A novel method for the establishment of autologous skin cell suspensions: characterisation of cellular sub-populations, epidermal stem cell content and wound response-enhancing biological properties.

Introduction: Autologous cell suspension (ACS)-based therapy represents a highly promising approach for burns and chronic wounds. However, existing technologies have not achieved the desired clinical success due to several limitations. To overcome practical and cost-associated obstacles of existing ACS methods, we have established a novel methodology for rapid, enzymatic disaggregation of human skin cells and their isolation using a procedure that requires no specialist laboratory instrumentation and is performed at room temperature. Methods: Cells were isolated using enzymatic disaggregation of split-thickness human skin followed by several filtration steps for isolation of cell populations, and cell viability was determined. Individual population recovery was confirmed in appropriate culture medium types, and the presence of epidermal stem cells (EpSCs) within keratinocyte sub-populations was defined by flow cytometry via detection of CD49 and CD71. Positive mediators of wound healing secreted by ACS-derived cultures established on a collagen-based wound-bed mimic were detected by proteome arrays and quantified by ELISA, and the role of such mediators was determined by cell proliferation assays. The effect of ACS-derived conditioned-medium on myofibroblasts was investigated using an in-vitro model of myofibroblast differentiation via detection of α-SMA using immunoblotting and immunofluorescence microscopy. Results: Our methodology permitted efficient recovery of keratinocytes, fibroblasts and melanocytes, which remained viable upon long-term culture. ACS-derivatives comprised sub-populations with the CD49-high/CD71-low expression profile known to demarcate EpSCs. Via secretion of mitogenic factors and wound healing-enhancing mediators, the ACS secretome accelerated keratinocyte proliferation and markedly curtailed cytodifferentiation of myofibroblasts, the latter being key mediators of fibrosis and scarring. Discussion: The systematic characterisation of the cell types within our ACS isolates provided evidence for their superior cell viability and the presence of EpSCs that are critical drivers of wound healing. We defined the biological properties of ACS-derived keratinocytes, which include ability to secrete positive mediators of wound healing as well as suppression of myofibroblast cytodifferentiation. Thus, our study provides several lines of evidence that the established ACS isolates comprise highly-viable cell populations which can physically support wound healing and possess biological properties that have the potential to enhance not only the speed but also the quality of wound healing.

A systematic review on the qualitative experiences of people living with lung cancer in rural areas.

PURPOSE: To synthesize the qualitative literature exploring the experiences of people living with lung cancer in rural areas. METHODS: Searches were performed in MEDLINE, CINAHL, and PsycINFO. Articles were screened independently by two reviewers against pre-determined eligibility criteria. Data were synthesized using Thomas and Harden's framework for the thematic synthesis of qualitative research. The CASP qualitative checklist was used for quality assessment and the review was reported in accordance with the ENTREQ and PRISMA checklists. RESULTS: Nine articles were included, from which five themes were identified: (1) diagnosis and treatment pathways, (2) travel and financial burden, (3) communication and information, (4) experiences of interacting with healthcare professionals, (5) symptoms and health-seeking behaviors. Lung cancer diagnosis was unexpected for some with several reporting treatment delays and long wait times regarding diagnosis and treatment. Accessing treatment was perceived as challenging and time-consuming due to distance and financial stress. Inadequate communication of information from healthcare professionals was a common concern expressed by rural people living with lung cancer who also conveyed dissatisfaction with their healthcare professionals. Some were reluctant to seek help due to geographical distance and sociocultural factors whilst others found it challenging to identify symptoms due to comorbidities. CONCLUSIONS: This review provides a deeper understanding of the challenges faced by people with lung cancer in rural settings, through which future researchers can begin to develop tailored support to address the existing disparities that affect this population.

Solar urticaria involves rapid mast cell STAT3 activation and neutrophil recruitment, with FcεRI as an upstream regulator.

