Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer.

BACKGROUND: Identification of residual disease in patients with localized non-small cell lung cancer (NSCLC) following treatment with curative intent holds promise to identify patients at risk of relapse. New methods can detect circulating tumour DNA (ctDNA) in plasma to fractional concentrations as low as a few parts per million, and clinical evidence is required to inform their use. PATIENTS AND METHODS: We analyzed 363 serial plasma samples from 88 patients with early-stage NSCLC (48.9%/28.4%/22.7% at stage I/II/III), predominantly adenocarcinomas (62.5%), treated with curative intent by surgery (n = 61), surgery and adjuvant chemotherapy/radiotherapy (n = 8), or chemoradiotherapy (n = 19). Tumour exome sequencing identified somatic mutations and plasma was analyzed using patient-specific RaDaR™ assays with up to 48 amplicons targeting tumour-specific variants unique to each patient. RESULTS: ctDNA was detected before treatment in 24%, 77% and 87% of patients with stage I, II and III disease, respectively, and in 26% of all longitudinal samples. The median tumour fraction detected was 0.042%, with 63% of samples <0.1% and 36% of samples <0.01%. ctDNA detection had clinical specificity >98.5% and preceded clinical detection of recurrence of the primary tumour by a median of 212.5 days. ctDNA was detected after treatment in 18/28 (64.3%) of patients who had clinical recurrence of their primary tumour. Detection within the landmark timepoint 2 weeks to 4 months after treatment end occurred in 17% of patients, and was associated with shorter recurrence-free survival [hazard ratio (HR): 14.8, P <0.00001] and overall survival (HR: 5.48, P <0.0003). ctDNA was detected 1-3 days after surgery in 25% of patients yet was not associated with disease recurrence. Detection before treatment was associated with shorter overall survival and recurrence-free survival (HR: 2.97 and 3.14, P values 0.01 and 0.003, respectively). CONCLUSIONS: ctDNA detection after initial treatment of patients with early-stage NSCLC using sensitive patient-specific assays has potential to identify patients who may benefit from further therapeutic intervention.

Impact of COVID-19 on radiology training: Royal College of Radiologists Junior Radiologists Forum national survey.

AIM: To obtain a national snapshot of radiology trainees' experience during the first wave of the pandemic. MATERIALS AND METHODS: A 25-item questionnaire was disseminated to representatives from all training regions across the UK in July 2020. Each representative collated the collective experiences of trainees in their training programme in key domains, including redeployment, shielding, training, and teaching. RESULTS: Ninety-five percent (38 of 40) of representatives completed the questionnaire. Trainees in up to 76% of training programmes were redeployed to wards and some trainees were shielding in 81% of programmes. Only 27% of programmes enabled remote reporting for isolating or shielding trainees. Sixty-two percent of respondents felt their well-being needs were supported. There was an overall increase in the attendance, volume, and quality of teaching and training nationally due to improved accessibility via remote-learning methods. Significant challenges were described with reporting, interventional procedures, and multidisciplinary team meeting attendance, although 62% of programmes noted an increase in service provision. Less in-person feedback was reported with in-person training still deemed necessary for practical skills. The Royal College of Radiologists Junior Radiologists Forum webinars were well received by all trainees with continuation of the series recommended. CONCLUSION: The COVID-19 pandemic has had a clear impact on many areas of radiology training in the UK. Early strategies have been adopted to mitigate the challenges faced by trainees and opportunities for future improvement are highlighted.

Accelerated implementation of remote reporting during the COVID-19 pandemic.

AIM: To assess, via a survey of UK radiological departments, if the COVID-19 pandemic led to a change in radiological reporting undertaken in a home environment with appropriate IT support. MATERIALS AND METHODS: All imaging departments in the UK were contacted and asked about the provision of home reporting and IT support before and after the first wave of the pandemic. RESULTS: One hundred and thirty-seven of the 217 departments contacted replied, producing a response rate of 61%. There was a 147% increase in the provision of remote access viewing and reporting platforms during the pandemic. Although 578 consultants had access to a viewing platform pre-pandemic, this had increased to 1,431 during the course of the first wave. CONCLUSION: This survey represents work undertaken by UK NHS Trusts in co-ordinating and providing increased home-reporting facilities to UK radiologists during the first wave of this global pandemic. The impact of these facilities has been shown to allow more than just the provision of reporting of both elective and emergency imaging and provides additional flexibility in how UK radiologists can help support and provide services. This is a good start, but there are potential problems that now need to be overcome.

A national UK audit for diagnostic accuracy of preoperative CT chest in emergency and elective surgery during COVID-19 pandemic.

