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Understanding how natural populations respond to climatic shifts is a fundamental goal of biological research in a fast-changing world. The Southern Ocean represents a fascinating system for assessing large-scale climate-driven biological change, as it contains extremely isolated island groups within a predominantly westerly, circumpolar wind and current system. Blue-eyed shags represent a paradoxical seabird radiation—a circumpolar distribution implies strong dispersal capacity yet their species-rich nature suggests local adaptation and isolation. Here we attempt to resolve this paradox in light of the history of repeated cycles of climate change in the Southern Ocean.

Hoplodactylus tohu n. sp. Figures 2A, 3A–D, 4A–C; Supplementary Figures 5A–C. ZooBank registration of Hoplodactylus tohu n. sp.: urn:lsid:zoobank.org:pub: BC2A430C-D97C-4F45-9AFB-228379864926. Naultinus pacificus.– Gray 1843: 203 (in part, not Gray, 1842). Hoplodactylus duvaucelii [sic] McCann 1955: 39, fig. 3, pl. 4; McCann 1956a: 46; McCann 1956b: 15; Bustard 1963: 218; Sharell 1966: 49, pls. 28–31; Thoresen 1967: 197; Whitaker 1973: 122; Domrow et al. 1980: 295; Barwick 1982: 377; Bauer 1985: 90; Halliday & Verrell 1988: 260; Wilson & Freeman 1993: 1 – all in part (not Duméril & Bibron, 1836). Hoplodactylus duvaucelii.– Holder 1960: 302; Kluge 1967a: 25; Kluge 1967b: 1013; Werner et al. 1978: 378;7 Kennedy 1979: 1; Bauer 1986: 9; Worthy 1987b: 416; Bauer 1990: 108; Thompson et al. 1992: 123; Daugherty et al. 1993: 439; Bauer & Henle 1994: 139; Cree 1994: 352 Daugherty et al. 1994: 318; Towns & Daugherty 1994: 327; Worthy & Holdaway 1994: 326; East et al. 1995: 256; Worthy & Holdaway 1995: 350; Worthy & Holdaway 1996: 314; Hitchmough 1997: 1; Worthy 1997: 93; Bauer 1998: 43; Girling et al. 1998: 139, fig. 4; Worthy 1998: 448; Bannock et al. 1999: 102; Lukis 1999: 12; Flannagan 2000: 4; Jones 2000: 1, fig. 2.9; Towns & Ferreira 2001: 219; Towns et al. 2001: 4; Seligmann 2002: 277; Whitaker et al. 2002: 1; Hay et al. 2003: 16; Todd 2003: 17; Seligmann et al. 2003: 130; Holmes 2004: 4; Naish 2004: 18; Hare & Cree 2005: 137; Armstrong & Davidson 2006: 74; Hare et al. 2007: 89; Nielsen 2008: 5; Kelly & Sullivan 2010: 208; Miskelly 2010: 3; Wilson 2010: 6; Frank & Wilson 2011: 16; Nielsen et al. 2011: 17; Bell & Herbert 2012: 8; Str̂ckens et al. 2012: 542; Garcia-Porta & Ord 2013: 2667; Hitchmough et al. 2013: 10; Bell 2014: 8; Romijn et al. 2014: 111; Heath & Whitaker 2015: 751; Mockett 2015: 73; Chapple 2016b: 4; Chapple & Hitchmough 2016: 116; Cree & Hare 2016: 174; Hare et al. 2016: 140; Hare & Cree 2016: 246; Hitchmough et al. 2016a: 9; Hitchmough et al. 2016b: 89; Morgan-Richards et al. 2016: 77, fig. 2; Romijn and Hartley 2016: 196; Towns et al. 2016b: 308; Worthy 2016: 71; Bell and Herbert 2017: 38; Bowers 2017: 64; Knox et al. 2017: 490; Lozito & Tuan 2017: 148, fig. 2 Sion 2017: 131; Stancher et al. 2018: 36; van Winkel et al. 2018: 114, pls. 31, 40, 46, 128; Skipwith et al. 2019: 10; Florence-Bennett 2020: 13; Glynne et al. 2020: 804; Herbert 2020: 12; Price et al. 2020: 231; Scarsbrook 2021: 19, figs. 1.5, 2.1, 3.1, 3.3, 4.1; Scarsbrook et al. 2021: 2; Scarsbrook et al. 2022: 3, fig. 1 – all in part (not Duméril & Bibron, 1836). Naultinus duvaucelii.– Chrapliwy et al. 1961: 6 (in part, not Duméril & Bibron, 1836). Woodworthia duvaucelii.– Jewell 2008: 50 (in part, not Duméril & Bibron, 1836). Type material.— Holotype: New Zealand, Marlborough Sounds, Middle Trios Island, male, Y. M. McCann, February 1950, RE.000503. Paratypes: New Zealand, Marlborough Sounds, Middle Trios Island, 40°50.53′ S, 174°0.00′ E, both male, C. H. Daugherty, 22 November 1988, RE.006685, RE.006686 (tissue clips: FT2047, FT2048 respectively). Material examined.