BACKGROUND: Solar urticaria is a rare photodermatosis characterized by rapid-onset sunlight-induced urticaria, but its pathophysiology is not well understood. OBJECTIVE: We sought to define cutaneous cellular and molecular events in the evolution of solar urticaria following its initiation by solar-simulated UV radiation (SSR) and compare with healthy controls (HC). METHODS: Cutaneous biopsy specimens were taken from unexposed skin and skin exposed to a single low (physiologic) dose of SSR at 30 minutes, 3 hours, and 24 hours after exposure in 6 patients with solar urticaria and 6 HC. Biopsy specimens were assessed by immunohistochemistry and bulk RNA-sequencing analysis. RESULTS: In solar urticaria specimens, there was enrichment of several innate immune pathways, with striking early involvement of neutrophils, which was not observed in HC. Multiple proinflammatory cytokine and chemokine genes were upregulated (including IL20, IL6, and CXCL8) or identified as upstream regulators (including TNF, IL-1ß, and IFN-γ). IgE and FcεRI were identified as upstream regulators, and phosphorylated signal transducer and activator of transcription 3 expression in mast cells was increased in solar urticaria at 30 minutes and 3 hours after SSR exposure, suggesting a mechanism of mast cell activation. Clinical resolution of solar urticaria by 24 hours mirrored resolution of inflammatory gene signature profiles. Comparison with available datasets of chronic spontaneous urticaria showed transcriptomic similarities relating to immune activation, but several transcripts were identified solely in solar urticaria, including CXCL8 and CSF2/3. CONCLUSIONS: Solar urticaria is characterized by rapid signal transducer and activator of transcription 3 activation in mast cells and involvement of multiple chemotactic and innate inflammatory pathways, with FcεRI engagement indicated as an early event.

Improving practice in PD-L1 testing of non-small cell lung cancer in the UK: current problems and potential solutions.

AIMS: Programmed cell death ligand 1 (PD-L1) expression, used universally to predict response of non-small cell lung cancer (NSCLC) to immune-modulating drugs, is a fragile biomarker due to biological heterogeneity and challenges in interpretation. The aim of this study was to assess current PD-L1 testing practices in the UK, which may help to define strategies to improve its reliability and consistency. METHODS: A questionnaire covering NSCLC PD-L1 testing practice was devised and members of the Association of Pulmonary Pathologists were invited to complete this online. RESULTS: Of 44 pathologists identified as involved in PD-L1 testing, 32 (73%) responded. There was good consistency in practice and approach, but there was wide variability in the distribution of PD-L1 scoring. Although the proportions of scores falling into the three groups (negative, low and high) defined by the 1% and 50% 'cut-offs' (38%, 33% and 27%, respectively) reflect the general experience, the range within each group was wide at 23-70%, 10-60% and 15-36%, respectively. CONCLUSIONS: There is inconsistency in the crucial endpoint of PD-L1 testing of NSCLC, the expression score that guides management. Addressing this requires formal networking of individuals and laboratories to devise a strategy for its reduction.

Impact of a Prior Cancer Diagnosis on Quality of Care and Survival Following Acute Myocardial Infarction: Retrospective Population-Based Cohort Study in England.

BACKGROUND: An increasing proportion of patients with cancer experience acute myocardial infarction (AMI). We investigated differences in quality of AMI care and survival between patients with and without previous cancer diagnoses. METHODS: A retrospective cohort study using Virtual Cardio-Oncology Research Initiative data. Patients aged 40+ years hospitalized in England with AMI between January 2010 and March 2018 were assessed, ascertaining previous cancers diagnosed within 15 years. Multivariable regression was used to assess effects of cancer diagnosis, time, stage, and site on international quality indicators and mortality. RESULTS: Of 512 388 patients with AMI (mean age, 69.3 years; 33.5% women), 42 187 (8.2%) had previous cancers. Patients with cancer had significantly lower use of ACE (angiotensin-converting enzyme) inhibitors/angiotensin receptor blockers (mean percentage point decrease [mppd], 2.6% [95% CI, 1.8-3.4]) and lower overall composite care (mppd, 1.2% [95% CI, 0.9-1.6]). Poorer quality indicator attainment was observed in patients with cancer diagnosed in the last year (mppd, 1.4% [95% CI, 1.8-1.0]), with later stage disease (mppd, 2.5% [95% CI, 3.3-1.4]), and with lung cancer (mppd, 2.2% [95% CI, 3.0-1.3]). Twelve-month all-cause survival was 90.5% in noncancer controls and 86.3% in adjusted counterfactual controls. Differences in post-AMI survival were driven by cancer-related deaths. Modeling improving quality indicator attainment to noncancer patient levels showed modest 12-month survival benefits (lung cancer, 0.6%; other cancers, 0.3%). CONCLUSIONS: Measures of quality of AMI care are poorer in patients with cancer, with lower use of secondary prevention medications. Findings are primarily driven by differences in age and comorbidities between cancer and noncancer populations and attenuated after adjustment. The largest impact was observed in recent cancer diagnoses (<1 year) and lung cancer. Further investigation will determine whether differences reflect appropriate management according to cancer prognosis or whether opportunities to improve AMI outcomes in patients with cancer exist.