AIM: To report on a snap audit of all departments in the UK as to the value of preoperative thoracic imaging, preferably computed tomography (CT), of patients undergoing any surgery to assess for changes consistent with COVID-19 preoperatively. MATERIALS AND METHODS: All Imaging departments in the UK were contacted and asked to record the number of preoperative CT examinations performed in patients being considered for both emergency and elective surgical intervention over a 5-day period in May 2020. RESULTS: Forty-seven percent of departments replied with data provided on >820 patients. Nineteen percent of additional preoperative CT was in patients undergoing elective intervention and 81% in patients presenting with surgical abdominal pain. There was a high rate of false positives in patients who tested negative for COVID-19, producing a sensitivity for thoracic CT of 68.4%. CONCLUSION: This UK-wide audit demonstrates that a large number of additional thoracic imaging examinations over a 5-day period were performed with a low sensitivity for the identification of COVID-19 in this preoperative group of patients. Given these findings, it is difficult to justify this additional examination in this group of patients.

Diagnostic utility of additional whole-chest CT as part of an acute abdominal pain CT imaging pathway during the COVID-19 pandemic.

AIM: To evaluate the diagnostic utility of additional whole-chest computed tomography (CT) in identifying otherwise unheralded COVID-19 lung disease as part of an acute abdominal pain CT imaging pathway in response to the COVID-19 pandemic. MATERIALS AND METHODS: Consecutive patients (n=172) who underwent additional whole-chest CT via a COVID-19 acute abdominal pain CT imaging pathway between 27 March and 3 May 2020 were evaluated in this retrospective single-centre study. Chest CT examinations were graded as non-COVID-19, indeterminate for, or classic/probable for COVID-19. CT examinations in the latter two categories were further divided into one of three anatomical distributions (lung base, limited chest [below carina], whole chest [above carina]) based on location of findings. Reverse transcriptase-polymerase chain reaction (RT-PCR) results and clinical features of COVID-19 were assessed to determine if COVID-19 was clinically suspected at the time of CT referral. RESULTS: Twenty-seven of the 172 (15.7%) patients had CT features potentially indicative of COVID-19 pneumonia, 6/27 (3.5%) demonstrating a classic/probable pattern and 21/27 (12.2%) demonstrating an indeterminate pattern. After correlation with clinical features and RT-PCR 8/172 (4.7%) were defined as COVID-19 positive, of which only 1/172 (0.6%) was clinically unsuspected of COVID-19 at the time of CT referral. All COVID-19 positive cases could be identified on review of the lung base alone. CONCLUSION: Whole-chest CT as part of an acute abdominal pain CT imaging pathway has a very low diagnostic yield for our cohort of patients. All COVID-19-positive patients in our cohort were identified on review of the lung bases on the abdominal CT and this offers an alternative imaging approach in this patient group.

The safe practice of CT coronary angiography in adult patients in UK imaging departments.

Computed tomography coronary angiography is increasingly used in imaging departments in the investigation of patients with chest pain and suspected coronary artery disease. Due to the routine use of heart rate controlling medication and the potential for very high radiation doses during these scans, there is a need for guidance on best practice for departments performing this examination, so the patient can be assured of a good quality scan and outcome in a safe environment. This article is a summary of the document on 'Standards of practice of computed tomography coronary angiography (CTCA) in adult patients' published by the Royal College of Radiologists (RCR) in December 2014.

MRI in adult patients with aortic coarctation: diagnosis and follow-up.

Aortic coarctation is a disease that usually presents in infancy; however, a proportion of patients present for the first time in adulthood. These lesions generally require repair with either surgery or interventional techniques. The success of these techniques means that increasing numbers of patients are presenting for follow-up imaging in adulthood, whether their coarctation was initially repaired in infancy or as adults. Thus, the adult presenting to the radiologist for assessment of possible coarctation or follow-up of coarctation repair is not an uncommon scenario. In this review, we present details of the MRI protocols and MRI findings in these patients so that a confident and accurate assessment can be made.

Quality of Decision Making in Radiation Oncology.

High-quality decision making in radiation oncology requires the careful consideration of multiple factors. In addition to the evidence-based indications for curative or palliative radiotherapy, this article explores how, in routine clinical practice, we also need to account for many other factors when making high-quality decisions. Foremost are patient-related factors, including preference, and the complex interplay between age, frailty and comorbidities, especially with an ageing cancer population. Whilst clinical practice guidelines inform our decisions, we need to account for their applicability in different patient groups and different resource settings. With particular reference to curative-intent radiotherapy, we explore decisions regarding dose fractionation schedules, use of newer radiotherapy technologies and multimodality treatment considerations that contribute to personalised patient-centred care.

