Lung Cancer

39MO Genomic framework of lung carcinoid: Analysis of the AACR GENIE database (2025)

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Type of publication:

Conference abstract

Author(s):

Immanuel A.; *Arunachalam J.; Advani K.

Citation:

ESMO Open. Conference: The ESMO Sarcoma and Rare Cancers Congress 2025. Lugano Switzerland. 10(Supplement 3) (no pagination), 2025. Article Number: 104350. Date of Publication: 01 Mar 2025.

Abstract:

Background: Carcinoid tumors, rare neuroendocrine tumors, occur in the lungs in approximately 25% of cases. The 5-year survival rate for lung carcinoid in the US is 98% for localized disease and 86% for regional disease, with a drop to 55% for metastatic cases. Patients with metastasis are often treated with temozolomide-based chemotherapy, mTOR inhibitors (everolimus), platinum-based chemotherapy, or peptide receptor radionuclide therapy. We aim to investigate potential unexplored genetic targets. We intend to explore if there is a role for immunotherapy for treatment for lung carcinoid as it is generally better tolerated and less toxic compared to chemotherapy. Method(s): Using the cBioPortal platform, we accessed the AACR GENIE version 15.0 database. Demographic data were gathered from patients with lung carcinoid. We outlined the frequency of mutated genes, copy number alterations, and structural variations in the population. Result(s): We analyzed 242 patients and 253 samples. 73.1% of the patients were females and 26.9% were males. 74.7% of samples were collected from a lung primary, while 16.2% of samples were from metastatic sites. The median age at sequencing was 62 years. The highest frequency of mutations was seen in LRP1B gene (18.4%), followed by the MN1 gene (15.8%) and the ARID1A gene (11.8%). The most structural variants were found in the MEN1 gene at 0.9% (n =2, total number of profiled samples = 226). The most common copy number alteration was PDCD1 (n=5, number of profiled samples=134) at 3.7% and CCND1 on 11q13.3 (n=4, number of profiled samples=201) at 2%. Conclusion(s): Prior studies have shown that one of the most frequently mutated pathways in pulmonary carcinoids involves MEN1 gene. We found that genomic alterations in LRP1B, ARID1A, PDCD1 and CCND1 are also frequently observed. It is well known that anti-PD1 therapy is efficient in PD1 expressing cancers. LRP1B mutation in lung cancers has been shown to affect the immune microenvironment and enhance the efficacy of immune checkpoint inhibitors. While ARID1A mutations correlate with longer median overall survival when treated with immunotherapy. The limited number of ongoing clinical trials on targeted therapies underscores the clear need to explore the genomic targets for precision therapies in lung carcinoids.

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259 Shortened High-dose Palliative Radiotherapy (SHiP-Rt) for Lung Cancer - a Single-arm, Multi-centre, Phase-II Study (NCT06483308) (2025)

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Type of publication:

Conference abstract

Author(s):

Raj S.; Ellanna G.; Vicky S.; Jo H.; Matthew J.; Louise H.; Manreet T.; Apurna J.; Qamar G.; *Anirban C.; Charles P.; Jane R.; Bleddyn J.; Janet D.

Citation:

Lung Cancer. Conference: 23rd Annual British Thoracic Oncology Group Conference 2025. Belfast Ireland. 200(Supplement 1) (no pagination), 2025. Article Number: 108368. Date of Publication: 01 Feb 2025.

Abstract:

