ORCID Profile
0000-0003-1003-5138
Current Organisations
Queen's University Belfast
,
Peter MacCallum Cancer Centre
,
Belfast Health and Social Care Trust
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Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.RADONC.2017.06.025
Abstract: To evaluate the impact of ATR inhibition using AZD6738 in combination with radiotherapy on the response of non-small cell lung cancer (NSCLC) tumour models and a murine model of radiation induced fibrosis. AZD6738 was evaluated as a monotherapy and in combination with radiation in vitro and in vivo using A549 and H460 NSCLC models. Radiation induced pulmonary fibrosis was evaluated by cone beam computed tomography (CBCT) and histological staining. AZD6738 specifically inhibits ATR kinase and enhanced radiobiological response in NSCLC models but not in human bronchial epithelial cells (HBECs) in vitro. Significant tumour growth delay was observed in cell line derived xenografts (CDXs) of H460 cells (p 0.5) and histological scoring of radiation induced fibrosis (p>0.5). Inhibition of ATR with AZD6738 in combination with radiotherapy increases tumour growth delay without observable augmentation of late radiation induced toxicity further underpinning translation towards clinical evaluation in NSCLC.
Publisher: No publisher found
Date: 2022
DOI: 10.1016/J.JTHO.2022.05.003
Abstract: Toxicity concerns from thoracic radiation therapy in the treatment of lung cancers have changed substantially over the past few decades. Survival in the treatment of lung cancer has markedly improved and the introduction of advanced radiation and imaging techniques to treatment planning and delivery has made reducing toxicity possible. Phase 3 dose-escalation trials have revealed that excess dose to critical organs within the thorax can negatively impact overall survival. We summarize the existing literature on the known toxicities of thoracic radiation therapy, summarize the technological advances that have made toxicity reduction possible, and provide an overview of emerging technologies and biomarkers that are being evaluated to assess future toxicity reductions.
Publisher: British Institute of Radiology
Date: 10-2011
DOI: 10.1259/BJR/29163167
Publisher: Elsevier BV
Date: 2022
Publisher: Frontiers Media SA
Date: 03-2019
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.CLON.2017.09.007
Abstract: Six UK studies investigating stereotactic ablative radiotherapy (SABR) are currently open. Many of these involve the treatment of oligometastatic disease at different locations in the body. Members of all the trial management groups collaborated to generate a consensus document on appropriate organ at risk dose constraints. Values from existing but older reviews were updated using data from current studies. It is hoped that this unified approach will facilitate standardised implementation of SABR across the UK and will allow meaningful toxicity comparisons between SABR studies and internationally.
Publisher: Elsevier BV
Date: 04-2021
Publisher: BMJ
Date: 12-2020
DOI: 10.1136/BMJOPEN-2020-042465
Abstract: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning systems, enabling conformal avoidance of highly functioning regions of lung, thereby facilitating increased doses to tumour while reducing normal tissue doses. This prospective interventional study will investigate the use of ventilation and perfusion PET/CT to identify highly functioning lung volumes and avoidance of these using VMAT planning. This single-arm trial will be conducted across two large public teaching hospitals in Australia. Twenty patients with stage III non-small cell lung cancer will be recruited. All patients enrolled will receive dose-escalated (69 Gy) functional avoidance radiation therapy. The primary endpoint is feasibility with this achieved if ≥15 out of 20 patients meet pre-defined feasibility criteria. Patients will be followed for 12 months post-treatment with serial imaging, biomarkers, toxicity assessment and quality of life assessment. Using advanced techniques such as VMAT functionally adapted radiation therapy may enable safe moderate dose escalation with an aim of improving local control and concurrently decreasing treatment related toxicity. If this technique is proven feasible, it will inform the design of a prospective randomised trial to assess the clinical benefits of functional lung avoidance radiation therapy. This study was approved by the Peter MacCallum Human Research Ethics Committee. All participants will provide written informed consent. Results will be disseminated via publications. NCT03569072 Pre-results
Publisher: Elsevier BV
Date: 03-2020
Publisher: Springer Science and Business Media LLC
Date: 11-05-2020
DOI: 10.1186/S12909-020-02054-Z
Abstract: The last two decades have seen revolutionary developments in both radiotherapy technology and postgraduate medical training. Trainees are expected to attain competencies using a mix of experiential learning, formal postgraduate teaching, self-directed learning and peer education. Radiation (Clinical) Oncology is a recognised ‘craft specialty’ where the apprenticeship model of training is applicable. This scoping review examines the evidence in relation to how medical trainees learn radiotherapy. A systematic search of MEDINE and EMBASE was undertaken to identify studies of trainee and/or trainer experience of radiotherapy learning published 1999–2018. Results pertaining to Medical Oncology, workforce trends, undergraduate radiotherapy exposure, academic training, global health, non-medical staff, health service infrastructure and recruitment to training programmes were not included. A total of 146 publications were included in the synthesis. Five themes were apparent through careful iterative analysis representing broadly inter-related issues. Most articles studied radiotherapy training from the perspective of the trainee doctor. Most literature reports results of observational, local or national surveys with a tightly defined scope. Considerable variation exists within hospitals, within countries, over time and between different curricular areas. Medical education has not kept pace with changes in the field of radiotherapy and large differences are demonstrated in experience between trainees in different hospitals, countries and training stages. Interpersonal relationships, departmental organisation, and national curricula impact on training quality. Qualitative and quantitative research examining modern radiotherapy learning has been uncommon and uncoordinated, until recently. To date no single study has been designed to comprehensively assess a department’s training scheme.
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.CLON.2019.10.004
Abstract: Radiotherapy clinical trials are integral to the development of new treatments to improve the outcomes of patients with cancer. A collaborative study by the National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group and the National Institute for Health Research was carried out to understand better if and why inefficiencies occur in the set-up of radiotherapy trials in the UK. Two online surveys collected information on the time taken for UK radiotherapy trials to reach key milestones during set-up and the research support currently being provided to radiotherapy centres to enable efficient clinical trial set-up. Semi-structured interviews with project managers and chief investigators identified better ways of working to improve trial set-up in the future. The timelines for the set-up of 39 UK radiotherapy trials were captured in an online survey showing that the median time from grant approval to trial opening was 600 days (range 169-1172). There were 38 responses from radiotherapy centres to a survey asking about the current support provided for radiotherapy research. Most of these centres have more than one type of staff member dedicated to supporting radiotherapy research. The most frequent barrier to radiotherapy trial set-up identified was lack of physicists' time and lack of time for clinical oncologists to carry out research activities. Four main themes around trial set-up were identified from semi-structured interviews: the importance of communication and building relationships, the previous experience of the chief investigator and clinical trials units, a lack of resources and having the time and personnel required to produce trial documentation and to process trial approval requests. This unique, collaborative project has provided up to date information about the current landscape of trial set-up and research support in the UK and identified several avenues on which to focus future efforts in order to support the excellent radiotherapy trial work carried out across the UK.