GrassGroTM simulation of pasture, animal performance and greenhouse emissions on low and high sheep productivity grazing systems: 1-year validation and 25-year analysis.

Globally, there is a focus on reducing the absolute methane (CH4) and nitrous oxide emissions, and the emissions intensity (EI, kg CO2e/kg animal product) of livestock production. Increasing the productivity of mixed pasture systems has the potential to increase food (e.g., lamb) and textile fibre (e.g., wool) production while reducing the EI of those products from grazing livestock. The objective of this study was to quantify the differences in greenhouse gas (GHG) emissions and EI between sheep on Low (i.e., low sustainable stocking rate) and High (i.e., high sustainable stocking rate) productivity grazing systems (PGSs). Therefore, a replicated breeding-ewe trial on 18 paddocks was established across 2 - years. Three flocks on Low (3 × 16 ewes/flock) and High PGSs (3 × 32 ewes/flock) rotated across three land-classes and three paddocks per PGS. In year 1, the observed on-farm pasture quantity, quality, and botanical composition, together with lamb BW (kg), and daily CH4 production (DMP, g CH4/head per day) using Open Path Fourier Transformed Infrared (OP-FTIR) spectrometers data were measured. Subsequently, two simulations using GrassGroTM were conducted: (1) a 1-year GrassGroTM simulation that used the observed on-farm data to adjust parameters: date of mating, paddock fertility, and weight of mature ewes to validate GrassGroTM predictions to achieve accuracy and precision targets; and (2) a 25-year (1986-2011) simulation to analyse the effects of Low and High PGSs on sheep production and GHG emissions across a variable climate. The 1-year validation predictions fitted well with the observed on-farm data for: pasture biomass (kg/ha), DM digestibility (%), botanical composition (kg/ha), lamb (kg) product, and DMP (g CH4/head per day). The subsequent predicted results from the 25-year GrassGroTM simulation showed minimal effect of PGS on the mean DM intake (kg DM/day) or DMP for Low and High PGSs, but this was thought to be due to the biomass in both PGSs exceeding 1 500 kg DM/ha. The EI, over the 25-year simulation, on the High PGS was 16.5% lower than the Low PGS. Additional calculations of DMP were conducted using a recent global equation, giving estimates of DMP that closely matched the observed on-farm OP-FTIR DMP measurements, but these were lower than the GrassGroTM predictions and improved the accuracy and precision. It is concluded that in some pasture situations, managing pastures and stock numbers to intensify grazing systems can allow increased livestock production, without increasing daily CH4 emissions/head while substantially decreasing the EI of the animal products generated.

What's Current and What's New in Mesothelioma?

Malignant mesothelioma is a rare disease with limited treatment options. In malignant pleural mesothelioma (MPM), radical trimodality approaches, including surgery, radiotherapy and systemic chemo- and immunotherapy, have been delivered in some countries but remain controversial due to a lack of randomised evidence. Even in the unresectable scenario, surgery and radiotherapy play an important role in managing pleural effusions and pain, which may optimise wellbeing and maintain performance status. From the systemic treatment point of view, the recent incorporation of anti-angiogenics and, more importantly, immunotherapy has changed the standard of care in a space where chemotherapy with platinum and pemetrexed was the only therapeutic intervention with demonstrated benefits in overall survival. Histology is essential in determining an initial treatment plan as non-epithelioid MPMs may have a higher substantial survival improvement with dual immunotherapy compared with chemotherapy, whereas chemotherapy remains an option for epithelioid MPM; however, predictive biomarkers for systemic therapy are not entirely validated to guide the selection, as a subgroup of MPM patients might not benefit from immunotherapy. This overview approaches how the overall management of mesothelioma is evolving to incorporate the recent changes in the standards of care.

Single-Fraction Stereotactic Ablative Body Radiotherapy to the Lung - The Knockout Punch.

This overview summarises the current evidence on efficacy and safety of single-fraction stereotactic ablative body radiotherapy (SABR) for primary lung cancers and lung metastases, in comparison with the more widely adapted multi-fraction SABR regimens. A literature search using the Medline database through PubMed was carried out using the following key words: ('stereotactic' or 'sabr' or 'sbrt'), ('radiotherapy' or 'radiation therapy'), ('lung' or 'thorax' or 'thoracic' or 'chest'), ('cancer' or 'metasta-' or 'oligometasta-'), alongside: (i) ('single-fraction' or 'single-dose') to identify trials and cohort studies with single-fraction SABR to lung malignant tumours and (ii) ('fraction' or 'schedule') limiting the search to 'clinical trial' and 'randomized controlled trial' to ensure thorough capture of lung SABR trials comparing different fractionations. The review discusses the radiobiological, technical and organ at risk considerations of single-fraction SABR to the lung.