Introduction Significant advances in systemic therapy have improved survival for patients with advanced-stage non-small cell lung cancer (NSCLC). However, current treatment strategies and dose-fractionation for high-dose palliative radiotherapy (RT) are based on trials from the 1990s, when RT planning was simple, typically parallel-pair or 3-dimensional conformal, with less precise delivery. Contemporary lung RT uses 4D-CT, volumetric modulated arc radiotherapy (VMAT), aided by online cone beam CT verification, which enable greater accuracy, better target volume coverage, whilst reducing doses to normal organs at risk. Methods and Results: The SHiP-Rt study aims to evaluate the safety and efficacy of reducing the number of RT fractions and RT duration, using contemporary planning, verification, and delivery techniques. This single-arm, multi-centre, phase-II study will evaluate the shortened hypofractionated accelerated palliative RT regimen of 30 Gy in 6 alternate-day fractions, with strict normal tissue dose constraints. We aim to recruit 37 patients, across 4 sites within the West Midlands. The RTTQA will support quality assurance for the RT. Patients with locally-advanced or metastatic NSCLC, who are candidates for high-dose palliative RT, before or after first-line systemic therapy are eligible for recruitment. The primary objective of this study is to assess the safety of the proposed dose-fractionation. Secondary objectives include evaluating toxicity profiles, patient-reported outcome measures (PROMS), Time to Progression (TTP), feasibility and the NHS cost-saving. Developed in collaboration with the Warwick CTU, this study was favourably reviewed by NCRI CTRad, NCRI lung CSG, and the RTTQA. Funding was awarded by the UHCW Charity and Coventry Hospitals Charity. Conclusion This study is open to recruitment. The potential advantages from this regimen include RT given in fewer fractions and hospital visits, resulting in cost-savings for the NHS and opportunity benefits for other patients. If successful, this study will support a phase-III randomised controlled trial to assess efficacy.

A Plasma Proteomics-Based Model for Clinical Benefit Prediction in Small Cell Lung Cancer Patients Receiving Immunotherapy (2024)

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Type of publication:

Conference abstract

Author(s):

Gandara D.R.; Carbone D.P.; Dicker A.P.; Christopoulos P.; Puzanov I.; Jain P.; Farrugia D.; Brown S.; Moskovitz M.; Bar J.; Hassani A.; *Chatterjee A.; Abu-Amna M.; Polychronis A.; Brewster A.; Lou Y.; VanderWalde N.A.; Gottfried M.; Lahav C.; Lowenthal G.; Sela I.; Harel M.; Elon Y.; Schneider M.A.

Citation:

Journal of Thoracic Oncology. Conference: The 2024 World Conference on Lung Cancer. San Diego United States. 19(10 Supplement) (pp S354-S355), 2024. Date of Publication: October 2024.

Abstract:

Introduction: Small cell lung cancer (SCLC) is an aggressive disease with limited treatment options. Immune checkpoint inhibitor (ICI) therapy with concurrent chemotherapy is the preferred first-line treatment for patients with extensive-stage SCLC. However, the addition of ICIs to chemotherapy only modestly improves clinical outcomes while posing a risk of ICI-related toxicities. Thus, identifying patients likely to benefit from ICIs is critical for optimizing treatment decisions. Here, we describe a test derived from a novel computational model that analyzes pretreatment plasma proteomic profiles to predict clinical outcomes in patients with SCLC receiving ICI-based therapies. Method(s): An observational study collected pretreatment plasma samples from 79 patients with extensive-stage SCLC treated with ICI-based therapy (NCT04056247). Proteomic profiling of plasma samples was performed using aptamer-based technology, measuring approximately 7000 proteins per sample. A machine learning model was developed to predict the clinical benefit (CB) from ICI-based therapy, where CB was defined as 6-month progression-free survival. Given the limited cohort size, CB prediction was achieved by integrating two computational models. Model 1, based on 146 plasma proteomic biomarkers, was developed from the SCLC dataset using cross-validation. Model 2, based on a 4-protein signature, was developed from a previously reported NSCLC dataset (Christopoulos et al. JCO prec. onc. 2024). The hybrid model stratified patients into two groups (i.e., 'positive' or 'negative') based on a pre-defined CB probability threshold. Bioinformatic analysis of the SCLC-specific proteomic biomarkers was performed to gain insight into the potential mechanisms driving ICI therapeutic benefit and resistance in SCLC. Result(s): The model displayed a robust predictive capability, as demonstrated by the area under the curve (AUC) of the receiver operating characteristic (ROC) plot of 0.63 (p-value = 0.02) and a high correlation between the predicted CB (i.e., model output) and the observed CB rate (R2 = 0.93). Furthermore, overall survival (OS) was significantly longer in patients stratified to the positive group compared to those in the negative group. Median OS was 14 months versus 8.8 months in positive versus negative patient groups (Hazard ratio = 0.47, 95% Confidence interval: 0.25-0.90, p-value = 0.02). Bioinformatic analysis of model proteins revealed significant enrichment of lung tumor-associated proteins, poor prognostic factors in lung cancer, extracellular matrix-related proteins, intermediate filaments, and replicative immortality (Fisher exact test; FDR<0.1). Multiple model proteins are also known to be involved in fibroblast growth factor signaling and glutathione metabolism. Given their association with different treatment resistance mechanisms, such proteins represent potential targets for intervention. Conclusion(s): We describe preliminary results from a novel pretreatment plasma proteomics-based predictive model that can potentially inform treatment decisions for patients with SCLC. Bioinformatic analysis demonstrates that the model is based on a composite of biologically and clinically relevant biomarkers. The potential clinical utility of this model is being investigated in a large prospective clinical trial.

