The National Lung Cancer Audit: The Impact of COVID-19.

Since 2014, the National Lung Cancer Audit (NLCA) has been evaluating the performance of the UK NHS lung cancer services against established standards of care. Prior to the onset of the COVID-19 pandemic, the NLCA's annual reports revealed a steady stream of improvements in early diagnosis, access to surgery, treatment with anti-cancer therapies, input from specialist nursing and survival for patients with lung cancer in the NHS. In January 2022, the NLCA reported on the negative impact COVID-19 has had on all aspects of the lung cancer diagnosis and treatment pathway within the NHS. This article details the fundamental changes made to the NLCA data collection and analysis process during the COVID-19 pandemic and details the negative impact COVID-19 had on NHS lung cancer patient outcomes during 2020.

Stage III Non-small Cell Lung Cancer Management in England.

AIMS: We present the first analysis of the management and outcomes of stage III non-small cell lung cancer (NSCLC) conducted in England using National Lung Cancer Audit data. MATERIALS AND METHODS: Patients diagnosed with stage III NSCLC in 2016 were identified. Linked datasets (including Hospital Episode Statistics, the National Radiotherapy Dataset, the Systemic Anti-Cancer Dataset, pathology reports and death certificate data) were used to categorise the treatment received. Kaplan-Meier survival curves were obtained, with survival defined from the date of diagnosis to the date of death. RESULTS: In total, 6276 cases of stage III NSCLC were analysed: 3827 stage IIIA and 2449 stage IIIB; 1047 (17%) patients were treated with radical radiotherapy with 676 (11%) of these also receiving chemotherapy. Twenty per cent of patients with stage IIIA disease underwent surgery, with half of these also receiving chemotherapy, predominantly delivered in the adjuvant setting. Of note, 2148 (34%) patients received palliative-intent treatment and 2265 (36%) received no active anti-cancer treatment. The 1-year survival was 32.9% (37.4% for stage IIIA), with the highest survival seen for those patients receiving chemotherapy and surgery. CONCLUSIONS: We highlight important gaps in the optimal care of patients with stage III NSCLC in England. Multimodality treatment with either surgery or radical radiotherapy combined with chemotherapy was delivered to less than one-fifth of patients, even though these regimens are considered optimal. Timely access to specialist resources and staff, the practice of effective shared decision making and challenging preconceptions have the potential to optimise management.

Pulmonary nodules and CT screening: the past, present and future.

Lung cancer screening has come a long way since the early studies with chest X-ray. Advancing technology and progress in the processing of images have enabled low dose CT to be tried and tested, and evidence suggests its use can result in a significant mortality benefit. There are several issues that need refining in order to successfully implement screening in the UK and elsewhere. Some countries have started patchy implementation of screening and there is increased recognition that the appropriate management of pulmonary nodules is crucial to optimise benefits of early detection, while reducing harm caused by inappropriate medical intervention. This review summarises and differentiates the many recent guidelines on pulmonary nodule management, discusses screening activity in other countries and exposes the present barriers to implementation in the UK.

Impact of EBUS-TBNA on modalities for tissue acquisition in patients with lung cancer.

BACKGROUND: The impact of the introduction of Endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) on the use of diagnostic modalities for tissue acquisition in patients with lung cancer is unknown. METHODS: A retrospective review of 328 consecutive patients diagnosed with lung cancer at a university teaching hospital, where they first presented in London in 2007, 2009 and 2011. EBUS was introduced in 2008. RESULTS: In total, 316 patients were included in the analysis. Comparing 2007 with 2011 data, there has been a significant reduction in standard bronchoscopy (P < 0.0001) and mediastinoscopy (P = 0.02). The proportion of cases diagnosed by EBUS-TBNA significantly increased from 0% in 2007 to 26.7% in 2009 and 25.4% in 2011 (P < 0.0001). In the same period there has also been an increased trend in the proportion of patients going directly to surgery without pathological confirmation with a 9.6% increase in diagnoses obtained at thoracotomy (P = 0.0526). CONCLUSION: The use of diagnostic modalities that provide information on diagnosis and staging in a single intervention are increasing. At our hospital, the use of EBUS-TBNA for providing a lung cancer diagnosis is increasing and this has led to a significant reduction in standard bronchoscopies and mediastinoscopies. These changes in practice may have implications for future service provision, training and commissioning.

Summary of the British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults.

Flexible bronchoscopy is an essential, established and expanding tool in respiratory medicine. Its practice, however, needs to be safe, effective and for the right indications to maximise clinical utility. This guideline is based on the best available evidence and is a revised update of the British Thoracic Society guideline on diagnostic flexible bronchoscopy.

Interim data from the Medical Research Council QUARTZ Trial: does whole brain radiotherapy affect the survival and quality of life of patients with brain metastases from non-small cell lung cancer?

