Impact of the COVID-19 Pandemic on Outcomes for Patients with Lung Cancer Receiving Curative-intent Radiotherapy in the UK.

AIMS: Previous work found that during the first wave of the COVID-19 pandemic, 34% of patients with lung cancer treated with curative-intent radiotherapy in the UK had a change to their centre's usual standard of care treatment (Banfill et al. Clin Oncol 2022;34:19-27). We present the impact of these changes on patient outcomes. MATERIALS AND METHODS: The COVID-RT Lung database was a prospective multicentre UK cohort study including patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between April and October 2020. Data were collected on patient demographics, radiotherapy and systemic treatments, toxicity, relapse and death. Multivariable Cox and logistic regression were used to assess the impact of having a change to radiotherapy on survival, distant relapse and grade ≥3 acute toxicity. The impact of omitting chemotherapy on survival and relapse was assessed using multivariable Cox regression. RESULTS: Patient and follow-up forms were available for 1280 patients. Seven hundred and sixty-five (59.8%) patients were aged over 70 years and 603 (47.1%) were female. The median follow-up was 213 days (119, 376). Patients with stage I-II non-small cell lung cancer (NSCLC) who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.859) or death (P = 0.884); however, they did have increased odds of grade ≥3 acute toxicity (P = 0.0348). Patients with stage III NSCLC who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.216) or death (P = 0.789); however, they did have increased odds of grade ≥3 acute toxicity (P < 0.001). Patients with stage III NSCLC who had their chemotherapy omitted had no significant increase in distant relapse (P = 0.0827) or death (P = 0.0661). CONCLUSION: This study suggests that changes to radiotherapy and chemotherapy made in response to the COVID-19 pandemic did not significantly affect distant relapse or survival. Changes to radiotherapy, namely increased hypofractionation, led to increased odds of grade ≥3 acute toxicity. These results are important, as hypofractionated treatments can help to reduce hospital attendances in the context of potential future emergency situations.

Ultra-Widefield OCT Angiography.

Optical Coherence Tomography Angiography (OCTA), a functional extension of OCT, has the potential to replace most invasive fluorescein angiography (FA) exams in ophthalmology. So far, OCTA's field of view is however still lacking behind fluorescence fundus photography techniques. This is problematic, because many retinal diseases manifest at an early stage by changes of the peripheral retinal capillary network. It is therefore desirable to expand OCTA's field of view to match that of ultra-widefield fundus cameras. We present a custom developed clinical high-speed swept-source OCT (SS-OCT) system operating at an acquisition rate 8-16 times faster than today's state-of-the-art commercially available OCTA devices. Its speed allows us to capture ultra-wide fields of view of up to 90 degrees with an unprecedented sampling density and hence extraordinary resolution by merging two single shot scans with 60 degrees in diameter. To further enhance the visual appearance of the angiograms, we developed for the first time a three-dimensional deep learning based algorithm for denoising volumetric OCTA data sets. We showcase its imaging performance and clinical usability by presenting images of patients suffering from diabetic retinopathy.

Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK.

AIMS: In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020. MATERIALS AND METHODS: Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression. RESULTS: In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease. CONCLUSIONS: The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes.

Hot or not? The 10% rule in sentinel lymph node biopsy for malignant melanoma revisited.

BACKGROUND: The surgeon needs a practical rule to follow when deciding whether to excise a lymph node during sentinel node biopsy (SLNB). The "10% rule" dictates that all nodes with a radiation count of greater than 10% of the hottest node and all blue nodes should be removed, and this study observes the effects of following this rule in SLNB in melanoma. METHODS: We reviewed the records of 665 patients with primary melanoma who underwent sentinel lymph node over a 5-year period (2007-2011). RESULTS: 2064 nodes were identified in 898 nodal basins in 665 patients. 141 (21%) patients had at least one positive sentinel node. 105 positive nodal basins were identified in which more than one sentinel node was removed. In 18 of these, a less radioactive node was positive for tumour when the most radioactive node was negative. Of 175 positive nodes 157 (90%) contained blue dye staining. For cases in which the positive sentinel node was not the hottest node, the positive node had apparent blue dye staining in all 18 cases (100%), and was the second hottest node in the basin. CONCLUSION: In this series removing just the hottest node and all blue nodes would not have missed a single positive basin and would have resulted in a 38% reduction in the number of nodes removed compared to those taken following the 10% rule, without changing the staging in any patient.

