behaviour were found in all 18 grade III/IV tumours. Oligodendroglial components with both necrosis and microvascular proliferation were present in 7. MIB-1 counts for the last 8 were all above 14%, mean 27%. Median survivals were: grade III 34 months, grade III/IV 10 months, GBM 11 months. Survival was not significantly different between grade III/IV and GBM. Patients with grade III/IV tumours had significantly worse outcome than grade III, with a hazard of death 3.7 times higher., Conclusions: The results highlight the current inconsistency in pathological grading of high grade tumours, especially those with oligodendroglial elements. Patients with histological grade III tumours but radiological appearances suggestive of GBM should be managed as glioblastoma.

Aims: To assess the local control and cranial nerve toxicity in vestibular schwannoma patients treated with fractionated conformal radiotherapy delivered using a linear accelerator., Materials and Methods: Ninety-five patients were referred for consultation to the Oncology Department in Addenbrookes Hospital between 1996 and 2005. The 42 cases who received fractionated conformal radiotherapy are the subject of this analysis. All patients had radiological or symptomatic progression. Conformal radiotherapy was prescribed at 50Gy in 30 fractions over 6 weeks, delivered using a linear accelerator. Patients were immobilised using either a beam direction shell or a Gill Thomas Cosman relocatable stereotactic head frame., Results: The median age was 63 years (range 28-81) with 57% men. The average tumour size was 21.5mm on magnetic resonance imaging. Before treatment, 20 (48%) patients were deemed to have useful hearing on the affected side. The median follow-up was 18.6 months (range 0.3-6.5 years) and the actuarial local control rate at 2.5 years was 96.9% (one patient progressed after treatment). In previously hearing patients, the actuarial rate of useful hearing preservation was 100%, and the rate of mild hearing loss was 20% at 1 year and 26.7% at 2.5 years of follow-up. There were five neurofibromatosis type 2 patients treated, two of whom had useful hearing before radiotherapy. In one patient this was affected, with a 20dB loss, although he still has useful hearing. In those with normal facial nerve function before radiotherapy (n=40), this was preserved in 96.8% at 2.5 years. Trigeminal nerve function was preserved in all patients (n=38) who had normal nerve function before radiotherapy., Conclusion: Although follow-up was relatively short in this single institution series, fractionated linear accelerator radiotherapy gave excellent local control, useful hearing preservation and retained cranial nerve function in vestibular schwannoma.

More years of life per patient are lost as the result of primary brain tumours than any other form of cancer. The most aggressive of these is known as glioblastoma (GBM). The median survival time of patients with GBM is under 10 months and the outlook has hardly improved over the past 20 years. Generally, these tumours are remarkably resistant to radiotherapy and yet about 2-3% of all GBMs appear to be cured. The objectives of this study were to formulate a mathematical and phenomenological model of tumour growth in a population of patients with GBM to predict survival, and to use the model to extract biological information from clinical data. The model describes the growth of the tumour and the resulting damage to the normal brain using simple concepts borrowed from chemical reaction engineering. Death is assumed to result when the amount of surviving normal brain falls to a critical level. Radiotherapy is assumed to destroy tumour but not healthy brain. Simple rules are included to represent approximately the clinician's decisions about what type of treatment to offer each patient. A population of patients is constructed by assuming that key parameters can be sampled from statistical distributions. Following Monte Carlo simulation, the model can be fitted to data from clinical trials. The model reproduces clinical data extremely accurately. This suggests that the long-term survivors are not a separate sub-population but are the 'lucky tail' of a unimodal distribution. The estimated values of radiation sensitivity (represented as SF2, the survival fraction after 2Gy) suggest the presence of severe hypoxia, which renders cells less sensitive to radiation. The model can predict the probable age distribution of tumours at presentation. The model shows the complicated effects of waiting times for treatment on the survival outcomes, and is used to predict the effects of escalation of radiotherapy dose. The model may aid the design of clinical trials using radiotherapy for patients with GBM, especially in helping to estimate the size of trial required. It is also designed in a generic form, and might be applicable to other tumour types.