Social Isolation and Lung Cancer: Does This Impact the Length of Time on The Lung Cancer Pathway Or Uptake Of MDT Recommended Treatments (2024)

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Type of publication:
Conference abstract

Author(s):
Anderson V.; Dalrymple P.; Crowley G.; Shephard P.; Holmes C.; *McAdams J.; Morley J.; Sarah E.; Ivey S.; Bentley K.; Bate G.B.; English P.; Russell G.; Bostock L.

Citation:
Lung Cancer. Conference: 22nd Annual British Thoracic Oncology Group Conference 2024. Belfast United Kingdom. 190(Supplement 1) (no pagination), 2024. Article Number: 107683. Date of Publication: April 2024.

Abstract:
Aims "Bridging The Gap" report by UKLCC (2022) suggested addressing health inequalities in lung cancer has a significant impact on patient outcomes. LCNUK investigated a possible correlation between social isolation (lack of social contacts and having few people to interact with regularly) and time on pathway. Methods A Literature review conducted, highlighted a lack of UK research in this area. LCNUK members were surveyed for feedback and data was collected on 90 patients across 9 regions in the UK. Results 56 completed surveys were received from LCNUK members. 50% of responders felt that social isolation impacted patient progress on the pathway & 41% believed it influenced uptake of treatment. [Formula presented] Conclusion 50% of lung cancer nurses felt social isolation would negatively impact upon the length of the pathway, this project found that to be unproven. Data suggested a possible link between social isolation and uptake of MDT recommended treatment. This is a small sample size and may not be representative of the national picture and therefore more research is needed. Disclosure: No significant relationships.

Pre-treatment plasma proteomics-based predictive biomarkers for immune related adverse events in non-small cell lung cancer (2023)

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Type of publication:
Conference abstract

Author(s):
Naidoo J.; Reinmuth N.; Puzanov I.; Bar J.; Kamer I.; Koch I.; Moskovitz M.; Levy-Barda A.; Agbarya A.; Zer A.; Abu-Amna M.; Farrugia D.; Lotem M.; Price G.; Harkovsky T.; Hassani A.; Katzenelson R.; *Chatterjee A.; Yelin B.; Sela I.; Dicker A.; Elon Y.; Harel M.; Leibowitz R.

Citation:
Journal for ImmunoTherapy of Cancer. Conference: 38th Annual Meeting of the Society for Immunotherapy of Cancer's, SITC 2023. San Diego, CA United States. 11(Supplement 1) (pp A1356), 2023. Date of Publication: November 2023.