Results of a national training programme in sentinel lymph node biopsy for breast cancer.

BACKGROUND: New Start, a structured, validated, multidisciplinary training programme in sentinel lymph node biopsy (SLNB), was established to allow the introduction and rapid transfer of appropriate knowledge and technical skills to ensure safe and competent practice across the UK. METHODS: Multidisciplinary teams attended a theory/skills laboratory course, following which they performed 30 consecutive SLNBs, either concurrently with their standard axillary staging procedure (training model A) or as stand-alone SLNB (training model B). SLNB was performed according to a standard protocol using the combined technique of isotope ((99m) Tc-labelled albumin colloid) and blue dye. An accredited New Start trainer mentored the first five procedures in the participant's hospital, or all 30 if stand-alone. Validation standards for model A and B were a localization rate of at least 90 per cent. In addition, for model A only, in which a minimum of ten patients were required to be node-positive, a false-negative rate (FNR) of 10 per cent or less was required. RESULTS: From October 2004 to December 2008, 210 SLNB-naive surgeons, in 103 centres, performed 6685 SLNB procedures. The overall sentinel lymph node (SLN) localization rate was 98·9 (95 per cent confidence interval 98·6 to 99·1) per cent (6610 of 6685) and the FNR 9·1 (7·9 to 10·5) per cent (160 of 1757). The FNR was related to nodal yield, ranging from 14·8 per cent for one node and declining to 9·7, 6·6, 4·7 and 4·1 per cent for two, three, four and more than four SLNs respectively. No learning curve was identified for localization or FNR. CONCLUSION: The programme successfully trained a wide range of UK breast teams to perform safe SLNB and suggested that a standard injection protocol and structured multidisciplinary training can abolish learning curves.

Overestimation of carboplatin doses is avoided by radionuclide GFR measurement.

BACKGROUND: Glomerular filtration rate (GFR) is used in the calculation of carboplatin dose. Glomerular filtration rate is measured using a radioisotope method (radionuclide GFR (rGFR)), however, estimation equations are available (estimated GFR (eGFR)). Our aim was to assess the accuracy of three eGFR equations and the subsequent carboplatin dose in an oncology population. PATIENTS AND METHODS: Patients referred for an rGFR over a 3-year period were selected; eGFR was calculated using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault (CG) equations. Carboplatin doses were calculated for those patients who had received carboplatin chemotherapy. Bias, precision and accuracy were examined. RESULTS: Two hundred and eighty-eight studies met the inclusion/exclusion criteria. Paired t-tests showed significant differences for all three equations between rGFR and eGFR with biases of 12.3 (MDRD), 13.6 (CKD-EPI) and 7.7 ml min(-1) per 1.73 m(2) (CG). An overestimation in carboplatin dose was seen in 81%, 87% and 66% of studies using the MDRD, CKD-EPI and CG equations, respectively. CONCLUSION: The MDRD and CKD-EPI equations performed poorly compared with the reference standard rGFR; the CG equation showed smaller bias and higher accuracy in our oncology population. On the basis of our results we recommend that the rGFR should be used for accurate carboplatin chemotherapy dosing and where unavailable the use of the CG equation is preferred.

Significant differences when using MDRD for GFR estimation compared to radionuclide measured clearance.

