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Robert Campbell Rintoul
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MA 11 - Emerging Diagnostic/Biomarkers in NSCLC (ID 668)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:M.I. Abdul Wahid, Martin Reck
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 313 + 314
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MA 11.02 - Circulating Tumour DNA in Early Stage NSCLC: High Sensitivity Analysis in Low Burden Disease. LUCID Study Update (ID 9598)
11:05 - 11:10 | Presenting Author(s): Robert Campbell Rintoul
- Abstract
- Presentation
Background:
To improve treatment selection and outcomes for patients with early stage non-small cell lung cancer (NSCLC) the development of an effective biomarker to diagnose and characterise the tumour and to detect residual disease after curative-intent treatment is crucial. Circulating tumour DNA (ctDNA) is a promising means to detect and track tumours non-invasively, as the genomic alterations in plasma are representative of the tumour’s clonal populations and their levels correlate with the burden of disease. Furthermore, ctDNA has shown promise for detecting minimal residual disease after treatment in several cancer types. This could help in the selection of patients that, after surgery or radical radiotherapy, will benefit from subsequent treatment. Nonetheless, more sensitive techniques are needed to enable the detection and study of ctDNA at very low concentrations in settings such as these.
Method:
The LUCID study (early stages of non-small cell LUng cancer - CIrculating tumour DNA) was designed to prospectively collect plasma samples from patients with early-stage NSCLC before and after treatment with surgery or radiotherapy (±chemotherapy), and during a minimum follow up of 3 years after diagnosis, in order to explore the clinical utility of ctDNA. For high sensitivity detection of ctDNA, TAilored Panel Sequencing (TAPAS) was developed: exome sequencing of tumour tissue enables the creation of patient-specific panels to analyse in parallel, large numbers of mutations with high sequencing depth. Plasma samples are being analysed using this approach to assess the levels of ctDNA at diagnosis and after radical treatment.
Result:
100 patients were recruited to the study. Longitudinal plasma sample collection and analysis are on-going. Preliminary analysis of the tumour tissue and pre-surgical plasma samples from 19 surgical patients show that most patients with early-stage NSCLC have detectable ctDNA. Analysis of additional samples will be presented.
Conclusion:
Preliminary data from LUCID suggest that the methods we have developed have high sensitivity and will allow detection of ctDNA at rates higher than previously reported. These methods will enable the study of ctDNA in early-stage cancers. We are also exploring the utility of these techniques for detection of minimal residual disease after radical treatment, as a potential tool to guide adjuvant or subsequent post-radiotherapy treatment.
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OA 02 - Mesothelioma: Challenges For New Treatment (ID 653)
- Event: WCLC 2017
- Type: Oral
- Track: Mesothelioma
- Presentations: 1
- Moderators:S. Hasegawa, Anna Nowak
- Coordinates: 10/16/2017, 11:00 - 12:30, F205 + F206 (Annex Hall)
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OA 02.03 - Prophylactic Irradiation of Tracts (PIT) in Patients with Pleural Mesothelioma: Results of a Multicentre Phase III Trial (ID 7980)
11:20 - 11:30 | Author(s): Robert Campbell Rintoul
- Abstract
- Presentation
Background:
It has been widespread practice across Europe to irradiate diagnostic or therapeutic chest wall (CW) intervention sites in patients with malignant pleural mesothelioma (MPM) post-procedure - a practice known as prophylactic irradiation of tracts (PIT). This study aims to determine the efficacy of PIT in reducing the incidence of CW metastases following a chest wall procedure in MPM.
Method:
In this multicentre phase III randomised controlled trial, MPM patients following a chest wall procedure were randomised 1: 1 to receive PIT (within 42-days of procedure) or no PIT. Large thoracotomies, needle biopsy sites and indwelling pleural catheters were excluded. PIT was delivered at a dose of 21Gy in 3 fractions over 3 consecutive weekdays using a single electron field adapted to maximise coverage of the tract from skin surface to pleura. The primary outcome was the incidence of CW metastases within 6 months from randomisation, assessed in the intention-to-treat population. Stratification factors included epitheloid histology and intention to give chemotherapy. Trial registration number NCT01604005.
