Defining target volumes for stereotactic ablative radiotherapy of early-stage lung tumours: a comparison of three-dimensional 18F-fluorodeoxyglucose positron emission tomography and four-dimensional computed tomography.:PETCT versus 4DCT for SABR in Early Stage NSCLC

AIMS: 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.

MATERIALS AND METHODS: 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).

RESULTS: 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.

CONCLUSIONS: 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.

Motion Management for Radical Radiotherapy in Non-small Cell Lung Cancer

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.

The Challenges Faced in Developing Novel Drug Radiation Combinations in Non-small Cell Lung Cancer

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.

Radiotherapy and Immunotherapy Combinations in Non-small Cell Lung Cancer: A Promising Future?

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.

'A terrible danger to the morals of the country': The Irish hospitals' sweepstake in Great Britain, 1930-87

This paper examines the importance of British contributions to the success of the Irish hospitals sweepstake. In its early years, up to three-quarters of these tickets were sold in Britain, bringing millions of pounds into Ireland annually to improve and expand the state's hospitals. The vast amount of money leaving Britain in this way angered the British government and forced it to introduce new legislation to curtail the activities of the Irish sweep. The paper will highlight the extent to which the success of the sweepstake depended on the market for tickets in Britain; the threat to the sweep's survival posed by the restriction of its activities in Britain after 1935; the role of the sweepstake controversy in exacerbating further already strained relations between Britain and the Irish Free State in the 1930s; how the success of the sweep raised the issue of legalising a British lottery; and the eventual decline of the sweepstake as a force in British gambling in the post-war years.

Cartographic veracity in medieval mapping: analyzing geographical variation in the Gough Map of Great Britain

This article explores statistical approaches for assessing the relative accuracy of medieval mapping. It focuses on one particular map, the Gough Map of Great Britain. This is an early and remarkable example of a medieval “national” map covering Plantagenet Britain. Conventionally dated to c. 1360, the map shows the position of places in and coastal outline of Great Britain to a considerable degree of spatial accuracy. In this article, aspects of the map's content are subjected to a systematic analysis to identify geographical variations in the map's veracity, or truthfulness. It thus contributes to debates among historical geographers and cartographic historians on the nature of medieval maps and mapping and, in particular, questions of their distortion of geographic space. Based on a newly developed digital version of the Gough Map, several regression-based approaches are used here to explore the degree and nature of spatial distortion in the Gough Map. This demonstrates that not only are there marked variations in the positional accuracy of places shown on the map between regions (i.e., England, Scotland, and Wales), but there are also fine-scale geographical variations in the spatial accuracy of the map within these regions. The article concludes by suggesting that the map was constructed using a range of sources, and that the Gough Map is a composite of multiscale representations of places in Great Britain. The article details a set of approaches that could be transferred to other contexts and add value to historic maps by enhancing understanding of their contents.