Patient Preparation and Radiation Protection Guidance for Adult Patients Undergoing Radioiodine Treatment for Thyroid Cancer in the UK.

Radioactive iodine is a highly effective treatment for thyroid cancer and has now been used in clinical practice for more than 80 years. In general, the treatment is well tolerated. However, it can be logistically quite complex for patients due to the need to reduce iodine intake and achieve high levels of thyroid-stimulating hormone prior to treatment. Radiation protection precautions must also be taken to protect others from unnecessary radiation exposure following treatment. It has been well documented by thyroid cancer patient support groups that there is significant variation in practice across the UK. It is clear that some patients are being asked to observe unnecessarily burdensome restrictions that make it more difficult for them to tolerate the treatment. At the instigation of these support groups, a multidisciplinary group was assembled to examine the evidence and generate guidance on best practice for the preparation of patients for this treatment and the management of subsequent radiation protection precautions, with a focus on personalising the advice given to individual patients. The guidance includes advice about managing particularly challenging situations, for example treating patients who require haemodialysis. We have also worked together to produce a patient information leaflet covering these issues. We hope that the guidance document and patient information leaflet will assist centres in improving our patients' experience of receiving radioactive iodine. The patient information sheet is available as Supplementary Material to this article.

Guidelines on the Use of Systemic Therapy in Patients with Advanced Thyroid Cancer.

With increasing understanding of the molecular alterations leading to thyroid cancers in recent years we have seen a rapid increase in the number of effective targeted systemic therapies available for patients with advanced thyroid cancer; firstly with the advent of the multi-kinase inhibitors and more recently with more specific RET, BRAF, MEK, ALK and NTRK inhibitors. Although these developments are very welcome, they have resulted in a paradigm shift in the management of advanced thyroid cancer to which thyroid oncologists have had to rapidly adapt, learning how to supervise treatment safely with novel agents, the management of novel toxicities, when and how to arrange molecular genetic testing of cancers and, perhaps most importantly, determining when the optimum time is to start these treatments in what can often be a relatively indolent, if progressive, disease. We hope that these guidelines will support clinicians in making these decisions with their patients, as well as signposting and providing useful supporting information both for patients and clinicians.

Cross-validation of good versus poor self-reported outcome trajectory types following knee arthroplasty.

OBJECTIVE: To determine whether good versus poor outcome trajectories and predictors of poor outcome obtained in a derivation study could be replicated in an independent sample of persons undergoing knee arthroplasty (KA). METHODS: We used data from TRIO-POPULAR, a prospective cohort study of 926 participants who underwent KA in the United Kingdom. The participants were assessed preoperatively and 6-weeks, 6- and 12-months postoperatively. The Oxford Knee Score was the primary outcome and a variety of pre-operative predictors of outcome were selected. The outcome measure and the predictors were selected to most closely align with a previously published derivation study of good versus poor outcome. Confirmatory two-piece latent class growth curve analyses were used to model outcome and regression was used to identify predictors of outcome class. RESULTS: Trajectories for the Oxford Knee Scores from TRIO-POPULAR replicated trajectories for WOMAC Pain and Function scores from the previously published derivation study. Multivariable predictors of poor outcome were pain catastrophizing (odds ratio = 1.125, 95% CI = 1.048, .206, p = 0.001) and comorbidity (odds ratio = 1.134, 95%CI = 1.049, 1.227, p = 0.002. Pain catastrophizing also predicted poor outcome in the derivation study. CONCLUSIONS: Good and poor outcome trajectories replicated those found in the previously published derivation study. Our model-based method produces stable outcome trajectories despite using data from different countries and participants with substantively different characteristics. Predictors of poor outcome were somewhat inconsistent between the cross-validation and derivation studies. Pain catastrophizing was the only consistent poor outcome predictor.

The Impact of Intra-thoracic Anatomical Changes upon the Delivery of Lung Stereotactic Ablative Radiotherapy.