Abstract:
Background Immune-related adverse events (irAEs) resulting from immune checkpoint inhibitors (ICIs) can substantially affect patient quality of life and treatment trajectory. Currently, there are no reliable pre-treatment biomarkers for predicting the development of irAEs; hence, there is a clinical need for irAE predictive biomarkers. Methods Plasma samples were obtained at baseline from 426 non-small cell lung cancer (NSCLC) patients treated with ICIs as part of an ongoing multi-center clinical trial (NCT04056247; approved by local IRB committees from each site) with irAE-related information. Proteomic profiling of plasma samples was performed using the SomaScan assay (SomaLogic Inc.), enabling deep coverage of approximately 7000 proteins in each sample. A machine learning-based model was developed to predict significant irAEs arising up to 3 months from treatment initiation; significant irAEs were defined as irAEs with CTCAE grade >=3 or irAEs that induced treatment discontinuation. Using the model, we identified a set of plasma proteins, termed Toxicity Associated Proteins (TAPs), that serve as indicators of irAEs depending on their plasma level in the individual patient. Bioinformatic analysis was performed to decipher the biology underlying immunerelated toxicity implied by the TAPs. Results Overall, 60 patients experienced significant irAEs at early onset; 197 patients had low grade irAEs, irAEs at late onset or AEs that are not immune-related; and 169 patients did not display any adverse event. A computational model was generated to predict significant irAEs, showing a strong correlation between the predicted probability of significant irAEs and the observed rate of such events (R2= 0.92; pvalue <0.0001), implying good prediction capabilities. The prediction was based on a set of 449 TAPs. Interestingly, nearly half of these TAPs were previously identified as proteins associated with clinical benefit from ICI therapy, suggesting a close relationship between irAEs and clinical benefit, in accordance with previous reports. A detailed examination of the TAPs revealed some key findings. Patients who experienced irAEs had a larger number of TAPs related to neutrophils, inflammation, and cell death resistance, while the number of lymphocyte-related TAPs was low in these patients. Patients who did not experience irAEs displayed higher levels of extracellular matrix-related proteins. Conclusions We describe a novel computational model for predicting significant irAEs in patients with NSCLC based on proteomic profiling of pre-treatment plasma samples. The TAPs provide insights into the biological processes underlying irAEs. Early prediction of irAEs could enable personalized management plans and mitigation strategies to reduce the risk of irAEs in NSCLC.

P2.23-07 Crucial, Complex, Caring: A Professional Development Framework for Lung Cancer Nurse Specialists (2023)

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Type of publication:Conference abstract

Author(s):Clayton K.J.; Fenemore J.; Barton P.; Roberts J.; Ivey S.; *McAdam J.; Shepherd P.; Magee L.

Citation:Journal of Thoracic Oncology. Conference: 2023 World Conference on Lung Cancer. Singapore Singapore. 18(11 Supplement) (pp S397), 2023. Date of Publication: November 2023.

Abstract:Introduction: Lung cancer specialist nursing is a varied, valuable and rewarding career, and the need for lung cancer nurse specialists (LCNS) is increasing. Lung Cancer Nursing UK (LCNUK) wants to encourage nurses to aspire to becoming an LCNS, and to support those already working in lung cancer teams to flourish professionally. We want employers to recognise LCNS' capabilities and to recruit and reward them accordingly. LCNUK therefore set out to draft the first professional development framework for LCNS. The Framework is intended to guide nurses, line managers and employers on the core skills, knowledge and expertise that LCNS will gain and demonstrate as they progress in role. Method(s): LCNUK convened a working group which reviewed exemplars and supporting literature., aligned with the four pillars of advanced practice. Feedback on the draft was sought from expert stakeholders and was approved by the LCNUK Steering Committee. The Framework was developed in a collaboration between LCNUK and MSD, who funded a policy consultancy to provide support. LCNUK retained editorial independence. Result(s): The Framework sets out the qualifications, clinical skills, knowledge, leadership and management and research capabilities that LCNUK expects aspiring and existing LCNS to demonstrate or be working towards. It includes case studies of nurses' career journeys and an example of a successful case for job matching and re-banding. The Framework is available on the LCNUK website at. Conclusion(s): The Framework asserts the crucial role of LCNS in managing safety-critical and complex patient care and in leading service delivery and improvement. We hope it will prove a valuable tool to nurses, employers and policymakers in understanding the complexity and importance of this essential role. Following collaboration with European lung cancer nursing colleagues, via ELCC 2022, while not implemented the value and importance of the framework has been acknowledged by Croatian colleagues.The framework has also been welcomed and acknowledged by the devolved nations of the United Kingdom, Wales, Scotland and Northern Ireland.

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Not All That Glows Is Malignant: Actinomycosis as a Rare Mimic of Lung Cancer (2022)

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Type of publication:Conference abstract

Author(s):*Ekhelikar S.; Muthusami R.; *Orme R.; *Ahmad N.

Citation:American Journal of Respiratory and Critical Care Medicine. Conference: International Conference of the American Thoracic Society, ATS 2022. San Francisco, CA United States. 205(1) (no pagination), 2022.