Changing from face-to-face to virtual meetings due to the COVID-19 pandemic: protocol for a mixed-methods study exploring the impact on cancer multidisciplinary team (MDT) meetings.

INTRODUCTION: In the UK, the National Cancer Plan (2000) requires every cancer patient's care to be reviewed by a multidisciplinary team (MDT). Since the introduction of these guidelines, MDTs have faced escalating demands with increasing numbers and complexity of cases. The COVID-19 pandemic has presented MDTs with the challenge of running MDT meetings virtually rather than face-to-face.This study aims to explore how the change from face-to-face to virtual MDT meetings during the COVID-19 pandemic may have impacted the effectiveness of decision-making in cancer MDT meetings and to make recommendations to improve future cancer MDT working based on the findings. METHODS AND ANALYSIS: A mixed-methods study with three parallel phases:Semistructured remote qualitative interviews with ≤40 cancer MDT members.A national cross-sectional online survey of cancer MDT members in England, using a validated questionnaire with both multiple-choice and free-text questions.Live observations of ≥6 virtual/hybrid cancer MDT meetings at four NHS Trusts.Participants will be recruited from Cancer Alliances in England. Data collection tools have been developed in consultation with stakeholders, based on a conceptual framework devised from decision-making models and MDT guidelines. Quantitative data will be summarised descriptively, and χ2 tests run to explore associations. Qualitative data will be analysed using applied thematic analysis. Using a convergent design, mixed-methods data will be triangulated guided by the conceptual framework.The study has been approved by NHS Research Ethics Committee (London-Hampstead) (22/HRA/0177). The results will be shared through peer-reviewed journals and academic conferences. A report summarising key findings will be used to develop a resource pack for MDTs to translate learnings from this study into improved effectiveness of virtual MDT meetings.The study has been registered on the Open Science Framework (https://doi.org/10.17605/OSF.IO/D2NHW).

Acute heart failure presentation, management, and outcomes in cancer patients: a national longitudinal study.

AIMS: Currently, little evidence exists on survival and quality of care in cancer patients presenting with acute heart failure (HF). The aim of the study is to investigate the presentation and outcomes of hospital admission with acute HF in a national cohort of patients with prior cancer. METHODS AND RESULTS: This retrospective, population-based cohort study identified 221 953 patients admitted to a hospital in England for HF during 2012-2018 (12 867 with a breast, prostate, colorectal, or lung cancer diagnosis in the previous 10 years). We examined the impact of cancer on (i) HF presentation and in-hospital mortality, (ii) place of care, (iii) HF medication prescribing, and (iv) post-discharge survival, using propensity score weighting and model-based adjustment. Heart failure presentation was similar between cancer and non-cancer patients. A lower percentage of patients with prior cancer were cared for in a cardiology ward [-2.4% age point difference (ppd) (95% CI -3.3, -1.6)] or were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists (ACEi/ARB) for heart failure with reduced ejection fraction [-2.1 ppd (-3.3, -0.9)] than non-cancer patients. Survival after HF discharge was poor with median survival of 1.6 years in prior cancer and 2.6 years in non-cancer patients. Mortality in prior cancer patients was driven primarily by non-cancer causes (68% of post-discharge deaths). CONCLUSION: Survival in prior cancer patients presenting with acute HF was poor, with a significant proportion due to non-cancer causes of death. Despite this, cardiologists were less likely to manage cancer patients with HF. Cancer patients who develop HF were less likely to be prescribed guideline-based HF medications compared with non-cancer patients. This was particularly driven by patients with a poorer cancer prognosis.

Prevalence of Cardiovascular Disease in Patients With Potentially Curable Malignancies: A National Registry Dataset Analysis.