AIMS: So far, the impact of intra-thoracic anatomical changes (ITACs) on patients treated with stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer is unknown. Studying these is important, as ITACs have the potential to impact the workflow and reduce treatment quality. The aim of this study was to assess and categorise ITACs, as detected on cone beam computed tomography scans (CBCT), and their subsequent impact upon treatment in lung cancer patients treated with SABR. MATERIALS AND METHODS: CBCTs from 100 patients treated with SABR for early non-small cell lung cancer were retrospectively reviewed. The presence of the following ITACs was assessed: atelectasis, infiltrative change, pleural effusion, baseline shift and gross tumour volume (GTV) increase and decrease. ITACs were graded using a traffic light protocol. This was adapted from a tool previously developed to assesses potential target undercoverage or organ at risk overdose. The frequency of physics or clinician review was noted. A linear mixed effects model was used to assess the relationship between ITAC grade and set-up time (time from first CBCT to beam delivery). RESULTS: ITACs were observed in 22% of patients. Twenty-one per cent of these were categorised as 'red', implying a risk of underdosage to the GTV. Most were 'yellow' (51%), indicating little impact upon planning target volume coverage of the GTV. Physics or clinician review was required in 10% of all treatment fractions overall. Three patients needed their treatment replanned. The mixed effect model analysis showed that ITACs cause a significant prolongation of set-up time (Χ2(3) = 9.22, P = 0.02). CONCLUSION: Most ITACs were minor, but associated with unplanned physics or clinician review, representing a potentially significant resource burden. ITACs also had a significant impact upon set-up time, with consequences for the wider workflow and intra-fraction motion. Detailed guidance on the management of ITACs is needed to provide support for therapeutic radiographers delivering lung SABR.

Intensity-modulated Radiotherapy for Rectal Cancer in the UK in 2020.

AIMS: Preoperative (chemo)radiotherapy followed by total mesorectal excision is the current standard of care for patients with locally advanced rectal cancer. The use of intensity-modulated radiotherapy (IMRT) for rectal cancer is increasing in the UK. However, the extent of IMRT implementation and current practice was not previously known. A national survey was commissioned to investigate the landscape of IMRT use for rectal cancer and to inform the development of national rectal cancer IMRT guidance. MATERIALS AND METHODS: A web-based survey was developed by the National Rectal Cancer IMRT Guidance working group in collaboration with the Royal College of Radiologists and disseminated to all UK radiotherapy centres. The survey enquired about the implementation of IMRT with a focus on the following aspects of the workflow: dose fractionation schedules and use of a boost; pre-treatment preparation and simulation; target volume/organ at risk definition; treatment planning and treatment verification. A descriptive statistical analysis was carried out. RESULTS: In total, 44 of 63 centres (70%) responded to the survey; 30/44 (68%) and 36/44 (82%) centres currently use IMRT to treat all patients and selected patients with rectal cancer, respectively. There was general agreement concerning several aspects of the IMRT workflow, including patient positioning, use of intravenous contrast and bladder protocols. Greater variation in practice was identified regarding rectal protocols; use of a boost to primary/nodal disease; target volume delineation; organ at risk delineation and dose constraints and treatment verification. Delineation of individual small bowel loops and daily volumetric treatment verification were considered potentially feasible by most centres. CONCLUSION: This survey identified that IMRT is already used to treat rectal cancer in many UK radiotherapy centres, but there is heterogeneity between centres in its implementation and practice. These results have been a valuable aid in framing the recommendations within the new National Rectal Cancer IMRT Guidance.

Prospects for Personalised Treatment of Patients with Radioiodine-avid Locally Recurrent or Metastatic Thyroid Cancer.

Although most patients with metastatic or inoperable locally recurrent differentiated thyroid cancer have radioiodine-avid disease, the outcome for patients who do not achieve remission with radioiodine therapy is poor. Most centres use fixed empirical activities of radioiodine to treat these patients, which is in contrast to other areas of oncology, where there is a shift to more individualised treatment. The use of dosimetry techniques to calculate a more appropriate activity of radioiodine for each patient may increase the effectiveness of radioiodine therapy but is more complex, time-consuming and of unproven benefit. This review addresses some of the limitations of empirical radioiodine therapy, discusses existing dosimetry-based approaches to individualising therapy and proposes further work in this area. A prospective randomised controlled trial comparing empirical activities of radioiodine with activities guided by a combination of lesional dosimetry and maximum safe dose has not been carried out previously. Although considerable challenges in the design of such a study remain, a network of centres in the UK now has the potential to take this forward.

