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Ruggieri R.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Naccarato S.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Nahum A.E.,Clatterbridge Center for Oncology
Acta Oncologica | Year: 2010

Background. The current rationale for severely hypofractionated schedules (35 fractions) used in stereotactic-body-radiotherapy (SBRT) of non-small-cell lung cancer (NSCLC) is the small size of the irradiated volumes. Being the dose prescribed to the 6080% isodose line enclosing the PTV, a non-homogeneous tumour-dose-delivery results which might impact on tumour hypoxia. A comparison between homogeneous and SBRT-like non-homogeneous tumour-dose-delivery is then proposed here, using severe hypofractionation on large tumour volumes where both dose prescription strategies are applicable. Materials and methods. For iso-NTCP hypofractionated schedules (1f/d*5d/w) with respect to standard fractionation (d=2Gy), computed from the individual DVHs for lungs, oesophagus, heart and spinal cord (Lyman-Kutcher-Burman NTCP-model), TCP values were calculated (α-averaged Poissonian-LQ model) for homogeneous and SBRT-like non-homogeneous plans both with and without tumour hypoxia. Two different estimates of the oxygen-enhancement-ratio (OER) in combination with two distinct assumptions on the kinetics of reoxygenation were considered. Homogeneous and SBRT-like non-homogeneous plans were finally compared in terms of therapeutic ratio (TR), as the product of TCP and the four (1-NTCPi) values. Results. For severe hypofractionation (35 fractions) and for any of the hypotheses on the kinetics of reoxygenation and the OER, there was a significant difference between the computed TRs with or without inclusion of tumour hypoxia (anova, p=0.01) for homogeneous tumour-dose-delivery, but no significant difference for the SBRT-like non-homogeneous one. Further, a significantly increased mean TR for the group of SBRT-like non-homogeneous plans resulted (t-test, p=0.05) with respect to the group with homogeneous target-dose-coverage. Conclusions. SBRT-like dose-boosting seems to counterbalance the loss of reoxygenation within a few fractions. For SBRT it then seems that, in addition to the high level of dose-sparing to the adjacent normal tissues, when severe hypofractionation is adopted it is probably the intrinsic ability of stereotactic techniques to perform intra-tumour simultaneous dose-boosting which yields the reported high clinical efficacy. © 2010 Informa Healthcare. Source


Shakeshaft J.,Clatterbridge Center for Oncology
Clinical Oncology | Year: 2010

In recent years, the use of the Picture Archiving and Communications System (PACS) has become widespread in the area of diagnostic radiology for archival, review and reporting of patient data. However, the adoption of PACS within the field of radiotherapy is still very limited, despite the fact that most radiotherapy systems now use Digital Imaging and Communications in Medicine (DICOM) for both storage and communication. This paper discusses the challenges of integrating PACS into a radiotherapy department as a long-term archive of patient treatments. A possible solution based on a large English department is used as an example. © 2010 The Royal College of Radiologists. Source


Rutkowska E.,University of Liverpool | Baker C.,University of Liverpool | Nahum A.,Clatterbridge Center for Oncology
Physics in Medicine and Biology | Year: 2010

A radiobiologically based 3D model of normal tissue has been developed in which complications are generated when 'irradiated'. The aim is to provide insight into the connection between dose-distribution characteristics, different organ architectures and complication rates beyond that obtainable with simple DVH-based analytical NTCP models. In this model the organ consists of a large number of functional subunits (FSUs), populated by stem cells which are killed according to the LQ model. A complication is triggered if the density of FSUs in any 'critical functioning volume' (CFV) falls below some threshold. The (fractional) CFV determines the organ architecture and can be varied continuously from small (series-like behaviour) to large (parallel-like). A key feature of the model is its ability to account for the spatial dependence of dose distributions. Simulations were carried out to investigate correlations between dose-volume parameters and the incidence of 'complications' using different pseudo-clinical dose distributions. Correlations between dose-volume parameters and outcome depended on characteristics of the dose distributions and on organ architecture. As anticipated, the mean dose and V20 correlated most strongly with outcome for a parallel organ, and the maximum dose for a serial organ. Interestingly better correlation was obtained between the 3D computer model and the LKB model with dose distributions typical for serial organs than with those typical for parallel organs. This work links the results of dose-volume analyses to dataset characteristics typical for serial and parallel organs and it may help investigators interpret the results from clinical studies. © 2010 Institute of Physics and Engineering in Medicine. Source


Syndikus I.,Clatterbridge Center for Oncology | Morgan R.C.,Cancer Group | Sydes M.R.,Cancer Group | Graham J.D.,Taunton and Somerset NHS Foundation Trust | Dearnaley D.P.,Institute of Cancer Research
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. Methods and Materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Management (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade ≥2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade ≥2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade ≥2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up. Crown Copyright © 2010. Source


Theis V.S.,University of Liverpool | Sripadam R.,Clatterbridge Center for Oncology | Ramani V.,Clatterbridge Center for Oncology | Lal S.,Intestinal Failure Unit
Clinical Oncology | Year: 2010

Chronic radiation enteritis is an increasing problem, as more patients receive radiotherapy as part of their cancer therapy and as the long-term survival of these patients improves. This review addresses the causes, investigation, treatment and prevention of this disease. A review of published studies was carried out using a variety of search terms, including radiation enteritis, investigation, treatment and prevention. Chronic radiation enteritis has been reported in up to 20% of patients receiving pelvic radiotherapy, although this may underestimate its true prevalence, as not all patients with gastrointestinal symptoms after radiotherapy will seek medical attention. Predisposing factors to chronic radiation enteritis include a low body mass index, previous abdominal surgery and the presence of co-morbid conditions; the radiation dose, fractionation and technique, as well as the concomitant use of chemotherapy, may also play a role. Clinical features of chronic radiation enteritis are multiple as the disease can affect any part of the gastrointestinal tract. Moreover, symptom aetiology within any one patient may be multifactorial and therefore it is important to adopt a structured approach when planning investigations. The evidence base for current therapies is limited, but nutrition, anti-diarrhoeals, anti-inflammatories, antibiotics, probiotics, pentoxifylline, tocopherol, cholestyramine, hyperbaric oxygen, endoscopic and surgical therapies have all received attention. Given the significant morbidity and mortality associated with chronic radiation enteritis, current available preventative strategies are reviewed, including tissue-sparing radiotherapy techniques. In conclusion, the evidence base for therapeutic and preventative strategies in treating chronic radiation enteritis is limited, but adopting a structured approach to investigating gastrointestinal symptoms after radiotherapy should allow better targeting of current therapies. Closer collaboration between oncologists and gastroenterologists will facilitate a more structured approach, not only in managing individual patients, but also in establishing clinical and research networks for this expanding disease, in order to improve the evidence base for its management. © 2009 The Royal College of Radiologists. Source

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