Trainee Enews January 2024

Welcome to the second BTOG trainee newsletter, where we aim to provide you with updates relevant to trainees working in the thoracic oncology space. In terms of content, the trainee newsletter will seek to summarise the ‘hot-off-the-press’ landmark papers, list updates for trainee-led multicentre projects, and sign-post readers to useful educational/professional content.

We are also interested in hearing what you would like from BTOG, following on from the great ideas proposed at the trainee session in Belfast at BTOG 2023, which will shape how BTOG caters for trainee needs in the future.

Please do use the BTOG trainee group-chat on Slack to continue your thoracic cancer conversations in the meantime. Feel free to contact the BTOG trainee representatives, Anand and Gerard, at anand.sundaralingam@ndm.ox.ac.uk or g.walls@qub.ac.uk

Respiratory

QuLIT1+2

Source: https://commons.wikimedia.org/wiki/File:Breaking_cigarette.jpg

In September 2022 the national screening committee recommended implementation for Targeted Lung Health Checks (TLHC) in the UK and that these programmes should incorporate smoking cessation. In November’s edition of Thorax, William et al compare two different approaches to smoking cessation in the Quit smoking Lung health Intervention Trials (QuLIT1 and QuLIT2) as part of a TLHC program in west London.

The authors have previously published findings at 3-months follow up in QuLIT1 and QuLIT2 and now present long-term outcome data. Both were RCTs of immediately offered smoking cessation support (six-sessions) alongside pharmacotherapy (SCS group) in smokers who attended for their first TLHC appointment compared to usual care (UC) which consisted of signposting to local stop smoking services and provided with Very Brief Advice (VBA). QuLIT1 was conducted face to face, whilst QuLIT2 consisted of remote sessions, both based on the NCSCT and Kick-it programmes.

430 participants were enrolled across both studies, with 77% completing 12-month follow up. Participants in the SCS group had greater rates of self-reported smoking cessation compared to the UC group (20% vs 12.8%; adjusted OR = 1.78, 95% CI 1.04 – 2.89) as well as exhaled carbon monoxide level-verified quit rates (12.1% vs 4.7%; AOR = 2.97, 95% CI 1.38-6.90). Those in the intervention arm were also more likely to have made a quit attempt compared to UC. Quit rates were not noticeably different between participants who were or were not offered a CT scan, nor was any difference noted between those with and without abnormal CT scans.

 

The authors conclude, providing immediate SCS as part of TLHC programs, results in greater smoking quit rates and therefore such services should be integrated into TLHC programs.

 

DOI: 10.1136/thorax-2023-220367

“This study from Williams et al confirms the importance of providing immediate smoking cessation support as part of any lung cancer screening programme. These results have also been replicated by Murray et al as part of the Yorkshire Enhanced Stop Smoking Study (YESS), with validated quit rates of 29% at 12 months with high-intensity, opt out smoking cessation support in their cohort. A recent systematic review by Williams et al (of 10 randomised controlled trials and three observational studies) confirmed that stop smoking interventions delivered within lung cancer screening programmes are effective, with high-intensity (≥3 behavioural counselling sessions) interventions demonstrating greater quit rates compared to usual care. Modelling studies have also shown that embedding stop-smoking support for individuals who smoke and attend lung-cancer screening can decrease deaths by 14% and increase overall life-years by 81%. It is clear that there needs to be a commitment to funding co-located stop smoking services, with provision of immediate, opt-out behavioural and pharmacologic support if we are to maximise the benefits of lung cancer screening.

Dr Emma O’Dowd
Consultant Respiratory Physician/ Honorary Associate Professor
Nottingham University Hospitals NHS Trust/University of Nottingham

Radiology

RadioX

The national optimal lung cancer pathway (NOLCP) was designed to accelerate the time to diagnosis and treatment for patients with lung cancer. A key feature of the program is for rapid reporting of chest X-rays (CXRs) and to arrange a CT if indicated, ideally on the same day. However, there are several logistical challenges to this approach, least of all a national shortage of consultant radiologists for said reporting.

Lung cancer seen on chest x-ray. by James Heilman, MD, edited by Andrew Meyerson used under a CC BY-SA 4.0 DEED license.

In the RadioX study, Woznitza et al compared the impact of immediate CXR reporting by radiographer, whilst the patient is in the department, on time to lung cancer diagnosis or discharge from the pathway. The study was conducted from 2017-2018 in a single inner-city NHS trust. Patients were randomised to either immediate reporting (IR) or standard radiographer reporting (SR) completed within 24 hours. CXRs in both arms were independently reported by a consultant radiologist (blinded to report), and both reports were assessed for agreement by respiratory physicians (blinded to reporter).