Background: Although a common challenge for patients and clinicians, there is little population-level evidence on the prevalence of cardiovascular disease (CVD) in individuals diagnosed with potentially curable cancer. Objectives: We investigated CVD rates in patients with common potentially curable malignancies and evaluated the associations between patient and disease characteristics and CVD prevalence. Methods: The study included cancer registry patients diagnosed in England with stage I to III breast cancer, stage I to III colon or rectal cancer, stage I to III prostate cancer, stage I to IIIA non-small-cell lung cancer, stage I to IV diffuse large B-cell lymphoma, and stage I to IV Hodgkin lymphoma from 2013 to 2018. Linked hospital records and national CVD databases were used to identify CVD. The rates of CVD were investigated according to tumor type, and associations between patient and disease characteristics and CVD prevalence were determined. Results: Among the 634,240 patients included, 102,834 (16.2%) had prior CVD. Men, older patients, and those living in deprived areas had higher CVD rates. Prevalence was highest for non-small-cell lung cancer (36.1%) and lowest for breast cancer (7.7%). After adjustment for age, sex, the income domain of the Index of Multiple Deprivation, and Charlson comorbidity index, CVD remained higher in other tumor types compared to breast cancer patients. Conclusions: There is a significant overlap between cancer and CVD burden. It is essential to consider CVD when evaluating national and international treatment patterns and cancer outcomes.

Association between time-to-treatment and outcomes in non-small cell lung cancer: a systematic review.

BACKGROUND: National targets for timely diagnosis and management of a potential cancer are driven in part by the perceived risk of disease progression during avoidable delays. However, it is unclear to what extent time-to-treatment impacts prognosis for patients with non-small cell lung cancer, with previous reviews reporting mixed or apparently paradoxical associations. This systematic review focuses on potential confounders in order to identify particular patient groups which may benefit most from timely delivery of care. METHODS: Medline, EMBASE and Cochrane databases were searched for publications between January 2012 and October 2020, correlating timeliness in secondary care pathways to patient outcomes. The protocol is registered with PROSPERO (the International Prospective Register of Systematic Reviews; ID 99239). Prespecified factors (demographics, performance status, histology, stage and treatment) are examined through narrative synthesis. RESULTS: Thirty-seven articles were included. All but two were observational. Timely care was generally associated with a worse prognosis in those with advanced stage disease (6/8 studies) but with better outcomes for patients with early-stage disease treated surgically (9/12 studies). In one study, patients with squamous cell carcinoma referred for stereotactic ablative radiotherapy benefited more from timely care, compared with patients with adenocarcinoma. One randomised controlled trial supported timeliness as being advantageous in those with stage I-IIIA disease. CONCLUSION: There are limitations to the available evidence, but observed trends suggest timeliness to be of particular importance in surgical candidates. In more advanced disease, survival trends are likely outweighed by symptom burden, performance status or clinical urgency dictating timeliness of treatment.

Promoting early diagnosis and recovering from the COVID-19 pandemic in lung cancer through public awareness campaigns: learning from patient and public insight work.

COVID-19 has had a devastating impact on outcomes in lung cancer leading to later stage presentation, less curative treatment and higher mortality. This has amplified the existing problem of late-stage presentation in lung cancer and is a call to arms for a multifaceted strategy to address this, including public awareness campaigns to promote healthcare review in patients with persistent chest symptoms. We report the learning from patient and public insight work from across the North of England exploring the barriers to seeking healthcare review with persistent chest symptoms. Members of the public described how a lack of importance is placed on the common symptoms of lung cancer and a feeling of being unworthy of review by healthcare professionals. They would feel motivated to seek review by dispelling the nihilism of lung cancer and would be able to take action more easily by removing the logistical hassle in the process. We propose a four-pillar framework (validation-endorsement-motivation-action) for developing the content of any public awareness campaigns promoting early diagnosis of lung cancer based on the findings of this comprehensive insight work. All providers and commissioners must work together to overcome the perceived and real barriers to patients with persistent chest symptoms.

Cooling-mediated protection from chemotherapy drug-induced cytotoxicity in human keratinocytes by inhibition of cellular drug uptake.