SCOTCERV: a phase II trial of docetaxel and gemcitabine as second line chemotherapy in cervical cancer.

OBJECTIVE: The aim of the study was to determine the response rate and response duration of cervical cancer previously treated by cisplatin (with or without radiation) to a combination of docetaxel and gemcitabine. Secondary endpoints were assessment of toxicity and quality of life (QoL) of patients receiving the treatment. METHODS: This was a multicentre phase II trial of 3 weekly docetaxel 75 mg/m(2) day 1 (reduced to 60 mg/m(2) after 32 cycles had been administered) and gemcitabine 1000 mg/m(2) (days 1 and 8). A two stage Gehan design was used initially. Twenty-nine patients recruited had disease outside the irradiated pelvis (Group 1), and 21 had disease confined to the irradiated pelvis (Group 2). The target response for the Gehan 2 design was 25% (Group 1) and 10% (Group 2). RESULTS: The overall response rate for Group 1 was 21.4% (95% CI 8.3-41.0%). Amongst those who had at least 3 cycles of chemotherapy the response rate was 27.3% (95% CI 10.7-50.2%). The median survival was 7.3 months (95% CI 5.4 to 9.2 months) with 39.3% (95% CI 21.7-56.5%) alive at 1 year. In Group 2 the overall response rate was 9.5% (95% CI 1.2%-30.4%). The response rate for those who had at least 3 cycles of chemotherapy was 12.5% (95% CI 1.6-38.4%). The median survival was 7.9 months (95% CI 2.2-13.6 months). Toxicity was mainly haematological with 51% developing grade 3 or 4 neutropenia after at least 1 cycle of chemotherapy. QoL showed a significant deterioration from baseline for physical and role function but there was an improvement in emotional function during treatment. CONCLUSION: Response rates and survival duration were similar to those reported following treatment with platinum based doublets. In view of the relatively poor response rates (no more than 36%) to conventional chemotherapy future developments should be a combination of chemotherapy and biological agents such as VEGFR inhibitors.

Cardiac drugs used in cross-sectional cardiac imaging: what the radiologist needs to know.

The demand for cross-sectional imaging of the heart is increasing dramatically and in many centres these imaging techniques are being performed by radiologists. Although radiologists are familiar with the computed tomography (CT) and magnetic resonance imaging (MRI) techniques to generate high-quality images and with using contrast agents, many are less familiar with administering the drugs necessary to perform CT coronary angiography and cardiac MR reliably. The aim of this article is to give an overview of the indications for and the contraindications to administering cardiac drugs in cross-sectional imaging departments. We also outline the complications that may be encountered and provide advice on how to treat these complications when they occur.

Cross-sectional imaging appearances of cardiac aneurysms.

Cardiac aneurysms are an uncommon presentation of cardiac disease, but are important to identify and accurately characterise. Traditionally, these aneurysms have been investigated with plain radiography, angiography and echocardiography. With the significant recent technical improvements in cross-sectional cardiac imaging, computed tomography (CT) and magnetic resonance imaging (MRI) are now becoming established as the definitive investigations. This article reviews the spectrum of locations of cardiac aneurysms and their appearance with particular reference to CT and MRI. We describe the relative merits of each technique and discuss how they may be used to direct clinical practice.

Image-guided Radiotherapy to Manage Respiratory Motion: Lung and Liver.

Organ motion as a result of respiratory and cardiac motion poses significant challenges for the accurate delivery of radiotherapy to both the thorax and the upper abdomen. Modern imaging techniques during radiotherapy simulation and delivery now permit better quantification of organ motion, which in turn reduces tumour and organ at risk position uncertainty. These imaging advances, coupled with respiratory correlated radiotherapy delivery techniques, have led to the development of a range of approaches to manage respiratory motion. This review summarises the key strategies of image-guided respiratory motion management with a focus on lung and liver radiotherapy.

Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a biomarker of tumour response.