— The type material. Stephens Island (OMVT949). Trios Islands: Middle Trios Island (RE.000505,FT2046); South Trios Island (RE.006687). Sentinel Rock (RE.000948). Chetwode Island (RE.000949). Brothers Islands: North Brother Island (RE.002561, RE.005496, RE.006509, RE.006510, RE.007265, FT277, FT278). Northwest South Island (mainland): Gouland Downs, Holocene fossil (S.38813.2). Canterbury (mainland): Waikari, Holocene fossil (S.33501, S.33703.1, S.33703.7, S.33703.10, S.33703.11); Waitaki, Holocene fossil (OMVT719 a, OMVT807 a, OMVT807 b, OMVT3331, OMVT3332, OMVT3333). Diagnosis.— Hoplodactylus tohu may be distinguished from its only congener, H. duvaucelii, by several characters: H. tohu (generally) does not attain as great a size at maturity (Supp. Fig. 1), has a more pronounced brillar fold (Fig. 3A–B, E–F, 4C, F), and less often bears a median cleft in the mental scale (Supp. Table 3). An abrupt size decrease at the 5 th infralabial scale characterizing H. tohu is far less common in H. duvaucelii, with most individuals of the latter examined exhibiting a gradual size decrease in infralabial scales (Fig. 3B, F). H. tohu further differs from H. duvaucelii in generally having fewer subdigital lamellae on all digits of both the right manus and pes (Fig. 3C–D, G–H, Supp. Fig. 3). The first digit of the right manus in H. duvaucelii differs in having a consistently less emergent claw and, usually, a comparatively bulbous distal end (Fig. 3C, G). Previously reported differences (Morgan-Richards et al. 2016) in the coloration and extent of patterning between these taxa (Fig. 4) are generalizations and can be misleading given fluid overlap between the two species. Dorsal body coloration and patterning in H. tohu often resembles those of young H. duvaucelii in being relatively more strongly contrasting (Fig. 4A–B, D–E), with patterning generally becoming weaker at maturity. However, considerable variation in coloration and pattern (see Supp. Fig. 5) was observed throughout ontogeny in both species. Description.— Coloration on dorsal surface grey to grey-brown, sometimes with olive and dark brown blotches; patterning of well-developed, roughly symmetrical transverse bands from nape to tail base centered along spine, resembling chevrons or paired diamonds, less defined on tail and generally less defined on older individuals; often bearing irregular series of longitudinal rows of pale grey or white spots dorsolaterally, extending onto limbs; ventral surface buff, with occasional light brown speckling, speckles less frequent on head. Mouth lining and tongue pink. Body moderately large (SVL: 81.2–115.7 mm), robust, stout (TrK: 25.4–50.3 mm). Head large (HL: 26.1–33.8 mm; HW: 18.3–27 mm; HH: 12.2–16 mm), robust, subtriangular; inflated laterally between posterior edge of orbit and ear opening (EE: 7.7–11.8 mm), narrowing towards craniovertebral junction; neck clearly demarcated. Snout oviform (EN: 7.4–11.1 mm); slight indentation in medial nasal region, often blunt along anteriormost margin between nares (IN: 4–5.8 mm). Dorsum of occiput/nape covered in small granular scales that abruptly increase in size at level of anterior edge of orbit towards anterior margin of snout (2–3 times diameter of occipital granules); one row of enlarged, oval scales posterior to internasal(s) and dorsal to supralabials, broader than high; twice the diameter of adjacent loreal scales. Eyes approximately one fifth head length; varying in shade from pale olive-buff to dark greens or browns; pupils lenticular with weakly crenulated margin. Supraciliary scales elongate, conical, directed increasingly posterior posteriorly; brillar fold very pronounced; frontal narrowing anteriorly (IO: 7.8–11.8 mm), supraocular portion deeply furrowed. Ear opening moderate (EL: 