Aims: The outcome of patients with glioblastoma (GBM) remains extremely poor. We have developed a mathematical model, using pathological and radiation biology concepts, to assess the detrimental effect of delay to start radiotherapy, the possible benefit from dose escalation, and to extract biological data from clinical data., Materials and Methods: Survival data were available for 154 adult patients with GBM treated in our centre with curative intent to a dose of 60 Gy in 30 fractions between 1996 and 2002. Survival data for 129 patients from the 60 Gy arm of the MRC BR02 randomised trial of radiotherapy dose were obtained for comparison. The model generates the equivalent of individual patients with a brain tumour, and produces an explicit outcome, either death or survival. The tumour, assumed to be growing exponentially, causes normal cell damage in the brain, and death occurs when the number of normal brain cells falls below a critical level. The outcome for an individual patient is determined by values of the variables assigned by the model. Parameters for the single patient include tumour doubling time, surviving fraction of tumour cells after each fraction of radiotherapy, and a waiting time from presentation to the start of radiotherapy. A surrogate for performance status is implemented, using a rule that rejects patients whose tumours are too advanced at presentation to be suitable for radical radiotherapy. Values for the parameters that determine individual patient outcome are randomly assigned from a set of probability distributions, using Monte Carlo simulation. The simulation constructs survival results for a population, typically 2000 individuals. The descriptors of the probability distributions that are used to determine the parameters that define the patient characteristics are adjusted to optimise the fit of the modelled population to real clinical data, using a combination of folding polygon and simulated annealing techniques., Results: The model fits the clinical data well. The results suggest that the surviving fraction of tumour cells after a radiation dose of 2 Gy (SF2) does influence patient outcome. The mean in vivo SF2 for the Addenbrooke's data is 0.80, implying that hypoxia is a serious problem in radiotherapy for GBM. The Addenbrooke's data suggest a mean tumour doubling time of 24 days, so that a delay to start radiotherapy would be expected to have an adverse effect. Considering patients by treatment intent, median survival plummets as delay increases, and almost no patients survive long term after a 70-day delay. Radiotherapy dose escalation has an important predicted effect on survival. Assuming that the treatment could be delivered safely, a dose of 74 Gy, given at 2 Gy/fraction, would extend the survival of all patients. The proportion of long-term survivors would increase, from 2.4% with 60 Gy, to 6.4% with 74 Gy. The model can be used to derive gamma50, which has a value of 0.42, lower than the typical value of 1-2., Conclusion: Using the model, we have extracted biological information from clinical data. The model could be used to assess the potential benefit, or lack of benefit, from a proposed radiotherapy trial, and to estimate the necessary size. It shows that a single modality is unlikely to achieve a major improvement in long-term survival, although radiotherapy dose escalation should have a role, provided it can be given safely. The model could be extended to include chemotherapy, bio-reductive drugs, or gene therapy.

Aims: Radiotherapy treatment planning for high-grade gliomas (HGG) is hampered by the inability to image peri-tumoural white-matter infiltration. Diffusion tensor imaging (DTI) is an imaging technique that seems to show white-matter abnormalities resulting from tumour infiltration that cannot be visualised by conventional computed tomography or magnetic resonance imaging (MRI). We propose a new term, the image-based high-risk volume (IHV) for such abnormalities, which are distinct from the gross-tumour volume (GTV). For IHV based on DTI, we use the term IHVDTI. This study assesses the value of DTI for the individualisation of radiotherapy treatment planning for patients with HGG., Methods: Seven patients with biopsy-proven HGG were included in a theoretical planning exercise, comparing standard planning techniques with individualised plans based on DTI. Standard plans were generated using a 2.5 cm clinical target volume (CTV) margin added to the GTV. For DTI-based plans, the CTV was generated by adding a 1 cm margin to the IHVDTI. Estimates of normal tissue complication probability (NTCP) were calculated and used to estimate the level of dose escalation that could be achieved using the DTI-based plans., Results: The use of DTI resulted in non-uniform margins being added to the GTV to encompass areas at high risk of tumour involvement, but, in six out of seven cases, the IHVDTI was encapsulated by the standard CTV margin. In all cases, DTI could be used to reduce the size of the planning-target volume (PTV) (mean 35%, range 18-46%), resulting in escalated doses (mean 67 Gy, range 64-74 Gy), with NTCP levels that matched the conventional treatment plans., Conclusion: DTI can be used to individualise radiotherapy target volumes, and reduction in the CTV permits modest dose escalation without an increase in NTCP. DTI may also be helpful in stratifying patients according to the degree of white-matter infiltration.