Publisher: Wiley
Date: 07-2021
DOI: 10.1111/IMJ.15414
Publisher: BMJ
Date: 10-2021
DOI: 10.1136/BMJOPEN-2021-055026
Abstract: To gather preliminary qualitative data that will assist in the codesign and development of a new informational and supportive website to assist informal cancer carers in Australia. Utilising a previously tested codesign process, informal carers’ experiences and perspectives, including those of healthcare professionals’, were examined via focus groups and/or interviews. Data were analysed via thematic analysis. Rural (n=9) and urban (n=11) carers’, and healthcare professionals’ (n=8) perspectives were collected. Carers participated in a focus group (n=9) or telephone interview (n=11). Healthcare professionals completed an interview (n=6) or online survey (n=2). Rural and urban carers typically felt ill prepared for their multitudinal caregiving responsibilities. Supporting patient-to-healthcare professional liaisons could especially challenge. Carers’ biopsychosocial and fiscal strains were affected by patients’ hardships and available informal supports. Rural carers described greater social support than urban carers. Both rural and urban carers also described discontentment related to a carer neglecting healthcare system. Both carers and healthcare professionals endorsed the need for a user-friendly, carer-specific website encompassing practical information and resources, peer-driven advice and evidence-based illness information, tailored to the Australian context. Carers and healthcare professionals recognise the pressing need for an Australian, cancer carer-specific online resource. Findings will inform the next phase, where a resource will be designed, developed and tested.
Publisher: Wiley
Date: 18-05-2020
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.RADONC.2016.09.002
Abstract: To assess the impact of a standardized delineation protocol and training interventions on PET/CT-based target volume delineation (TVD) in NSCLC in a multicenter setting. Over a one-year period, 11 pairs, comprised each of a radiation oncologist and nuclear medicine physician with limited experience in PET/CT-based TVD for NSCLC from nine different countries took part in a training program through an International Atomic Energy Agency (IAEA) study (NCT02247713). Teams delineated gross tumor volume of the primary tumor, during and after training interventions, according to a provided delineation protocol. In-house developed software recorded the performed delineations, to allow visual inspection of strategies and to assess delineation accuracy. Following the first training, overall concordance indices for 3 repetitive cases increased from 0.57±0.07 to 0.66±0.07. The overall mean surface distance between observer and expert contours decreased from -0.40±0.03cm to -0.01±0.33cm. After further training overall concordance indices for another 3 repetitive cases further increased from 0.64±0.06 to 0.80±0.05 (p=0.01). Mean surface distances decreased from -0.34±0.16cm to -0.05±0.20cm (p=0.01). Multiple training interventions improve PET/CT-based TVD delineation accuracy in NSCLC and reduce interobserver variation.
Publisher: British Institute of Radiology
Date: 03-2017
DOI: 10.1259/BJR.20160732
Publisher: BMJ
Date: 04-2016
Publisher: AME Publishing Company
Date: 12-2019
Publisher: SAGE Publications
Date: 19-04-2019
Publisher: Frontiers Media SA
Date: 10-10-2018
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.IJROBP.2018.12.010
Abstract: The aim of this study was to define the dose and dose-volume relationship of radiation-induced pulmonary toxicities occurring in and out-of-field in mouse models of early inflammatory and late fibrotic response. Early radiation-induced inflammation and fibrosis were investigated in C3H/NeJ and C57BL/6J mice, respectively. Animals were irradiated with 20 Gy delivered to the upper region of the right lung as a single fraction or as 3 consecutive fractions using the Small Animal Radiation Research Platform (Xstrahl Inc, Camberley, UK). Cone beam computed tomography was performed for image guidance before irradiation and to monitor late toxicity. Histologic sections were examined for neutrophil and macrophage infiltration as markers of early inflammatory response and type I collagen staining as a marker of late-occurring fibrosis. Correlation was evaluated with the dose-volume histogram parameters calculated for in idual mice and changes in the observed cone beam computed tomography values. Mean lung dose and the volume receiving over 10 Gy (V10) showed significant correlation with late responses for single and fractionated exposures in directly targeted volumes. Responses observed outside the target volume were attributed to nontargeted effects and showed no dependence on either mean lung dose or V10. Quantitative assessment of normal tissue response closely correlates early and late pulmonary response with clinical parameters, demonstrating this approach as a potential tool to facilitate clinical translation of preclinical studies. Out-of-field effects were observed but did not correlate with dosimetric parameters, suggesting that nontargeted effects may have a role in driving toxicities outside the treatment field.
Publisher: Elsevier BV
Date: 09-2023
Publisher: American Medical Association (AMA)
Date: 04-2023
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.CLON.2017.06.014
Abstract: The National Institute for Healthcare Excellence recommends continuous hyperfractionated, accelerated radiotherapy (CHART), concurrent chemoradiation (cCRT) and stereotactic ablative radiotherapy (SABR) for appropriate patients with non-small cell lung cancer (NSCLC), but these are not universally available in all UK radiotherapy centres. Reduced access to these treatments may be contributing to reduced survival, with the concern that elderly patients are less likely to receive guideline-recommended therapy (GRT). We report a prospective, UK national study of patients treated with curative-intent radiotherapy for NSCLC over a 2 month period. Clinical oncologists in all UK radiotherapy centres were contacted and asked to complete a proforma on all patients treated with curative-intent radiotherapy. Three hundred and seventeen records were returned from 82% of centres. Only 49% (95% confidence interval 43-55%) of patients received the GRT for their tumour type. Patients aged 70 years or over were less likely to access GRT than those under 70 years (40% compared with 60%, P = 0.001), both as a result of clinicians offering therapy less frequently (52% compared with 65%, P = 0.03) and a higher refusal of therapy (22% versus 8%, P = 0.02). A reluctance to travel to a different centre was a key component of these decisions. SABR was delivered to only 52% of suitable patients, mainly because it was not available in the local centre. In this study of UK curative-intent radiotherapy practice, a lack of local access seems to limit uptake of advanced radiotherapy techniques such as SABR, especially for patients aged over 70 years.
Publisher: Elsevier BV
Date: 07-2014
Publisher: British Institute of Radiology
Date: 08-2023
Abstract: Interstitial lung disease (ILD) is relatively common in patients with lung cancer with an incidence of 7.5%. Historically pre-existing ILD was a contraindication to radical radiotherapy owing to increased radiation pneumonitis rates, worsened fibrosis and poorer survival compared with non-ILD cohorts. Herein, the clinical and radiological toxicity outcomes of a contemporaneous cohort are described. Patients with ILD treated with radical radiotherapy for lung cancer at a regional cancer centre were collected prospectively. Radiotherapy planning, tumour characteristics, and pre- and post-treatment functional and radiological parameters were recorded. Cross-sectional images were independently assessed by two Consultant ThoracicRadiologists. Twenty-seven patients with co-existing ILD received radical radiotherapyFebruary 2009–April 2019, with predominance ofusual interstitial pneumonia subtype (52%). According to ILD-GAP scores, most patients were stage I. After radiotherapy, localised (41%) or extensive (41%) progressive interstitial changes were noted for most patients yetdyspnoea scores (n = 15 available) and spirometry (n = 10 available) were stable. One-third of patients with ILD went on to receive long-term oxygen therapy, which was significantly more than the non-ILD cohort. Median survival trended towards being worse compared with non-ILD cases (17.8 v 24.0 months, p = 0.834). Radiological progression of ILD and reduced survival were observed post-radiotherapy in this small cohort receiving lung cancer radiotherapy, although a matched functional decline was frequently absent. Although there is an excess of early deaths, long-term disease control is achievable. For select patients with ILD long-term lung cancer control without severely impacting respiratory function may be possible with radical radiotherapy, albeit with a slightly higher risk of death.