Physical vapor deposition of a polyamorphic system: Triphenyl phosphite.

In situ AC nanocalorimetry and dielectric spectroscopy were used to analyze films of vapor-deposited triphenyl phosphite. The goal of this work was to investigate the properties of vapor-deposited glasses of this known polyamorphic system and to determine which liquid is formed when the glass is heated. We find that triphenyl phosphite forms a kinetically stable glass when prepared at substrate temperatures of 0.75-0.95Tg, where Tg is the glass transition temperature. Regardless of the substrate temperature utilized during deposition of triphenyl phosphite, heating a vapor-deposited glass always forms the ordinary supercooled liquid (liquid 1). The identity of liquid 1 was confirmed by both the calorimetric signal and the shape and position of the dielectric spectra. For the purposes of comparison, the glacial phase of triphenyl phosphite (liquid 2) was prepared by the conventional method of annealing liquid 1. We speculate that these new results and previous work on vapor deposition of other polyamorphic systems can be explained by the free surface structure being similar to one polyamorph even in a temperature regime where the other polyamorph is more thermodynamically stable in the bulk.

Relationship between aged and vapor-deposited organic glasses: Secondary relaxations in methyl-m-toluate.

In situ interdigitated electrode broadband dielectric spectroscopy was used to characterize the excess wing relaxations in vapor-deposited and aged glasses of methyl-m-toluate (MMT, Tg = 170 K). MMT displays typical excess wing relaxations in dielectric spectra of its supercooled liquid and glasses. Physical vapor deposition produced glasses with degrees of suppression of the excess wing relaxation that varied systematically with deposition conditions, up to a maximum suppression of more than a factor of 3. The glass deposited at a relatively high temperature, 0.96 Tg (163 K), showed the same amount of suppression as that of a liquid-cooled glass aged to equilibrium at this temperature. The suppression of the excess wing relaxation was strongly correlated with the kinetic stability of the vapor-deposited glasses. Comparisons with aged MMT glasses allowed an estimate of the structural relaxation time of the vapor-deposited glasses. The dependence of the estimated structural relaxation times upon the substrate temperature was found to be stronger than Arrhenius but weaker than Vogel-Fulcher-Tammann dependence predicted from extrapolation of relaxation times in the supercooled liquid. Additionally, this work provides the first example of the separation of primary and secondary relaxations using physical vapor deposition.

Vapor-Deposited Ethylbenzene Glasses Approach "Ideal Glass" Density.

Spectroscopic ellipsometry was used to characterize vapor-deposited glasses of ethylbenzene (Tg = 115.7 K). For this system, previous calorimetric experiments have established that a transition to the ideal glass state is expected to occur near 101 K (the Kauzmann temperature, TK) if the low-temperature supercooled liquid has the properties expected based upon extrapolation from above Tg. Ethylbenzene glasses were vapor-deposited at substrate temperatures between 100 (∼0.86 Tg) and 116 K (∼Tg), using deposition rates of 0.02-2.1 nm/s. Down to 103 K, glasses prepared in the limit of low deposition rate have densities consistent with the extrapolated supercooled liquid. The highest density glass is within 0.15% of the density expected for the ideal glass. These results support the hypothesis that the extrapolated properties of supercooled ethylbenzene are correct to within just a few Kelvin of TK, consistent with the existence of a phase transition to an ideal glass state at TK.

Strain-engineering Mott-insulating La2CuO4.

The transition temperature Tc of unconventional superconductivity is often tunable. For a monolayer of FeSe, for example, the sweet spot is uniquely bound to titanium-oxide substrates. By contrast for La2-xSrxCuO4 thin films, such substrates are sub-optimal and the highest Tc is instead obtained using LaSrAlO4. An outstanding challenge is thus to understand the optimal conditions for superconductivity in thin films: which microscopic parameters drive the change in Tc and how can we tune them? Here we demonstrate, by a combination of x-ray absorption and resonant inelastic x-ray scattering spectroscopy, how the Coulomb and magnetic-exchange interaction of La2CuO4 thin films can be enhanced by compressive strain. Our experiments and theoretical calculations establish that the substrate producing the largest Tc under doping also generates the largest nearest neighbour hopping integral, Coulomb and magnetic-exchange interaction. We hence suggest optimising the parent Mott state as a strategy for enhancing the superconducting transition temperature in cuprates.