Result:
375 patients (186 PIT and 189 no PIT) were randomised between 06/2012-12/2015 from 54 UK centres. Comparing PIT vs no PIT, %male patients was 89.8/88.4%, median age 72.8/74.6 years, %ECOG PS (0,1,2) 32.2,56.5,11.3/23.8,56.1,20.1%, %confirmed epithelioid histology 79.6/74.1%, and %with intention to give chemotherapy 71.5/71.4%. The chest wall procedures were VATS (58.1/51.3%), open surgical biopsy (2.7/5.3%), local-anaesthetic-thoracoscopy (26.9/27.0%), chest drain (5.9/8.5%) and others (6.5/7.9%) for the PIT vs no PIT arm respectively. Radiotherapy was received as intended by 181/186 patients in the PIT arm. The proportion of CW metastases by 6 months was 6/186 (3.2%) vs 10/189 (5.3%) for the PIT vs no PIT arm respectively (odds ratio 0.60 [95% CI 0.17-1.86]; p=0.44) and by 12 months 15/186 (8.1%) versus 19/189 (10.1%) respectively (OR=0.79 [95% CI 0.36-1.69];p=0.59). Cumulative incidence of CW metastases at 6months/12 months/24 months was 3.3/8.5/10.0% in the PIT arm vs 5.6/10.9/18.7% in the no PIT arm. Evaluable patients who developed CW metastases reported a mean increase in visual analogue scale pain score of 13.3 (p<0.01) compared to baseline. Skin toxicity was the most common radiotherapy-related adverse event in the PIT arm with 96(51.6%) grade 1, 19(10.2%) grade 2, and 1(0.5%) grade 3 radiation dermatitis (CTCAE V4.0). There were no other grade 3 or higher radiotherapy-related adverse events.
Conclusion:
There is no role for the routine use of PIT following diagnostic or therapeutic CW procedures in patients with MPM.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P3.05 - Early Stage NSCLC (ID 721)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.05-001 - Breath Analysis for Early Detection of Lung Cancer: The LuCID Study (ID 10067)
09:30 - 09:30 | Author(s): Robert Campbell Rintoul
- Abstract
Background:
There is an urgent need for methods to detect lung cancer earlier. If detected early, over half of lung cancer patients could be cured with existing treatments. Therefore, our greatest opportunity lies in increasing rates of early diagnosis through improved cancer screening. Exhaled breath contains over 1,000 Volatile Organic Compounds (VOCs), which are the products of metabolic activity, hence they directly reflect the current state of cells and represent a valuable source of information about the health of an individual. As the earliest stages of tumour development are characterized by profound changes in cellular metabolic activity, VOCs are potential non-invasive biomarkers for early detection of lung cancer. The LuCID study aims to collect breath samples and evaluate VOCs in exhaled breath as non-invasive biomarkers for early detection of lung cancer.
Method:
LuCID is an international multi-centre prospective case-control cohort study (ClinicalTrials.gov ID NCT02612532) currently in progress, evaluating breath VOCs in patients with a clinical suspicion of lung cancer. A clinical suspicion is based on symptoms and/or suspicious finding on incidental imaging. Using tidal breathing, patients breathe into the ReCIVA Breath Sampler for 7 minutes to collect alveolar- and bronchial-enriched breath fractions on stable sorbent tubes for later analysis by Gas Chromatography-Mass Spectrometry and Field Asymmetric Ion Mobility Spectrometry (FAIMS, Owlstone Medical Ltd). A classification algorithm will be constructed from chemical spectral data, and undergo internal and external blinded validation to provide a ROC-curve detailing diagnostic accuracy. The LuCID study has an adaptive trial design, recruiting up to 2,600 patients depending on interim results.