Publisher: Elsevier BV
Date: 03-2021
Publisher: British Institute of Radiology
Date: 02-2013
DOI: 10.1259/BJR.20120434
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 04-2021
Publisher: Frontiers Media SA
Date: 12-04-2022
Abstract: Biology-guided radiotherapy (BgRT) uses real-time functional imaging to guide radiation therapy treatment. Positron emission tomography (PET) tracers targeting prostate-specific membrane antigen (PSMA) are superior for prostate cancer detection than conventional imaging. This study aims at describing nodal and distant metastasis distribution from prostate cancer and at determining the proportion of metastatic lesions suitable for BgRT. A single-institution patient subset from the ProPSMA trial (ID ACTRN12617000005358) was analysed. Gross tumour volumes (GTV) were delineated on the CT component of a PSMA PET/CT scan. To determine the suitability of BgRT tracking zones, the normalized SUV (nSUV) was calculated as the ratio of SUVmax inside the GTV to the SUVmean of adjacent three-dimensional shells of thickness 5 mm/10 mm/20 mm as a measure of signal to background contrast. Targets were suitable for BgRT if (1) nSUV was larger than an nSUV threshold and (2) non-tumour tissue inside adjacent shell was free of PET-avid uptake. Of this cohort of 84 patients, 24 had at least one pelvic node or metastatic site disease, 1 to 13 lesions per patient, with a total of 98 lesions (60 pelvic nodes/38 extra-pelvic nodal diseases and haematogenous metastases). Target volumes ranged from 0.08 to 9.6 cm 3 while SUVmax ranged from 2.1 to 55.0. nSUV ranged from 1.9 to 15.7/2.4 to 25.7/2.5 to 34.5 for the 5 mm/10 mm/20 mm shell expansion. Furthermore, 74%/68%/34% of the lesions had nSUV ≥ 3 and were free of PSMA PET uptake inside the GTV outer shell margin expansion of 5 mm/10 mm/20 mm. Adjacent avid organs were another lesion, bladder, bowel, ureter, prostate, and liver. The majority of PSMA PET/CT-defined radiotherapy targets would be suitable for BgRT by using a 10-mm tracking zone in prostate cancer. A subset of lesions had adjacent non-tumour uptake, mainly due to the proximity of ureter or bladder, and may require exclusion from emission tracking during BgRT.
Publisher: IEEE
Date: 06-2009
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.CLON.2019.07.008
Abstract: Curative-intent (radical) radiotherapy aims to control local disease and cure non-small cell lung cancer (NSCLC). The predominant subtypes of NSCLC are adenocarcinoma and squamous cell carcinoma (SCC). The radiotherapy paradigm offered to patients does not differ according to these two subtypes. Relapse patterns and disease control rates for adenocarcinoma and SCC treated with radical radiotherapy were determined. A radical radiotherapy database covering the period from 2004 to June 2016 was examined to determine the first sites of relapse and the actuarial local and distant control rates. In total, 537 patients with known pathological subtype were treated over the period. In 39 (7%), the site of first relapse was uncertain. Of the remainder, 203 (41%) had adenocarcinoma and 295 (59%) had SCC. At a median follow-up of 16.4 months, 58% had relapsed. There was a difference in relapse patterns (chi-squared test P < 0.0005), with a higher rate of first relapse locally in SCC (42% of all patients versus 24%) and a higher rate of first relapse in the brain for adenocarcinoma (14% versus 3%). The actuarial local control rate was worse for SCC (hazard ratio 0.6, 95% confidence interval 0.5-0.9, P = 0.002). The brain metastasis-free survival was worse for adenocarcinoma (hazard ratio 4.1, 95% confidence interval 2.2-7.5, P < 0.0001). There is a difference in relapse patterns between NSCLC histological subtypes, indicating that these are distinct entities. This may have implications for follow-up policy and strategies to improve disease control.
Publisher: Wiley
Date: 29-03-2020
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.IJROBP.2009.04.045
Abstract: Positron emission tomography (PET), in addition to computed tomography (CT), has an effect in target volume definition for radical radiotherapy (RT) for non-small-cell lung cancer (NSCLC). In previously PET-CT staged patients with NSCLC, we assessed the effect of using an additional planning PET-CT scan for gross tumor volume (GTV) definition. A total of 28 patients with Stage IA-IIIB NSCLC were enrolled. All patients had undergone staging PET-CT to ensure suitability for radical RT. Of the 28 patients, 14 received induction chemotherapy. In place of a RT planning CT scan, patients underwent scanning on a PET-CT scanner. In a virtual planning study, four oncologists independently delineated the GTV on the CT scan alone and then on the PET-CT scan. Intraobserver and interobserver variability were assessed using the concordance index (CI), and the results were compared using the Wilcoxon signed ranks test. PET-CT improved the CI between observers when defining the GTV using the PET-CT images compared with using CT alone for matched cases (median CI, 0.57 for CT and 0.64 for PET-CT, p = .032). The median of the mean percentage of volume change from GTV(CT) to GTV(FUSED) was -5.21% for the induction chemotherapy group and 18.88% for the RT-alone group. Using the Mann-Whitney U test, this was significantly different (p = .001). PET-CT RT planning scan, in addition to a staging PET-CT scan, reduces interobserver variability in GTV definition for NSCLC. The GTV size with PET-CT compared with CT in the RT-alone group increased and was reduced in the induction chemotherapy group.
Publisher: Elsevier BV
Date: 09-2022
Publisher: Springer Science and Business Media LLC
Date: 09-11-2018
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.CLON.2019.04.006
Abstract: An 'abscopal' effect if often used to refer to distant tumour regression after localised irradiation. Since the first report of the abscopal effect in the 1950s, well-documented cases with radiotherapy alone are very rare. It is widely accepted that the immune response plays an important role in the abscopal effect, although the mechanism is still unclear. With the recent success of cancer immunotherapy, there is growing interest in combining immunotherapy with radiotherapy to boost abscopal response rates. Compared with conventional radiotherapy, stereotactic ablative radiotherapy (SABR) not only delivers ablative dose to the tumour, but may also induce robust immune responses. In this review we examine studies that combine SABR and immunotherapy. We review the preclinical rationale for SABR and immunotherapy combinations, the case for and against abscopal effects, and the current landscape of clinical trials.
Publisher: British Institute of Radiology
Date: 03-2019
DOI: 10.1259/BJR.20180473
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.CLON.2022.02.010
Abstract: The use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice.
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.IJROBP.2009.09.060
Abstract: (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has benefits in target volume (TV) definition in radiotherapy treatment planning (RTP) for non-small-cell lung cancer (NSCLC) however, an optimal protocol for TV delineation has not been determined. We investigate volumetric and positional variation in gross tumor volume (GTV) delineation using a planning PET/CT among three radiation oncologists and a PET radiologist. RTP PET/CT scans were performed on 28 NSCLC patients (Stage IA-IIIB) of which 14 patients received prior induction chemotherapy. Three radiation oncologists and one PET radiologist working with a fourth radiation oncologist independently delineated the GTV on CT alone (GTV(CT)) and on fused PET/CT images (GTV(PETCT)). The mean percentage volume change (PVC) between GTV(CT) and GTV(PETCT) for the radiation oncologists and the PVC between GTV(CT) and GTV(PETCT) for the PET radiologist were compared using the Wilcoxon signed-rank test. Concordance index (CI) was used to assess both positional and volume change between GTV(CT) and GTV(PETCT) in a single measurement. For all patients, a significant difference in PVC from GTV(CT) to GTV(PETCT) exists between the radiation oncologist (median, 5.9%), and the PET radiologist (median, -0.4%, p = 0.001). However, no significant difference in median concordance index (comparing GTV(CT) and GTV(FUSED) for in idual cases) was observed (PET radiologist = 0.73 radiation oncologists = 0.66 p = 0.088). Percentage volume changes from GTV(CT) to GTV(PETCT) were lower for the PET radiologist than for the radiation oncologists, suggesting a lower impact of PET/CT in TV delineation for the PET radiologist than for the oncologists. Guidelines are needed to standardize the use of PET/CT for TV delineation in RTP.