Across a total of 8682 CXRs, 4096 (47.2%) took place in sessions block randomised to IR and 4586 (52.8%) to SR. 49 (0.6%) lung cancers were diagnosed out of the entire study population (27 = IR, 22 = SR group). Participants in the IR group had a shorter time from CXR to lung cancer diagnosis compared to the SR group (median 32 days vs 63 days, p=0.03, respectively). The median time to diagnosis in the SR group was comparable to that of an external control group at a nearby DGH, during the study period and operating a similar SR pathway. No significant differences were noted in the time to discharge from the pathway between either group for non-lung cancer diagnoses. Agreement between the radiologist and radiographer reports was generally good (84% concordance).

 

The authors conclude that a radiographer delivered immediate CXR reporting service can achieve the aims set out in the NOLCP and improve time to diagnosis for lung cancer patients.

 

DOI: https://doi.org/10.1136/thorax-2022-219210

“The study by Woznitza et al highlights the significant impact in time to lung cancer diagnosis that can be achieved with immediate chest radiograph reporting (IR), in this case delivered by radiographers. Reassuringly, this faster diagnosis did not compromise observations, interpretation, recommendations, or accuracy, with good agreement between radiologists and radiographers in these domains.

It is salutary that the faster diagnosis is not attributable to a reduced turnaround time (TAT) for reports alone; indeed, the median (IQR) for immediate reporting was 0 (0-1) hours, achieved for 71% of reports, while that for SR was 1 (0-2), with 99% reported in less than 24 hours – a difference in orders of magnitude smaller than the 31-day reduction in time from CXR to lung cancer diagnosis achieved with IR. This suggests that there is probably larger, exponential downstream impact- a ‘butterfly effect’; an initial small reduction of TAT achieved by immediate reporting then accelerates the time taken between the various subsequent elements of the diagnostic chain. The RadioX study should galvanise further research into further quantifying these downstream impacts.”

 

Dr Arjun Nair
Consultant Radiologist | UCLH NHS Foundation Trust
Honorary Associate Professor | UCL Division of Medicine – Respiratory Medicine
Joint Clinical Lead | Targeted Lung Health Checks Programme, NHS England and NHS Improvement

Medical Oncology

DeLLphi-301
Figure 1A from https://tlcr.amegroups.org/article/view/74703/html#B2 used under a CC BY-NC-ND 4.0 license.

In this international, phase 2 study, Ahn et al evaluated the clinical efficacy of a novel immunotherapy agent in pre-treated metastatic small cell lung cancer. Tarlatamab is  a bispecific T cell engager agent, with affinity for both delta-like ligand 3 (DLL3) on SCLC cells and CD3 on T cells. The Notch pathway is a key driver of cell fate in neuroendocrine tumours, and DLL3 is a ligand in this pathway that is highly expressed on the cell surface in ~95% SCLC cases. In forming a link between tumour cells and T-cells, tumour cell lysis is enhanced. A phase 1 study confirmed the expected toxicity profile including cytokine release syndrome (CRS) and auto-immune adverse events.

The primary endpoint for this study was objective response. Patients with PS 0–1 were randomly assigned to either 10mg or 100mg in the initial part, and after interim analysis by an independent body, the optimal dose of 10mg was selected for the subsequent parts of the trial based on better safety and efficacy. Tarlatamab is administered as an intravenous infusion over 1 hour on alternate weeks, and cycle 1 included a ‘run in’ dose of 1mg on day 1 in relation to reducing the risk of CRS.

A total of 222 patients were enrolled, some of which had a history of brain (26%) and liver (36%) metastases, and the cohort was heavily pre-treated (median 2 previous treatments, range 1–6) and largely platinum-refractory (45% progression-free interval <6 months). An objective response to 10mg tarlatamab treatment was recorded for 40% patients and the median time to response was 1.4 months. The median duration of response was not reached but was ≥6 months for 59% of responders. The 6-month progression-free and overall survival estimates were 40% and 70% respectively. CRS occurred in 51% patients, primarily during cycle 1 and usually grade 1–2) and other common toxicities were anorexia and pyrexia. Only 3% patients discontinued tarlatamab because of treatment-related adverse events. As well as CRS, the other notable side effect was immune effector cell–associated neurotoxicity syndrome (ICANS), which affected 8% of 10mg group, typically during cycle 1. ICANS presents as confusion, impaired attention, tremor, and motor findings such as weakness, but is responsive to corticosteroids.

 

The authors conclude that tarlatamab provides durable objective responses and that no new safety issues were noted. A phase 3 study is recruiting patients at present (DeLLphi-304, NCT05740566).

 

DOI: 10.1056/NEJMoa2307980

“This is ostensibly very exciting data. It’s rare for anything to look significantly active in this disease and a huge unmet need remains.  The mechanistic mode of action for tarlatamab looks very exciting and potentially a strategy to engage immune effector cells into the tumour microenvironment.  The current stipulations for overnight stay and CRS management protocols will limit the impact of this drug in routine practice currently but it looks highly active and in time I suspect we will learn how to give this safely in the outpatient setting.”