2–4.1 mm), ovoid, twice as high as wide; oriented obliquely (widest posterodorsally to anteroventrally), skin fold covering dorsal limit. Rostral subpentagonal, much broader than high; contacted dorsally by 2 enlarged, oval supranasals and 1–3 smaller (homogenous), round internasals; medial rostral crease extending ventrally from upper margin ½ to ¾ length of rostral; usually terminating diffusely, but sometimes as an ovoid crease. Nares rounded, situated anterolaterally; bordered by rostral, supranasal, 3–5 small postnasals and first supralabial. Supralabials rectangular, rounded dorsally; slightly higher than broad; numbering 13–16 per side; gradually decreasing in size posteriorly; final 3–4 more narrowly convex; supralabials terminating beneath the posterior orbital margin (with 11 or 12 beneath orbit midline); posteriormost twice the size of loreal scales. Mental trapezoidal to subtriangular, with longest face along jaw margin, narrowing posteriorly; mental crease usually absent, extending ½ length of scale where present; mental shorter than laterally adjacent first infralabials; contacted posteriorly by 1 large or 2 smaller hexagonal postmentals, which separate infralabials. Infralabials numbering 9–14 per side; from the snout, infralabials 1–4 on each side are quadrate, more rounded ventrally, higher than broad; infralabial 5 usually marks commencement of a significant and discrete infralabial size decrease, sometimes on one side only, with subsequent infralabials becoming progressively smaller and increasingly circular in shape, terminating in-line with the posterior orbital margin. Anterior infralabials and postmental(s) bordered posteriorly by series of enlarged irregular chin shields; rows indistinct; anteriormost approximately ¾ diameter of postmental, with gradual transition to very small, rounded throat granules posteriorly. Dorsal scales small, mostly homogenous in size, bead-like, apically flattened, partially overlain; indistinct from scales of nape. Ventral scales roughly twice diameter of dorsal scales, circular, flattened, subimbricate, slightly enlarged in precloacal region, extending in rows onto thighs where they form a subtriangular patch; transition to granules at throat abrupt. Skin folds extending ventrolaterally along trunk; anteroposterior folds above fore- and hindlimb insertion. Limbs relatively short and robust, hindlimbs longer; scales on forelimb dorsum larger than dorsal body scales, subimbricate distally; ventral forelimb scales smaller than those dorsally; clear transition to enlarged scales of palm which resemble ventral body scales. Scales on preaxial surface of thigh enlarged, up to three times diameter of dorsal body scales at knee; circular, subimbricate; gradually decreasing in size both posteriorly and distally (along shin) to smaller granules; transition to scales of soles indistinct (resembling ventral body scales). 5–6 rows of precloacal pores in males, anteriormost 2 rows extending distally just over halfway along hind thigh; absent in females. Digits broad, with dilated pads on digits II–V that rapidly transition into slender distal extension, mostly of constant width but becoming narrowly tapered near distal end; digit I smallest on all feet, digit IV longest on manus, digit V longest on pes; angle at rest between digits IV and V greatest, greater on pes than manus; digits II–V of pes and I–IV of manus very weakly webbed; dorsal scales on digits large, especially on first digit; all digits bear recurved, mostly exposed claws. Basalmost 1–2 subdigital lamellae sometimes fragmented; unfragmented subdigital lamellae curved outwards, usually smoothly but sometimes more sharply curved medially; lamellar counts of right manus: 6–7 (I), 9–11 (II), 12–14 (III), 12–15 (IV), 9–11 (V), and pes: 6–9 (I), 