Publisher: Elsevier BV
Date: 11-2022
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.CLON.2010.05.006
Abstract: Radiotherapy target volume definition is a critical step in the radiotherapy treatment planning process for all tumour sites. New technology may improve the identification of tumour from normal tissue for the purposes of target volume definition. In assessing the proffered benefits of new technologies, rigorous methods of comparison are necessary. A review of published studies was conducted using PubMed (National Library of Medicine) between 1 January 1995 and 1 January 2009 using predefined search terms. The frequency of usage of the various methods of geometrical comparison (simple volume assessment, centre of mass analysis, concordance index and volume edge analysis) was recorded. Sixty-three studies were identified, across a range of primary tumour sites. The most common method of target volume analysis was simple volume measurement this was described in 84% of the papers analysed. The concordance index type analysis was described in 30%, the centre of mass analysis in 9.5% and the volume edge analysis in 4.8%. In reporting geometrical differences between target volumes no standard exists. However, to optimally describe geometrical changes in target volumes, simple volume change and a measure of positional change should be assessed.
Publisher: Elsevier BV
Date: 10-2019
Publisher: Elsevier BV
Date: 06-2018
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.RADONC.2010.05.003
Abstract: Correct target definition is crucial in stereotactic radiotherapy for lung tumors. We evaluated use of deformable registration (DR) for target contouring on 4-dimensional (4D) CT scans. Three clinicians contoured gross tumor volume (GTV) in an end-inspiration phase of 4DCT of 6 patients on two occasions. Two clinicians contoured GTVs in all phases of 4DCT and on maximum intensity projections (MIP). The initial GTV was auto-propagated to 9 other phases using a B-spline algorithm (VelocityAI). Internal target volumes (ITVs) generated were (i) ITV(10manual) encompassing all physician-contoured GTVs, (ii) ITV-MIP(optimized) from MIP after review of in idual 4DCT phases, (iii) ITV(10deformed) encompassing auto-propagated GTVs using DR, and (iv) ITV(10deformed-optimized), from an ITV(10deformed) target that was modified to form a 'clinically optimal' ITV. Volume-overlaps were scored using Dice's Similarity Coefficients (DSCs). Intra-clinician GTV reproducibility was greater than inter-clinician reproducibility (mean DSC 0.93 vs. 0.88, p<0.0004). In five of 6 patients, ITV-MIP(optimized) differed from the ITV(10deformed-optimized). In all patients, the DSC between ITV(10deformed-optimized) and ITV(10deformed) was higher than that between ITV(10deformed-optimized) and ITV-MIP(optimized) (p<0.02 T-test). ITVs created in stage I tumors using DR were closer to 'clinically optimal' ITVs than was the case with a MIP-modified approach.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Springer Science and Business Media LLC
Date: 12-2020
DOI: 10.1038/S41416-020-01072-4
Abstract: The type of patients with stage III non-small-cell lung cancer (NSCLC) selected for concurrent chemoradiotherapy (cCRT) varies between and within countries, with higher-volume centres treating patients with more co-morbidities and higher-stage disease. However, in spite of these disease characteristics, these patients have improved overall survival, suggesting that there are additional approaches that should be optimised and potentially standardised. This paper aims to review the current knowledge and best practices surrounding treatment for patients eligible for cCRT. Initially, this includes timely acquisition of the full diagnostic workup for the multidisciplinary team to comprehensively assess a patient for treatment, as well as imaging scans, patient history, lung function and genetic tests. Such information can provide prognostic information on how a patient will tolerate their cCRT regimen, and to perhaps limit the use of additional supportive care, such as steroids, which could impact on further treatments, such as immunotherapy. Furthermore, knowledge of the safety profile of in idual double-platinum chemotherapy regimens and the technological advances in radiotherapy could aid in optimising patients for cCRT treatment, improving its efficacy whilst minimising its toxicities. Finally, providing patients with preparatory and ongoing support with input from dieticians, palliative care professionals, respiratory and care-of-the-elderly physicians during treatment may also help in more effective treatment delivery, allowing patients to achieve the maximum potential from their treatments.
Publisher: Springer Science and Business Media LLC
Date: 29-05-2020
DOI: 10.1186/S13014-020-01583-7
Abstract: The evaluation of circulating tumour DNA (ctDNA) from clinical blood s les, liquid biopsy, offers several diagnostic advantages compared with traditional tissue biopsy, such as shorter processing time, reduced patient risk and the opportunity to assess tumour heterogeneity. The historically poor sensitivity of ctDNA testing, has restricted its integration into routine clinical practice for non-metastatic disease. The early kinetics of ctDNA during radical radiotherapy for localised NSCLC have not been described with ultra-deep next generation sequencing previously. Patients with CT/PET-staged locally advanced, NSCLC prospectively consented to undergo serial venepuncture during the first week of radical radiotherapy alone. All patients received 55Gy in 20 fractions. Plasma s les were processed using the commercially available Roche AVENIO Expanded kit (Roche Sequencing Solutions, Pleasanton, CA, US) which targets 77 genes. Tumour-specific mutations were found in all patients (1 in 3 patients 2 in 1 patient, and 3 in 1 patient). The variant allele frequency of these mutations ranged from 0.05–3.35%. In 2 patients there was a transient increase in ctDNA levels at the 72 h timepoint compared to baseline. In all patients there was a non-significant decrease in ctDNA levels at the 7-day timepoint in comparison to baseline ( p = 0.4627). This study demonstrates the feasibility of applying ctDNA-optimised NGS protocols through specified time-points in a small homogenous cohort of patients with localised lung cancer treated with radiotherapy. Studies are required to assess ctDNA kinetics as a predictive biomarker in radiotherapy. Priming tumours for liquid biopsy using radiation warrants further exploration.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2018
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.CLON.2016.08.004
Abstract: Lung cancer is the most common cancer diagnosed in the UK. Outcomes for patients with this disease remain poor and new strategies to treat this disease require investigation. One potential option is to combine novel agents with radiotherapy in clinical studies. Here we discuss some of the important issues to consider when combining novel agents with radiotherapy, together with potential solutions as discussed at a recent Clinical Translational Radiotherapy Group (CTRad) workshop.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.CLON.2015.02.003
Abstract: Stereotactic body radiotherapy (SBRT) is now an established therapy in stage I lung cancer with comparable local control rates to surgical resection. Owing to the conformity of treatment dose delivery and with appropriate fractionation considerations, minimal side-effects to surrounding normal tissues are observed in most patients. SBRT is now being used in the treatment of oligometastatic disease, alone or alongside systemic therapy. At present there is a paucity of evidence available showing a clinical benefit, but several international studies are being set-up or have started recruitment. This overview considers the clinical entity of an oligometastatic state, discusses the role of SBRT in the management of oligometastatic disease and discusses potential novel therapy combinations with SBRT.
Publisher: BMJ
Date: 05-2020
DOI: 10.1136/BMJOPEN-2020-037171
Abstract: Radiotherapy technology and postgraduate medical training have both evolved significantly over the last 20 years. Clinical Oncology is a recognised craft specialty where the apprenticeship model of clinical training is applicable. The challenges of learning radiotherapy in the modern radiotherapy department workplace have not been comprehensively described and no optimal method has been identified. Five Clinical Oncology trainers and five Clinical Oncology trainees at a regional cancer centre will be invited to undertake a semistructured interview regarding their personal accounts of learning radiotherapy. Both trainees and consultants will be treated as equal co-investors in the process of radiotherapy learning, with the common shared aim of passing radiotherapy skills from trainers to trainees. Interviews will last up to 40 min. After transcription, an interpretative phenomenological analysis will be performed. All trainees and trainers at the same centre (n=34) will then be invited to complete the same purpose-built questionnaire. Four trainers and three trainees have piloted the questionnaire, and input was sought from the national leads of the biennial UK Clinical Oncology training survey. Significance testing will be performed on predefined questions and thematic analysis on white space questions. Medical education research is evolving in Clinical Oncology and Radiation Oncology but there are few studies comprehensively assessing this from the viewpoint of trainees and trainers. Pending the success of the proposed study, the approach detailed represents a novel method that could be used to identify the strengths and weaknesses of radiotherapy training in other centres and settings. Ethical and governance approvals have been granted by the University Research Ethics Committee and the Integrated Research Application System, respectively. This study has been funded by Friends of the Cancer Centre.