Dr Riyaz Shah
Consultant Medical Oncologist
Kent Oncology Centre, Maidstone

Clinical oncology

iSABR

In a multicentre, phase 2, non-randomised controlled study, Gensheimer et al evaluated the individualisation of SABR dose-fractionation according to tumour size, location and histology. Three patient cohorts were recruited within the iSABR trial: 1) first localised node-negative NSCLC primary; 2) new localised node-negative NSCLC on a background of previous NSCLC; and 3) pulmonary metastases from any other solid organ malignancy.

Image copyright Journal of Thoracic Oncology used under a CC BY-NC-ND 4.0 license.

Multiple tumours could be treated if the sum of 3 orthogonal diameters was <15cm. Single tumours were permitted to be up to 20cm in 3 measurements.

Patients were staged with PET-CT (88%) and tissue was acquired (89%). Note this trial of “individualised SABR”, shouldn’t confused with I-SABR, which described the successful combination of SABR with immunotherapy around the same time as the presented paper (Chang et al, Lancet Oncol 2023).

Enrolled patients received SABR to up to 4 lung tumours simultaneously with a dose ranging between 25–60Gy in 1–8 fractions, leading to a range of biologically effective doses (α/β ratio of 10) i.e. BED10, being evaluated.

Small tumours (≤10cm3) received 25Gy/1# (BED10 87.5 Gy) for peripheral and 40Gy/4# (BED10 80 Gy) for central, whereas large tumours (>30cm3) received 54Gy/3# (BED10 151.2 Gy) for peripheral and 60Gy/8# (BED10 105 Gy) for central. Medium tumours (>10cm3, ≤30cm3) received 50Gy/4# (BED10 112.5 Gy)regardless of location, as did metastases from a colorectal primary (due to their reported radioresistance). The primary endpoint was freedom from local recurrence (same lobe) at 1 year, with censoring of cases with distant recurrence, death, or loss to follow-up.

Over 7 years, 217 patients were enrolled into balanced groups, and 285 tumours were treated (74% peripheral, 26% peripheral). The most common dose-fractionation utilised was 25Gy/1# (55%) and 9% patients were treated more than once in this pragmatic study design. Of 26 recurrence events, 65% were in-field, 12% were marginal and 23% were elsewhere in the lobe. With a follow-up of 33 months, the freedom from local recurrence at 1 year was 97% for group 1, 94% for group 2, and 96% for group 3. The median overall survival was 59 months. Interestingly, less than 10% of small tumours recurred at 5 years despite being prescribed a BED <100Gy. The proportion of patients with grade 3+ adverse events was 5%. One grade 5 event was recorded as being possibly due to SABR – pulmonary haemorrhage in an large ultracentral tumour without local recurrence.

 

The authors conclude that iSABR may allow minimisation of total dose, and that it should interrogated further in future clinical trials.

 

DOI: 10.1001/jamaoncol.2023.3495

“This pragmatic study adds to the current literature, which already supports a “risk-adapted” individualised approach to lung SABR practice. A balance needs to be struck between minimising toxicity in an often frail population group, with the risks of “in-field” failures, which still occur in 5-10% of patients.  Ideally, future clinical trials utilising such individualised risk-adapted regimens (iSABR) will be combined with genomic studies and rigorous toxicity and QoL assessment to identify those who are most of local failure, and those most at risk of toxicity. We can then begin to better understand how best to select those patients who would benefit from dose de-escalation or escalation.”

Dr Clive Peedell
Consultant Clinical Oncologist
James Cook University Hospital, Middlesbrough

Noticeboard

Check out these resources that are ideal for trainees (Royal College of Radiologists membership required):

Assurances in radiotherapy through education and assessment (ARENA)
These online cases help standardise high-quality delineation training for UK and international clinical oncology trainees to improve skills in outlining tumours, with individual feedback provided on each performance against the gold standard. Each learning pathway contains a presentation, an interactive course and an online contouring exercise – making this first-class training widely accessible. More information.


Reporting lung cancer series
Produced in association with The Christie PET-CT Academy and presented by clinical experts, these short CPD courses are free to access:

 


Please send us news on your recent achievements as trainees to share on this noticeboard – email info@btog.org.

We have a BTOG trainee group-chat on Slack!

Jon us to continue your thoracic cancer conversations.

BTOG 2024 Scholarship Applications Close 28th February 2024

BTOG 2024 (Belfast, 17th – 19th April, 2024)
  • Applicants must:
    • Be a healthcare professional involved in care or treatment of patients with thoracic malignancies or involved in research in the UK and
    • Be an allied health professional, nurse specialist, radiographer or trainee doctor up to and including specialist registrar grade or consultant and
    • Submit an abstract to the annual conference and will attend annual conference.

    Submit your application here.

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