Trainee Enews October 2023

Welcome to the inaugural 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

A TRACERX Study
Extracted from Extended Data Figure 1 under under a CC BY 4.0 International license.

It wouldn’t be a respiratory journal club if we didn’t talk about air pollution. In April’s edition of Nature, Hill et al explored the relationship between air pollution and cancer risk. Lung cancer in never smokers (LCINS) is increasingly a concern and the 8th most common cause of cancer death in the UK. LCINS will typically harbour EGFR mutations, but have a lower mutation burden compared to LCIS. There also marked differences in the demographic and geographical patterns of disease between the two.

The authors hypothesise that air pollution may promote inflammation in the normal tissue environment, that allows pre-existent mutated clones to proliferate and initiate tumours. They studied 447,392 UK Biobank participants and confirmed a link between PM2.5 exposure and both lung cancer and mesothelioma incidence (HR: 1.16, p <0.001 and 1.19 p = 0.0032, respectively). They also demonstrated a positive association between PM2.5 levels and incidence of EGFR mutant lung cancers across datasets in England, South Korea and Taiwan.

Finally, in a mouse model harbouring EGFR mutation positive lung epithelial cells exposure to PM resulted in a dose-dependent increase in the number of mutant cells and eventual neoplastic lesions.

Thus, the authors conclude, that air pollution may indeed be the critical factor, that promotes tumour growth, in dormant cells harbouring oncogenic mutations, in LCINS.

https://doi.org/10.1038/s41586-023-05874-3

“The study by Hill et al. confirms the important role that pollution plays in the development of lung cancer in never smokers. However, this landmark study led by the Swanton lab also provides novel insights into the mechanism of carcinogenesis in this important group of patients with lung cancer. Rather than pollution causing mutations, the authors provide compelling evidence that EGFR mutations pre-exist in healthy lung tissue and that PM2.5 drives these cells towards a cancer stem like state, mediated by IL-1β. This finding may open up further areas for lung cancer prevention in the future but in the meantime the study highlights the importance of urgent public health measures to reduce pollution.”

Dr Neal Navani
Consultant/Associate Professor in Respiratory Medicine
University College London Hospital

Surgery

JCOG0802/WJOG4607L

Saji et al, in The Lancet present their RCT of segmentectomy vs lobectomy in small-sized peripheral NSCLC. To date, sublobar resections have not compared favourably to lobectomies as the curative treatment of choice in lung cancer, largely due to greater risk of local relapse. However, lung sparing surgery holds numerous advantages and given the likely increase in the incidence of early stage lung cancers, with the advent of screening programmes, the authors aimed to demonstrate non-inferiority.

Adaptation of Lungs_diagram_detailed.svg by Patrick Lynch showing example tumors (black) and the extent of the major surgery options to remove them, used under a CC BY 4.0 International license.

This was a multi-centre RCT across 70 hospitals in Japan, with 1106 patients enrolled from 2009-2014. Patients with stage 1A, small (≤2cm, consolidation-to-tumour ratio >0.5), peripheral NSCLC were recruited with a median follow-up of 7.3 years.

5-year overall survival in lobectomy vs segmentectomy was 91% vs 94% (HR 0.66, p<0.0001) and the 5-year relapse free survival was 88% vs 88% (HR 0.998), respectively. Segmentectomies had a greater rate of locoregional recurrence (11% vs 5%), but 5-year survival for this group was still greater, with the authors suggesting that due to lung sparing, these patients were more likely to be offered further curative surgery, after recurrence. Adverse events between groups were comparable.

The authors conclude that segmentectomy should now be the standard of care for patients with small, peripheral NSCLC.  

https://doi.org/10.1016/s0140-6736(21)02333-3

“For a generation, pulmonary lobectomy has been the procedure of choice for early-stage lung cancer. Recent changes in imaging, earlier diagnosis and screening have led the lung cancer community to question this. Saji’s paper on behalf of JCOG and WJOG has been a welcome addition to the evidence and confirms the non-inferiority of anatomical segmentectomy compared to lobectomy for small peripheral lung cancers <2cm.

A similar study was also published this year (PMID 36780674and is worthwhile reading in conjunction. The main difference with this study was that wedge resections as well as segmentectomies were included as sublobar options.

The emergence of other potential modalities to treat stage 1 lung cancers (SABR, ablation, with or without targeted therapies) is really exciting. It is important that surgical options are included in patient choice, with the acceptance that any treatment pathways should be evidence based. Saji’s paper has provided significant evidence of the benefits of segmentectomy. I would however tone down the conclusion to “segmentectomy should be considered as a potential option for this population of patients”.

Mr Alan Kirk
Consultant Thoracic Surgeon
West of Scotland Regional Heart & Lung Centre

Medical Oncology

CODEBREAK200
Sotorasib AMG510 binding to KRAS G12C protein Orange Switch II domain Yellow C12, used under a CC BY 4.0 International license.