OBJECTIVES: To evaluate Estimated Glomerular Filtration Rate (eGFR), using the Modification of Diet in Renal Disease equation, and compare with radionuclide GFR (rGFR) in a Radiology setting to assess renal function prior to contrast administration. METHODS: Five hundred and sixteen retrospective rGFR studies from a mixed referral population were selected and the eGFR calculated. Regression and Bland-Altman analysis was performed. The percentage of rGFR and eGFR studies below 30 ml/min/1.73 m² and 60 ml/min/1.73 m² were calculated; these are important thresholds for classifying renal insufficiency. RESULTS: A significant correlation between eGFR and rGFR (R² = 0.62, p < 0.0001) and significant differences in the medians (p < 0.0001) were found. eGFR overestimated rGFR with a bias (mean difference) of 10.8 ml/min/1.73 m² over the whole range of rGFR. Studies with an rGFR of under 30 ml/min/1.73 m² had a mean bias of 4.6 ml/min/1.73 m² (difference range -5.9 to 26.3 ml/min/1.73 m²). The bias over the range 30 to 60 ml/min/1.73 m² was 13.2 ml/min/1.73 m² (difference range -16.8 to 88.3 ml/min/1.73 m²). In 25.4% of studies, eGFR was less than 60 ml/min/1.73 m² compared with 40.5% of rGFR studies. CONCLUSIONS: Awareness of the bias between eGFR and rGFR is important when assessing Radiology patients for risks of nephrotoxicity and Nephrogenic Systemic Fibrosis from contrast medium.

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma.

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method for determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histologic nodal staging and avoids overtreating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This document is designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. Preparation of this guideline was carried out by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial (SENT) Committee.

Differential expression of HLA-DQ alleles in peripheral blood mononuclear cells: alleles associated with susceptibility to and protection from autoimmune type 1 diabetes.

Differential expression of human leucocyte antigen (HLA) class II genes has been postulated to influence the risk of developing autoimmune disease. In this study, we investigated the relationship between the level of mRNA expression of DQA1 and DQB1 alleles in peripheral blood mononuclear cells and the influence of the alleles on susceptibility to type 1 diabetes (T1D). Transcripts from pairs of DQA1 and DQB1 alleles were quantified in 59 DQ-heterozygous individuals (29 patients with T1D and 30 healthy control subjects). Luciferase reporter gene assays were used to investigate the relative promoter activities of the alleles associated with high and low risk of disease. DQA1*0301 and the DQB1*06 group of alleles (*0601, *0602, *0603 and *0604) were generally overexpressed in comparison to other alleles. In contrast, mRNA for DQB1*0201/*0202 was generally less abundant than other DQB1 transcripts. These data correlated well with the relative promoter activities observed for the diabetes-associated alleles; the strongest promoters were those derived from DQA1*0301 and DQB1*0602, while a 700-bp fragment derived from the DQB1*0201 promoter showed the lowest activity of the DQB1 constructs. There was no simple correlation between the level of expression of specific DQ alleles and their influence on the risk of diabetes. The functional relevance of our findings and their implications for the pathogenesis of autoimmunity remain to be determined.

Accurate geometric calibration in stepping-table digital subtraction angiography.

Accurate measurements of vessel dimensions are desirable in many clinical applications. This work uses the known relative motion between X-ray source and the patient in stepping-table digital subtraction angiography (DSA) to provide an accurate geometric calibration for quantitative measurements. The method results in a calibration factor that converts the size of the object measured in pixels on the image to its size in millimetres. The main sources of error relate to: (i) the assessment of relative displacement of a structure in a series of images; (ii) patient motion throughout data acquisition; and (iii) image distortion. Error was evaluated both with a test object consisting of a large grid of ball bearings (2x2 cm spaced) and, in vivo, in five renal DSA examinations performed with identical catheters of known diameter. The calibration factor was calculated with 0.1% accuracy for the test object and at least 2% accuracy in vivo, even with breath holding and pulsatile motion. This demonstrates that the calculation of the calibration factor can be very accurate, and that the method we propose is capable of the submillimetre accuracy required for clinical studies if used in conjunction with an accurate measurement of the vessel size in pixels. In conclusion, accurate geometric measurements can be performed in stepping-table DSA, without the need for external reference objects.

Highlights of the European Association of Nuclear Medicine Congress, Athens, Greece, 30 September to 4 October 2006.