Chemotherapy-induced alopecia (CIA) represents the most distressing side-effect for cancer patients. Scalp cooling is currently the only treatment to combat CIA, yet little is known about its cytoprotective effects in human hair follicles (HF). We have previously established in vitro human keratinocyte models to study the effects of taxanes and anthracyclines routinely-used clinically and reported that cooling markedly-reduced or even completely-prevented cytotoxicity in a temperature dependent manner. Using these models (including HF-derived primary keratinocytes), we now demonstrate that cooling markedly attenuates cellular uptake of the anthracyclines doxorubicin and epirubicin to reduce or prevent drug-mediated human keratinocyte cytotoxicity. We show marked reduction in drug uptake and nuclear localization qualitatively by fluorescence microscopy. We have also devised a flow cytometry-based methodology that permitted semi-quantitative analysis of differences in drug uptake, which demonstrated that cooling can reduce drug uptake by up to ~8-fold in comparison to normal/physiological temperature, an effect that was temperature-dependent. Our results provide evidence that attenuation of cellular drug uptake represents at least one of the mechanisms underpinning the ability of cooling to rescue human keratinocytes from chemotherapy drug-cytotoxicity, thus supporting the clinical efficacy of scalp cooling.

Impact on survival of modelling increased surgical resection rates in patients with non-small-cell lung cancer and cardiovascular comorbidities: a VICORI study.

BACKGROUND: The impact of cardiovascular disease (CVD) comorbidity on resection rates and survival for patients with early-stage non-small-cell lung cancer (NSCLC) is unclear. We explored if CVD comorbidity explained surgical resection rate variation and the impact on survival if resection rates increased. METHODS: Cancer registry data consisted of English patients diagnosed with NSCLC from 2012 to 2016. Linked hospital records identified CVD comorbidities. We investigated resection rate variation by geographical region using funnel plots; resection and death rates using time-to-event analysis. We modelled an increased propensity for resection in regions with the lowest resection rates and estimated survival change. RESULTS: Among 57,373 patients with Stage 1-3A NSCLC, resection rates varied considerably between regions. Patients with CVD comorbidity had lower resection rates and higher mortality rates. CVD comorbidity explained only 1.9% of the variation in resection rates. For every 100 CVD comorbid patients, increasing resection in regions with the lowest rates from 24 to 44% would result in 16 more patients resected and alive after 1 year and two fewer deaths overall. CONCLUSIONS: Variation in regional resection rate is not explained by CVD comorbidities. Increasing resection in patients with CVD comorbidity to the levels of the highest resecting region would increase 1-year survival.

Sequential screening for lung cancer in a high-risk group: randomised controlled trial: LungSEARCH: a randomised controlled trial of Surveillance using sputum and imaging for the EARly detection of lung Cancer in a High-risk group.

BACKGROUND: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. METHODS: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). RESULTS: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. CONCLUSIONS: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening.

Establishing population-based surveillance of diagnostic timeliness using linked cancer registry and administrative data for patients with colorectal and lung cancer.

BACKGROUND: Diagnostic timeliness in cancer patients is important for clinical outcomes and patient satisfaction but, to-date, continuous monitoring of diagnostic intervals in nationwide incident cohorts has been impossible in England. METHODS: We developed a new methodology for measuring the secondary care diagnostic interval (SCDI - first relevant secondary care contact to diagnosis) using linked cancer registration and healthcare utilisation data. Using this method, we subsequently examined diagnostic timeliness in colorectal and lung cancer patients (2014-15) by socio-demographic characteristics, diagnostic route and stage at diagnosis. RESULTS: The approach assigned SCDIs to 94.4% of all incident colorectal cancer cases [median length (90th centile) of 25 (104) days] and 95.3% of lung cancer cases [36 (144) days]. Advanced stage patients had shorter intervals (median, colorectal: stage 1 vs 4 - 34 vs 19 days; lung stage 1&2 vs 3B&4 - 70 vs 27 days). Routinely referred patients had the longest (colorectal: 61, lung: 69 days) and emergency presenters the shortest intervals (colorectal: 3, lung: 14 days). Comorbidities and additional diagnostic tests were also associated with longer intervals. CONCLUSION: This new method can enable repeatable nationwide measurement of cancer diagnostic timeliness in England and identifies actionable variation to inform early diagnosis interventions and target future research.

