Biomarker Testing for People With Advanced Lung Cancer in England

Introduction: Optimal management of people with advanced NSCLC depends on accurate identification of predictive markers. Yet, real-world data in this setting are limited. We describe the impact, timeliness, and outcomes of molecular testing for patients with advanced NSCLC and good performance status in England. // Methods: In collaboration with Public Health England, patients with stages IIIB to IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 0 to 2, in England, between June 2017 and December 2017, were identified. All English hospitals were invited to record information. // Results: A total of 60 of 142 invited hospitals in England participated in this study and submitted data on 1157 patients. During the study period, 83% of patients with advanced adenocarcinoma underwent molecular testing for three recommended predictive biomarkers (EGFR, ALK, and programmed death-ligand 1). A total of 80% of patients with nonsquamous carcinomas on whom biomarker testing was performed had adequate tissue for analysis on initial sampling. First-line treatment with a tyrosine kinase inhibitor was received by 71% of patients with adenocarcinoma and a sensitizing EGFR mutation and by 59% of those with an ALK translocation. Of patients with no driver mutation and a programmed death-ligand 1 expression of greater than or equal to 50%, 47% received immunotherapy. // Conclusions: We present a comprehensive data set for molecular testing in England. Although molecular testing is well established in England, timeliness and uptake of targeted therapies should be improved

Predictors of patient preference for either whole body magnetic resonance imaging (WB-MRI) or CT/ PET-CT for staging colorectal or lung cancer.

INTRODUCTION: Whole body magnetic resonance imaging (WB-MRI) may be more efficient in staging cancers, but can be harder for patients to tolerate. We examined predictors of patient preference for WB-MRI vs. CT/ PET-CT for staging colorectal or lung cancer. METHODS: Patients recruited prospectively to two multicentre trials comparing diagnostic accuracy of WB-MRI with standard staging scans were sent two questionnaires: the first, administered at trial registration, captured demographics, educational level and comorbidities; the second, administered after staging completion, measured emotional distress (GHQ-12), positive mood (PANAS), perceived scan burden, patients' beliefs about WB-MRI, and preference for either WB-MRI or CT (colorectal trial), WB-MRI or PET-CT (lung trial). Preference for WB-MRI or CT/ PET-CT was analysed using logistic regression. RESULTS: Baseline and post-staging questionnaires were completed by 97 and 107 patients, respectively. Overall, 56/107 (52%) preferred WB-MRI over standard scans and were more likely to have no additional comorbidities, higher positive mood, greater awareness of potential benefits of WB-MRI and lower levels of perceived WB-MRI scan burden. In adjusted analyses, only awareness of potential WB-MRI benefits remained a significant predictor (OR: 1.516, 95% CIs 1.006-2.284, P = 0.047). Knowledge that WB-MRI does not use radiation predicted preference (adjusted OR: 3.018, 95% CIs 1.099-8.288, P = 0.032), although only 45/107 (42%) patients were aware of this attribute. CONCLUSIONS: A small majority of patients undergoing staging of colorectal or lung cancer prefer WB-MRI to CT/ PET-CT. Raising awareness of the potential benefits of WB-MRI, notably lack of ionizing radiation, could influence preference

Lung Screen Uptake Trial (LSUT): Randomized Controlled Clinical Trial Testing Targeted Invitation Materials

Rationale: Low uptake of low-dose computed tomography (LDCT) lung cancer screening, particularly by current smokers of a low socioeconomic position, compromises effectiveness and equity. Objectives: To compare the effect of a targeted, low-burden, and stepped invitation strategy versus control on uptake of hospital-based Lung Health Check appointments offering LDCT screening. Methods: In a two-arm, blinded, between-subjects, randomized controlled trial, 2,012 participants were selected from 16 primary care practices using these criteria: 1) aged 60 to 75 years, 2) recorded as a current smoker within the last 7 years, and 3) no prespecified exclusion criteria contraindicating LDCT screening. Both groups received a stepped sequence of preinvitation, invitation, and reminder letters from their primary care practitioner offering prescheduled appointments. The key manipulation was the accompanying leaflet. The intervention group’s leaflet targeted psychological barriers and provided low-burden information, mimicking the concept of the U.K. Ministry of Transport’s annual vehicle test (“M.O.T. For Your Lungs”). Measurements and Main Results: Uptake was 52.6%, with no difference between intervention (52.3%) and control (52.9%) groups in unadjusted (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.82–1.16) or adjusted (OR, 0.98; 95% CI, 0.82–1.17) analyses. Current smokers were less likely to attend (adjusted OR, 0.70; 95% CI, 0.56–0.86) than former smokers. Socioeconomic deprivation was significantly associated with lower uptake for the control group only (P < 0.01). Conclusions: The intervention did not improve uptake. Regardless of trial arm, uptake was considerably higher than previous clinical and real-world studies, particularly given that the samples were predominantly lower socioeconomic position smokers. Strategies common to both groups, including a Lung Health Check approach, could represent a minimum standard. Clinical trial registered with www.clinicaltrials.gov (NCT02558101) and registered prospectively with the International Standard Registered Clinical/Social Study (N21774741)

Whole-body MRI compared with standard pathways for staging metastatic disease in lung and colorectal cancer: the Streamline diagnostic accuracy studies.