The role of citizen science in addressing grand challenges in food and agriculture research.

The power of citizen science to contribute to both science and society is gaining increased recognition, particularly in physics and biology. Although there is a long history of public engagement in agriculture and food science, the term 'citizen science' has rarely been applied to these efforts. Similarly, in the emerging field of citizen science, most new citizen science projects do not focus on food or agriculture. Here, we convened thought leaders from a broad range of fields related to citizen science, agriculture, and food science to highlight key opportunities for bridging these overlapping yet disconnected communities/fields and identify ways to leverage their respective strengths. Specifically, we show that (i) citizen science projects are addressing many grand challenges facing our food systems, as outlined by the United States National Institute of Food and Agriculture, as well as broader Sustainable Development Goals set by the United Nations Development Programme, (ii) there exist emerging opportunities and unique challenges for citizen science in agriculture/food research, and (iii) the greatest opportunities for the development of citizen science projects in agriculture and food science will be gained by using the existing infrastructure and tools of Extension programmes and through the engagement of urban communities. Further, we argue there is no better time to foster greater collaboration between these fields given the trend of shrinking Extension programmes, the increasing need to apply innovative solutions to address rising demands on agricultural systems, and the exponential growth of the field of citizen science.

Glasses of three alkyl phosphates show a range of kinetic stabilities when prepared by physical vapor deposition.

In situ AC nanocalorimetry was used to characterize vapor-deposited glasses of three phosphates with increasing lengths of alkyl side chains: trimethyl phosphate, triethyl phosphate, and tributyl phosphate. The as-deposited glasses were assessed in terms of their reversing heat capacity, onset temperature, and isothermal transformation time. Glasses with a range of kinetic stabilities were prepared, including kinetically stable glasses, as indicated by high onset temperatures and long transformation times. Trimethyl phosphate forms kinetically stable glasses, similar to many other organic molecules, while triethyl phosphate and tributyl phosphate do not. Triethyl phosphate and tributyl phosphate present the first examples of non-hydrogen bonding systems that are unable to form stable glasses via vapor deposition at 0.2 nm/s. Based on experiments utilizing different deposition rates, we conclude that triethyl phosphate and tributyl phosphate lack the surface mobility required for stable glass formation. This may be related to their high enthalpies of vaporization and the internal structure of the liquid state.

New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center.