The 2006 EANM Congress, held in Athens, Greece, was once again a major event in the nuclear medicine scientific and educational calendar. The scientific programme, which included the second biennial ISRTRD meeting, confirmed the major developments taking place in (1) the diagnostic and prognostic uses of nuclear medicine imaging (both in PET and in single-photon studies), (2) radionuclide therapies, (3) radiochemistry and radiopharmacy, and (4) physics. This paper outlines the major findings in each of these areas.

Mycoplasma mastitis: a review of transmission and control.

The Mycoplasma sp. that cause mastitis are simple, cell wall-less, bacteria that can colonize and cause diseases in other extramammary sites in the bovine. Prevalence of mycoplasma mastitis appears to be increasing in many locations throughout the world. The best method to identify this group of pathogens is through direct culture on mycoplasma agar media. However, limitations with this culture procedure are the duration of culture, 10 days, special conditions required and thus added expense, and the lack of primary specificity to distinguish between true pathogens and commensal organisms. Thus culture of bulk tank milk samples has been advocated as a primary screening method to determine the mycoplasma status of a herd. This monitoring system is reasonably successful but the sensitivity of detection of Mycoplasma sp. in bulk tank milk is affected by a significant minority of cows that might shed the organism at levels below the threshold of detection. Contagious mastitis control procedures have been effective in controlling outbreaks of mycoplasma mastitis. Yet new methods of control might be warranted, methods that may prevent the outbreak. Current data suggests that a significant number of new outbreaks may occur via internal or animal-to-animal transmission of mycoplasma mastitis pathogens from asymptomatic carriers.

The addition of computer simulated noise to investigate radiation dose and image quality in images with spatial correlation of statistical noise: an example application to X-ray CT of the brain.

This study validates a method to add spatially correlated statistical noise to an image, applied to transaxial X-ray CT images of the head to simulate exposure reduction by up to 50%. 23 patients undergoing routine head CT had three additional slices acquired for validation purposes, two at the same clinical 420 mAs exposure and one at 300 mAs. Images at the level of the cerebrospinal fluid filled ventricles gave readings of noise from a single image, with subtraction of image pairs to obtain noise readings from non-uniform tissue regions. The spatial correlation of the noise was determined and added to the acquired 420 mAs image to simulate images at 340 mAs, 300 mAs, 260 mAs and 210 mAs. Two radiologists assessed the images, finding little difference between the 300 mAs simulated and acquired images. The presence of periventricular low density lesions (PVLD) was used as an example of the effect of simulated dose reduction on diagnostic accuracy, and visualization of the internal capsule was used as a measure of image quality. Diagnostic accuracy for the diagnosis of PVLD did not fall significantly even down to 210 mAs, though visualization of the internal capsule was poorer at lower exposure. Further work is needed to investigate means of measuring statistical noise without the need for uniform tissue areas, or image pairs. This technique has been shown to allow sufficiently accurate simulation of dose reduction and image quality degradation, even when the statistical noise is spatially correlated.

Bulk tank milk analysis: factors associated with appearance of Mycoplasma sp. in milk.

Factors associated with the presence of Mycoplasma sp. in bulk tank milk samples were evaluated from 664 herds during 2.25 years. Milk quality components were not strongly related to the presence of Mycoplasma sp. in bulk tank milk. The presence of other contagious mastitis pathogens, Staphylococcus aureus and Streptococcus agalactiae, was also not related to the presence of mycoplasma, suggesting that the aetiology and transmission of mycoplasma mastitis were different from transmission of other contagious mastitis pathogens. The occurrence of the first isolation of mycoplasma from a bulk tank was not correlated to season of the year. Mycoplasma in bulk tank milk samples were more likely to be found in herds shipping more milk, an indirect measure of herd size. This suggests that larger herds are more likely to have mycoplasma mastitis. However, the first appearance of mycoplasma mastitis in a bulk tank sample was followed by a sample without this pathogen in more than 60% of herds. Mycoplasma sp. was not detected in any herd a year after first isolation. These findings suggest that this pathogen could be controlled and eliminated from herds.