Recently, cancer mortality has been compared to research spending by the National Cancer Research Institute (NCRI), whose research budget is approximately pound sterling 250 million. The analysis shows a mis-match between mortality and research spending. As well as crude mortality rates, other measures of cancer burden should be considered because they contribute additional information. 'Years of life lost' (YLL) summed over each individual dying after a diagnosis of cancer represents a population-based mortality indicator of the impact of that disease on society. Years of life lost divided by the number of deaths for each cancer site produces an additional statistic, the average years of life lost (AYLL), which is a measure of the burden of cancer to the individual patient. For 17 cancer sites where data are available, four tumour sites have a rather large difference in mortality, comparing YLL to crude mortality. Years of life lost shows the population burden from cancers of the ovary, cervix, and CNS to be rather larger than suggested by crude mortality, despite screening programmes for cervix cancer. Using YLL, the underprovision of funding for lung cancer research is similar to that reported using percentage mortality. Breast cancer and leukaemia receive a relatively higher research spend than the population burden of these cancers, and the spending on leukaemia is quite extreme. Prostate cancer has a low per cent YLL but attracts a moderate amount of research spending. The use of AYLL as an indicator of individual cancer burden considerably changes the ranking of the mortality from different tumours. The mean AYLL is 12.5 years. Prostate cancer has the lowest AYLL, only 6.1 years; brain tumour patients have the highest, at just over 20 years. Comparing AYLL to research spending suggests four 'Cinderella' cancer sites with high individual cancer burden but low research spending: CNS tumours, cervix and kidney cancers, and melanoma. Breast cancer and leukaemia have roughly average AYLL but a considerable excess of research spending. YLL emphasises the discrepancy between research spending and mortality, and may be helpful for decisions concerning research support. Average years of life lost measures the burden to individual patients and may be helpful where individuals' needs are relevant, such as palliative care. As well as crude mortality, more subtle and comprehensive calculations of mortality statistics would be useful in debates on research funding and public health issues.

Patients with bony and soft tissue sarcomas may require intensive treatment with chemotherapy and radiotherapy, which often leads to a fall in haemoglobin levels, requiring blood transfusion. There may be advantages in predicting which patients will require transfusion, partly because anaemia and hypoxia may worsen the response of tumours to chemotherapy and radiotherapy. Between 1997 and 2003, a total of 26 patients who received intensive treatment with curative intent were identified. Transfusions were given to maintain the haemoglobin at 10g/dl or above during chemotherapy, and at 12 g/dl or above during radiotherapy. Eighteen (69%) required a transfusion, the majority as a result of both the chemotherapy and RT criteria. There were 78 transfusion episodes, and 181 units of blood given. In the 18 patients who required transfusion, the average number of units was 10.1, but seven patients required more blood than this. The most significant factor influencing blood transfusion was choice of intensive chemotherapy. Intensive chemotherapy and presenting Hb less than 11.6 g/dl identified 13 out of 18 patients who needed transfusion. Adding a drop in haemoglobin of greater than 1.7 g/dl after one cycle of chemotherapy identified 16 out of 18 patients who required transfusion. The seven patients who had heavy transfusion requirements were identified by age 32 or less, intensive chemotherapy and a presenting Hb of 12 g/dl or less. Erythropoietin might be a useful alternative to transfusion in selected patient groups, especially those with heavy transfusion requirements.

