Radiotherapy Related Research

Manchester, United Kingdom

Radiotherapy Related Research

Manchester, United Kingdom
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Groom N.,Mount Vernon Cancer Center | Wilson E.,University College London | Faivre-Finn C.,University of Manchester | Faivre-Finn C.,Radiotherapy Related Research
British Journal of Radiology | Year: 2017

Objective: This study investigated the effect of deviation from protocol in heart delineation for the Concurrent Oncedaily Versus twice-daily Radiotherapy (CONVERT) Trial ( Identifier NCT00433563) quality assurance (QA) programme and the effect of that on mean cardiac dose and percentage of heart volume receiving ≥5Gy (V5%) and percentage of heart volume receiving ≥30Gy (V30%). Methods: Patients with limited-stage small-cell lung cancer in the CONVERT trial were randomized to receive 45Gy in 30# twice daily or 66Gy in 33# once daily radiotherapy, with concurrent chemotherapy in both arms. Of the 100 trial patient cases reviewed by the QA team [for patient selection, disease/organs at risk (OARs) outlining and treatment planning], 50 patient cases were selected, and the heart was reoutlined according to the "gold standard" trial protocol. Dose-volume histogram (DVH) data were extracted. The impact of change in heart volume on cardiac DVH is presented. Results: For gold standard cardiac outlines, an increase in V5% and V30% was seen in 77.3% and 81.8% of cases, respectively, in the control arm (45 Gy) and in 78.6% and 82.1% of cases, respectively, in the experimental arm (66 Gy). The median increase in V5% was 1.4% and in V30%, it was 3.4%. The average of the mean cardiac dose for the control arm increased by 2.1Gy (from 15.2Gy for the centres outline to 17.3Gy for the gold standard outline) and for the experimental arm by 2.4Gy (from 16.2 to 18.6 Gy). Conclusion: This study demonstrates the importance of having a robust QA programme in place to ensure accuracy of cardiac delineation to facilitate future studies investigating the impact of cardiac dose on toxicity. Advances in knowledge: This study highlights the importance of ensuring accurate delineation of OARs in clinical trials, where conclusions about normal tissue toxicity are to be drawn. © 2017 The Authors.

PubMed | Mount Vernon Hospital, Queen's University of Belfast, Weston Park Hospital, Beatson West of Scotland Cancer Center and 7 more.
Type: Journal Article | Journal: BMJ open | Year: 2016

The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of isotoxic radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable.Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5years.The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West-Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally.NCT01836692; Pre-results.

Christodoulou M.,University of Manchester | Bayman N.,Christie NHS Foundation Trust | McCloskey P.,Radiotherapy Related Research | Rowbottom C.,Radiotherapy Related Research | And 3 more authors.
European Journal of Cancer | Year: 2014

Radiotherapy plays a major role in the treatment of patients with locally advanced non-small cell lung cancer (NSCLC), particularly since most patients are not suitable for surgery due to the extent of their disease, advanced age and multiple co-morbidities. Despite advances in local and systemic therapies local control and survival remain poor and there is a sense that a therapeutic plateau has been reached with conventional approaches. Strategies for the intensification of radiotherapy such as dose escalation have shown encouraging results in phase I-II trials, but the outcome of the phase III Radiation Therapy Oncology Group 0617 trial was surprisingly disappointing. Hyperfractionated and/or accelerated fractionating schedules have demonstrated superior survival compared to conventional fractionation at the expense of greater oesophageal toxicity. Modern radiotherapy techniques such as the integration of 4-dimensional computed tomography for planning, intensity modulated radiotherapy and image-guided radiotherapy have substantially enhanced the accuracy of the radiotherapy delivery through improved target conformality and incorporation of tumour respiratory motion. A number of studies are evaluating personalised radiation treatment including the concept of isotoxic radiotherapy and the boosting of the primary tumour based on functional imaging. Proton beam therapy is currently under investigation in locally advanced NSCLC. These approaches, either alone or in combination could potentially allow for further dose escalation and improvement of the therapeutic ratio and survival for patients with NSCLC. © 2013 Elsevier Ltd. All rights reserved.