10–13 (II), 14–16 (III), 14–18 (IV), 11–16 (V) digits. Tail (original) stout, shorter than SVL, gradually tapered to end, roughly circular in cross-section; often lost through autotomy and then regenerated. Regenerated tail demarcated by abrupt decrease in scale size and anteroposterior striations from point of detachment distally. Base of tail distinctly swollen (TW: 8.7–14.7), most notable in males at cloacal spurs, with enlarged hexagonal scales on underside roughly twice size of more anterior ventral scales. Caudal scales usually arranged in discrete, irregular rows, generally decreasing in size distally from the septum; autotomy septa visibly marked by one, sometimes two rows of large or smaller scales, separated by 9–11 scale rows; dorsal caudal scales approximately 1.5 times size of dorsal body scales, demarcating tail base; highly variable in both size and shape, circular to rounded rectangular; ventral caudal scales enlarged medially, twice as large as dorsal; rectangular to hexagonal, higher than broad, subimbricate. Cloacal spurs consisting of a set of greatly enlarged, conical scales, with most acute point orientated posterodorsally, situated adjacent to cloaca (laterally); often asymmetric in number: 2–5 (L) and 1–4 (R), first (largest) roughly twice size of ventral scales, decreasing in size posteriorly. Distribution.— New Zealand: formerly throughout the South Island (Holocene); presently restricted to some islands in the outer Marlborough Sounds and Cook Strait (Fig. 1). Remarks.— Hoplodactylus tohu has been recognized as distinct from H. duvaucelii for several years (MorganRichards et al. 2016; Hitchmough et al. 2021a). However, it has been unclear what rank to apply to this taxon. New Zealand diplodactylids frequently have highly conserved morphologies, and often greater intra- than inter-specific morphological variation (Hitchmough et al. 2016b). With both Hoplodactylus species recognized here having undergone recent major range contractions resulting in significant declines in morphological and genetic diversity (Scarsbrook et al. 2021; Scarsbrook et al. 2022), it is difficult to weight subtle character differences as these may have arisen, or increased in prevalence, recently, through chance, in relictual populations, and therefore not reflect deeper evolutionary divergences. That these taxa have been reported to produce viable cross-bred offspring in captive populations (Morgan-Richards et al. 2016) fails to meet the criteria of the Biological Species Concept (Mayr 1942). Reproductive isolation in the wild cannot be tested given their allopatric distributions. However, several pairings of lizard species that are widely recognized to be distinct (Brennan et al. 2016; Leaché & Cole 2006; Olave et al. 2011), including some other New Zealand diplodactylids (e.g., Naultinus sp.; Hitchmough et al. 2016b), have been shown to similarly produce viable hybrid offspring. Intergeneric hybrids have even been reported (RH pers. obs). Genetic distance (i.e., ~2.2% and ~4.0% across the mitochondrial genome and ND2 respectively) and estimated timing of lineage divergence of ~4.51 mya (Scarsbrook et al. 2022) between the two Hoplodactylus species recognized here are comparable with those of other recognized diplodactylid species pairings (e.g., 3.8% ND2 divergence between Mokopirirakau kahutarae Whitaker, 1985, and Mokopirirakau granulatus Gray, 1845; Knox et al. 2021). Their discrete (allopatric) distributions reflect commonly observed biogeographic patterns in other taxa (Baker et al. 1995; Efford et al. 2002; Greaves et al. 2007; Liggins et al. 2008; Lloyd 2003), which further influences our treatment of species-level distinction. Reports of interbreeding between H. tohu and H. duvaucelii in captivity makes careful management of both