Purpose: The clinical target volume (CTV) of post-operative radiotherapy for soft tissue sarcoma of the limbs conventionally includes the whole of the transverse cross-section of the affected anatomical compartment. In the anterior thigh sartorius appears to lie within its own fascial compartment and can be safely excluded. We investigated the potential impact of omitting sartorius from the anterior muscle compartment on patients with soft tissue sarcoma of the thigh., Patients and Methods: We used the planning CT data from six patients who had previously received post-operative radiotherapy for soft tissue sarcoma of the thigh. The anterior compartments were outlined twice, initially including and then excluding the sartorius muscle. The volumes of the anterior compartment (i.e., the CTVs), both with and without sartorius, and the corresponding planning target volumes (PTVs) were calculated. Treatment plans were prepared for each PTV. For both volumes the unirradiated normal tissue corridor was outlined on each CT slice. The volume and circumference of the unirradiated corridor were then calculated., Results: For all six patients there was an important improvement in normal tissue sparing by excluding sartorius. The mean reduction in volume of the anterior compartment when sartorius was excluded was 10% (95% Confidence Interval 8-12%), whilst the mean decrease in PTV was 11% (95% CI 7-14%). There was a substantial increase in the volume of the unirradiated normal tissue corridor, with a mean value of 77% (95% CI 41-114%) when sartorius was excluded. In addition, the percentage increase in the size of the unirradiated normal tissue corridor, expressed as a percentage of the whole leg circumference, was 10% (95% CI 8-13%). When sartorius was included in the anterior compartment, the circumference of the unirradiated corridor was less than one-third of the whole leg circumference in four of the six patients. When sartorius was excluded, the circumference of the unirradiated corridor was greater than one-third of the leg circumference over the entire length of the target volume in all patients., Discussion: It is essential to know the anatomy of the sartorius muscle to be able to exclude it from the anterior compartment. The increase in the size of the normal tissue corridor when sartorius is excluded should deliver clinical advantage by decreasing the normal tissue adverse effects.

Radiotherapy is a localised treatment. The definition of tumour and target volumes for radiotherapy is vital to its successful execution. This requires the best possible characterisation of the location and extent of tumour. Diagnostic imaging, including help and advice from diagnostic specialists, is therefore essential for radiotherapy planning. There are three main volumes in radiotherapy planning. The first is the position and extent of gross tumour, i.e. what can be seen, palpated or imaged; this is known as the gross tumour volume (GTV). Developments in imaging have contributed to the definition of the GTV. The second volume contains the GTV, plus a margin for sub-clinical disease spread which therefore cannot be fully imaged; this is known as the clinical target volume (CTV). It is the most difficult because it cannot be accurately defined for an individual patient, but future developments in imaging, especially towards the molecular level, should allow more specific delineation of the CTV. The CTV is important because this volume must be adequately treated to achieve cure. The third volume, the planning target volume (PTV), allows for uncertainties in planning or treatment delivery. It is a geometric concept designed to ensure that the radiotherapy dose is actually delivered to the CTV. Radiotherapy planning must always consider critical normal tissue structures, known as organs at risk (ORs). In some specific circumstances, it is necessary to add a margin analogous to the PTV margin around an OR to ensure that the organ cannot receive a higher-than-safe dose; this gives a planning organ at risk volume. This applies to an organ such as the spinal cord, where damage to a small amount of normal tissue would produce a severe clinical manifestation. The concepts of GTV, CTV and PTV have been enormously helpful in developing modern radiotherapy. Attention to detail in radiotherapy planning is vital, and does affect outcomes: 'the devil is in the detail'. Radiotherapy planning is also dependent on high quality imaging, and the better the imaging the better will be the outcomes from radiotherapy.