Bayman N.,Christie NHS Foundation Trust | Blackhall F.,Christie NHS Foundation Trust | McCloskey P.,Radiotherapy Related Research | Taylor P.,University of Manchester | And 2 more authors.
Lung Cancer | Year: 2014

Latest evidence sets a clear mandate for concurrent chemoradiotherapy as the current standard of care for inoperable stage III non small cell lung cancer patients with good performance status and minimal co-morbidities. However, a survival plateau has been reached, with disappointing results from dose escalation studies using conventional fractionation and studies investigating the addition of systemic doses of chemotherapy delivered before or after concurrent chemoradiotherapy.A review was carried out to address three questions considered fundamental to improving outcome in patients with stage III non-small cell lung cancer:. 1.Can radiotherapy regimens be optimised using advanced radiotherapy techniques to improve local control rate and overall survival?2.Can systemic therapy regimens be optimised to reduce the risk of distant metastases?3.Should concurrent chemoradiotherapy be considered standard of care for locally advanced non-small cell lung cancer in the elderly?It is clear that further improvement in outcome for these patients will be determined by better local control and by reducing the risk of distant recurrence. Given the technological advances in radiotherapy planning and delivery in recent years plus the abundance of novel targeted therapies exploiting critical oncogenic pathways, further advances in combined drug-radiation treatment for lung cancer seem highly possible. © 2013 Elsevier Ireland Ltd.

Khalifa J.,Radiotherapy Related Research | Amini A.,Aurora University | Popat S.,Royal Marsden Hospital | Gaspar L.E.,Aurora University | And 2 more authors.
Journal of Thoracic Oncology | Year: 2016

Brain metastases (BMs) will develop in a large proportion of patients with NSCLC throughout the course of their disease. Among patients with NSCLC with oncogenic drivers, mainly EGFR activating mutations and anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangements, the presence of BM is a common secondary localization of disease both at the time of diagnosis and at relapse. Because of the limited penetration of a wide range of drugs across the blood-brain barrier, radiotherapy is considered the cornerstone of treatment of BMs. However, evidence of dramatic intracranial response rates has been reported in recent years with targeted therapies such as tyrosine kinase inhibitors and has been supported by new insights into pharmacokinetics to increase rates of tyrosine kinase inhibitors' penetration of the cerebrospinal fluid (CSF). In this context, the combination of brain radiotherapy and targeted therapies seems relevant, and there is a strong radiobiological rationale to harness the radiosentizing effect of the drugs. Nevertheless, to date, there is a paucity of high-level clinical evidence supporting the combination of brain radiotherapy and targeted therapies in patients with NSCLC and BMs, and there are often methodological biases in reported studies, such as the lack of stratification by mutation status. Moreover, among asymptomatic patients not suitable for ablative treatment, this strategy is challenged by the promising results associated with the administration of targeted therapies alone. Herein, we review the biological rationale to combine targeted therapies and brain radiotherapy for patients with NSCLC and BMs, report the clinical data available to date, and discuss future directions to improve outcome in this group of patients. © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

McCloskey P.,Radiotherapy Related Research | Balduyck B.,University of Antwerp | Van Schil P.E.,University of Antwerp | Faivre-Finn C.,Radiotherapy Related Research | O'Brien M.,Royal Marsden Hospital
European Journal of Cancer | Year: 2013