INTRODUCTION: The 2015 WHO classification of tumors categorized malignant mesothelioma into epithelioid, biphasic (BMM), and sarcomatoid (SMM) for prognostic relevance and treatment decisions. The survival of BMM is suspected to correlate with the amount of the sarcomatoid component. The criteria for a sarcomatoid component and the interobserver variability between pathologists for identifying this component are not well described. In ambiguous cases, a "transitional" (TMM) subtype has been proposed but was not accepted as a specific subtype in the 2015 WHO classification. The aims of this study were to evaluate the interobserver agreement in the diagnosis of BMM, to determine the nature and the significance of TMM subtype, and to relate the percentage of sarcomatoid component with survival. The value of staining for BRCA-1-associated protein (BAP1) and CDKN2A(p16) fluorescence in situ hybridization (FISH) were also assessed with respect to each of the tumoral components. METHODS: The study was conducted by the International Mesothelioma Panel supported by the French National Cancer Institute, the network of rare cancer (EURACAN) and in collaboration with the International Association for the Study of Lung Cancer (IASLC). The patient cases include a random group of 42 surgical biopsy samples diagnosed as BMM with evaluation of SMM component by the French Panel of MESOPATH experts was selected from the total series of 971 BMM cases collected from 1998 to 2016. Fourteen international pathologists with expertise in mesothelioma reviewed digitally scanned slides (hematoxylin and eosin - stained and pan-cytokeratin) without knowledge of prior diagnosis or outcome. Cases with at least 7 of 14 pathologists recognizing TMM features were selected as a TMM group. Demographic, clinical, histopathologic, treatment, and follow-up data were retrieved from the MESOBANK database. BAP1 (clone C-4) loss and CDKN2A(p16) homozygous deletion (HD) were assessed by immunohistochemistry (IHC) and FISH, respectively. Kappa statistics were applied for interobserver agreement and multivariate analysis with Cox regression adjusted for age and gender was performed for survival analysis. RESULTS: The 14 panelists recorded a total of 544 diagnoses. The interobserver correlation was moderate (weighted Kappa = 0.45). Of the cases originally classified as BMM by MESOPATH, the reviewers agreed in 71% of cases (385 of 544 opinions), with cases classified as pure epithelioid in 17% (93 of 544), and pure sarcomatoid in 12% (66 of 544 opinions). Diagnosis of BMM was made on morphology or IHC alone in 23% of the cases and with additional assessment of IHC in 77% (402 of 544). The median overall survival (OS) of the 42 BMM cases was 8 months. The OS for BMM was significantly different from SMM and epithelioid malignant mesothelioma (p < 0.0001). In BMM, a sarcomatoid component of less than 80% correlated with a better survival (p = 0.02). There was a significant difference in survival between BMM with TMM showing a median survival at 6 months compared to 12 months for those without TMM (p < 0.0001). BAP1 loss was observed in 50% (21 of 42) of the total cases and in both components in 26%. We also compared the TMM group to that of more aggressive patterns of epithelioid subtypes of mesothelioma (solid and pleomorphic of our large MESOPATH cohort). The curve of transitional type was persistently close to the OS curve of the sarcomatoid component. The group of sarcomatoid, transitional, and pleomorphic mesothelioma were very close to each other. We then considered the contribution of BAP1 immunostaining and loss of CDKN2A(p16) by FISH. BAP1 loss was observed in 50% (21 of 41) of the total cases and in both component in 27% of the cases (11 of 41). There was no significant difference in BAP1 loss between the TMM and non-TMM groups. HD CDKN2A(p16) was detected in 74% of the total cases with no significant difference between the TMM and non-TMM groups. In multivariate analysis, TMM morphology was an indicator of poor prognosis with a hazard ratio = 3.2; 95% confidence interval: 1.6 - 8.0; and p = 0.003 even when compared to the presence of HD CDKN2A(p16) on sarcomatoid component (hazard ratio = 4.5; 95% confidence interval: 1.2 - 16.3, p = 0.02). CONCLUSIONS: The interobserver concordance among the international mesothelioma and French mesothelioma panel suggests clinical utility for an updated definition of biphasic mesothelioma that allows better stratification of patients into risk groups for treatment decisions, systemic anticancer therapy, or selection for surgery or palliation. We also have shown the usefulness of FISH detection of CDKN2A(p16) HD compared to BAP1 loss on the spindle cell component for the separation in ambiguous cases between benign florid stromal reaction from true sarcomatoid component of biphasic mesothelioma. Taken together our results further validate the concept of transitional pattern as a poor prognostic indicator.

Limited surface mobility inhibits stable glass formation for 2-ethyl-1-hexanol.

Previous work has shown that vapor-deposition can prepare organic glasses with extremely high kinetic stabilities and other properties that would be expected from liquid-cooled glasses only after aging for thousands of years or more. However, recent reports have shown that some molecules form vapor-deposited glasses with only limited kinetic stability when prepared using conditions expected to yield a stable glass. In this work, we vapor deposit glasses of 2-ethyl-1-hexanol over a wide range of deposition rates and test several hypotheses for why this molecule does not form highly stable glasses under normal deposition conditions. The kinetic stability of 2-ethyl-1-hexanol glasses is found to be highly dependent on the deposition rate. For deposition at Tsubstrate = 0.90 Tg, the kinetic stability increases by 3 orders of magnitude (as measured by isothermal transformation times) when the deposition rate is decreased from 0.2 nm/s to 0.005 nm/s. We also find that, for the same preparation time, a vapor-deposited glass has much more kinetic stability than an aged liquid-cooled glass. Our results support the hypothesis that the formation of highly stable 2-ethyl-1-hexanol glasses is inhibited by limited surface mobility. We compare our deposition rate experiments to similar ones performed with ethylcyclohexane (which readily forms glasses of high kinetic stability); we estimate that the surface mobility of 2-ethyl-1-hexanol is more than 4 orders of magnitude less than that of ethylcyclohexane at 0.85 Tg.