Publisher: Springer Science and Business Media LLC
Date: 31-07-2019
Publisher: Elsevier BV
Date: 05-2020
Publisher: Springer Science and Business Media LLC
Date: 07-04-2022
DOI: 10.1038/S41698-022-00263-X
Abstract: Immune checkpoint inhibitors and related molecules can achieve tumour regression, and even prolonged survival, for a subset of cancer patients with an otherwise dire prognosis. However, it remains unclear why some patients respond to immunotherapy and others do not. PET imaging has the potential to characterise the spatial and temporal heterogeneity of both immunotherapy target molecules and the tumor immune microenvironment, suggesting a tantalising vision of personally-adapted immunomodulatory treatment regimens. Personalised combinations of immunotherapy with local therapies and other systemic therapies, would be informed by immune imaging and subsequently modified in accordance with therapeutically induced immune environmental changes. An ideal PET imaging biomarker would facilitate the choice of initial therapy and would permit sequential imaging in time-frames that could provide actionable information to guide subsequent therapy. Such imaging should provide either prognostic or predictive measures of responsiveness relevant to key immunotherapy types but, most importantly, guide key decisions on initiation, continuation, change or cessation of treatment to reduce the cost and morbidity of treatment while enhancing survival outcomes. We survey the current literature, focusing on clinically relevant immune checkpoint immunotherapies, for which novel PET tracers are being developed, and discuss what steps are needed to make this vision a reality.
Publisher: Wiley
Date: 08-04-2020
Publisher: Elsevier BV
Date: 03-2021
Publisher: BMJ
Date: 04-2018
Publisher: Wiley
Date: 13-09-2020
Publisher: Elsevier BV
Date: 07-2022
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.CANLET.2015.04.007
Abstract: By virtue of being a localized treatment modality, radiotherapy is unable to deliver a tumoricidal radiation dose to tissues outside of the irradiated field. Nevertheless, ionizing radiation may result in radiation damage mediated by a bystander like effect away from the irradiated field, but this response is likely to be modest when radiotherapy is the sole treatment modality. Over the last decade there has been a re-emergence of immune modulating therapies as anti-cancer treatment modalities. Clinical trials on vaccines have on the whole been largely disappointing, but greater response rates have been observed from the immune checkpoint modulators. A clinical benefit of using such agents has been shown in disease sites such as melanoma and non-small cell lung cancer. There is growing pre-clinical data and a number of case reports which suggest the presence of abscopal effects when radiotherapy is co-administered with immune checkpoint inhibitors, suggesting that this combination may lead to an enhanced tumour response outside of the primary treatment field. In this review, the mechanisms of such an enhanced out-of-field tumour response, the potential clinical utilities, the optimal radiotherapy delivery and considerations for clinical follow-up following treatment are discussed.
Publisher: Wiley
Date: 31-03-2022
Abstract: To evaluate the proportion of cancer patients who received radiation therapy (RT) within 12 months of cancer diagnosis (RTU12) and identify factors associated with RTU12. This is a population‐based cohort of in iduals with incident cancer, diagnosed between 2013 and 2017 in Victoria. Data linkages were performed between the Victorian Cancer Registry and Victorian Radiotherapy Minimum Dataset. The primary outcome was the proportion of patients who had RTU12. For the three most common cancers (i.e., prostate, breast and lung cancer), the time trend in RTU12 and factors associated with RTU12 were evaluated. The overall RTU12 in our study cohort was 26–20% radical RT and 6% palliative RT. Of the 21,735 men with prostate cancer, RTU12 was 17%, with no significant change over time ( P ‐trend = 0.53). In multivariate analyses, increasing age and lower socioeconomic status were independently associated with higher RTU12 for prostate cancer. Of the 20,883 women with breast cancer, RTU12 was 64%, which increased from 62% in 2013 to 65% in 2017 ( P ‐trend 0.05). In multivariate analyses, age, socioeconomic status and area of residency were independently associated with RTU12 for breast cancer. Of the 13,093 patients with lung cancer, RTU12 was 42%, with no significant change over time ( P ‐trend = 0.16). In multivariate analyses, younger age, male and lower socioeconomic status were independently associated with higher RTU12. In this large population‐based state‐wide cohort of cancer patients, only 1 in 4 had RT within 12 months of diagnosis. There were marked sociodemographic disparities in RTU12 for prostate, breast and lung cancer patients.
Publisher: BMJ
Date: 11-2022
DOI: 10.1136/BMJOPEN-2021-056708
Abstract: ImmunoPET is a multicentre, single arm, phase 0–1 study that aims to establish if 89 Zr-durvalumab PET/CT can be used to interrogate the expression of PD-L1 in larger, multicentre clinical trials. The phase 0 study recruited 5 PD-L1+ patients with metastatic non-small cell lung cancer (NSCLC). Patients received 60MBq/70 kg 89 Zr-durva up to a maximum of 74 MBq, with scan acquisition at days 0, 1, 3 or 5±1 day. Data on (1) Percentage of injected 89 Zr-durva dose found in organs of interest (2) Absorbed organ doses (µSv/MBq of administered 89 Zr-durva) and (3) whole-body dose expressed as mSv/100MBq of administered dose was collected to characterise biodistribution. The phase 1 study will recruit 20 patients undergoing concurrent chemoradiotherapy for stage III NSCLC. Patients will have 89 Zr-durva and FDG-PET/CT before, during and after chemoradiation. In order to establish the feasibility of 89 Zr-durva PET/CT for larger multicentre trials, we will collect both imaging and toxicity data. Feasibility will be deemed to have been met if more than 80% of patients are able complete all trial requirements with no significant toxicity. This phase 0 study has ethics approval (HREC/65450/PMCC 20/100) and is registered on the Australian Clinical Trials Network (ACTRN12621000171819). The protocol, technical and clinical data will be disseminated by conference presentations and publications. Any modifications to the protocol will be formally documented by administrative letters and must be submitted to the approving HREC for review and approval. Australian Clinical Trials Network ACTRN12621000171819.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.RADONC.2015.03.014
Abstract: This document describes best practice and evidence based recommendations for the use of FDG-PET/CT for the purposes of radiotherapy target volume delineation (TVD) for curative intent treatment of non-small cell lung cancer (NSCLC). These recommendations have been written by an expert advisory group, convened by the International Atomic Energy Agency (IAEA) to facilitate a Coordinated Research Project (CRP) aiming to improve the applications of PET based radiation treatment planning (RTP) in low and middle income countries. These guidelines can be applied in routine clinical practice of radiotherapy TVD, for NSCLC patients treated with concurrent chemoradiation or radiotherapy alone, where FDG is used, and where a calibrated PET camera system equipped for RTP patient positioning is available. Recommendations are provided for PET and CT image visualization and interpretation, and for tumor delineation using planning CT with and without breathing motion compensation.