The management of non-small cell lung cancer (NSCLC) has continued to improve over the last 5 years due to advances in surgery, radiological staging, combined modality therapies and advances in radiation technology. We have an updated staging classification (7th Edition American Joint Committee on Cancer staging) and now in 2011, a new histology classification introducing the concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma. This classification has profound surgical implications as the role of limited resection is reconsidered for early stage lesions. Surgery is curative in early stage disease. The role of surgery in locally advanced NSCLC remains controversial. The principal aim is a complete resection as this will determine long-term prognosis. Intraoperative staging of lung cancer is extremely important to determine the extent of resection according to the tumour and nodal status. Systematic nodal dissection is generally advocated to obtain accurate intraoperative staging and to help decide on adjuvant therapy. Radiotherapy currently plays a major role in the management of lung cancer as most patients are not surgical candidates due to disease stage, fitness and co-morbidities. In the last 5 years we have seen continuing optimisation of chemo-radiotherapy combinations and technological advances including the development of image guided radiotherapy (IGRT), stereotactic ablative body radiotherapy (SABR) and intensity modulated radiotherapy (IMRT). Quality of life evaluation is becoming increasingly important and should be considered when deciding on a specific treatment, especially in a multimodality setting. © 2013 Elsevier Ltd. All rights reserved.

Warren M.,The Christie NHS Foundation Trust | Webster G.,University of Birmingham | Ryder D.,MAHSC CTU Trials Coordination Unit | Rowbottom C.,The Christie NHS Foundation Trust | Faivre-Finn C.,Radiotherapy Related Research
Clinical Oncology | Year: 2014

Aims: Recent clinical series suggest that treating patients with isotoxic twice-daily radiotherapy may be beneficial. This dosimetric planning study compared the use of intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DRT) to deliver isotoxic treatment for non-small cell lung cancer (NSCLC) patients. Materials and methods: Twenty patients with stage II/III NSCLC were selected. A dose-escalated plan was produced retrospectively for each using three different methods: (i) three to five beams 3DRT; (ii) seven beams inverse-planned conformal radiotherapy; (iii) seven beams IMRT. The starting point for dose escalation was 55.8Gy in 1.8Gy per fraction twice-daily. The number of fractions was then increased until one or more organ at risk tolerance dose was exceeded or a maximum dose of 79.2Gy was reached. Results: The median escalated doses were 70.2, 66.6 and 64.8Gy for IMRT, 3DRT and inverse-planned conformal radiotherapy, respectively. IMRT allowed a significant dose increase in comparison with the other two methods (P<0.05), whereas no significant difference was found between 3DRT and inverse-planned conformal radiotherapy. IMRT was more successful at escalating dose in patients where the brachial plexus and spinal canal were close to the planning target volume. IMRT did not allow the escalation of dose beyond 70.2Gy (82.8Gy BED10, 69Gy EQD2) due to the proximity of disease to the great vessels and the proximal bronchial tree. Conclusions: IMRT allows increased dose escalation compared with conformal radiotherapy. However, there is limited opportunity to escalate the prescription dose beyond 70.2Gy twice-daily in disease close to the central mediastinal structures. © 2014 The Royal College of Radiologists.

Haslett K.,Radiotherapy Related Research | Pottgen C.,University of Duisburg - Essen | Stuschke M.,University of Duisburg - Essen | Faivre-Finn C.,Radiotherapy Related Research | Faivre-Finn C.,University of Manchester
Journal of Thoracic Disease | Year: 2014

Radical radiotherapy plays a major role in the treatment of non-small cell lung cancer (NSCLC) due to the fact that many patients are medically or surgically inoperable. Advances in technology and radiotherapy delivery allow targeted treatment of the disease, whilst minimizing the dose to organs at risk. This in turn creates an opportunity for dose escalation and the prospect of tailoring radiotherapy treatment to each patient. This is especially important in patients deemed unsuitable for chemotherapy or surgery, where there is a need to increase the therapeutic gain from radical radiotherapy alone. Recent research into fractionation schedules, with hyperfractionated and accelerated radiotherapy regimes has been promising. How to combine these new fractionated schedules with dose escalation and chemotherapy remains open to debate and there is local, national and international variation in management with a lack of overall consensus. An overview of the current literature on hyperfractionated and accelerated radiotherapy in NSCLC is provided. © Pioneer Bioscience Publishing Company.