Abstract:Introduction: Pulmonary actinomycosis is a rare bacterial infection that can mimic malignant and chronic suppurative lung conditions, and therefore is often misdiagnosed initially as one of the more common differential diagnoses. The challenge lies in diagnosing this condition prior to surgery as it is completely curable with antibiotics. Case description: A 48 year old man, cigarette smoker and previous intravenous drug user, presented with exertional breathlessness, persistent cough and night sweats. There was no fever or weight loss. A Chest Xray (CXR) and Computerised Tomography (CT) scan showed a left upper lobe cavitating lesion leading to differential diagnoses of bronchogenic malignancy and tuberculosis (TB). A Positron Emission Tomography (PET) scan confirmed a fluorodeoxyglucose (FDG) avid left upper lobe cavitating lesion with enlarged FDG avid thoracic lymphadenopathy. Bronchoscopy and Endobronchial Ultrasound (EBUS) were nondiagnostic. He underwent left upper lobectomy with histopathology confirming Pulmonary actinomycosis and was commenced on Amoxicillin treatment. <br/>Discussion(s): Pulmonary actinomycosis is the third most common type of actinomycosis, behind cervicofacial and abdominal, constituting 15% of total cases. It can occur at all ages, but most case series describe a peak incidence in the 4th and 5th decades. Symptoms are non-specific and often mimic those of it's more common differentials as above and so diagnosing this condition early presents a challenge. Basic laboratory tests reflect the non-specific inflammatory nature of the disease. Imaging modalities (CXR, CT, PET) are helpful, but not diagnostic. The gold standard for diagnosis remains histological examination & bacterial culture of lung biopsy specimen. Histopathologic evidence of granulomas containing neutrophils and sulfur granules with Actinomyces colonies are the hallmark of actinomycosis. Recent data suggests it is increasingly possible to avoid unwarranted surgical procedures, by performing bronchoscopic and percutaneous biopsy techniques. These represent the best chance at preventing unnecessary surgery and should be pursued as they can help exclude malignancy. Penicillin remains the drug of choice for Pulmonary actinomycosis and with correct treatment, the prognosis is excellent. However, those with complications may still require surgery. The chief challenge with Pulmonary actinomycosis is identifying it early, because it is rare, and it also mimics diseases like lung cancer and TB often. We were unable to exclude malignancy with pre-surgical diagnostics and so our patient had surgery. However, clinicians should be aware and consider Pulmonary actinomycosis as an important differential when investigating cavitating lung lesions as diagnosing it early could help prevent physical and psychological morbidity, including unwarranted surgery. (Figure Presented).

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Direct to surgery treatment of suspected lung cancer – results from a UK lung cancer multidisciplinary team (MDT) (2021)

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Type of publication:
Conference abstract

Author(s):
*Manoj Marathe, *Tinaye Mandishona, *Harmesh Moudgil, *Nawaid Ahmad, *Emma Crawford, *Annabel Makan, *Koottalai Srinivasan

Citation:
European Respiratory Journal 2021 58 Suppl 65, OA2640

Abstract:
Introduction: The selective resection of suspicious nodules and masses without pre-operative tissue diagnosis is an established treatment that can shorten time to curative lung cancer treatment. We evaluated the outcomes of this practice in our local MDT.
Methods: We performed a retrospective review of 84 patients with curatively resectable single lung lesions who underwent surgical resection from January 2017 to December 2018 without histological diagnosis.
Results: Malignancy was confirmed in 68/84 (81%) patients. 57/68 patients were diagnosed with a primary lung malignancy and 11/68 with metastatic disease. Figures 1 and 2 show significant and non significant differentiators determined by the chi squared test.
Conclusion: These results support the use of spiculated and / or irregular lesion appearance along with SUV uptake >=2.5 as significant pre-histology differentiators of malignant and benign lesions. Neither past history of cancer nor size of lesion in isolation were predictive of malignancy. Our study gives further evidence that a direct-to-surgery approach is a suitable treatment option for appropriate suspicious nodules.