BACKGROUND: Whole-body magnetic resonance imaging is advocated as an alternative to standard pathways for staging cancer. OBJECTIVES: The objectives were to compare diagnostic accuracy, efficiency, patient acceptability, observer variability and cost-effectiveness of whole-body magnetic resonance imaging and standard pathways in staging newly diagnosed non-small-cell lung cancer (Streamline L) and colorectal cancer (Streamline C). DESIGN: The design was a prospective multicentre cohort study. SETTING: The setting was 16 NHS hospitals. PARTICIPANTS: Consecutive patients aged ≥ 18 years with histologically proven or suspected colorectal (Streamline C) or non-small-cell lung cancer (Streamline L). INTERVENTIONS: Whole-body magnetic resonance imaging. Standard staging investigations (e.g. computed tomography and positron emission tomography-computed tomography). REFERENCE STANDARD: Consensus panel decision using 12-month follow-up data. MAIN OUTCOME MEASURES: The primary outcome was per-patient sensitivity difference between whole-body magnetic resonance imaging and standard staging pathways for metastasis. Secondary outcomes included differences in specificity, the nature of the first major treatment decision, time and number of tests to complete staging, patient experience and cost-effectiveness. RESULTS: Streamline C - 299 participants were included. Per-patient sensitivity for metastatic disease was 67% (95% confidence interval 56% to 78%) and 63% (95% confidence interval 51% to 74%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -5% to 13%; p = 0.51). Specificity was 95% (95% confidence interval 92% to 97%) and 93% (95% confidence interval 90% to 96%) respectively, a difference of 2% (95% confidence interval -2% to 6%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 96% and 95% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 8 days (95% confidence interval 6 to 9 days) and 13 days (95% confidence interval 11 to 15 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 5 days (95% confidence interval 3 to 7 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £216 (95% confidence interval £211 to £221) versus £285 (95% confidence interval £260 to £310). Streamline L - 187 participants were included. Per-patient sensitivity for metastatic disease was 50% (95% confidence interval 37% to 63%) and 54% (95% confidence interval 41% to 67%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -7% to 15%; p = 0.73). Specificity was 93% (95% confidence interval 88% to 96%) and 95% (95% confidence interval 91% to 98%), respectively, a difference of 2% (95% confidence interval -2% to 7%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 98% and 99% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 13 days (95% confidence interval 12 to 14 days) and 19 days (95% confidence interval 17 to 21 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 6 days (95% confidence interval 4 to 8 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £317 (95% confidence interval £273 to £361) versus £620 (95% confidence interval £574 to £666). Participants generally found whole-body magnetic resonance imaging more burdensome than standard imaging but most participants preferred the whole-body magnetic resonance imaging staging pathway if it reduced time to staging and/or number of tests. LIMITATIONS: Whole-body magnetic resonance imaging was interpreted by practitioners blinded to other clinical data, which may not fully reflect how it is used in clinical practice. CONCLUSIONS: In colorectal and non-small-cell lung cancer, the whole-body magnetic resonance imaging staging pathway has similar accuracy to standard staging pathways, is generally preferred by patients, improves staging efficiency and has lower staging costs. Future work should address the utility of whole-body magnetic resonance imaging for treatment response assessment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN43958015 and ISRCTN50436483. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 66. See the NIHR Journals Library website for further project information

Lung Screen Uptake Trial: results from a single lung cancer screening round

The Lung Screen Uptake Trial tested a novel invitation strategy to improve uptake and reduce socioeconomic and smoking-related inequalities in lung cancer screening (LCS) participation. It provides one of the first UK-based 'real-world' LCS cohorts. Of 2012 invited, 1058 (52.6%) attended a 'lung health check'. 768/996 (77.1%) in the present analysis underwent a low-dose CT scan. 92 (11.9%) and 33 (4.3%) participants had indeterminate pulmonary nodules requiring 3-month and 12-month surveillance, respectively; 36 lung cancers (4.7%) were diagnosed (median follow-up: 1044 days). 72.2% of lung cancers were stage I/II and 79.4% of non-small cell lung cancer had curative-intent treatment

Uptake and 4-week outcomes of an ‘opt-out’ smoking cessation referral strategy in a London-based lung cancer screening setting