Contrast-enhanced magnetic resonance angiography of the iliac arteries: optimization by injection simulation.

Protocols for contrast-enhanced magnetic resonance angiography (CE-MRA) of the iliac arteries were optimized by computer simulations based on an impulse response function (IRF) of contrast agent (CA) concentration as a function of time obtained for 20 patients. Protocols with sequential, centric, and elliptical k-space coverage, different repetition rates (5 and 10 ms), and CA doses (0.1, 0.2, and 0.3 mmol/kg b.w.) were compared in terms of signal-to-noise ratio (SNR), distortion of vessel profiles, and sensitivity to timing errors. IRF-based simulations successfully characterized CA recirculation. Slow-rate CA infusions were found to achieve relatively high enhancement. In terms of SNR, there is no advantage in increasing the repetition rate. Distortion of vessel profiles is more likely in elliptic and centric k-space coverage. Protocols based on sequential k-space coverage and relatively long CA infusions proved to be particularly suited to large-FOV iliac examinations as they are relatively insensitive to timing errors.

Inter-observer reproducibility of quantitative radionuclide colonic transit imaging.

The colonic transit of an indium-111 enteric coated capsule was imaged with a gamma camera over a period of 3 days. The geometric centre of activity in the colon was calculated from regions drawn over four segments of the colon, plus a fifth segment as the estimated passed stool activity. Fifteen healthy subjects were scanned and the results analysed. The images were analysed by two observers to assess reproducibility of the geometric centre quantitative index (correlation, r = 0.985). In conclusion, although it can be difficult to identify the anatomical segments of the colon from the gamma camera images, by following a protocol with clear guidelines for ROI placement, good inter-observer reproducibility can be obtained.

Performance assessment of a slat gamma camera collimator for 511 keV imaging.

The physical performance of a prototype slat collimator is described for gamma camera planar imaging at 511 keV. Measurements were made of sensitivity, spatial resolution and a septal penetration index at 511 keV. These measurements were repeated with a commercial parallel hole collimator designed for 511 keV imaging. The slat collimator sensitivity was 22.9 times that of the parallel hole collimator with 10 cm tissue equivalent scatter material, and 16.8 times the parallel hole collimator sensitivity in air. Spatial resolution was also better for the slat collimator than the parallel hole collimator (FWHM at 10 cm in air 17.9 mm and 21.2 mm respectively). Septal penetration was compared by a single value for the counts at 120 mm from the point source profile peak, expressed as a percentage of the peak counts, showing less penetration for the slat collimator than the parallel hole collimator (1.9% versus 3.6% respectively). In conclusion, these results show that the slat collimator may have advantages over the parallel hole collimator for 511 keV imaging, though the greater complexity of operation of the slat collimator and potential sources of artefact in slat collimator imaging are recognized.

A method to evaluate intra-operative gamma probes for sentinel lymph node localisation.

A method is described to allow objective evaluation of intra-operative gamma probe performance for the task of sentinel lymph node localisation. The method uses simple simulation based upon standard sensitivity and spatial resolution measurements at depth in water, with technetium-99m sources. The aim is to predict the minimum separation between the injection site and lymph node required to allow the sentinel lymph node to be identified in the presence of high injection site activity. The simulation methodology allows rapid investigation of probe performance for a range of node and injection site activities, and a range of node and injection site depths, without the need to perform a large number of physical measurements. Examples of practical performance simulations are given from five probes, showing that nodes at less than 115 mm from the injection site may be poorly localised, with even the best performing probe requiring at least 51 mm separation to allow detection in the high background from the injection site. This method provides data to allow the ranking of probe system performance in terms of the practical task of sentinel lymph node localisation, rather than arbitrary ranking based upon basic physical performance measures such as spatial resolution and sensitivity. The best probes allow sentinel lymph node localisation at between 20 and 30 mm closer to the injection site than the poorest performing probes, for situations which represent intra-operative localisation in melanoma and breast surgery. The method is also shown to assist in optimising system settings such as energy detection thresholds, and may allow users to understand the limitations and capabilities of intra-operative gamma probes.