species essential to maintain species/genetic integrity. Individuals sourced for reintroduction or translocation purposes need to be of the correct species, and sourced from moderately large and stable populations (e.g. North Brother Island; Wilson 2010) to minimise impact on the source population. Further, source populations should be proximate (where practicable) to the site of translocation to ensure preservation of regional adaptations; a consideration more applicable to H. duvaucelii as extant populations are more numerous and occupy more ecologically varied habitats. It seems probable, for example, that H. duvaucelii rather than H. tohu, would have naturally occurred at Mana Island, off the southern North Island. However, the latter was translocated there from North Brother Island in 1998 through the release of 40 individuals (Miskelly 2010), with a self-sustaining population reported 15-years later (Bell & Herbert 2017). H. tohu has been recognized as a distinct management unit by the Department of Conservation since 2021 (Hitchmough et al. 2021a), listed as “nationally increasing” with the ‘Conservation Dependant’ and ‘Range Restricted’ qualifiers. H. tohu has a severely restricted distribution comprising a few islands (Fig. 1; Supp. Table 1) with highly anthropogenically modified habitats. The estimated total population size of the largest extant population, on the Brothers Islands, is between 583–677 (Wilson 2010). Based on this, the suggested IUCN Red List status of H. tohu is ‘Critically Endangered A1 (a, b, c, e)’: population reduction of>90% observed, estimated, inferred, or suspected in the past where the causes of the reduction are clearly reversible AND understood AND have ceased. Occurrence of H. tohu on several managed predator-free islands that already have conservation management strategies in place does at least render moderate security to this species from localized disturbances such as fire or predator incursions. However, additional protection through translocations to fenced and more distant mainland sanctuaries (e.g. Orokonui Ecosanctuary near Dunedin, and the Mokomoko Dryland Sanctuary in Central Otago) could be beneficial, given the increased vulnerability of small and sparsely forested islands to the effects of climate change (e.g. sea-level rise, coastal erosion, storm intensity; Macinnis-Ng et al. 2021). Such translocation may also facilitate the re-establishment of ‘lost’ ecological interactions and morphological diversity (e.g. Scarsbrook et al. 2021) specific to mainland and densely forested ecosystems. There is evidence of genetic sub-structuring (Scarsbrook et al. 2022) within the distribution of H. tohu, although this has been greatly reduced with the extinction of mainland South Island populations. Careful management, and possible further research should consider if individual populations are experiencing inbreeding depression and might benefit from genetic rescue – establishment of ‘new’ populations through interbreeding of individuals from different populations to increase genetic ‘fitness’ (i.e., adaptability). Conversely, continued maintenance of discrete lineages may also be appropriate if those lineages reflect local habitat adaptations or if pooled populations would comprise too few individuals to maintain the resulting genetic diversity due to genetic drift. Etymology.— The specific epithet was proposed by Dr Sharon Barcello-Gemmel, Rangatira of Te Ātiawa o Te Waka-a-Māui Trust, in recognition of the tupuna [ancestor] Tohu Kākahi. Tohu Kākahi was one of the two Parihaka prophets with whakapapa [genealogical] connections to Te Ātiawa – the iwi [tribe] with mana whenua [authority] over Ngāwhatu Kai Ponu [The Brothers], where the largest extant population occurs. Name used as noun in apposition.