Publisher: Elsevier BV
Date: 07-2018
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.RADONC.2018.05.029
Abstract: Standard of care radiotherapy in LA-NSCLC is 60-66 Gy in 30-33 fractions. However outcomes for these patients are poor with 5-year survival in the range of 10-20%. Randomised controlled trials have shown that dose escalation in a linear fashion does not improve outcomes for all patients, thus there is a need to tailor the prescription to the in idual patient. This review assesses the strategies published to personalise the radiation therapy dose prescription in LA-NSCLC. A systematic and scoping search of the literature was performed to identify studies that met the inclusion criteria. 19 relevant studies were identified ranging from prospective clinical trials to mathematically modelled concept studies. Heterogeneity existed between all clinical studies. Nine heterogeneous publications proposed methodology to adapt the dose prescription to the in idual patient. A number of encouraging strategies have been identified but fall short of the evidence level required to influence clinical practice.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.CLON.2015.05.010
Abstract: Modern radiotherapy uses techniques to reliably identify tumour and reduce target volume margins. However, this can potentially lead to an increased risk of geographic miss. One source of error is the accuracy of target volume delineation (TVD). Colleague peer review (CPR) of all curative-intent lung cancer plans has been mandatory in our institution since May 2013. At least two clinical oncologists review plans, checking treatment paradigm, TVD, prescription dose tumour and critical organ tolerances. We report the impact of CPR in our institution. Radiotherapy treatment plans of all patients receiving radical radiotherapy were presented at weekly CPR meetings after their target volumes were reviewed and signed off by the treating consultant. All cases and any resultant change to TVD (including organs at risk) or treatment intent were recorded in our prospective CPR database. The impact of CPR over a 13 month period from May 2013 to June 2014 is reported. One hundred and twenty-two patients (63% non-small cell lung carcinoma, 17% small cell lung carcinoma and 20% 'clinical diagnosis') were analysed. On average, 3.2 cases were discussed per meeting (range 1-8). CPR resulted in a change in treatment paradigm in 3% (one patient proceeded to induction chemotherapy, two patients had high-dose palliative radiotherapy). Twenty-one (17%) had a change in TVD and one (1%) patient had a change in dose prescription. In total, 6% of patients had plan adjustment after review of dose volume histogram. The introduction of CPR in our centre has resulted in a change in a component of the treatment plan for 27% of patients receiving curative-intent lung radiotherapy. We recommend CPR as a mandatory quality assurance step in the planning process of all radical lung plans.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.CLON.2017.11.003
Abstract: In spite of recent improvements in both the technical delivery of radiotherapy and systemic therapy in the treatment of non-small cell lung cancer, local recurrence rates after radiotherapy remain a significant challenge. In the setting of local relapse after radiotherapy, treatments such as surgical resection or radiofrequency ablation are often not appropriate owing to disease and patient factors. Re-irradiation may be a potential treatment option. This overview considers the published evidence and potential treatment strategies.
Publisher: Elsevier BV
Date: 08-2017
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.IJROBP.2021.11.027
Abstract: Posttreatment surveillance for local recurrence (LR) after stereotactic ablative body radiotherapy (SABR) can include both fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT). Radiation-induced lung injury shares a similar appearance to LR after treatment, making the detection of LR on imaging difficult for clinicians. We aimed to summarize radiologic features of CT and FDG-PET predicting LR and to evaluate radiomics as another tool for detecting LR. We searched MEDLINE, EMBASE, and PubMed databases for published studies and Web of Science, Wiley Online, and Science Direct databases for conference abstracts that had patient populations with non-small cell lung cancer and reported post-SABR radiologic features of FDG-PET or CT and radiomics from either FDG-PET or CT. Studies for inclusion were independently reviewed by 2 authors. Across 32 relevant studies, the incidence of LR was 13% (222/1726). On CT, certain gross radiologic appearances and kinetic features of changes in size, diameter, volume, or 3 consecutive rises in volume of masslike consolidation are suggestive of LR. **Particular regard should be made for the presence of any ≥3 high-risk features on CT or the in idual high-risk features of enlarging opacity at ≥12 month's post-SABR as being highly suspicious of LR. On FDG-PET a relative reduction of <5% of maximum standardised uptake value (SUV This research has identified common features of LR compared with radiation-induced lung injury, which may aid in early and accurate detection of LR post-SABR further research is required to validate these findings.
Publisher: Wiley
Date: 25-10-2021
Abstract: Stereotactic ablative radiotherapy offers a radical treatment approach for early stage lung cancers and an aggressive local therapy for pulmonary oligometastases from other tumour sites. Chest wall toxicity is one of the key dose-limiting toxicities for intrathoracic stereotactic treatments. The description of stereotactic radiotherapy chest wall toxicity using functional imaging has not been reported previously. A 56-year-old male received 60 Gy in 8 fractions delivered by volumetric modulated arc therapy for a T1bN0M0 clinical left upper lobe lung cancer. The past medical history included poorly controlled type 1 diabetes mellitus, severe peripheral vascular disease and obesity. The patient attended 9 months later with left-sided, slowly progressive chest pain. An
Publisher: Elsevier BV
Date: 05-2020
Publisher: Springer Science and Business Media LLC
Date: 27-07-2022
DOI: 10.1038/S41598-022-16520-9
Abstract: Artificial intelligence and radiomics have the potential to revolutionise cancer prognostication and personalised treatment. Manual outlining of the tumour volume for extraction of radiomics features (RF) is a subjective process. This study investigates robustness of RF to inter-observer variation (IOV) in contouring in lung cancer. We utilised two public imaging datasets: ‘NSCLC-Radiomics’ and ‘NSCLC-Radiomics-Interobserver1’ (‘Interobserver’). For ‘NSCLC-Radiomics’, we created an additional set of manual contours for 92 patients, and for ‘Interobserver’, there were five manual and five semi-automated contours available for 20 patients. Dice coefficients (DC) were calculated for contours. 1113 RF were extracted including shape, first order and texture features. Intraclass correlation coefficient (ICC) was computed to assess robustness of RF to IOV. Cox regression analysis for overall survival (OS) was performed with a previously published radiomics signature. The median DC ranged from 0.81 (‘NSCLC-Radiomics’) to 0.85 (‘Interobserver’—semi-automated). The median ICC for the ‘NSCLC-Radiomics’, ‘Interobserver’ (manual) and ‘Interobserver’ (semi-automated) were 0.90, 0.88 and 0.93 respectively. The ICC varied by feature type and was lower for first order and gray level co-occurrence matrix (GLCM) features. Shape features had a lower median ICC in the ‘NSCLC-Radiomics’ dataset compared to the ‘Interobserver’ dataset. Survival analysis showed similar separation of curves for three of four RF apart from ‘original_shape_Compactness2’, a feature with low ICC (0.61). The majority of RF are robust to IOV, with first order, GLCM and shape features being the least robust. Semi-automated contouring improves feature stability. Decreased robustness of a feature is significant as it may impact upon the features’ prognostic capability.
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.CLON.2013.11.001
Abstract: Intrafraction tumour motion is an issue that is of increased interest in the era of image-guided radiotherapy. It is particularly relevant for non-small cell lung cancer, for which a number of recent developments are in use to aid with motion management in the delivery of radical radiotherapy. The ability to deliver hypofractionated ablative doses, such as in stereotactic radiotherapy, has been aided by improvements in the ability to analyse tumour motion and amend treatment delivery. In addition, accounting for tumour motion can enable dose escalation to occur by reducing the normal tissue being irradiated by virtue of a reduction in target volumes. Motion management for lung tumours incorporates five key components: imaging, breath-hold techniques, abdominal compression, respiratory tracking and respiratory gating. These will be described, together with the relevant benefits and associated complexities. Many studies have described improved dosimetric coverage and reduced normal tissue complication probability rates when using motion management techniques. Despite the widespread uptake of many of these techniques, there is a paucity of literature reporting improved outcome in overall survival and local control for patients whenever motion management techniques are used. This overview will review the extent of lung tumour motion, ways in which motion is detected and summarise the key methods used in motion management.