INTRODUCTION: Lung cancer screening (LCS) enables the delivery of smoking cessation interventions to a population experiencing long-term tobacco dependence, but the optimal delivery method remains unclear. Here, we report uptake and short-term outcomes of an ‘opt-out’ smoking cessation referral strategy in an LCS cohort. METHODS: Individuals currently smoking tobacco who attended a face-to-face lung health check in the SUMMIT study (NCT03934866) were offered very brief advice on smoking cessation and where possible, an ‘opt-out’ referral to their local stop smoking service (SSS). Aggregate data on referral outcomes were obtained from each SSS individually. RESULTS: 33.7% (n=2090/6203) of individuals currently smoking tobacco consented to a practitioner-made ‘opt-out’ smoking cessation referral. 42.7% (n=893/2090) of these individuals resided in boroughs where SSS were not present or required self-referral. Males (adjusted OR (aOR) 1.16), younger individuals (55–59: aOR 1.70, 60–64: aOR 1.71 and 65–69: aOR 1.78) and those of ethnic minority backgrounds (Asian: aOR 1.31, Black: aOR 1.71 and Mixed: aOR 1.72) were more likely to consent, while individuals from the most deprived socioeconomic quintile were less likely to do so (aOR 0.65). High level of motivation to quit within a defined time frame (aOR 1.92), previous quit attempts in the past 12 months (1–4: aOR 1.65 and ≥5: aOR 1.54) and time to first cigarette of ≤60 min (<5: aOR 2.07, 6–30: aOR 1.55 and 31–60: aOR 1.56) were measures of tobacco dependence associated with a higher likelihood of providing consent. Outcomes were available for 742 referrals. An appointment with the service was accepted by 47.3% (n=351/742) of individuals, following which 65.5% (n=230/351) set a quit date. The 4-week quit rate among those setting a quit date and all individuals referred was 57.4% (n=132/230) and 17.8% (n=132/742), respectively. CONCLUSION: A proactive, ‘opt-out’ smoking cessation referral strategy for individuals currently smoking tobacco who interact with an LCS programme may be beneficial

Regenerative Medicine: Pharmacological Considerations and Clinical Role in Pain Management

Purpose of review: Low back pain affects at least 80% of individuals at some point in their lifetime and is the fifth most common reason for physician visits in the USA. Treatment of an acute episode of LBP generally includes rest, activity modification, physical therapy, NSAIDs, and patient education. Recent findings: A small percentage of patients will develop chronic pain lasting > 6 months duration. Platelet-rich plasma (PRP) is one of the main pillars of regenerative medicine, as its release of bioactive proteins supports the aim of RM of restoring the anatomical function in degenerative conditions. Mesenchymal stem cells (MSCs) are multipotent stem cells, multipotent progenitor cells, or marrow stromal cells found in various body tissues, including bone marrow, lung, and adipose tissue. Evidence from well-designed case-control or cohort studies for the use of PRP and MSCs in lumbar facet joint, lumbar epidural, and sacroiliac joint injections is currently described as level IV evidence. PRP and MSCs are used autogenously to help facilitate the healing process, and their injection has been studied in the long-term management of discogenic low back pain. PRP has been compared to steroid injections in the sacroiliac joint for chronic low back pain, with favorable results. MSCs have also been shown to be useful in intervertebral disc regeneration and treatment of chronic low back pain associated with degenerative disc disease. Currently, the price for these treatments is extremely high, and thus the standard of care continues to be steroid injections and other treatments. This could change, however, with more robust data and research on the safety and long-term efficacy of biologics compared to other interventional management

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Patient experience and perceived acceptability of whole-body magnetic resonance imaging for staging colorectal and lung cancer compared with current staging scans: a qualitative study

Objective To describe the experience and acceptability of whole-body magnetic resonance imaging (WB-MRI) staging compared with standard scans among patients with highly suspected or known colorectal or lung cancer. Design Qualitative study using one-to-one interviews with thematic analysis. Setting Patients recruited from 10 hospitals in London, East and South East England between March 2013 and July 2014. Participants 51 patients (31 male, age range 40–89 years), with varying levels of social deprivation, were recruited consecutively from two parallel clinical trials comparing the diagnostic accuracy and cost-effectiveness of WB-MRI with standard scans for staging colorectal and lung cancer (‘Streamline-C’ and ‘Streamline-L’). WB-MRI was offered as an additional scan as part of the trials. Results In general WB-MRI presented a greater challenge than standard scans, although all but four patients completed the WB-MRI. Key challenges were enclosed space, noise and scan duration; reduced patient tolerance was associated with claustrophobia, pulmonary symptoms and existing comorbidities. Coping strategies facilitated scan tolerance and were grouped into (1) those intended to help with physical and emotional challenges, and (2) those focused on motivation to complete the scan, for example focusing on health benefit. Our study suggests that good staff communication could reduce anxiety and boost coping strategies. Conclusions Although WB-MRI was perceived as more challenging than standard scans, it was sufficiently acceptable and tolerated by most patients to potentially replace them if appropriate. Trial registration number ISRCTN43958015 and ISRCTN50436483