Prophylactic Irradiation of Tracts in Patients With Malignant Pleural Mesothelioma: An Open-Label, Multicenter, Phase III Randomized Trial.

PURPOSE: Prophylactic irradiation to the chest wall after diagnostic or therapeutic procedures in patients with malignant pleural mesothelioma (MPM) has been a widespread practice across Europe, although the efficacy of this treatment is uncertain. In this study, we aimed to determine the efficacy of prophylactic radiotherapy in reducing the incidence of chest wall metastases (CWM) after a procedure in MPM. METHODS: After undergoing a chest wall procedure, patients with MPM were randomly assigned to receive prophylactic radiotherapy (within 42 days of the procedure) or no radiotherapy. Open thoracotomies, needle biopsies, and indwelling pleural catheters were excluded. Prophylactic radiotherapy was delivered at a dose of 21 Gy in three fractions over three consecutive working days, using a single electron field adapted to maximize coverage of the tract from skin surface to pleura. The primary outcome was the incidence of CWM within 6 months from random assignment, assessed in the intention-to-treat population. Stratification factors included epithelioid histology and intention to give chemotherapy. RESULTS: Between July 30, 2012, and December 12, 2015, 375 patients were recruited from 54 centers and randomly assigned to receive prophylactic radiotherapy (n = 186) or no prophylactic radiotherapy (n = 189). Participants were well matched at baseline. No significant difference was seen in the incidence of CWM at 6 months between the prophylactic radiotherapy and no radiotherapy groups (no. [%]: 6 [3.2] v 10 [5.3], respectively; odds ratio, 0.60; 95% CI, 0.17 to 1.86; P = .44). Skin toxicity was the most common radiotherapy-related adverse event in the prophylactic radiotherapy group, with 96 patients (51.6%) receiving grade 1; 19 (10.2%), grade 2; and 1 (0.5%) grade 3 radiation dermatitis (Common Terminology Criteria for Adverse Events, version 4.0). CONCLUSION: There is no role for the routine use of prophylactic irradiation to chest wall procedure sites in patients with MPM.

Incidence of second and higher order smoking-related primary cancers following lung cancer: a population-based cohort study.

BACKGROUND: Lung cancer 5-year survival has doubled over 15 years. Although the risk of second primary cancer is recognised, quantification over time is lacking. We describe the incidence of second and higher order smoking-related primary cancers in lung cancer survivors, identifying high-incidence groups and how incidence changes over time from first diagnosis. METHODS: Data on smoking-related primary cancers (lung, laryngeal, head and neck, oesophageal squamous cell carcinoma and bladder) diagnosed in England between 2000 and 2014 were obtained from Public Health England National Cancer Registration and Analysis Service. We calculated absolute incidence rates and standardised incidence rate ratios, both overall and for various subgroups of second primary cancer for up to 10 years from the initial diagnosis of lung cancer, using Poisson regression. RESULTS: Elevated incidence of smoking-related second primary cancer persists for at least 10 years from first lung cancer diagnosis with those aged 50 and 79 at first diagnosis at particularly high risk. The most frequent type of second malignancy was lung cancer although the highest standardised incidence rate ratios were for oesophageal squamous cell carcinoma (2.4) and laryngeal cancers (2.8) and consistently higher in women than in men. Over the last decade, the incidence of second primary lung cancer has doubled. CONCLUSION: Lung cancer survivors have increased the incidence of subsequent lung, laryngeal, head and neck and oesophageal squamous cell carcinoma for at least a decade from the first diagnosis. Consideration should be given to increasing routine follow-up from 5 years to 10 years for those at highest risk, alongside surveillance for other smoking-related cancers.

Impact of variation in cancer registration practice on observed international cancer survival differences between International Cancer Benchmarking Partnership (ICBP) jurisdictions.