Publisher: Elsevier BV
Date: 10-2021
Publisher: American Association for Cancer Research (AACR)
Date: 10-2016
DOI: 10.1158/1535-7163.MCT-16-0211
Abstract: Resistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non–small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor FLIP is a critical regulator of cell death that is frequently overexpressed in NSCLC and is an established inhibitor of apoptotic cell death induced via the extrinsic death receptor pathway. Apoptosis induced by ionizing radiation (IR) has been considered to be mediated predominantly via the intrinsic apoptotic pathway however, we found that IR-induced apoptosis was significantly attenuated in NSCLC cells when caspase-8 was depleted using RNA interference (RNAi), suggesting involvement of the extrinsic apoptosis pathway. Moreover, overexpression of wild-type FLIP, but not a mutant form that cannot bind the critical death receptor adaptor protein FADD, also attenuated IR-induced apoptosis, confirming the importance of the extrinsic apoptotic pathway as a determinant of response to IR in NSCLC. Importantly, when FLIP protein levels were downregulated by RNAi, IR-induced cell death was significantly enhanced. The clinically relevant histone deacetylase (HDAC) inhibitors vorinostat and entinostat were subsequently found to sensitize a subset of NSCLC cell lines to IR in a manner that was dependent on their ability to suppress FLIP expression and promote activation of caspase-8. Entinostat also enhanced the antitumor activity of IR in vivo. Therefore, FLIP downregulation induced by HDAC inhibitors is a potential clinical strategy to radiosensitize NSCLC and thereby improve response to radiotherapy. Overall, this study provides the first evidence that pharmacological inhibition of FLIP may improve response of NCSLC to IR. Mol Cancer Ther 15(10) 2432–41. ©2016 AACR.
Publisher: Cambridge University Press (CUP)
Date: 10-11-2018
DOI: 10.1017/S1460396917000577
Abstract: Accurate and reproducible patient positioning is a critical step in radiotherapy for breast cancer. This has seen the use of permanent skin markings becoming standard practice in many centres. Permanent skin markings may have a negative impact on long-term cosmetic outcome, which may in turn, have psychological implications in terms of body image. The aim of this study was to investigate the feasibility of using a semi-permanent tattooing device for the administration of skin marks for breast radiotherapy set-up. This was designed as a phase II double-blinded randomised-controlled study comparing our standard permanent tattoos with the Precision Plus Micropigmentation (PPMS) device method. Patients referred for radical breast radiotherapy were eligible for the study. Each study participant had three marks applied using a randomised combination of the standard permanent and PPMS methods and was blinded to the type of each mark. Follow up was at routine appointments until 24 months post radiotherapy. Participants and a blind assessor were invited to score the visibility of each tattoo at each follow-up using a Visual Analogue Scale. Tattoo scores at each time point and change in tattoo scores at 24 months were analysed by a general linear model using the patient as a fixed effect and the type of tattoo (standard or research) as covariate. A simple questionnaire was used to assess radiographer feedback on using the PPMS. In total, 60 patients were recruited to the study, of which 55 were available for follow-up at 24 months. Semi-permanent tattoos were more visible at 24 months than the permanent tattoos. Semi-permanent tattoos demonstrated a greater degree of fade than the permanent tattoos at 24 months (final time point) post completion of radiotherapy. This was not statistically significant, although it was more apparent for the patient scores ( p =0·071) than the blind assessor scores ( p =0·27). No semi-permanent tattoos required re-marking before the end of radiotherapy and no adverse skin reactions were observed. The PPMS presents a safe and feasible alternative to our permanent tattooing method. An extended period of follow-up is required to fully assess the extent of semi-permanent tattoo fade.
Publisher: Elsevier BV
Date: 11-2020
Publisher: British Institute of Radiology
Date: 02-2015
DOI: 10.1259/BJR.20140624
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.CLON.2012.03.002
Abstract: High local control rates are achieved in stage I lung cancer using stereotactic ablative radiotherapy. Target delineation is commonly based on four-dimensional computed tomography (CT) scans. Target volumes defined by positron emission tomography/computed tomography (PET/CT) are compared with those defined by four-dimensional CT and conventional ('three-dimensional') (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT. For 16 stage I non-small cell lung cancer tumours, six approaches for deriving PET target volumes were evaluated: manual contouring, standardised uptake value (SUV) absolute threshold of 2.5, 35% of maximum SUV (35%SUV(MAX)), 41% of SUV(MAX) (41%SUV(MAX)) and two different source to background ratio techniques (SBR-1 and SBR-2). PET-derived target volumes were compared with the internal target volume (ITV) from the modified maximum intensity projection (MIP(MOD) ITV). Volumetric and positional correlation was assessed using the Dice similarity coefficient (DSC). PET-based target volumes did not correspond to four-dimensional CT-based target volumes. The mean DSC relative to MIP(MOD) ITV were: PET manual = 0.64, SUV2.5 = 0.64, 35%SUV(MAX) = 0.63, 41%SUV(MAX) = 0.57. SBR-1 = 0.52, SBR-2 = 0.49. PET-based target volumes were smaller than corresponding MIP ITVs. Conventional three-dimensional (18)F-FDG PET-derived target volumes for lung stereotactic ablative radiotherapy did not correspond well with those derived from four-dimensional CT, including those in routine clinical use (MIP(MOD) ITV). Caution is required in using three-dimensional PET for motion encompassing target volume delineation.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 08-2015
Publisher: AME Publishing Company
Date: 06-2021
Publisher: Wiley
Date: 25-09-2020
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.CLON.2021.10.006
Abstract: Lung cancer's radiomic phenotype may potentially inform clinical decision-making with respect to radical radiotherapy. At present there are no validated biomarkers available for the in idualisation of radical radiotherapy in lung cancer and the mortality rate of this disease remains the highest of all other solid tumours. MEDLINE was searched using the terms 'radiomics' and 'lung cancer' according to the Preferred Reporting Items for Systematic Reviews and Met-Analyses (PRISMA) guidance. Radiomics studies were defined as those manuscripts describing the extraction and analysis of at least 10 quantifiable imaging features. Only those studies assessing disease control, survival or toxicity outcomes for patients with lung cancer following radical radiotherapy ± chemotherapy were included. Study titles and abstracts were reviewed by two independent reviewers. The Radiomics Quality Score was applied to the full text of included papers. Of 244 returned results, 44 studies met the eligibility criteria for inclusion. End points frequently reported were local (17%), regional (17%) and distant control (31%), overall survival (79%) and pulmonary toxicity (4%). Imaging features strongly associated with clinical outcomes include texture features belonging to the subclasses Gray level run length matrix, Gray level co-occurrence matrix and kurtosis. The median cohort size for model development was 100 (15-645) in the 11 studies with external validation in a separate independent population, the median cohort size was 84 (21-295). The median number of imaging features extracted was 184 (10-6538). The median Radiomics Quality Score was 11% (0-47). Patient-reported outcomes were not incorporated within any studies identified. No studies externally validated a radiomics signature in a registered prospective study. Imaging-derived indices attained through radiomic analyses could equip thoracic oncologists with biomarkers for treatment response, patterns of failure, normal tissue toxicity and survival in lung cancer. Based on routine scans, their non-invasive nature and cost-effectiveness are major advantages over conventional pathological assessment. Improved tools are required for the appraisal of radiomics studies, as significant barriers to clinical implementation remain, such as standardisation of input scan data, quality of reporting and external validation of signatures in randomised, interventional clinical trials.