Aims: This international study aimed to assess: 1) the prevalence of preoperative and postoperative COVID-19 among patients with hip fracture, 2) the effect on 30-day mortality, and 3) clinical factors associated with the infection and with mortality in COVID-19-positive patients. Methods: A multicentre collaboration among 112 centres in 14 countries collected data on all patients presenting with a hip fracture between 1st March-31st May 2020. Demographics, residence, place of injury, presentation blood tests, Nottingham Hip Fracture Score, time to surgery, management, ASA grade, length of stay, COVID-19 and 30-day mortality status were recorded. Results: A total of 7090 patients were included, with a mean age of 82.2 (range 50–104) years and 4959 (69.9%) being female. Of 651 (9.2%) patients diagnosed with COVID-19, 225 (34.6%) were positive at presentation and 426 (65.4%) were positive postoperatively. Positive COVID-19 status was independently associated with male sex (odds ratio (OR) 1.38, p = 0.001), residential care (OR 2.15, p < 0.001), inpatient fall (OR 2.23, p = 0.003), cancer (OR 0.63, p = 0.009), ASA grades 4 (OR 1.59, p = 0.008) or 5 (OR 8.28, p < 0.001), and longer admission (OR 1.06 for each increasing day, p < 0.001). Patients with COVID-19 at any time had a significantly lower chance of 30-day survival versus those without COVID-19 (72.7% versus 92.6%, p < 0.001). COVID-19 was independently associated with an increased 30-day mortality risk (hazard ratio (HR) 2.83, p < 0.001). Increasing age (HR 1.03, p = 0.028), male sex (HR 2.35, p < 0.001), renal disease (HR 1.53, p = 0.017), and pulmonary disease (HR 1.45, p = 0.039) were independently associated with a higher 30-day mortality risk in patients with COVID-19 when adjusting for confounders. Conclusion: The prevalence of COVID-19 in hip fracture patients during the first wave of the pandemic was 9%, and was independently associated with a three-fold increased 30-day mortality risk. Among COVID-19-positive patients, those who were older, male, with renal or pulmonary disease had a significantly higher 30-day mortality risk.

Peer reviewed: True, Acknowledgements: We are grateful for the invaluable contribution provided by patient representatives. HW is funded by The Urology Foundation and Pan London Cancer Alliance (Royal Marsden Partners, North Central London Cancer Alliance, North East London Cancer Alliance, South East London Cancer Alliance and the NIHR BRCs). VK receives funding from Prostate Cancer UK and the John Black Charitable Foundation. GDS and IAM are supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and GDS by the Cancer Research UK Cambridge Centre [C9685/A25177]. EP is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames at Bart’s Health NHS Trust. Mark Emberton receives research support from the United Kingdom’s National Institute of Health Research (NIHR) UCLH / UCL Biomedical Research Centre. He was conferred NIHR Senior Investigator Status in 2015. MGBT receives research funding from NIHR, St Peter’s Trust, Royal Free Charity, RCS, Facing up 2 Kidney Cancer and Kidney Cancer UK. The views expressed are those of the authors and not necessarily those of the funders., INTRODUCTION: The incidence of renal tumours is increasing and anatomic imaging cannot reliably distinguish benign tumours from renal cell carcinoma. Up to 30% of renal tumours are benign, with oncocytomas the most common type. Biopsy has not been routinely adopted in many centres due to concerns surrounding non-diagnostic rate, bleeding and tumour seeding. As a result, benign masses are often unnecessarily surgically resected. 99mTc-sestamibi SPECT/CT has shown high diagnostic accuracy for benign renal oncocytomas and other oncocytic renal neoplasms of low malignant potential in single-centre studies. The primary aim of MULTI-MIBI is to assess feasibility of a multicentre study of 99mTc-sestamibi SPECT/CT against a reference standard of histopathology from surgical resection or biopsy. Secondary aims of the study include obtaining estimates of 99mTc-sestamibi SPECT/CT sensitivity and specificity and to inform the design and conduct of a future definitive trial. METHODS AND ANALYSIS: A feasibility prospective multicentre study of participants with indeterminate, clinical T1 renal tumours to undergo 99mTc-sestamibi SPECT/CT (index test) compared with histopathology from biopsy or surgical resection (reference test). Interpretation of the index and reference tests will be blinded to the results of the other. Recruitment rate as well as estimates of sensitivity, specificity, positive and negative predictive value will be reported. Semistructured interviews with patients and clinicians will provide qualitative data to inform onward trial design and delivery. Training materials for 99mTc-sestamibi SPECT/CT interpretation will be developed, assessed and optimised. Early health economic modelling using a decision analytic approach for different diagnostic strategies will be performed to understand the potential cost-effectiveness of 99mTc-sestamibi SPECT/CT. ETHICS AND DISSEMINATION: Ethical approval has been granted (UK HRA REC 20/YH/0279) protocol V.5.0 dated 21/6/2022. Study outputs will be presented and published nationally and internationally. TRIAL REGISTRATION NUMBER: ISRCTN12572202.