AIMS: Over 30% of patients with non-small cell lung cancer (NSCLC) develop brain metastases. If inoperable, optimal supportive care (OSC), including steroids, and whole brain radiotherapy (WBRT) are generally considered to be standard care, although there is no randomised evidence demonstrating that the addition of WBRT to OSC improves survival or quality of life. MATERIALS AND METHODS: QUARTZ is a randomised, non-inferiority, phase III trial comparing OSC + WBRT versus OSC in patients with inoperable brain metastases from NSCLC. The primary outcome measure is quality-adjusted life years (QALYs). QUARTZ was threatened with both loss of funding and early closure due to poor accrual. A lack of preliminary randomised data supporting the trial's hypotheses was thought to underlie the poor accrual, so, with no knowledge of the data, the independent trial steering committee agreed to the unusual step of releasing interim data. RESULTS: Between March 2007 and April 2010, 151 (of the planned 534) patients were randomised (75 OSC + WBRT, 76 OSC). Participants' baseline demographics included median age 67 years (interquartile range 62-73), 60% male, 50% with a Karnofsky performance status <70; steroid usage was similar in the two groups; 64/75 (85%) received WBRT (20 Gy in five fractions). Median survival was: OSC + WBRT 49 days (95% confidence interval 39-61), OSC 51 days (95% confidence interval 27-57) - hazard ratio 1.11 (95% confidence interval 0.80-1.53) in favour of WBRT. Quality of life assessed using EQ-5D showed no evidence of a difference. The estimated mean QALYs was: OSC + WBRT 31 days and OSC 30 days, difference -1 day (95% confidence interval -12.0 to +13.2 days). CONCLUSION: These interim data indicate no early evidence of detriment to quality of life, overall survival or QALYs for patients allocated to OSC alone. They provide key information for discussing the trial with patients and strengthen the argument for continuing QUARTZ to definitively answer this important clinical question.

Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade.

Cancers are a heterogeneous mix of cells, some of which exhibit cancer stem cell-like characteristics including ATP-dependent drug efflux and elevated tumorigenic potential. To determine whether aerodigestive squamous cell carcinomas (SCCs) contain a subpopulation of cancer stem cell-like cells, we performed Hoechst dye efflux assays using four independent cell lines. Results revealed the presence of a rare, drug effluxing stem cell-like side population (SP) of cells within all cell lines tested (SCC-SP cells). These cells resembled previously characterised epithelial stem cells, and SCC-SP cell abundance was positively correlated with overall cellular density and individual cell quiescence. Serial SCC-SP fractionation and passaging increased their relative abundance within the total cell population. Purified SCC-SP cells also exhibited increased clonogenic potential in secondary cultures and enhanced tumorigenicity in vivo. Despite this, SCC-SP cells remained chemotherapeutically sensitive upon ATP-dependent transporter inhibition. Overall, these findings suggest that the existence of ATP transporter-dependent cancer stem-like cells may be relatively common, particularly within established tumours. Future chemotherapeutic strategies should therefore consider coupling identification and targeting of this potential stem cell-like population with standard treatment methodologies.

A set of cattle microsatellite DNA markers for genome analysis of riverine buffalo (Bubalus bubalis).

One hundred and eight microsatellite primer pairs, originally identified from cattle, were evaluated for their applicability in buffalo. Eighty-one primer pairs (75%) amplified discrete products, and of these, 61 pairs (56%) gave polymorphic band patterns on a panel of 25 buffaloes. The mean number of alleles per polymorphic marker was 4.50 +/- 0.20, and the mean heterozygosity per polymorphic marker was 0.66 +/- 0.02. Successful genotyping of buffaloes using cattle specific primers suggests that the latter can be a valuable resource for genome analysis in bubaline species.

Site-directed mutagenesis of bacterial hemoglobin: the role of glutamine (E7) in oxygen-binding in the distal heme pocket.

The bacterial and yeast hemoglobins have a glutamine instead of histidine in the E7 position of the distal heme pocket. The recently determined crystal structure of Vitreoscilla hemoglobin (VHb) indicates that this residue is oriented out of the heme pocket and may not ligand the bound oxygen. This is in contrast to elephant myoglobin which also has a Gln(E7) but which does ligand the bound oxygen. This residue was changed in VHb using site-directed mutagenesis to leucine (VHbL) or to histidine (VHbH). Spectral and kinetic studies of the binding of oxygen and CO to VHbL showed that this substitution had little effect on the ligand-binding properties of this protein, evidence that Gln(E7) does not H-bond the bound ligand, in agreement with the findings of the crystallographic study of VHb. In contrast, the functional properties of VHbH were drastically altered in a way suggesting that the E7His may itself be liganded to the heme iron. These studies are further evidence that the distal heme pocket in VHb and related microbial hemoglobins differs from that in mammalian hemoglobins and may resemble in some ways the heme pocket in cytochrome b5.

Genetic transformation of Vitreoscilla sp.

Of all the methods customarily used to transform E. coli we found only electroporation to be effective for transformation of the Gram-negative bacterium Vitreoscilla, yielding 5.10(5) transformants/microgram of plasmid DNA. The conditions used were close to those described for E. coli E. coli plasmids are stably maintained in Vitreoscilla. This is the first report of exogenous DNA transfer in Vitreoscilla which opens the way for the application of recombinant-DNA techniques to study this unique group of organisms.