Publisher: Elsevier BV
Date: 2021
Publisher: Editorial Office of Chinese Journal of Cancer
Date: 05-10-2013
Publisher: Elsevier BV
Date: 10-2023
Publisher: Elsevier BV
Date: 06-2022
Publisher: Elsevier BV
Date: 05-2008
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.CLON.2016.07.014
Abstract: The goal of re-programming the host immune system to target malignancy with durable anti-tumour clinical responses has been speculated for decades. In the last decade such speculation has been transformed into reality with unprecedented and durable responses to immune checkpoint inhibitors seen in solid tumours. This mini-review considers the mechanism of action of immune modulating agents and the potential for combination with radiotherapy in the treatment of non-small cell lung cancer.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 11-2021
Publisher: AME Publishing Company
Date: 04-2021
DOI: 10.21037/TLCR-20-583
Publisher: Elsevier BV
Date: 12-2018
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.CLON.2013.11.024
Abstract: To investigate the potential dosimetric and clinical benefits predicted by using four-dimensional computed tomography (4DCT) compared with 3DCT in the planning of radical radiotherapy for non-small cell lung cancer. Twenty patients were planned using free breathing 4DCT then retrospectively delineated on three-dimensional helical scan sets (3DCT). Beam arrangement and total dose (55 Gy in 20 fractions) were matched for 3D and 4D plans. Plans were compared for differences in planning target volume (PTV) geometrics and normal tissue complication probability (NTCP) for organs at risk using dose volume histograms. Tumour control probability and NTCP were modelled using the Lyman-Kutcher-Burman (LKB) model. This was compared with a predictive clinical algorithm (Maastro), which is based on patient characteristics, including: age, performance status, smoking history, lung function, tumour staging and concomitant chemotherapy, to predict survival and toxicity outcomes. Potential therapeutic gains were investigated by applying isotoxic dose escalation to both plans using constraints for mean lung dose (18 Gy), oesophageal maximum (70 Gy) and spinal cord maximum (48 Gy). 4DCT based plans had lower PTV volumes, a lower dose to organs at risk and lower predicted NTCP rates on LKB modelling (P < 0.006). The clinical algorithm showed no difference for predicted 2-year survival and dyspnoea rates between the groups, but did predict for lower oesophageal toxicity with 4DCT plans (P = 0.001). There was no correlation between LKB modelling and the clinical algorithm for lung toxicity or survival. Dose escalation was possible in 15/20 cases, with a mean increase in dose by a factor of 1.19 (10.45 Gy) using 4DCT compared with 3DCT plans. 4DCT can theoretically improve therapeutic ratio and dose escalation based on dosimetric parameters and mathematical modelling. However, when in idual characteristics are incorporated, this gain may be less evident in terms of survival and dyspnoea rates. 4DCT allows potential for isotoxic dose escalation, which may lead to improved local control and better overall survival.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Estonian Literary Museum Scholarly Press
Date: 30-12-2021
Abstract: ‘Dame Edna Everage’, a persona originally created by the Australian comedian Barry Humphries in 1955, is a character designed to simultaneously shock and amuse. Dame Edna voices (and satirizes) the discourse of ‘average’, older, politically conservative Anglo-Australians who feel compelled to ‘tell it like it is’ – no matter how offensive their opinions might be. In the Anglosphere, Edna’s humour is well understood and sustained international success has followed Edna for more than 60 years in Britain, Canada, the US and Australia. However, Edna occasionally misfires. In 2003, for instance, Edna’s satire outraged Latinos across the USA, in fulfillment of Poe’s Law (Aikin, 2009). Simply put, Latinos assumed that Edna’s comments satirising negative mainstream attitudes towards them were expressive of Edna’s authentic racism. This paper investigates the Edna joke in the overall context of failed humour and then specifically for the offensiveness it generated amongst the Latino minority in the United States. It then tests whether this reaction was the result of a discursive frame specific to the US context, by conducting an exploratory study amongst a small s le of highly educated Australian bilingual Latin American immigrants and their adult children, to see whether they thought Edna’s joke was funny. These Australian in iduals of Latin American heritage responded via an online questionnaire, and an analysis of their responses is presented here. The study’s main finding is that while these in iduals generally demonstrated a high comedic literacy across both English and Spanish, including a prior awareness of Edna’s and Australian humour, they overall rejected the intention and humour of Edna’s joke. This paper asserts that, when it comes to humour, some transnational migrant speech community loyalties transcend other notions of identity and language competence.
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.IJROBP.2022.05.034
Abstract: Medical operability is prognostic for survival after SABR in primary malignancies. This study investigated the prognostic significance of medical operability and total versus subtotal ablation of all oligometastatic disease sites. Consecutive patients with 1 to 5 sites of active extracranial oligometastases had medical operability status and presence of subtotal versus total metastatic ablation recorded prospectively in an institutional database. We retrospectively compared overall survival (OS) and progression-free survival (PFS) for medically operable or inoperable patients and patients undergoing total or subtotal metastatic ablation. Secondary endpoints were patterns of failure, high-grade treatment toxic effects (Common Terminology Criteria for Adverse Events version 4.0), and freedom from systemic therapy. The threshold dose per fraction considered ablative was 8 Gy. A total of 401 patients with 530 treated oligometastases were included, with a median follow-up of 3 years. Three hundred and two and 99 patients had metachronous and synchronous presentations of oligometastatic disease, respectively. Common histologies included prostate (24%), lung (18%), gastrointestinal (19%), and breast (11%). More than 90% of doses delivered were Biologically Effective Dose [BED Medical operability was not prognostic in patients with oligometastatic disease treated with SABR. Total metastatic ablation was associated with superior OS and PFS compared with subtotal metastatic ablation. Our data support ablation of all sites of oligometastases wherever feasible.
Publisher: British Institute of Radiology
Date: 05-2015
DOI: 10.1259/BJR.20140686
Publisher: Springer Science and Business Media LLC
Date: 23-03-2021
DOI: 10.1186/S12885-021-08042-W
Abstract: The enhanced knowledge of cancer biology has led to considerable advancement in systemic therapy for advanced breast cancer. Recently, studies showed that cyclin-dependent kinase (CDK) 4/6 inhibitor, when added to endocrine therapy, had improved the outcomes of patients with advanced ER-positive HER2-negative breast cancer. However, the disease often progresses following a period of treatment response. In a subset of patients, disease progression may occur at limited sites, i.e., oligoprogressive disease (OPD). In the past few years, stereotactic radiotherapy (SRT) has emerged as a safe and effective treatment for advanced cancer when delivered to limited metastatic sites. Hence, it is worth investigating the role of SRT in the setting of oligoprogressive breast cancer. AVATAR is a multicentre phase II registry trial of SRT with endocrine therapy and CDK 4/6 inhibitor for the management of advanced ER-positive HER2-negative breast cancer. The study aims to enrol 32 patients with OPD limited to 5 lesions. The primary endpoint of the study is time to change systemic therapy measured from the commencement of SRT to change in systemic therapy. Secondary objectives include overall survival, progression free survival and treatment related toxicity. The exploratory objective is to describe the time to change in systemic therapy by the site (bone only vs. non-bone lesions) and number (1 vs. 1) of OPD. This study aims to explore the effect of SRT in maximising the benefit of systemic therapy in patients with oligoprogressive ER-positive HER2-negative breast cancer. This approach might help reduce the burden of disease and improve the life quality in these patients. ACTRN, ACTRN12620001212943 . Date of registration 16 November 2020- Retrospectively registered.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-02-2009
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Gerard Hanna.