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Manchester, United Kingdom

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. Source

Warren M.,Christie Medical Physics and Engineering | Webster G.,University of Birmingham | Ryder D.,MAHSC CTU Trials Coordination Unit | Rowbottom C.,Christie Medical Physics and Engineering | 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. Source

Faivre-Finn C.,University of Manchester | Faivre-Finn C.,Radiotherapy Related Research | Falk S.,Manchester Academic Health Science Center Trials Coordination Unit | Ashcroft L.,Manchester Academic Health Science Center Trials Coordination Unit | And 9 more authors.
BMJ Open | Year: 2016

Introduction: Concurrent ONce-daily VErsus twicedaily RadioTherapy (CONVERT) is the only multicentre, international, randomised, phase III trial open in Europe and Canada looking at optimisation of chemoradiotherapy (RT) in limited stage small cell lung cancer (LS-SCLC). Following on from the Turrisi trial of once-daily versus twice-daily (BD) concurrent chemoradiotherapy, there is a real need for a new phase III trial using modern conformal RT techniques and investigating higher once-daily radiation dose. This trial has the potential to define a new standard chemo-RT regimen for patients with LS-SCLC and good performance status. Methods and analysis: 447 patients with histologically or cytologically proven diagnosis of SCLC were recruited from 74 centres in eight countries between 2008 and 2013. Patients were randomised to receive either concurrent twice-daily RT(45 Gy in 30 twice-daily fractions over 3 weeks) or concurrent oncedaily RT(66 Gy in 33 once-daily fractions over 6.5 weeks) both starting on day 22 of cycle 1. Patients are followed up until death. The primary end point of the study is overall survival and secondary end points include local progression-free survival, metastasis-free survival, acute and late toxicity based on the Common Terminology Criteria for Adverse Events V.3.0, chemotherapy and RTdose intensity. Ethics and dissemination: The trial received ethical approval from NRES Committee North West-Greater Manchester Central (07/H1008/229). There is a trial steering committee, including independent members and an independent data monitoring committee. Results will be published in a peer-reviewed journal and presented at international conferences. Trial registration number: ISRCTN91927162; Pre-results. Source

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. Source

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. Source

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