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COVID-19 and the multidisciplinary care of patients with lung cancer: an evidence-based review and commentary (2021)

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Type of publication:
Journal article

Author(s):
Round, Thomas; L'Esperance, Veline; Bayly, Joanne; Brain, Kate; Dallas, Lorraine; Edwards, John G; Haswell, Thomas; Hiley, Crispin; Lovell, Natasha; *McAdam, Julia; McCutchan, Grace; Nair, Arjun; Newsom-Davis, Thomas; Sage, Elizabeth K; Navani, Neal

Citation:
British Journal of Cancer; Aug 2021; vol. 125 (no. 5); p. 629-640

Abstract:
Delivering lung cancer care during the COVID-19 pandemic has posed significant and ongoing challenges. There is a lack of published COVID-19 and lung cancer evidence-based reviews, including for the whole patient pathway. We searched for COVID-19 and lung cancer publications and brought together a multidisciplinary group of stakeholders to review and comment on the evidence and challenges. A rapid review of the literature was undertaken up to 28 October 2020, producing 144 papers, with 113 full texts screened. We focused on new primary data collection (qualitative or quantitative evidence) and excluded case reports, editorials and commentaries. Following exclusions, 15 published papers were included in the review and are summarised. They included one qualitative paper and 14 quantitative studies (surveys or cohort studies), with a total of 2295 lung cancer patients data included (mean study size 153 patients; range 7-803). Review of current evidence and commentary included awareness and help-seeking; lung cancer screening; primary care assessment and referral; diagnosis and treatment in secondary care, including oncology and surgery; patient experience and palliative care. Cross-cutting themes and challenges were identified using qualitative methods for patients, healthcare professionals and service delivery, with a clear need for continued studies to guide evidence-based decision-making.

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Can Improving Working Partnerships with Primary Care Prevent Avoidable Emergency Admissions for Patients with Lung Cancer? (2018)

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Type of publication:
Conference abstract

Author(s):
Morley J.; Anderson V.; Beattie V.; Clayton K.; Denby D.; Eaton M.; Glover S.; Griffiths A.; Maddock N.; *McAdam J.; Morgan S.; Rees P.; Perkins T.; Phillips S.; Pugh B.; Roberts J.; Robinson W.; Rose P.

Citation:
Journal of Thoracic Oncology; Oct 2018; vol. 13 (no. 10)

Abstract:
Background: A literature search was performed. Primary Care Professionals (PCP'S) and National Lung Cancer Forum for Nurses (NLCFN) members were surveyed. Patients with a known diagnosis of lung cancer and their carers were interviewed following emergency care admissions. Lung Cancer Nurse Specialists (LCNS) from 15 NHS Trusts/Health Boards (HB) throughout the United Kingdom participated in data collection between May and August 2017. Method: A literature search (CINAHL, Embase, Proquest, PubMed, Medline) was performed. 120 PCP's from 7 CCG's/HB were surveyed to ask how and why they would contact a LCNS; any difficulties experienced contacting a LCNS and what support the LCNS could provide. 86 (72%) responded. 27 patients and their carers from 5 NHS/HB who were admitted as an emergency with a symptom related to their lung cancer were interviewed by a LCNS. A questionnaire was sent to all NLCFN members, asking "What do you do in your current practice to help prevent avoidable emergency hospital attendances?" Result: There was no published literature specific to the project aim. 46 (53%) PCP's knew how to contact the LCNS, 24 (28%) did not and 16 (19%) were unaware the service existed. PCP's reported that the LCNS could improve communication and provide education and specialist advice to help reduce avoidable emergency admissions. Following review by the LCNS, 25 (92%) of emergency admissions were deemed necessary. 2 (8%) patients contacted 999, with the rest seeking advice from the LCNS, Acute Oncology Service or GP prior to admission. 282 NLCFN members were surveyed with 59 respondents. Findings highlighted wide variations in practice, although a number of common themes were evident. Proactive communication with patients and HCP's and timely referrals and signposting were key to identifying and addressing potential problems as early as possible. Conclusion: This small data sample suggests that patients were admitted appropriately. The NLCFN survey highlighted the role of the LCNS in providing expert specialist knowledge and advice to patients and Health Care Professionals throughout the patients journey. PCP's expressed that they would like to know more about the role of the LCNS and would value better means of communication, advice and specialist support to improve patient care.