The New Zealand endemic gecko genus Hoplodactylus is revised. Two species are recognized: Hoplodactylus duvaucelii (Duméril & Bibron, 1836) from the North Island and some near-shore islands, and H. tohu n. sp., which was formerly widespread throughout the South Island but is presently restricted to some islands in the Cook Strait region. H. delcourti (Bauer & Russell, 1986) is retained in Hoplodactylus sensu lato in the interest of taxonomic stability, pending further research, but is probably neither congeneric nor from New Zealand.

Background: Incomplete response on FDG PET-CT following (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC) hinders optimal management. The study assessed the utility of an interval (second look) PET-CT. Methods: Patients with oropharyngeal squamous cell carcinoma cancer (OPSCC) treated with CRT at a single centre between 2013 and 2020 who underwent baseline, response, and second-look PET-CT were included. Endpoints were conversion rate to complete metabolic response (CMR) and test characteristics of second-look PET-CT. Results: In total, 714 patients with OPSCC underwent PET-CT post-radiotherapy. In total, 88 patients with incomplete response underwent second-look PET-CT a median of 13 weeks (interquartile range 10–15 weeks) after the initial response assessment. In total, 27/88 (31%) second-look PET-CTs showed conversion to CMR, primary tumour CMR in 20/60 (30%), and nodal CMR in 13/37 (35%). In total, 1/34 (3%) with stable tumour/nodal uptake at the second-look PET-CT relapsed. Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of second-look PET-CT were 95%, 49%, 50%, and 95% for tumour and 92%, 50%, 50%, and 92% for nodes, respectively. Primary tumour progression following CMR occurred in one patient, two patients with residual nodal uptake at second-look PET-CT progressed locoregionally, and one patient developed metastatic disease following CMR in residual nodes. Conclusion: Most patients undergoing second-look PET-CT converted to CMR or demonstrated stable PET signal. NPV was high, suggesting the potential to avoid unnecessary surgical intervention.

Background: Data on the accuracy of response assessment 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography-computed tomography (PET-CT) following (chemo)radiotherapy in patients with oropharynx squamous cell carcinoma (OPSCC) is predominantly based on HPV-positive disease. There is a paucity of data for HPV-negative disease, which has a less favourable prognosis. Methods: 96 patients treated with (chemo)radiotherapy for HPV-negative OPSCC with baseline and response assessment FDG PET-CT between 2013–2020, were analysed. PET-CT response was classified as negative, equivocal, or positive based on qualitative reporting. PET-CT response categories were analysed with reference to clinicopathological outcomes. Test characteristics were evaluated, comparing negative results to equivocal and positive results together. Post-test probabilities were calculated separately for positive and equivocal or negative results. Results: Median follow-up was 26 months. The negative predictive value of a negative scan was 93.7 and 93.2%, respectively, for primary tumour and nodal disease. For a negative scan, the post-test probability was 0.06 for primary and 0.07 for nodal disease. The post-test probability of an equivocal scan was 0.51 and 0.72 for primary and lymph node, respectively. The post-test probability of a positive scan approached 1. For patients with/without a negative scan, two-year overall survival and progression-free survival were 83% versus 30% and 79% versus 17% (p < 0.001), respectively. Conclusion: The NPV of a negative response assessment PET-CT in HPV-negative OPSCC is high, supporting a strategy of clinical monitoring. Contrasting with the published literature for HPV-positive OPSCC, an equivocal response scan was associated with a moderate rate of residual disease.

The atomCAT2 project will analyse retrospective data from anal cancer patients treated with (chemo)radiotherapy across institutions in the UK and internationally. The study aims to develop and validate outcome prediction models using baseline patient characteristics and simple treatment-related factors. It will use distributing learning methodology, which facilitates multi-centre data analysis without individual patient data leaving the local data repository. This will allow us to examine which factors predict for effect of radiotherapy on the primary cancer, and which factors predict for metastatic spread. Ultimately, this could aid in the design of better trials for anal cancer as well as improve treatment for future patients.