BACKGROUND: Plasma biomarkers may be particularly useful as a predictor or early marker of clinical response to treatment in addition to radiological imaging. Cytokeratin 18 (CK18) is an epithelial-specific cytokeratin that undergoes cleavage by caspases during apoptosis. Measurement of caspase-cleaved (CK18-Asp396) or total cytokeratin 18 (CK18) from epithelial-derived tumours could be a simple, non-invasive way to monitor or predict responses to treatment. METHODS: Soluble plasma CK18-Asp396 and CK18 were measured by ELISA from 73 patients with advanced gastrointestinal adenocarcinomas before treatment and during chemotherapy, as well as 100 healthy volunteers. RESULTS: Both CK18-Asp396 and total CK18 plasma levels were significantly higher in patients compared with the healthy volunteers (P=0.015, P<0.001). The total CK18 baseline plasma levels before treatment were significantly higher (P=0.009) in patients who develop progressive disease than those who achieve partial response or stable disease and this correlation was confirmed in an independent validation set. The peak plasma levels of CK18 occurring in any cycle following treatment were also found to be associated with tumour response, but peak levels of CK18-Asp396 did not reach significance (P=0.01, and P=0.07, respectively). CONCLUSION: Plasma levels CK18 are a potential marker of tumour response in patients with advanced gastrointestinal malignancy.

Weight management perceptions and clinical practices among gynaecology providers caring for reproductive-aged patients.

OBJECTIVE: Research suggests that patient and provider conversations about healthy eating and physical activity behaviours may lead to patients' increased health behaviours, access to dietary and physical activity resources, and weight management. The American College of Obstetrics and Gynecology (ACOG) has a number of weight management intervention options, but it is unclear if providers have conversations about intervention options with their patients who are of reproductive age. The purpose of this work was to evaluate the degree to which gynaecology healthcare providers offer the weight management intervention options as recommended by ACOG. METHODS: Cross-sectional study of gynaecology providers in Southwest Virginia utilizing an electronic survey to identify weight management perceptions and current clinical practices. Responses were measured using quantitative methods, and agreeability and frequency responses were measured using a 5-point Likert scale. RESULTS: Twenty-three of the 31 eligible providers (74.2%) completed the survey. Providers acknowledge that patients need weight management discussions and they feel comfortable and are willing to have these discussions. While physical activity recommendations were consistent among providers, they did not reflect the complete physical activity recommendations for Americans. Consistency in dietary recommendations was lacking. Although providers make recommendations for physical activity and/or diet at least sometimes, they rarely utilize other methods of weight management as outlined in the ACOG recommendations, such as referrals to other providers, programmes or medications. CONCLUSIONS: Areas for improvement in weight management practices include frequency of counselling, consistency in dietary counselling and frequency of utilization of weight loss medications and referrals to ancillary services. These results can be used to aid the development of methods for targeting these deficiencies.

Stereotactic Ablative Body Radiotherapy Versus Radical Radiotherapy: Comparing Real-World Outcomes in Stage I Lung Cancer.

AIMS: Stereotactic ablative body radiotherapy (SABR) is now considered the standard of care for medically inoperable stage I non-small cell lung cancer (NSCLC). The English National Cancer Registration and Analysis Service (NCRAS) collects data on all patients diagnosed with lung cancer, including information on treatment. We wanted to compare outcomes for patients with stage I NSCLC treated with radical radiotherapy with either SABR or fractionated radiotherapy. MATERIALS AND METHODS: All patients diagnosed with stage I NSCLC in 2015 and 2016 were identified from the NCRAS dataset, validated by the National Lung Cancer Audit, and their treatment data were collated. For patients who received radiotherapy, those receiving radical dose fractionations, including SABR, were identified through linkage to the national Radiotherapy Dataset. Clinical outcomes for those receiving SABR or more fractionated radical radiotherapy were compared using univariate and fully adjusted Cox proportional hazards models. RESULTS: In total, 12 384 patients with stage I NSCLC were identified during the study period; 53.5% underwent surgical resection, 24.3% received no documented treatment, 18.6% received radical radiotherapy and 3.5% received other non-curative-intent treatments. For those receiving radical radiotherapy, 69% received SABR and 31% received fractionated treatment. The hazard ratio of death for the 1587 patients who received SABR was 0.69 (95% confidence interval 0.61-0.79) compared with 717 patients who received radical fractionated radiotherapy; this benefit was seen for both stage Ia and stage Ib disease. The median overall survival was also longer for SABR versus radical radiotherapy (715 days versus 648 days). Exploratory travel time analysis shows that compared with stage I NSCLC patients receiving SABR, those receiving fractionated radiotherapy and those receiving no active treatment would have to travel longer and further to reach their nearest radiotherapy SABR centre. CONCLUSION: This study adds to the data that SABR has a survival benefit when compared with fractionated radical radiotherapy. Although the use of SABR increased in England over this study period, it has still not reached levels of use seen in other countries. This study also highlights that one quarter of stage I NSCLC patients overall received no active treatment.