In an industry-sponsored phase 3, randomised, open label study across 148 international centres, de Langen et al report the disease control and survival outcomes for sotorasib compared with docetaxel in pre-treated KRAS-G12C mutant NSCLC.

Recruited patients had ≥1 previous line of platinum-based chemotherapy, or immunotherapy, and brain metastases must have been treated and asymptomatic. Sotorasib was given as 960mg as a once-daily tablet, and docetaxel as 75mg/m2 every 3 weeks intravenously, both until progression or intolerance. Randomisation was stratified by previous lines of therapy, ethnicity and CNS metastases. The primary endpoint was progression-free survival (PFS) based on the intention-to-treat population.

After a median follow-up of 18 months, n=171 patients received sotorasib, n=174 received docetaxel. The median PFS was 5.6 months for sotorasib compared with 4.5 months for docetaxel (p=0.0017). The sotorasib arm had fewer grade ≥3 (33% versus 40%) and serious treatment-related adverse events (11% versus 23%) compared to the docetaxel arm. The most common side effects of sotorasib were diarrhoea and transaminitis.

The investigators concluded that sotorasib is an effective second-line systemic therapy, and has a favourable efficacy and toxicity profile compared with docetaxel.

https://doi.org/10.1016/s0140-6736(23)00221-0

“Sotorasib is likely to make a big clinical difference in disease control in the second line setting. This might not be true for first-line, as the KRAS G12C patient cohort is often  sensitive to checkpoint inhibitors and chemo, unlike other mutational drivers. We may see more progress with sotorasib in combination with other drugs. As always, testing of all patients will be key for patients to benefit from this targeted therapy.”

Professor Samreen Ahmed
Consultant Medical Oncologist
University Hospitals of Leicester

Clinical oncology

PET-BOOST

In a multicentre, phase 2, randomised study, Cooke et al recently reported on the outcomes from integrating PET/CT appearances to guide dose escalation in stage II-III disease.

Image copyright ERS 2017 used under a CC BY 4.0 International license.

Patients were randomised between two 24-fraction dose-escalated chemoradiotherapy plans: either 70Gy+ to the whole planning target volume (PTV) or 70Gy+ to the whole PTV plus ~10Gy to FDG-avid region.

The two treatment plan options were ‘pulmonary isotoxic’ in that the mean lung doses were equivalent in both (mean lung dose 19.5–20.5Gy). Heart dose constraints were mean <46Gy, maximum <70.6Gy. The primary endpoint was freedom from local failure at 1-year (FFLF).

The trial closed early due to slow recruitment and therefore was underpowered to meet statistical significance, but n=54 got ‘whole PTV’ dose-escalation and n=53 got ‘FDG-avid sub-volume’ dose escalation. The 1-year FFLF was 97% versus 91% and the 1-year PFS 46% versus 43%. The grade 3 event rate was 43% versus 38% and 15 of the 19 grade 5 events were possibly RT-related so neither arm proceeded to a larger trial. For grade 5 events, there were 7 x haemorrhage, 6 x cardiac events, 4 x respiratory events, 4 x fistulae.

The authors conclude that dose escalation in unselected locally advanced NSCLC is currently not warranted.

https://doi.org/10.1016/j.radonc.2023.109492

“In 2010 this study was a trailblazer by using functional imaging, isotoxic doses and complex planning strategies. The 1-year FFLF is greater than other dose escalation trials but there is a high associated toxicity cost. The premise of tumour sub-volume dose escalation based on 18F-FDG is lacking, but newer tracers as tools to direct radiotherapy are an exciting ongoing strategy. This study shows that there is still merit in well-designed dose escalation radiotherapy trials in NSCLC.”

Dr Stephen Harrow

Consultant Clinical Oncologist Thoracic Malignancies & OMD
Clinical Lead – Scottish Cancer Research Network
Clinical Lead – Cancer Innovation
NHS Scotland Research Fellow
Edinburgh Cancer Centre

Noticeboard

  • Check out the RCR’s new stage III lung cancer practice case on the ARENA platform (access via RCR Learning website)
  • Ongoing trainee project – Oncogenic NSCLC Radiotherapy Outcomes. This multicentre retrospective analysis aims to investigate if cancer control outcomes are the same in patients receiving radiotherapy for NSCLC with a mutation compared with those without a mutation. Contact Gerard Walls if your centre would be interested – g.walls@qub.ac.uk.

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 Abstract Submission and Registration Opens Wednesday 18th October 2023

BTOG 2024 (Belfast, 17th – 19th April, 2024)
  • Original, previously unpublished, research or audit carried out by your department or group.
  • Encores – previously submitted/presented at another conference – must contain additional information or data to the original and the previous submission/presentation must be declared on the submission.
  • Case reports can be submitted but these are generally only accepted if there is a significant learning point associated with the case or series of cases.

Dates for your diary

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