Christodoulou M.,University of Manchester | McCloskey P.,Radiotherapy Related Research | Stones N.,Radiotherapy Related Research | Bayman N.,The Christie NHS Foundation Trust | And 10 more authors.
Radiotherapy and Oncology | Year: 2014

Background and purpose There is a paucity of data regarding the feasibility and relevance of Patient Reported Outcome (PRO) tools to assess radiotherapy-related toxicity in lung cancer.Material and methods From January to June 2013, lung cancer patients undergoing thoracic radiotherapy/chemo-radiotherapy completed nine patient-adapted Common Terminology Criteria for Adverse Events (CTCAE), the European Organisation for Research and Treatment of Cancer Quality of Life (QoL) questionnaire and the Hospital Anxiety and Depression Scale (HADS) at baseline, the end of radiotherapy and at follow-up. Clinicians completed the same CTCAE items and agreement between patients' and clinicians' reporting was assessed using weighted kappa coefficients. QoL and HADS scores were correlated with the patients' and clinicians' reported toxicity.Results 70/116 patients completed the questionnaires for at least one time point excluding baseline. Agreement between patients' and clinicians' reported toxicity ranged from slight to substantial. Most discrepancies were within one grade and patients reported greater severity than clinicians for most symptoms. QoL and HADS scores were more strongly correlated with the patients' compared to clinicians' matching toxicity reports. The PRO tool was found to be statistically reliable.Conclusions The use of a PRO tool in lung cancer radiotherapy is feasible, reliable and acceptable to patients. PROs should be integrated in future clinical trials evaluating new radiotherapy approaches to assess toxicity. ©2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology.

Lee S.M.,University College London | Lewanski C.R.,Charing Cross Hospital | Counsell N.,Cancer Research UK Research Institute | Ottensmeier C.,Southampton General Hospital | And 6 more authors.
Journal of the National Cancer Institute | Year: 2014

Background Median survival of non-small cell lung cancer (NSCLC) patients with brain metastases is poor. We examined concurrent erlotinib and whole brain radiotherapy (WBRT) followed by maintenance erlotinib in patients with untreated brain metastases, given the potential radiosensitizing properties of erlotinib and its direct effect on brain metastases and systemic activity. Methods Eighty NSCLC patients with KPS of 70 and greater and multiple brain metastases were randomly assigned to placebo (n = 40) or erlotinib (100mg, n = 40) given concurrently with WBRT (20 Gy in 5 fractions). Following WBRT, patients continued with placebo or erlotinib (150mg) until disease progression. The primary end point was neurological progression-free survival (nPFS); hazard ratios (HRs) were calculated using Cox regression. All P values were two-sided. Results Fifteen patients (37.5%) from each arm were alive and without neurological progression 2 months after WBRT. Median nPFS was 1.6 months in both arms; nPFS HR 0.95 (95% CI = 0.59 to1.54; P =. 84). Median overall survival (OS) was 2.9 and 3.4 months in the placebo and erlotinib arms; HR 0.95 (95% CI = 0.58 to 1.55; P =. 83). The frequency of epidermal growth factor receptor (EGFR) mutations was low with only 1 of 35 (2.9%) patients with available samples had activating EGFR-mutations. Grade 3/4 adverse event rates were similar between the two groups (70.0% in each arm), except for rash 20.0% (erlotinib) vs 5.0% (placebo), and fatigue 17.5% vs 35.0%. No statistically significant quality of life differences were found. Conclusions Our study showed no advantage in nPFS or OS for concurrent erlotinib and WBRT followed by maintenance erlotinib in patients with predominantly EGFR wild-type NSCLC and multiple brain metastases compared to placebo. Future studies should focus on the role of erlotinib with or without WBRT in patients with EGFR mutations. © 2014 The Author 2014. Published by Oxford University Press.

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