Result:
The LuCID study has recruited 980 patients to date from 20 centres (mean age 67.5, SD 12.0). Of patients with completed follow-up (n=802), 33% have histologically confirmed lung cancer (of those with lung cancer: 40% early stage 1a-2b, 60% advanced stage 3a-4). Non Small Cell Lung Cancer (NSCLC) comprised 87% of these cancers, and Small Cell Lung Cancer 9%. NSCLC were further categorized as adenocarcinoma (50%), squamous cell carcinoma (38%), with the remaining 12% belonging to other categories.
Conclusion:
The LuCID study is evaluating the analysis of exhaled VOC biomarkers as a new diagnostic modality for early detection of lung cancer. Successful completion of the LuCID study will pave the way for the development of a non-invasive, easy-to-implement test that could markedly improve screening and early detection rates, reducing lung cancer morbidity and mortality.
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WS 01 - IASLC Supporting the Implementation of Quality Assured Global CT Screening Workshop (By Invitation Only) (ID 632)
- Event: WCLC 2017
- Type: Workshop
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/14/2017, 08:30 - 21:00, F203 (Annex Hall)
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WS 01.18 - Lung Cancer Indicator Detection Trial (LuCID) (ID 10656)
11:45 - 12:00 | Author(s): Robert Campbell Rintoul
- Abstract
Abstract:
Background There is an urgent need for methods to detect lung cancer earlier. If detected early, over half of lung cancer patients could be cured with existing treatments. Therefore, our greatest opportunity lies in increasing rates of early diagnosis through improved cancer screening. Exhaled breath contains over 1,000 Volatile Organic Compounds ﴾VOCs﴿, which are the products of metabolic activity, hence they directly reflect the current state of cells and represent a valuable source of information about the health of an individual. As the earliest stages of tumour development are characterized by profound changes in cellular metabolic activity, VOCs are potential non‐invasive biomarkers for early detection of lung cancer. The LuCID study aims to collect breath samples and evaluate VOCs in exhaled breath as non‐invasive biomarkers for early detection of lung cancer. Method LuCID is an international multi‐centre prospective case‐control cohort study ﴾ClinicalTrials.gov ID NCT02612532﴿ currently in progress, evaluating breath VOCs in patients with a clinical suspicion of lung cancer. A clinical suspicion is based on symptoms and/or suspicious finding on incidental imaging. Using tidal breathing, patients breathe into the ReCIVA Breath Sampler for 7 minutes to collect alveolar‐ and bronchial enriched breath fractions on stable sorbent tubes for later analysis by Gas Chromatography‐Mass Spectrometry and Field Asymmetric Ion Mobility Spectrometry ﴾FAIMS, Owlstone Medical Ltd﴿. A classification algorithm will be constructed from chemical spectral data, and undergo internal and external blinded validation to provide a ROC‐curve detailing diagnostic accuracy. The LuCID study has an adaptive trial design, recruiting up to 2,600 patients depending on interim results. Figure 1 Results The LuCID study has recruited 980 patients to date from 20 centres ﴾mean age 67.5, SD 12.0﴿. Of patients with completed follow‐up ﴾n=802﴿, 33% have histologically confirmed lung cancer ﴾of those with lung cancer: 40% early stage 1a‐2b, 60% advanced stage 3a‐4﴿. Non Small Cell Lung Cancer ﴾NSCLC﴿ comprised 87% of these cancers, and Small Cell Lung Cancer 9%. NSCLC were further categorized as adenocarcinoma ﴾50%﴿, squamous cell carcinoma ﴾38%﴿, with the remaining 12% belonging to other categories. Most recent data on study progress and results will be presented at the conference. Conclusion The LuCID study is evaluating the analysis of exhaled VOC biomarkers as a new diagnostic modality for early detection of lung cancer. Successful completion of the LuCID study will pave the way for the development of a non‐invasive, easy‐to‐implement test that could markedly improve screening and early detection rates, reducing lung cancer morbidity and mortality.