BACKGROUND: International cancer survival comparisons use cancer registration data to report cancer survival, which informs the development of cancer policy and practice. Studies like the International Cancer Benchmarking Partnership (ICBP) have a duty to understand how registration differences impact on survival prior to drawing conclusions. METHODS: Key informants reported differences in registration practice for capturing incidence date, death certificate case handling and registration of multiple primary tumours. Sensitivity analyses estimated their impact on one-year survival using baseline and supplementary cancer registration data from England and Sweden. RESULTS: Variations in registration practice accounted for up to a 7.3 percentage point difference between unadjusted (estimates from previous ICBP survival data) and adjusted (estimates recalculated accounting for registration differences) one-year survival, depending on tumour site and jurisdiction. One-year survival estimates for four jurisdictions were affected by adjustment: New South Wales, Norway, Ontario, Sweden. Sweden and Ontario's survival reduced after adjustment, yet they remained the jurisdictions with the highest survival for breast and ovarian cancer respectively. Sweden had the highest unadjusted lung cancer survival of 43.6% which was adjusted to 39.0% leaving Victoria and Manitoba with the highest estimate at 42.7%. For colorectal cancer, Victoria's highest survival of 85.1% remained unchanged after adjustment. CONCLUSION: Population-based cancer survival comparisons can be subject to registration biases that may impact the reported 'survival gap' between populations. Efforts should be made to apply consistent registration practices internationally. In the meantime, survival comparison studies should provide acknowledgement of or adjustment for the registration biases that may affect their conclusions.

Associations between general practice characteristics with use of urgent referrals for suspected cancer and endoscopies: a cross-sectional ecological study.

BACKGROUND: Large variation in measures of diagnostic activity has been described previously between English general practices, but related predictors remain understudied. OBJECTIVE: To examine associations between general practice population and characteristics, with the use of urgent referrals for suspected cancer, and use of endoscopy. METHODS: Cross-sectional observational study of English general practices. We examined practice-level use (/1000 patients/year) of urgent referrals for suspected cancer, gastroscopy, flexible sigmoidoscopy and colonoscopy. We used mixed-effects Poisson regression to examine associations with the sociodemographic profile of practice populations and other practice attributes, including the average age, sex and country of qualification of practice doctors. RESULTS: The sociodemographic characteristics of registered patients explained much of the between-practice variance in use of urgent referrals (32%) and endoscopic investigations (18-25%), all being higher in practices with older and more socioeconomically deprived patients. Practice-level attributes explained a substantial amount of between-practice variance in urgent referral (19%) but little of the variance in endoscopy (3%-4%). Adjusted urgent referral rates were higher in training practices and those with younger GPs. Practices with mean doctor ages of 41 and 57 years (at the 10th/90th centiles of the national distribution) would have urgent referral rates of 24.1 and 19.1/1000 registered patients, P < 0.001. CONCLUSION: Most between-practice variation in use of urgent referrals and endoscopies seems to reflect health need. Some practice characteristics, such as the mean age of GPs, are associated with appreciable variation in use of urgent referrals, though these associations do not seem strong enough to justify targeted interventions.

Association between age, deprivation and specific comorbid conditions and the receipt of major surgery in patients with non-small cell lung cancer in England: A population-based study.

INTRODUCTION: We investigated socioeconomic disparities and the role of the main prognostic factors in receiving major surgical treatment in patients with lung cancer in England. METHODS: Our study comprised 31 351 patients diagnosed with non-small cell lung cancer in England in 2012. Data from the national population-based cancer registry were linked to Hospital Episode Statistics and National Lung Cancer Audit data to obtain information on stage, performance status and comorbidities, and to identify patients receiving major surgical treatment. To describe the association between prognostic factors and surgery, we performed two different analyses: one using multivariable logistic regression and one estimating cause-specific hazards for death and surgery. In both analyses, we used multiple imputation to deal with missing data. RESULTS: We showed strong evidence that the comorbidities 'congestive heart failure', 'cerebrovascular disease' and 'chronic obstructive pulmonary disease' reduced the receipt of surgery in early stage patients. We also observed gender differences and substantial age differences in the receipt of surgery. Despite accounting for sex, age at diagnosis, comorbidities, stage at diagnosis, performance status and indication of having had a PET-CT scan, the socioeconomic differences persisted in both analyses: more deprived people had lower odds and lower rates of receiving surgery in early stage lung cancer. DISCUSSION: Comorbidities play an important role in whether patients undergo surgery, but do not completely explain the socioeconomic difference observed in early stage patients. Future work investigating access to and distance from specialist hospitals, as well as patient perceptions and patient choice in receiving surgery, could help disentangle these persistent socioeconomic inequalities.