Objectives Relapse occurs in ~20% of patients with classical Hodgkin lymphoma (cHL) despite treatment adaption based on 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography response. The objective was to evaluate pre-treatment FDG PET/CT–derived machine learning (ML) models for predicting outcome in patients with cHL. Methods All cHL patients undergoing pre-treatment PET/CT at our institution between 2008 and 2018 were retrospectively identified. A 1.5 × mean liver standardised uptake value (SUV) and a fixed 4.0 SUV threshold were used to segment PET/CT data. Feature extraction was performed using PyRadiomics with ComBat harmonisation. Training (80%) and test (20%) cohorts stratified around 2-year event-free survival (EFS), age, sex, ethnicity and disease stage were defined. Seven ML models were trained and hyperparameters tuned using stratified 5-fold cross-validation. Area under the curve (AUC) from receiver operator characteristic analysis was used to assess performance. Results A total of 289 patients (153 males), median age 36 (range 16–88 years), were included. There was no significant difference between training (n = 231) and test cohorts (n = 58) (p value > 0.05). A ridge regression model using a 1.5 × mean liver SUV segmentation had the highest performance, with mean training, validation and test AUCs of 0.82 ± 0.002, 0.79 ± 0.01 and 0.81 ± 0.12. However, there was no significant difference between a logistic model derived from metabolic tumour volume and clinical features or the highest performing radiomic model. Conclusions Outcome prediction using pre-treatment FDG PET/CT–derived ML models is feasible in cHL patients. Further work is needed to determine optimum predictive thresholds for clinical use. Key points • A fixed threshold segmentation method led to more robust radiomic features. • A radiomic-based model for predicting 2-year event-free survival in classical Hodgkin lymphoma patients is feasible. • A predictive model based on ridge regression was the best performing model on our dataset.

Background A systematic literature review of the performance of 18Fluorine-fluciclovine PET/CT for imaging of men with recurrent prostate cancer was performed. Methods Scientific literature databases (MEDLINE, ScienceDirect and Cochrane Libraries) were searched systematically during Oct 2020 using PRISMA criteria. No limit was put on the date of publication. Prospective studies reporting a patient-level 18F-fluciclovine detection rate (DR) from ≥25 patients with recurrent prostate cancer were sought. Proceedings of relevant meetings held from 2018 through Oct 2020 were searched for abstracts meeting criteria. Results Searches identified 321 unique articles. In total, nine articles (six papers and three conference abstracts), comprising a total of 850 patients met inclusion criteria. Most studies (n = 6) relied on ASTRO-Phoenix Criteria, EAU-ESTRO-SIOG, and/or ASTRO-AUA guidelines to identify patients with biochemical recurrence. Patients’ PSA levels ranged from 0.02–301.7 ng/mL (median level per study, 0.34–4.10 ng/mL [n = 8]). Approximately 64% of patients had undergone prostatectomy, but three studies focused solely on post-prostatectomy patients. Adherence to imaging protocol guidelines was heterogeneous, with variance seen in administered activity, uptake and scan times. Overall patient-level DR varied between studies from 26% to 83%, with 78% of studies reporting a DR > 50%. DR was proportional to PSA, but even at PSA n = 7) ranged from 18% to 78% and extra-prostatic rates (n = 6) from 8% to 72%. Pelvic node and bone lesion DR ranged from 8% to 47% and 0% to 26%, respectively (n = 5). 18F-Fluciclovine PET/CT was shown to impact patient management and outcomes. Two studies reported 59–63% of patients to have a management change post-scan. A further study showed significant increase in failure-free survival following 18F-fluciclovine-guided compared with conventional imaging-guided radiotherapy planning. Conclusions 18F-Fluciclovine PET/CT shows good performance in patients with recurrent prostate cancer leading to measurable clinical benefits. Careful adherence to recommended imaging protocols may help optimize DR.