Aims: Paraspinal tumours, such as chordoma, represent a treatment challenge for oncologists, requiring high dose to the target volume without exceeding the tolerance dose of the spinal cord. Intensity-modulated radiotherapy (IMRT) is helpful in achieving sharp dose gradients and conformation of dose to the target volume. We present a simpler technique--conformal rotation therapy with a central axis beam block (CRT + BB), which can provide similar dose distributions., Materials and Methods: A patient with a cervical chordoma developed postoperative recurrence and was treated with high-dose palliative radiotherapy. Treatment was delivered using CRT + BB, with three fixed beams and three coplanar arcs. A dose of 62 Gy in 31 fractions was delivered to the 100% isodose, giving a maximum spinal cord dose of 49.6 Gy. The patient relapsed 2 years later, and was re-treated using the same technique to a dose of 57 Gy in 30 fractions. Estimates of spinal cord repair rates in primates were used to determine the tolerance dose of the spinal cord for re-treatment. The patient remained well for a further 25 months before developing local recurrence, which was treated with palliative chemotherapy., Results: Re-treatment plans using CRT + BB and IMRT were compared. Dose-volume histograms show equivalence of dose to the spinal cord, although the IMRT plan delivered a slightly higher dose to tumour and lower dose to surrounding soft tissues., Conclusion: Treatment using CRT + BB requires careful planning and discussion with neurosurgeons before surgery. The normal curvature of the cervical spine must be eliminated if possible, and the patient must be immobilised with the neck horizontal. If these geometric constraints can be satisfied, then CRT + BB can be used as a safe and effective alternative treatment to IMRT for tumours at this site.

Purpose: Controversy exists as to whether sartorius muscle is completely invested in fascia. If it is, then direct tumour involvement from soft tissue sarcoma of the anterior thigh would be unlikely and would justify omitting sartorius from the radiotherapy volume., Subjects and Methods: Eight thighs in six cadavers were examined in the dissecting room. Using a previous case, conformal radiotherapy plans were prepared to treat the anterior compartment of the thigh including and excluding sartorius. The corridor of unirradiated normal tissue was outlined separately., Results: In all cases, sartorius was enclosed within a fascial sheath of its own. In four of the six cadavers, there was clear evidence of a fascial envelope surrounding sartorius, fused to the fascia lata and medial intermuscular septum. In two, sartorius was fully ensheathed in the upper half of the thigh; in the lower half the intermuscular septum became thin, and blended with the tendinous aponeurosis on the surface of vastus medialis in an example case. By excluding sartorius, the volume of the anterior compartment was reduced by 8%, but the volume of the unirradiated normal tissue corridor increased by 134%. With sartorius included, the unirradiated corridor became very small inferiorly, only 6% of the circumference of the whole leg, compared to 27% with sartorius excluded., Discussion: The anatomy suggests that sartorius could be safely omitted from the clinical target volume of anterior compartment soft tissue sarcomas. This substantially increases the size of the unirradiated normal tissue corridor, expressed as a volume and a circumference, which could give a clinical advantage by reducing normal tissue complications.

For a study sponsored by the International Atomic Energy Agency (IAEA), Pacific Northwest Laboratory (PNL) made lung counting measurements of lung deposition in 10 women who had inhaled 92mNb in England. These women were measured in both the supine and sitting (torso 45 degrees from horizontal) positions with a counting system of Ge planar detectors and another counting system of Phoswich detectors. The average increase in counting efficiency from the supine to the sitting position was 108% for the Ge detectors and 310% for the Phoswich detectors. Individual counting efficiency increases ranged from 15-260% for the Ge detectors and from 40-480% for the Phoswich detectors. The increase in counting efficiency was roughly proportional to the total chest wall thickness of the measured individuals. By using the equivalent muscle tissue thickness of the individual's chest wall, the increase in counting efficiency could be attributed to the decrease in the tissue absorption in the sitting position. The decreased distance between the lungs and the detector achieved in the sitting positions may also account for some of the improvement in counting efficiency. In addition, some undetermined internal change in activity distribution (source-to-detector geometry) and tissue absorption may possibly contribute to the improved counting efficiency of the sitting vs. the supine position.