Vapor-deposited alcohol glasses reveal a wide range of kinetic stability.

In situ AC nanocalorimetry was used to characterize vapor-deposited glasses of six mono- and di-alcohol molecules. Benzyl alcohol glasses with high kinetic stability and decreased heat capacity were prepared. When annealed above the glass transition temperature Tg, transformation of these glasses into the supercooled liquid took 103.4 times longer than the supercooled liquid relaxation time (τα). This kinetic stability is similar to other highly stable organic glasses prepared by vapor deposition and is the first clear demonstration of an alcohol forming a stable glass. Vapor deposited glasses of five other alcohols exhibited moderate or low kinetic stability with isothermal transformation times ranging from 100.7 to 102 τα. This wide range of kinetic stabilities is useful for investigating the factors that control stable glass formation. Using our current results and literature data, we compare the kinetic stability of vapor deposited glasses prepared from 14 molecules and find a correlation with the value of τα at 1.25 Tg. We also observe that some vapor-deposited glasses exhibit decreased heat capacity without increased kinetic stability.

Oropharyngeal cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. There has been significant debate in the management of oropharyngeal cancer in the last decade, especially in light of the increased incidence, clarity on the role of the human papilloma virus in this disease and the treatment responsiveness of the human papilloma virus positive cancers. This paper discusses the evidence base pertaining to the management of oropharyngeal cancer and provides recommendations on management for this group of patients receiving cancer care. Recommendations • Cross-sectional imaging is required in all cases to complete assessment and staging. (R) • Magnetic resonance imaging is recommended for primary site and computed tomography scan for neck and chest. (R) • Positron emission tomography combined with computed tomography scanning is recommended for the assessment of response after chemoradiotherapy, and has a role in assessing recurrence. (R) • Examination under anaesthetic is strongly recommended, but not mandatory. (R) • Histological diagnosis is mandatory in most cases, especially for patients receiving treatment with curative intent. (R) • Oropharyngeal carcinoma histopathology reports should be prepared according to The Royal College of Pathologists Guidelines. (G) • Human papilloma virus (HPV) testing should be carried out for all oropharyngeal squamous cell carcinomas as recommended in The Royal College of Pathologists Guidelines. (R) • Human papilloma virus testing for oropharyngeal cancer should be performed within a diagnostic service where the laboratory procedures and reporting standards are quality assured. (G) • Treatment options for T1-T2 N0 oropharyngeal squamous cell carcinoma include radical radiotherapy or transoral surgery and neck dissection (with post-operative (chemo)radiotherapy if there are adverse pathological features on histological examination). (R) • Transoral surgery is preferable to open techniques and is associated with good functional outcomes in retrospective series. (R) • If treated surgically, neck dissection should include levels II-IV and possibly level I. Level IIb can be omitted if there is no disease in level IIa. (R) • If treated with radiotherapy, levels II-IV should be included, and possibly level Ib in selected cases. (R) • Altering the modalities of treatment according to HPV status is currently controversial and should be undertaken only in clinical trials. (R) • Where possible, patients should be offered the opportunity to enrol in clinical trials in the field. (G).

Strain Control of Fermiology and Many-Body Interactions in Two-Dimensional Ruthenates.

Here we demonstrate how the Fermi surface topology and quantum many-body interactions can be manipulated via epitaxial strain in the spin-triplet superconductor Sr_{2}RuO_{4} and its isoelectronic counterpart Ba_{2}RuO_{4} using oxide molecular beam epitaxy, in situ angle-resolved photoemission spectroscopy, and transport measurements. Near the topological transition of the γ Fermi surface sheet, we observe clear signatures of critical fluctuations, while the quasiparticle mass enhancement is found to increase rapidly and monotonically with increasing Ru-O bond distance. Our work demonstrates the possibilities for using epitaxial strain as a disorder-free means of manipulating emergent properties, many-body interactions, and potentially the superconductivity in correlated materials.